Device for preparing hydrogel microspheres and method for preparing the same

Abstract

The application relates to the technical field of biomaterial preparation, and discloses a preparation device and a preparation method of hydrogel microspheres. The preparation device comprises: an aqueous phase preparation unit configured to prepare an aqueous phase solution, the aqueous phase preparation unit being connected with one end of a fluid conveying unit; a reaction emulsification unit configured to be used for oil phase preparation, emulsification and crosslinking reaction, the reaction emulsification unit being connected with the other end of the fluid conveying unit, and the aqueous phase solution being conveyed into the reaction emulsification unit; and a main control system electrically connected with the reaction emulsification unit and the aqueous phase preparation unit. The preparation device can integrate the preparation of the aqueous phase and the oil phase, uniform emulsification, crosslinking solidification and temperature control into one, and can significantly improve the particle size uniformity of the hydrogel microspheres, production efficiency and process stability.

Description

Technical Field

[0001] This invention relates to the field of biomaterial preparation technology, and in particular to a device and method for preparing hydrogel microspheres. Background Technology

[0002] Hydrogel microspheres have attracted widespread attention due to their unique properties in controlled drug release, cosmetic encapsulation, tissue engineering, and biomaterials. Traditional processes for preparing hydrogel microspheres involve dispersed equipment, leading to complex operations, frequent material transfers, increased contamination risks and production costs, and hindering the continuity and stability of microsphere preparation. Furthermore, ensuring droplet uniformity during emulsification is difficult, resulting in a wide droplet size distribution, affecting the consistency of microsphere performance and consequently impacting the reliability and stability of microsphere preparation. Summary of the Invention

[0003] The present invention aims to solve at least one of the technical problems existing in the prior art or related art.

[0004] In view of this, the present invention provides a preparation apparatus and method for hydrogel microspheres, wherein the preparation apparatus can integrate the preparation of aqueous phase and oil phase, uniform emulsification, cross-linking and curing and temperature control into one unit, which can significantly improve the particle size uniformity, production efficiency and process stability of hydrogel microspheres.

[0005] Specifically, the following technical solutions are included: According to a first aspect of the present invention, an apparatus for preparing hydrogel microspheres is provided. The apparatus includes: An aqueous phase preparation unit is configured to prepare an aqueous solution, and the aqueous phase preparation unit is connected to one end of a fluid delivery unit. A reactive emulsification unit is configured for oil phase preparation, emulsification, and crosslinking reactions. The reactive emulsification unit is connected to the other end of the fluid delivery unit to deliver the aqueous phase solution into the reactive emulsification unit. The main control system is electrically connected to the reaction emulsification unit and the aqueous phase preparation unit.

[0006] Optionally, the reactive emulsification unit includes: The reaction vessel is equipped with a sealing cover; A mechanical stirrer, including a stirring paddle, the stirring paddle passing through the sealing cover, the stirring paddle being disposed inside the reaction vessel, and the mechanical stirrer being electrically connected to the main control system; A magnetic heating stirrer is disposed at the bottom of the reaction vessel. The magnetic heating stirrer includes a first electric heating element and a first magnetic stirrer, which are electrically connected to the main control system.

[0007] Optionally, the reactive emulsification unit further includes: An ultrasonic emulsifier includes an amplitude rod and an ultrasonic probe connected to each other. The amplitude rod passes through the sealing cover, and the ultrasonic probe is located inside the reaction vessel. The ultrasonic emulsifier is electrically connected to the main control system.

[0008] Optionally, the reactive emulsification unit further includes: An aqueous inlet is provided on the sealing cover and is connected to the other end of the fluid delivery unit. The aqueous solution enters the reactor through the aqueous inlet. A crosslinking agent inlet is provided on the sealing cap, and the crosslinking agent inlet is connected to a crosslinking agent supply device; The discharge port is located at the end of the reactor furthest from the sealing cover, and the discharge port is connected to a product collection container or a filtration device.

[0009] Optionally, the reactive emulsification unit further includes: A temperature sensor penetrates the sealing cover and is located inside the reactor. The temperature sensor is electrically connected to the main control system.

[0010] Optionally, the reactive emulsification unit further includes: A semiconductor refrigeration chip is disposed on the outer wall of the sidewall of the reactor, and the semiconductor refrigeration chip is electrically connected to the main control system.

[0011] Optionally, the aqueous phase preparation unit includes: An aqueous phase container is configured to contain the aqueous phase solution; A water-phase heating magnetic stirring table is disposed at the bottom of the water phase container. The water-phase heating magnetic stirring table includes a second electric heating element and a second magnetic stirrer. The second electric heating element and the second magnetic stirrer are respectively electrically connected to the main control system.

[0012] Optionally, the fluid delivery unit includes a delivery pump and a connecting pipe, the connecting pipe including a first pipe and a second pipe, a first end of the first pipe being connected to the aqueous phase preparation unit, a second end of the first pipe being connected to the inlet of the delivery pump, a first end of the second pipe being connected to the outlet of the delivery pump, and a second end of the second pipe being connected to the reaction emulsification unit. The delivery pump is a peristaltic pump or an injection pump, and the delivery pump is electrically connected to the main control system.

[0013] A second aspect of the present invention provides a method for preparing hydrogel microspheres, utilizing the aforementioned preparation apparatus, the method comprising the following steps: Aqueous solutions were prepared using an aqueous phase preparation unit. Oil phase solutions were prepared based on reactive emulsification units; The aqueous solution is fed into the oil phase solution, and a crude emulsion is obtained based on the reaction emulsification unit; Based on the reactive emulsification unit and the crude emulsion, a water-in-oil emulsion is obtained; Hydrogel microspheres are obtained based on the reactive emulsification unit and the water-in-oil emulsion.

