Special-shaped core-shell microparticle as well as preparation method and application thereof

Abstract

The invention relates to the technical field of microparticle materials, in particular to a special-shaped core-shell microparticle as well as a preparation method and application thereof. The preparation method comprises the following steps: respectively preparing a continuous phase fluid, an intermediate phase fluid and an innermost phase fluid; preparing a multiple emulsion mixed flow by using a continuous phase fluid, an intermediate phase fluid and an innermost phase fluid, cross-linking the multiple emulsion mixed flow to obtain a fiber gel network, and curing an emulsion in the fiber gel network to obtain a preset part; and dissolving the fiber gel network in the preset part, and washing. The invention further provides the particles prepared by the method, and the particles comprise the irregular special-shaped shell and the preset number of particles embedded in the shell. The invention further provides application of the method. The problems that in the prior art, complex special-shaped core-shell microparticles cannot be prepared, and the particle shape, the particle size and the number of embedded particles are difficult to effectively adjust are solved. The microparticles are good in monodispersity, adjustable in size and diversified in morphology, and the preparation method can effectively adjust the shape and size of the particles and the number of the particles embedded in the shell.

Description

Technical Field

[0001] This invention relates to the field of microparticle materials technology, specifically to an irregular core-shell microparticle, its preparation method, and its application. Background Technology

[0002] Microparticles, as advanced functional materials, have been widely used in the biomedical field, such as drug delivery, tissue engineering, biosensing, and cell life sciences. Traditional methods such as emulsion polymerization, dispersion polymerization, and spray drying often result in microparticles with poor reproducibility, limited functionality, and untunable morphology. Therefore, to improve the practicality and reliability of microparticles, the controlled fabrication of microparticles has significant practical application value. Various technologies, including droplet microfluidics, flowing photolithography microfluidics, electrohydrodynamic co-jetting, photolithography, soft photolithography-based imprinting, and micromolding, have been used to fabricate microparticles with size control, monodispersity, and multiple morphologies.

[0003] Droplet microfluidics technology allows for precise control of various fluids at the microscale. Each heterogeneous phase or compartment within the generated droplet can serve as a template, enabling physical and chemical reactions at or between interfaces through polymerization, ionic crosslinking, and solvent evaporation, thereby transforming the droplet into solid microparticles. While these methods can flexibly adjust the size and morphology of core-shell structured particles, the resulting particle morphologies are relatively limited, and there are still certain limitations in effectively controlling the preparation of microparticles with specific heteromorphic structures. Therefore, it is necessary to develop new preparation methods to further enrich existing preparation techniques and the types of core-shell structured particles. Summary of the Invention

[0004] This invention aims to address the limitations of existing droplet microfluidics technologies in preparing complex, irregularly shaped core-shell microparticles, and in effectively controlling particle shape, size, and the number of embedded particles. It provides microparticles with good monodispersity, adjustable size, and diverse morphologies, along with a method for their preparation. The preparation method effectively controls particle shape and size, as well as the number of embedded particles within the shell.

[0005] The specific technical solution of the present invention is as follows: In a first aspect, the present invention provides a method for preparing heteromorphic core-shell microparticles, comprising the following steps: Continuous phase fluid, intermediate phase fluid, and innermost phase fluid were prepared separately. A complex emulsion mixture was prepared using a continuous phase fluid, an intermediate phase fluid, and an innermost phase fluid. The complex emulsion mixture was cross-linked to obtain a fiber gel network. The emulsion in the fiber gel network was solidified to obtain a pre-designed component. The fiber gel network in the pre-made component is dissolved, washed, and the finished product is obtained.

[0006] Furthermore, the method for preparing the continuous phase fluid is as follows: for thermosetting microspheres, PVA solution and sodium alginate are provided, and sodium alginate is dissolved in PVA solution to obtain a continuous phase fluid; for photocurable microspheres, F127 and sodium alginate are provided, and sodium alginate and F127 are dissolved in deionized water to obtain a continuous phase fluid.