[0014] Optionally, the reaction emulsification unit includes a reaction vessel, a magnetic heating stirrer, a mechanical stirrer, an ultrasonic emulsifier, a semiconductor refrigeration chip, a temperature sensor, an aqueous phase inlet, and a crosslinking agent feeding port; The preparation of the oil phase solution based on the reaction emulsification unit includes: using a hydrophobic solvent as the oil phase, adding an emulsifier, and heating and stirring in the reaction vessel using the magnetic heating stirrer to obtain the oil phase solution; The process of obtaining a crude emulsion based on the reaction emulsification unit includes: adjusting the stirring speed and heating temperature of the magnetic heating stirrer, inputting the aqueous solution into the oil solution through the aqueous inlet, while maintaining the stirring speed and heating temperature of the magnetic heating stirrer, to form the crude emulsion in which the aqueous phase is dispersed in the oil phase; The process of obtaining a water-in-oil emulsion includes: turning on the ultrasonic emulsifier to perform ultrasonic emulsification, while adjusting the stirring speed of the magnetic heating stirrer to obtain the water-in-oil emulsion, wherein the emulsification temperature is controlled by controlling the heating temperature of the magnetic heating stirrer and the semiconductor cooling chip; The process of obtaining hydrogel microspheres includes: adding a crosslinking agent solution into the water-in-oil emulsion through the crosslinking agent feeding port, turning on the mechanical stirrer and the semiconductor cooling chip, and continuously stirring under a preset temperature condition to obtain the hydrogel microspheres.

[0015] The present invention provides an apparatus and method for preparing hydrogel microspheres. The apparatus includes an aqueous phase preparation unit and a reaction emulsification unit. An aqueous solution prepared in the aqueous phase preparation unit is introduced into the reaction emulsification unit via a fluid transport unit. The apparatus also includes a main control system that controls the operation of the aqueous phase preparation unit and the reaction emulsification unit. In the reaction emulsification unit, in cooperation with the main control system, oil phase preparation, emulsification, and cross-linking reactions are performed sequentially. This avoids the cumbersome process of frequent material transfer and equipment switching in traditional processes, improving experimental efficiency, reducing the labor intensity of workers, and minimizing the risk of material loss and cross-contamination. It also improves the continuity and stability of hydrogel microsphere preparation. During the emulsification reaction, the configuration of the reaction emulsification unit and the cooperation of the main control system enable stable temperature control. Stable temperature control is also achieved during the cross-linking and curing stage, improving the reliability of the physical gelation of the hydrogel precursor and the chemical cross-linking reaction, which is beneficial for obtaining hydrogel microspheres with more stable morphology and structure.

[0016] The above description is only an overview of the technical solution of this application. In order to better understand the technical means of this application and to implement it in accordance with the contents of the specification, and to make the above and other objects, features and advantages of this application more obvious and understandable, the following are specific embodiments of this application. Attached Figure Description

[0017] To more clearly illustrate the technical solutions in the embodiments of the present invention, the accompanying drawings used in the description of the embodiments will be briefly introduced below. Obviously, the accompanying drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0018] Figure 1 This is a schematic diagram of a device for preparing hydrogel microspheres according to an embodiment of the present invention; Figure 2 This is a schematic diagram of hydrogel microspheres prepared according to a preparation method of an embodiment of the present invention.

[0019] in, Figure 1 The correspondence between the reference numerals and component names in the attached drawings is as follows: 100 Preparation apparatus, 110 Main control system, 120 Aqueous phase preparation unit, 121 Aqueous phase container, 122 Aqueous phase heating magnetic stirring table, 130 Reaction emulsification unit, 131 Reaction vessel, 132 First magnetic stirrer, 133 Mechanical stirrer, 1331 Stirring paddle, 134 Ultrasonic emulsifier, 1341 Ultrasonic probe, 135 Aqueous phase inlet, 136 Crosslinking agent feed port, 137 Temperature sensor, 138 Discharge port, 139 Semiconductor refrigeration chip, 140 Fluid transport unit, 141 Transport pump, 142 First pipeline, 143 Second pipeline. Detailed Implementation

[0020] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some, not all, of the embodiments of the present invention. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0021] Before providing a further detailed description of the embodiments of the present invention, the directional terms used in the embodiments of the present invention, such as "upper part", "lower part" and "side part", are not intended to limit the scope of protection of the present invention.

[0022] To make the technical solutions and advantages of the present invention clearer, the embodiments of the present invention will be described in further detail below with reference to the accompanying drawings.

[0023] like Figure 1 As shown, one embodiment of the present invention provides an apparatus for preparing hydrogel microspheres, the apparatus 100 comprising: Aqueous phase preparation unit 120 is configured to prepare aqueous solution, and one end of aqueous phase preparation unit 120 is connected to fluid delivery unit 140. The reaction emulsification unit 130 is configured for oil phase preparation, emulsification and crosslinking reactions. The other end of the reaction emulsification unit is connected to the fluid delivery unit 140 to deliver the aqueous phase solution into the reaction emulsification unit 130. The main control system 110 is electrically connected to the reaction emulsification unit 130 and the aqueous phase preparation unit 120.

[0024] The hydrogel microsphere preparation device 100 includes an aqueous phase preparation unit 120 and a reaction emulsification unit 130. The aqueous phase solution prepared by the aqueous phase preparation unit 120 is introduced into the reaction emulsification unit 130 through a fluid transport unit 140. The device also includes a main control system 110, which controls the operation of the aqueous phase preparation unit 120 and the reaction emulsification unit 130. In this application, the oil phase preparation, emulsification, and cross-linking reactions are sequentially performed within the reaction emulsification unit 130 in cooperation with the main control system 110. This avoids the cumbersome process of frequent material transfer and equipment switching in traditional processes, improves experimental efficiency, reduces the labor intensity of staff, and also reduces the risk of material loss and cross-contamination, thereby improving the continuity and stability of hydrogel microsphere preparation. During the emulsification reaction, the configuration of the reaction emulsification unit 130 and the cooperation of the main control system 110 enable stable control of the emulsification reaction temperature. Stable temperature control can also be achieved during the cross-linking and curing stage, improving the reliability of the physical gelation and chemical cross-linking reactions of the hydrogel precursor, which is beneficial for obtaining hydrogel microspheres with more stable morphology and structure.

[0025] Specifically, this application integrates the key steps of aqueous phase preparation, oil phase preparation, ultrasonic emulsification, and cross-linking curing for preparing hydrogel microspheres into one unit, effectively reducing the problems of frequent material transfer and equipment switching. The integrated preparation apparatus 100 of this application can perform efficient ultrasonic emulsification simultaneously with the formation of the crude emulsion. Combined with stable temperature control, this facilitates the preparation of water-in-oil emulsions with narrower particle size distribution and better uniformity, laying the foundation for the subsequent formation of high-quality hydrogel microspheres. The main control system 110 controls the required temperature and stirring speed, achieving automated management, improving the repeatability and controllability of the experiment, and facilitating the standardized preparation and industrial production of hydrogel microspheres.

[0026] Furthermore, the main control system 110 is a PLC control cabinet with a touch screen operating interface, which centrally controls the operation of the entire preparation device 100. In one feasible implementation, the reactive emulsification unit 130 includes: Reactor 131, which is equipped with a sealing cover; The mechanical stirrer 133 includes a stirring paddle 1331, which passes through a sealing cover and is disposed inside the reaction vessel 131. The mechanical stirrer 133 is electrically connected to the main control system 110. A magnetic heating stirrer is installed at the bottom of the reactor 131. The magnetic heating stirrer includes a first electric heating element and a first magnetic stirrer 132. The first electric heating element and the first magnetic stirrer 132 are electrically connected to the main control system 110.

[0027] The reaction emulsification unit 130 is located between the main control system 110 and the aqueous phase preparation unit 120. The reaction emulsification unit 130 includes a reaction vessel 131, a magnetic heating stirrer, and a mechanical stirrer 133. The magnetic heating stirrer is located outside the reaction vessel 131, directly below it. It contains a rotating magnet that drives the magnetic stir bar of the first magnetic stirrer 132 at the bottom of the reaction vessel 131 to rotate, providing non-contact stirring during the initial emulsification stage. Essentially, the rotating magnet of the first magnetic stirrer 132 is located outside the reaction vessel 131, directly below it, while the magnetic stir bar is located inside the reaction vessel 132. The rotating magnet drives the magnetic stir bar to rotate, forming the first magnetic stirrer 132. The stirring paddle 1331 of the mechanical stirrer 133 is inserted into the reaction vessel 131 from its sealed cover, providing gentle and uniform stirring during the crosslinking reaction stage and high-speed shear stirring during the emulsification stage. Furthermore, the magnetic heating stirrer includes a first electric heating element and a first magnetic stirrer 132. During the preparation of the crude emulsion, the heating and stirring functions are achieved through the first electric heating element and the first magnetic stirrer 132.

[0028] Specifically, a hydrophobic solvent (such as one or more of liquid paraffin, vegetable oil, and silicone oil) is used as the oil phase, and an emulsifier (such as one or more of Span 80, Span 60, and Tween 85) is added. The oil phase solution is prepared in the reaction vessel 131. The hydrophobic solvent and emulsifier are heated and stirred by a magnetic stirrer. The magnetic stirring speed is usually around 500 rpm, which can avoid premature emulsification caused by shear force, which would affect the interfacial stability when the aqueous phase solution is added later. This ensures that the two are mixed evenly to obtain the oil phase solution. At this point, the aqueous solution is slowly added dropwise to the reaction vessel 131 through the aqueous inlet 135 at a rate of 1 mL / min to 10 mL / min to 10 mL / min. Further, the dropwise addition rate can be 2 mL / min to 5 mL / min. Simultaneously, the magnetic heating stirrer below the reaction vessel 131 is activated via the main control system 110, raising the temperature of the mixture of oil and aqueous solutions to 40°C to 60°C. This provides gentle mixing, allowing the aqueous solution to disperse in larger droplets within the oil solution, forming a crude emulsion. The heating temperature of 40°C to 60°C reduces the viscosity of the polymer aqueous solution, facilitating dispersion. The first magnetic stirrer 132 provides consistent macroscopic mixing, preventing premature formation of small droplets and interface disruption, which would hinder subsequent ultrasonic treatment control.

[0029] It should be noted that the mechanical stirrer 133 includes a motor, a first connecting rod connected to the motor's output shaft, a first bevel gear fixedly mounted at the end of the first connecting rod away from the motor, and a second bevel gear fixedly mounted at the end of the second connecting rod. The second bevel gear meshes with the first bevel gear. Thus, rotation of the first connecting rod drives rotation of the first bevel gear, which in turn drives rotation of the second bevel gear and the second connecting rod. A stirring paddle 1331 is mounted at the end of the second connecting rod away from the second bevel gear. This ensures that the axis of the stirring paddle 1331 is perpendicular to the height direction of the reaction vessel 131, causing convection and diffusion of the fluid under the action of the stirring paddle 1331, forming an instantaneous constant state, overcoming separation and segregation problems, and improving mixing uniformity. Simultaneously, the first connecting rod drives the stirring paddle to rotate around the first connecting rod, while the second connecting rod also drives the rotation of the stirring paddle 1331, achieving fluid stirring. It can be understood that a second bevel gear can mesh on each side of the first bevel gear, thus forming two second connecting rods and two stirring paddles 1331, improving stirring efficiency.

[0030] In one feasible implementation, the reactive emulsification unit 130 further includes: The ultrasonic emulsifier 134 includes an amplitude rod and an ultrasonic probe 1341 connected to each other. The amplitude rod passes through a sealing cover, and the ultrasonic probe 1342 is located inside the reaction vessel 131. The ultrasonic emulsifier 134 is electrically connected to the main control system 110.

[0031] In this ultrasonic emulsifier 134, the ultrasonic probe 1341 passes through the sealed cover via an amplitude rod and is inserted into the reaction vessel 131. The insertion depth and ultrasonic power are adjusted via the amplitude rod to efficiently microemulsify the crude emulsion. Furthermore, the ultrasonic emulsifier utilizes the mechanical vibration of the amplitude rod to generate a cavitation effect in the liquid, creating extremely strong local shear forces that break large droplets in the crude emulsion into fine and uniform droplets. The amplitude of the amplitude rod is typically between 50 μm and 300 μm, controlled by adjusting the transducer's drive voltage via a controller within the main control system 110. A larger amplitude results in higher ultrasonic power and a stronger emulsification effect. The ultrasonic cavitation effect generates strong local shear, enabling the preparation of nano- to micron-sized fine emulsions with narrow particle size distribution and low energy consumption. In this application, the amplitude rod converts electrical energy into mechanical vibration through a piezoelectric ceramic transducer. The amplitude is proportional to the input voltage / current. The amplitude is controlled and adjusted (50μm to 300μm) to control the ultrasonic power (100W to 1000W).

[0032] It should be noted that this application integrates precise dropwise addition, magnetic stirring, and ultrasonic emulsifier 134, enabling efficient ultrasonic emulsification while the crude emulsion is being formed. Combined with stable temperature control, this facilitates the preparation of water-in-oil emulsions with narrower particle size distribution and better uniformity, laying the foundation for the subsequent formation of high-quality hydrogel microspheres.