[0007] Furthermore, the mass fraction of sodium alginate in the continuous phase fluid is 0.5%-5.0%.

[0008] Furthermore, the method for preparing the intermediate phase fluid is as follows: For photocurable microspheres, a photoinitiator and a prepolymer monomer are provided, and the photoinitiator is dissolved in the prepolymer monomer to obtain an intermediate phase fluid; For thermosetting microspheres, PDMS prepolymer A and PDMS curing agent B are provided; the two are mixed evenly to obtain an intermediate phase fluid.

[0009] Furthermore, for thermosetting microspheres, the innermost phase fluid is a PVA aqueous solution; For photocurable microspheres, the innermost phase is deionized water or contains any one or more of PVA, gelatin, polymer monomers, EGDA, acrylamide, crosslinking agent MBA, and initiator 2959.

[0010] Furthermore, the specific operation of obtaining the preset component involves providing a microfluidic device and a receiving liquid phase; injecting the continuous phase fluid, intermediate phase fluid, and innermost phase fluid into different inlets of the microfluidic device to generate a mixed emulsion flow in the device; introducing the mixed emulsion flow into the receiving liquid phase through the outlet of the microfluidic device, where the mixed emulsion flow crosslinks to form a fiber gel network; and solidifying the mixed emulsion in the fiber gel network in situ to obtain the preset component.

[0011] Furthermore, the operation of dissolving the pre-form involves dissolving the fiber gel network in the pre-form using sodium citrate solution, followed by washing with deionized water to obtain the finished product.

[0012] Furthermore, the liquid phase is a calcium chloride solution.

[0013] Secondly, the present invention also provides an irregularly shaped core-shell microparticle prepared based on the aforementioned preparation method, the microparticle comprising an irregularly shaped shell and a predetermined number of particles embedded in the shell.

[0014] Thirdly, the present invention also provides an application based on the aforementioned preparation method, which adjusts the flow rate of the microfluidic device to regulate the size, shape, and number of particles embedded in the microparticle shell.

[0015] Compared with the prior art, the advantages of the present invention are as follows: 1. This invention provides a method for preparing heteromorphic core-shell microparticles. It utilizes microfluidic technology to prepare a complex emulsion through continuous phase fluid, intermediate phase fluid, and innermost phase fluid. A liquid phase of calcium chloride is used to rapidly crosslink the complex emulsion mixture obtained through the microfluidic device, forming hydrogel fibers containing encapsulated droplet cavities. The complex emulsion droplets within the cavities are then solidified in situ to prepare heteromorphic core-shell microparticles. Furthermore, by adjusting the parameters of the preparation method, the particle shape and size, as well as the number of particles embedded in the shell, can be effectively controlled. The microparticles exhibit good monodispersity, adjustable size, and diverse morphologies. The preparation method effectively adjusts the particle shape, size, and the number of particles embedded in the shell. This solves the problems of existing droplet microfluidic technologies being unable to prepare complex-structured heteromorphic microparticles and finding it difficult to effectively control particle shape, size, and the number of embedded particles.

[0016] 2. The present invention provides an irregularly shaped core-shell microparticle, the outer shell of which is irregularly shaped and contains multiple particles, the size and shape of which are controllable.

[0017] Most existing solid microparticles are simple spherical, ellipsoidal, rod-shaped, or spindle-shaped, making them difficult to apply in certain specific fields. The heteromorphic core-shell microparticles of this invention have a morphology that is completely different from existing solid microparticles, enabling them to have a wider range of applications in fields such as displays, sensing, microrobotics, and material capture and delivery.

[0018] 3. The application of the preparation method provided by this invention is to initially adjust the morphology of the complex emulsion mixed flow by changing the microfluidic preparation parameters such as the composition of each phase solution, flow rate conditions, and device structure. After the sodium alginate-calcium ion gelation process occurs in the contact liquid phase, the complex emulsion mixed flow will further deform and transform into a fiber cavity structure, thereby controlling the structure and morphology of the droplets encapsulated in the cavity. It has a wide range of applications and strong advantages.