[0033] It should be noted that the reactive emulsification unit 130 also includes: A semiconductor refrigeration element 139 is disposed on the outer wall of the side wall of the reactor 131, and the semiconductor refrigeration element 139 is electrically connected to the main control system 110.

[0034] Specifically, the ultrasonic emulsifier 134 is turned on to perform ultrasonic emulsification of the crude emulsion, while a heated magnetic stirrer is simultaneously activated. This results in a uniformly dispersed, finely-particle-sized water-in-oil emulsion (W / O emulsion). During this process, the main control system 110 adjusts the first electric heating element and the thermoelectric cooler 139 to achieve precise control of the emulsification temperature. When the ultrasonic emulsifier 134 is activated, the high-frequency mechanical vibration generates cavitation in the liquid, causing localized heating and potentially a rapid rise in liquid temperature. At this point, the thermoelectric cooler 139 begins to operate: the temperature sensor 137 monitors the temperature inside the reaction vessel 131 in real time. When the detected temperature exceeds the set upper limit (e.g., 57°C), the main control system 110 immediately activates the thermoelectric cooler 139, intermittently cooling in pulse width modulation (PWM) mode (e.g., on / off ratio 1:2) to quickly absorb localized overheating heat, restoring the liquid temperature to 55±1°C. Cooling is stopped when the detected temperature drops below 54°C. This process is repeated throughout the entire ultrasonic emulsification stage (usually lasting 10 to 30 minutes) to ensure that the emulsion forms under constant temperature conditions and to avoid droplet aggregation or uneven particle size due to temperature fluctuations.

[0035] It should be noted that the semiconductor cooling chip 139 can counteract local overheating and maintain a basically constant temperature environment. The cross-linking stage is used for rapid cooling and maintaining a low-temperature environment, promoting the physical gelation of the hydrogel precursor, while simultaneously preventing local temperature rise caused by the exothermic chemical cross-linking reaction. The semiconductor cooling chip 139 is based on the Peltier effect. When direct current passes through a couple composed of two different semiconductor materials (P-type and N-type), the direction of the current determines the direction of heat transfer: one side absorbs heat (cooling surface), and the other side releases heat (heat dissipation surface). In the preparation apparatus 100 of this application, the cooling surface is tightly attached to the outer wall of the reaction vessel 131, and the heat dissipation surface is air-cooled. The main control system 110, through feedback from the temperature sensor 137, uses PID and pulse width modulation (PWM) strategies to control the operating current and on / off ratio of the semiconductor cooling chip 139: in the precision constant temperature mode, i.e., the ultrasonic emulsification stage, it intermittently powers on with a duty cycle of 20% to 50%, achieving an accuracy of ±1℃; when rapid cooling is required, it operates continuously with full current; when the temperature is lower than the set value, cooling is stopped or the current is reversed.

[0036] In one feasible implementation, the reactive emulsification unit 130 further includes: Aqueous inlet 135 is provided on the sealing cover. Aqueous inlet 135 is connected to the other end of fluid delivery unit 140. Aqueous solution enters reactor 131 through aqueous inlet 135. Crosslinking agent inlet 136 is located on the sealing cover and is connected to the crosslinking agent supply device; The discharge port 138 is located at the end of the reactor 131 away from the sealing cover, and the discharge port 138 is connected to the product collection container or the filtration device.

[0037] The aqueous phase inlet 135 is used to input the aqueous phase solution into the reactor 131. Crosslinking agent is added to the water-in-oil emulsion through the crosslinking agent inlet 136 to initiate the crosslinking and curing reaction. The crosslinking agent inlet 136 is typically connected to a crosslinking agent supply device, which can be an injection pump or syringe for automatic dripping, or a funnel with a stopcock for manual dripping. When no material is being added, the device should be sealed with a nut or sealing plug to prevent evaporation or contamination. The outlet 138 is equipped with a shut-off valve. After the reaction is complete, the valve is opened, and the product flows out of the reactor 131 under gravity and enters the product collection container. If the product viscosity is high, a peristaltic pump or isolation pump can be connected in series after the outlet 138 to assist in discharge. Washing liquid can also be pumped into this outlet for online cleaning, forming a filtration device.

[0038] Specifically, a crosslinking agent solution (such as glutaraldehyde aqueous solution, genipin solution, calcium chloride solution, etc.) is slowly added dropwise to the water-in-oil emulsion at a rate of 0.5 mL / min to 5 mL / min through the crosslinking agent adhesive port 136 on the sealed lid of the reactor 131. Simultaneously, the mechanical stirrer 133 and the semiconductor cooling chip 139 are activated via the main control unit 110, and mechanical stirring is continuously performed at a preset temperature to promote crosslinking and solidification of the hydrogel precursor, thus preparing gel microspheres. The preset temperature is set according to the type of hydrogel; for example, 10±1℃ for a gelatin system. In this case, mechanical stirring at a speed of 100 rpm to 300 rpm provides gentle laminar flow mixing, preventing emulsion breakage and ensuring uniform dispersion of the crosslinking agent. The semiconductor cooling chip 139 actively absorbs heat through the Peltier effect, rapidly reducing and maintaining the temperature inside the reactor 131 to the preset low temperature, ensuring physical gelation of the gelatin molecules and synergistic solidification with chemical crosslinking of glutaraldehyde. The preset temperature for sodium alginate systems is 25±1℃. The preset temperature for other synthetic polymer systems is determined according to the crosslinking conditions and can be room temperature or 37℃.

[0039] It should be noted that during the crosslinking and curing stage, the emulsion temperature has dropped to a low level (e.g., 10°C). At this point, the viscosity of the continuous phase (oil phase) of the emulsion increases significantly, and the overall consistency becomes quite viscous. Under these conditions, the magnetic stir bar is difficult to rotate effectively and may be blocked or even stop rotating due to the viscous liquid, failing to provide sufficient mixing. Therefore, the preparation apparatus 100 uses a top-feed mechanical stirrer 133, whose stirring paddle 1331 (anchor or inclined blade paddle) has a large blade area and sufficient driving force, enabling stable rotation in high-viscosity media to ensure overall flow and mixing. By controlling the rotation speed of the stirring paddle 1331 (100 rpm to 300 rpm), a gentle laminar flow can be formed, avoiding shear damage to the formed emulsion droplets and preventing demulsification. The mechanical stirrer 133 can rapidly disperse the added crosslinking agent throughout the system, avoiding uneven crosslinking caused by excessively high local concentrations, and also ensuring the reliability of the process. After the ultrasonic emulsification reaction, the semiconductor cooling chip 139 rapidly reduces the temperature from approximately 55°C (the emulsification temperature) to a preset temperature of approximately 10°C, creating conditions for physical gelation. Simultaneously, it maintains a constant low temperature during the crosslinking process to prevent the exothermic chemical crosslinking reaction from causing a localized temperature rise. Finally, it also counteracts residual heat, maintaining temperature stability during the crosslinking stage. The semiconductor cooling chip 139 achieves a cooling rate of at least 3°C / min, completing the temperature drop from 55°C to 10°C within 15 minutes. At this low temperature, the microspheres undergo helical restructuring, forming a physical gel network that synergistically solidifies with the chemical crosslinking of glutaraldehyde. The resulting microspheres have a complete structure, smooth surface, and uniform particle size.

[0040] In the steps of forming and cross-linking curing of the water-in-oil emulsion, the heating and stirring of the first heating element and the first magnetic stirrer 132 are combined to achieve precise control of the fluid temperature. In particular, during the cross-linking curing stage, the semiconductor cooling chip 139 can quickly cool down and maintain the preset low temperature, ensuring the smooth progress of the physical gelation and chemical cross-linking reaction of the hydrogel precursor, which is conducive to obtaining hydrogel microspheres with better morphology and structure.

[0041] In one feasible implementation, the reactive emulsification unit 130 further includes: Temperature sensor 137 penetrates the sealed cover and is located inside reactor 131. Temperature sensor 137 is electrically connected to main control system 110.

[0042] Temperature sensor 137 monitors the temperature of the emulsion in reactor 131 and transmits the signal to main control system 110. When the measured temperature is lower than the set value, the control system increases the heating power of the magnetic stirrer; when the measured temperature is higher than the set value, the semiconductor cooling chip 139 is activated or the cooling current is increased; after reaching the set value, the system enters PID constant temperature regulation.

[0043] It should be noted that the temperature sensor 137 feeds back the temperature inside the reactor 131 to the main control system 110. The main control system 110 compares the set value with the set value and performs PID calculation, and outputs a command to adjust the power of the first electric heating element or the semiconductor cooling chip 139.

[0044] In one feasible embodiment, the aqueous phase preparation unit 120 includes: Aqueous phase container 121 is configured to contain an aqueous phase solution; A water-phase heating magnetic stirring table 122 is disposed at the bottom of the water phase container 121. The water-phase heating magnetic stirring table 122 includes a second electric heating element and a second magnetic stirrer. The second electric heating element and the second magnetic stirrer are electrically connected to the main control system 110 respectively.

[0045] The aqueous phase preparation unit 120 is located on one side of the reaction emulsification unit 130. The aqueous phase preparation unit 120 includes an aqueous phase container 121 and an aqueous phase heating magnetic stirrer 122. The aqueous phase container 121 is used to contain and prepare an aqueous phase solution, and the aqueous phase heating magnetic stirrer 122 heats and magnetically stirs the aqueous phase container 121.

[0046] Furthermore, hydrogel precursor powder and deionized water are added to the aqueous phase container 121, and the aqueous phase container 121 is heated and magnetically stirred by the aqueous phase heating magnetic stirrer 122 to form an aqueous hydrogel precursor aqueous solution for use as an aqueous phase solution.

[0047] It should be noted that the aqueous phase heating magnetic stirring table 122 consists of a second magnetic stirrer with a heating function. Its table surface has a built-in electric heating wire and a rotating magnet. The aqueous phase container 121 (such as a beaker) is placed on the table surface, and a magnetic stir bar is placed inside the aqueous phase container 121. After startup, the table surface heats up and the magnet rotates simultaneously, driving the magnetic stir bar to rotate, achieving simultaneous heating and stirring. Specifically, the aqueous phase heating magnetic stirring table 122 is an integrated device, with a heating plate at the top containing an electric heating wire, and a rotating magnet below the heating plate. The magnetic stir bar is placed inside the aqueous phase container 121, which is placed on the heating plate. The rotation of the magnet drives the stir bar to rotate. The heating plate is energized and generates heat, which is conducted through the bottom of the aqueous phase container 121 to heat the solution.

[0048] In one feasible embodiment, the fluid delivery unit 140 includes a delivery pump 141 and a connecting pipe, the connecting pipe including a first pipe 142 and a second pipe 143, a first end of the first pipe 142 being connected to the aqueous phase preparation unit 120, a second end of the first pipe 142 being connected to the inlet of the delivery pump 141, a first end of the second pipe 143 being connected to the outlet of the delivery pump 141, and a second end of the second pipe 143 being connected to the reaction emulsification unit 130; The delivery pump 141 is a peristaltic pump or an injection pump, and the delivery pump 141 is electrically connected to the main control system 110.

[0049] It should be noted that the fluid delivery unit 140 includes a delivery pump 141 and connecting pipes. The delivery pump 141 can be either a peristaltic pump or a syringe pump. The use of a peristaltic pump avoids cross-contamination of the aqueous solution, is easy to clean, requires only periodic replacement of the connecting pipes, is less prone to clogging, and exerts less shear stress on the aqueous solution. The syringe pump, on the other hand, offers higher flow rate control accuracy and stability, enabling low-flow delivery. It also supports complex flow curve programming, such as linear acceleration and step changes, allowing for precise control of the delivery process. The peristaltic pump's rotation speed can be adjusted to control the rate at which the aqueous solution enters the reaction emulsification unit 130, while the syringe pump's injection rate can be programmed to precisely control the drip rate of the aqueous solution.

[0050] Furthermore, the connecting pipes include a first pipe 142 and a second pipe 143. The first end of the first pipe 142 extends below the liquid surface of the aqueous phase container 121, and the second end of the first pipe 142 is connected to the inlet of the transfer pump 141. The first end of the second pipe 143 is connected to the outlet of the transfer pump 141, and the second end of the second pipe 143 is connected to the aqueous phase inlet 135 of the reaction emulsification unit 130. Starting the transfer pump 141 can input the aqueous phase solution in the aqueous phase preparation unit 120 into the reaction vessel 131 of the reaction emulsification unit 130.

[0051] It should be noted that the main control system 110 of this application is an integrated console, which integrates controllers for controlling and adjusting the first magnetic stirrer 132 and the first electric heating element in the magnetic heating stirrer, the second magnetic stirrer and the second electric heating element in the water phase heating magnetic stirring table, the mechanical stirrer 133, the ultrasonic emulsifier 134, the semiconductor cooling chip 139 and the fluid delivery unit 140 respectively, and is equipped with a user interface to facilitate operation and control by staff.

[0052] Another embodiment of the present invention provides a method for preparing hydrogel microspheres, utilizing the above-described preparation apparatus, the method comprising the following steps: Aqueous solutions were prepared using an aqueous phase preparation unit. Oil phase solutions were prepared based on reactive emulsification units; An aqueous solution is input into an oil phase solution, and a crude emulsion is obtained based on a reactive emulsification unit. Based on the reactive emulsification unit and the crude emulsion, a water-in-oil emulsion is obtained; Hydrogel microspheres were obtained based on reactive emulsification units and water-in-oil emulsions.

[0053] Specifically, the aqueous solution is first prepared within the aqueous preparation unit 120. The hydrogel precursor powder is added to the aqueous container 121, along with deionized water. The hydrogel precursor powder is then heated and stirred using the second electric heating element and the second magnetic stirrer of the aqueous heating magnetic stirring table 122, forming an aqueous hydrogel precursor solution for use as the aqueous phase solution. In this embodiment, the hydrogel precursor powder is type A gelatin 250 Bloom gelatin.

[0054] The aqueous phase preparation unit 120 includes a 1000mL beaker as the aqueous phase container, placed on an aqueous phase heating magnetic stirring table 122. This table 122 incorporates a second electric heating element and a second magnetic stirrer, allowing for independent temperature control from room temperature to 350°C and adjustment of the magnetic stirring speed. The advantages of magnetic stirring here include the absence of mechanical seals, ease of cleaning, prevention of contamination, and suitability for small-scale preparation.

[0055] In one feasible implementation, the reaction emulsification unit 130 includes a reaction vessel 131, a magnetic heating stirrer, a mechanical stirrer 133, an ultrasonic emulsifier 134, a semiconductor cooling chip 139, a temperature sensor 137, an aqueous phase inlet 135, and a crosslinking agent feeding port 136. The preparation of an oil phase solution based on a reactive emulsification unit includes: using a hydrophobic solvent as the oil phase, adding an emulsifier, and heating and stirring in a reaction vessel using a magnetic heating stirrer to obtain an oil phase solution; Obtaining a crude emulsion based on a reactive emulsification unit includes: adjusting the stirring speed and heating temperature of a magnetically heated stirrer, introducing an aqueous solution into an oil solution through an aqueous inlet, while maintaining the stirring speed and heating temperature of the magnetically heated stirrer, to form a crude emulsion in which the aqueous phase is dispersed in the oil phase; Obtaining a water-in-oil emulsion includes: turning on an ultrasonic emulsifier to perform ultrasonic emulsification, while adjusting the stirring speed of a magnetically heated stirrer to obtain a water-in-oil emulsion. The emulsification temperature is controlled by controlling the heating temperature of the magnetically heated stirrer and the semiconductor cooling chip. The process of obtaining hydrogel microspheres includes: adding a crosslinking agent solution into a water-in-oil emulsion through a crosslinking agent feeding port, turning on a mechanical stirrer and a semiconductor cooling chip, and continuously stirring under a preset temperature condition to obtain hydrogel microspheres.

[0056] For the oil phase preparation, simple mixing is sufficient; magnetic stirring is recommended to avoid generating excessive bubbles. Mechanical stirring is also acceptable, but the stirring speed should be controlled to no more than 100 rpm.

[0057] Furthermore, a hydrophobic solvent (including but not limited to one or more of liquid paraffin, vegetable oil, and silicone oil) is used as the oil phase, and an emulsifier (including but not limited to one or more of Span 80, Span 60, and Tween 85) is added. The mixture is stirred in the reactor 131 by the first magnetic stirrer 132 of the magnetic heating stirrer to obtain a uniform oil phase solution. Then, the aqueous phase solution is slowly added to the oil phase solution via the transfer pump 141 of the fluid transfer unit 140 through the connecting pipe at a rate of 1 mL / min to 10 mL / min (preferably 2 mL / min to 5 mL / min). Simultaneously, the first magnetic stirrer 132 and the first electric heating element of the magnetic heating stirrer are turned on, and the heating temperature is set to the target emulsification temperature (e.g., 55°C). The stirring speed is adjusted to 500 rpm to 800 rpm, forming a coarse emulsion in which the aqueous phase is dispersed in the oil phase. Subsequently, the ultrasonic emulsifier 134 is started to perform ultrasonic emulsification. The stirring speed of the first magnetic stirrer 132 in the magnetic heating stirrer is adjusted to maintain the macroscopic flow of the emulsion, obtaining a uniformly dispersed, water-in-oil (W / O) emulsion with fine droplets. During the ultrasonic process, the cavitation effect generated by the high-frequency mechanical vibration causes localized and intense heating of the liquid, resulting in an upward trend in liquid temperature; therefore, a magnetic stirring mode is adopted. At this point, the semiconductor cooling chip 139 is activated, and the temperature sensor 137 monitors the temperature inside the reaction vessel 131. When the detected temperature exceeds the set upper limit (e.g., 57°C), the main control system 110 immediately activates the semiconductor cooling chip 139, intermittently cooling in pulse width modulation mode to quickly absorb local overheating heat, restoring the liquid temperature to the target temperature (e.g., 55±1°C), thus achieving stable control of the emulsification temperature. After obtaining the water-in-oil emulsion, crosslinking and curing treatment is performed. A crosslinking agent solution (e.g., glutaraldehyde aqueous solution, genipin solution, calcium chloride solution, etc.) is slowly added dropwise through the crosslinking agent feeding port 136 on the sealed cap at a rate of 0.5 mL / min to 5 mL / min (preferably 1 mL / min to 2 mL / min), mixing the crosslinking agent solution with the water-in-oil solution. The main control system 110 shuts off the heating function of the magnetic heating stirrer and activates the semiconductor cooling chip 139 for rapid cooling. The preset crosslinking temperature is set according to the material: 10±1°C for the gelatin system and 25±1°C for the sodium alginate system. The semiconductor cooling chip 139 first operates continuously at full power, rapidly reducing the emulsion from its emulsification temperature (e.g., 55°C) to a preset low temperature (cooling rate ≥3°C / min, time 10 to 15 minutes); then it switches to intermittent cooling mode (e.g., on / off ratio 1:3) to maintain a constant low temperature (fluctuation ≤ ±0.5°C). During the crosslinking and curing stage, the mechanical stirrer 133 is turned on and the first magnetic stirrer 132 is turned off. The mechanical stirring (speed 100 rpm to 300 rpm) has high torque, effectively agitating the high-viscosity medium, providing gentle laminar mixing, avoiding damage to the emulsion droplets, and promoting uniform diffusion of the crosslinking agent.The mechanical stirrer 133 and the semiconductor cooling chip 139 work together to continuously react for 1 to 4 hours, causing the hydrogel precursor to undergo physical gelation (such as low-temperature helical structure recombination of gelatin) and chemical cross-linking for dual curing, thus preparing gel microspheres.

[0058] The reaction vessel 131 of the reaction emulsification unit 130 is a 2000mL jacketed glass reaction vessel. Four semiconductor cooling chips 139 are evenly attached to the outer wall of the reaction vessel 131. A magnetic heating stirrer is installed below the reaction vessel 131. The Teflon sealing cap of the reaction vessel 131 has multiple standard ports for installing a mechanical stirrer 133, a titanium alloy probe of a high-power ultrasonic emulsifier 134, a temperature sensor 137, an aqueous phase inlet 135, and a crosslinking agent feed port 136 with a valve.

[0059] Furthermore, an adjustable-speed peristaltic pump and a high-temperature resistant silicone hose are configured as the first pipe 142 and the second pipe 143 to form a fluid transport unit 140, which connects the aqueous phase container 121 and the aqueous phase inlet 135 of the reactor 131.

[0060] Example 1 The specific steps for this implementation are as follows: (1) Aqueous phase preparation: Add 450mL of deionized water to the aqueous phase container, weigh 50g of gelatin powder (Type A, 250g) and add it to it. Set the heating temperature of the aqueous phase heating magnetic stirrer to 60℃ and the stirring speed to 400rpm on the main control system 110. Run for 30 minutes to obtain a homogeneous gelatin aqueous solution with a mass percentage of 10%, which is the aqueous phase solution.

[0061] (2) Preparation of oil phase: Add 1000 mL of liquid paraffin and 30 mL of dehydrated sorbitan monooleate (Span80) to the reaction vessel, set the speed of the first magnetic stirrer to 500 rpm, and stir at room temperature for 10 minutes to form an oil phase solution.

[0062] (3) Formation of a water-in-oil emulsion: The aqueous phase solution is dripped into the oil phase solution at a rate of 5 mL / min through the fluid delivery unit 140. At the same time, the first electric heating element of the magnetic heating stirrer (set to 40℃ to 60℃) and the first magnetic stirrer 132 (300 rpm to 800 rpm) are turned on to form a crude emulsion. Then, the ultrasonic emulsifier 134 is started, the power is set to 400W, the working mode is continuous ultrasonic, and ultrasonic emulsification is performed for 10 minutes. At the same time, the first magnetic stirrer 132 continues to run. During the ultrasonic process, the main control system 110 starts the semiconductor cooling chip 139 to perform pulsed cooling based on the feedback from the temperature sensor 137, so as to counteract the heat generated by the ultrasonication and maintain the emulsion temperature within the set value ±1℃ range to obtain a water-in-oil emulsion.

[0063] (4) Crosslinking and curing: Turn off the first electric heating element of the magnetic heating stirring table, stop the ultrasonic emulsifier 134, and start the mechanical stirrer 133 (speed from 100 rpm to 300 rpm). At the same time, slowly add 10 mL of 2% glutaraldehyde aqueous solution through the crosslinking agent feeding port at a rate of 0.5 mL / min to 5 mL / min. Start the semiconductor cooling chip 139 to cool the water-in-oil emulsion in the reaction vessel 131 to 10°C within 15 minutes. Continue mechanical stirring for 120 minutes to complete the crosslinking and curing, and obtain hydrogel microspheres.

[0064] (5) Post-processing: After the cross-linking and curing reaction is completed, the product is washed several times alternately with petroleum ether and isopropanol, collected by centrifugation, and stored in buffer solution at low temperature for later use. The product is characterized using an optical microscope. Figure 2 The results showed that the obtained microspheres were regular spherical with smooth surfaces, a particle size of 15.3 μm ± 1.9 μm, and a particle size distribution CV of 12.4%.

[0065] Example 2 The specific steps for this implementation are as follows: (1) Aqueous phase preparation: Add 3g sodium alginate and 97g deionized water to aqueous phase container 121, set the heating temperature of the aqueous phase heating magnetic stirring table 122 to 40℃, the magnetic stirring speed to 300rpm, dissolve for 30 minutes, and obtain a sodium alginate solution with a mass ratio of 3%.

[0066] (2) Oil phase preparation: Add 1000mL of liquid paraffin and 25mL of Span80 to the reactor 131, turn on the magnetic heating stirrer, set the heating temperature to 40℃, the magnetic stirring speed to 500rpm, and mix for 10 minutes.

[0067] (3) Formation of W / O emulsion: Set the heating temperature of the magnetic heating stirring table to 40℃, and use a peristaltic pump to drop the aqueous phase solution into the oil phase solution at a flow rate of 5mL / min. Start the ultrasonic emulsifier 134 (amplitude 100μm, ultrasonic treatment for 5 minutes), while the semiconductor cooling chip 139 works intermittently to maintain the emulsion temperature at 40℃±1℃.

[0068] (4) Crosslinking and curing: Turn off the first electric heating element of the magnetic heating stirring table, start the mechanical stirrer (stirring speed is 200 rpm), add 20 mL of calcium chloride solution with a mass ratio of 4 at a rate of 2 mL / min, and at the same time start the semiconductor cooling chip 139 to maintain the temperature at 251℃±1℃. The crosslinking and curing reaction takes 30 minutes.

[0069] (5) Results: The obtained microspheres were regular spherical with smooth surfaces. The microsphere diameter was 52.7 μm ± 7.5 μm and the CV was 12.4%.

[0070] Comparative Example In the prior art, using separate equipment, the obtained hydrogel microspheres have a particle size of 42.3 μm ± 12.1 μm, a CV of 28.6%, a yield of 72%, and exhibit adhesion and irregular shapes.

[0071] The microspheres prepared by the preparation apparatus 100 of this application have an extremely narrow particle size distribution, with a CV of only 12.4%, and the yield can reach more than 95%, and there is no adhesion.

[0072] As can be seen, the uniform droplet addition of the aqueous solution and the uniform cavitation shearing of the ultrasonic emulsifier make the droplet size more uniform; the constant temperature control during the emulsification stage can avoid temperature fluctuations (heating to reduce viscosity, and cooling balance by ultrasonic heat generation using a semiconductor cooling chip); the integrated design can avoid transfer losses.

[0073] In this invention, the terms "first" and "second" are used for descriptive purposes only and should not be construed as indicating or implying relative importance. The term "a plurality" refers to two or more unless otherwise expressly defined.

[0074] Other embodiments of the invention will readily occur to those skilled in the art upon consideration of the specification and practice of the invention disclosed herein. The invention is intended to cover any variations, uses, or adaptations of the invention that follow the general principles of the invention and include common knowledge or customary techniques in the art not disclosed herein. The specification and examples are to be considered exemplary only.

[0075] The above are merely preferred embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. An apparatus for preparing hydrogel microspheres, characterized in that, The preparation apparatus includes: An aqueous phase preparation unit is configured to prepare an aqueous solution, and the aqueous phase preparation unit is connected to one end of a fluid delivery unit. A reactive emulsification unit is configured for oil phase preparation, emulsification, and crosslinking reactions. The reactive emulsification unit is connected to the other end of the fluid delivery unit to deliver the aqueous phase solution into the reactive emulsification unit. The main control system is electrically connected to the reaction emulsification unit and the aqueous phase preparation unit.

2. The apparatus for preparing hydrogel microspheres according to claim 1, characterized in that, The reactive emulsification unit includes: The reaction vessel is equipped with a sealing cover; A mechanical stirrer, including a stirring paddle, the stirring paddle passing through the sealing cover, the stirring paddle being disposed inside the reaction vessel, and the mechanical stirrer being electrically connected to the main control system; A magnetic heating stirrer is disposed at the bottom of the reaction vessel. The magnetic heating stirrer includes a first electric heating element and a first magnetic stirrer, which are electrically connected to the main control system.

3. The apparatus for preparing hydrogel microspheres according to claim 2, characterized in that, The reactive emulsification unit further includes: An ultrasonic emulsifier includes an amplitude rod and an ultrasonic probe connected to each other. The amplitude rod passes through the sealing cover, and the ultrasonic probe is located inside the reaction vessel. The ultrasonic emulsifier is electrically connected to the main control system.

4. The apparatus for preparing hydrogel microspheres according to claim 2, characterized in that, The reactive emulsification unit further includes: An aqueous inlet is provided on the sealing cover and is connected to the other end of the fluid delivery unit. The aqueous solution enters the reactor through the aqueous inlet. A crosslinking agent inlet is provided on the sealing cap, and the crosslinking agent inlet is connected to a crosslinking agent supply device; The discharge port is located at the end of the reactor furthest from the sealing cover, and the discharge port is connected to a product collection container or a filtration device.

5. The apparatus for preparing hydrogel microspheres according to claim 2, characterized in that, The reactive emulsification unit further includes: A temperature sensor penetrates the sealing cover and is located inside the reactor. The temperature sensor is electrically connected to the main control system.

6. The apparatus for preparing hydrogel microspheres according to claim 2, characterized in that, The reactive emulsification unit further includes: A semiconductor refrigeration chip is disposed on the outer wall of the sidewall of the reactor, and the semiconductor refrigeration chip is electrically connected to the main control system.

7. The apparatus for preparing hydrogel microspheres according to claim 1, characterized in that, The aqueous phase preparation unit includes: An aqueous phase container is configured to contain the aqueous phase solution; A water-phase heating magnetic stirring table is disposed at the bottom of the water phase container. The water-phase heating magnetic stirring table includes a second electric heating element and a second magnetic stirrer. The second electric heating element and the second magnetic stirrer are respectively electrically connected to the main control system.

8. The apparatus for preparing hydrogel microspheres according to claim 1, characterized in that, The fluid delivery unit includes a delivery pump and a connecting pipe. The connecting pipe includes a first pipe and a second pipe. The first end of the first pipe is connected to the aqueous phase preparation unit, the second end of the first pipe is connected to the inlet of the delivery pump, the first end of the second pipe is connected to the outlet of the delivery pump, and the second end of the second pipe is connected to the reaction emulsification unit. The delivery pump is a peristaltic pump or an injection pump, and the delivery pump is electrically connected to the main control system.

9. A method for preparing hydrogel microspheres, using the preparation apparatus according to any one of claims 1 to 8, characterized in that, The preparation method includes the following steps: Aqueous solutions were prepared using an aqueous phase preparation unit. Oil phase solutions were prepared based on reactive emulsification units; The aqueous solution is fed into the oil phase solution, and a crude emulsion is obtained based on the reaction emulsification unit; Based on the reactive emulsification unit and the crude emulsion, a water-in-oil emulsion is obtained; Hydrogel microspheres are obtained based on the reactive emulsification unit and the water-in-oil emulsion.

10. The method for preparing hydrogel microspheres according to claim 9, characterized in that, The reaction emulsification unit includes a reaction vessel, a magnetic heating stirrer, a mechanical stirrer, an ultrasonic emulsifier, a semiconductor cooling chip, a temperature sensor, an aqueous phase inlet, and a crosslinking agent feeding port; The preparation of the oil phase solution based on the reaction emulsification unit includes: using a hydrophobic solvent as the oil phase, adding an emulsifier, and heating and stirring in the reaction vessel using the magnetic heating stirrer to obtain the oil phase solution; The process of obtaining a crude emulsion based on the reaction emulsification unit includes: adjusting the stirring speed and heating temperature of the magnetic heating stirrer, inputting the aqueous solution into the oil solution through the aqueous inlet, while maintaining the stirring speed and heating temperature of the magnetic heating stirrer, to form the crude emulsion in which the aqueous phase is dispersed in the oil phase; The process of obtaining a water-in-oil emulsion includes: turning on the ultrasonic emulsifier to perform ultrasonic emulsification, while adjusting the stirring speed of the magnetic heating stirrer to obtain the water-in-oil emulsion, wherein the emulsification temperature is controlled by controlling the heating temperature of the magnetic heating stirrer and the semiconductor cooling chip; The process of obtaining hydrogel microspheres includes: adding a crosslinking agent solution into the water-in-oil emulsion through the crosslinking agent feeding port, turning on the mechanical stirrer and the semiconductor cooling chip, and continuously stirring under a preset temperature condition to obtain the hydrogel microspheres.

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