[0019] By changing the conditions, such as temperature, used in this invention to solidify the multiemulsion droplets in the fiber cavity, the morphology and structure of the final particles can be further controlled. Attached Figure Description

[0020] Figure 1 This is a schematic flowchart of the method for preparing heteromorphic core-shell microparticles according to the present invention.

[0021] Figure 2 Optical photographs and scanning electron microscope images of irregularly shaped particles prepared by PVA encapsulation using PDMS in Example 1 of this invention.

[0022] Figure 3 This is a schematic diagram of the addition of a secondary transition pipe at the outlet end of the re-emulsification device according to the present invention.

[0023] Figure 4 Optical photographs and scanning electron microscope images of irregularly shaped particles prepared by PVA encapsulation using PDMS in Examples 1-2 to 1-5 of this invention.

[0024] Figure 5 Optical images and scanning electron microscope photographs of the preparation of irregularly shaped particles using ETPTA water-in-oil reemulsion in Examples 2-1 to 2-3 of this invention.

[0025] Figure 6 Optical images and scanning electron microscope photographs of irregularly shaped particles prepared by water-encapsulated reemulsion of ETPTA-soybean oil mixture in Example 3 of the present invention.

[0026] Figure 7 Optical images and scanning electron microscope photographs of irregularly shaped particles prepared by ETPTA-coated PVA-AM re-emulsion and ETPTA-coated PVA-EGDA re-emulsion in Examples 4 and 5 of the present invention, respectively.

[0027] Figure 8 Optical images and scanning electron microscope photographs of irregularly shaped particles prepared by ETPTA-packaged PVA-Gel re-emulsion in Example 6 of the present invention.

[0028] Figure 9 This is an optical photograph of the irregularly shaped particles prepared by adjusting the photocuring time and temperature of ETPTA-packaged PVA-Gel re-emulsion in Example 6 of the present invention.

[0029] Figure 10 This is an optical photograph of Chlorella encapsulated in irregularly shaped particles prepared by ETPTA-PVA-Gel re-emulsion in Example 6 of the present invention.

[0030] Figure 11 Optical photographs and scanning electron microscope images of irregularly shaped particles prepared by ETPTA-coated PVA-AM-NIPAM or PVA-AM-NIPAM-Agar-coated emulsions with doped thermochromic particles in Example 7 of this invention are shown. Specific Implementation In an embodiment of the present invention, in a first aspect, the present invention provides a method for preparing heteromorphic core-shell microparticles, comprising the following steps: Continuous phase fluid, intermediate phase fluid, and innermost phase fluid were prepared separately. A complex emulsion mixture was prepared using a continuous phase fluid, an intermediate phase fluid, and an innermost phase fluid. The complex emulsion mixture was cross-linked to obtain a fiber gel network. The emulsion in the fiber gel network was solidified to obtain a pre-designed component. The fiber gel network in the pre-made component is dissolved, washed, and the finished product is obtained.

[0032] It is understandable that after preparing a complex emulsion mixture using a continuous phase fluid, an intermediate phase fluid, and an innermost phase fluid, the complex emulsion mixture is crosslinked to obtain a fiber cavity (fiber gel network) encapsulating emulsion droplets. The emulsion droplets in the fiber cavity (fiber gel network) are then solidified to obtain a pre-designed part. The fiber gel in the pre-designed part is then dissolved to obtain solidified emulsion droplets, i.e., microparticles. These microparticles are then washed to obtain the finished microparticles.

[0033] Understandably, microfluidic technology is used to prepare complex emulsions through continuous phase fluid, intermediate phase fluid, and innermost phase fluid. Calcium chloride, a liquid phase, is then used to rapidly crosslink the complex emulsion mixture obtained through the microfluidic device, forming hydrogel fibers containing encapsulated droplet cavities. The complex emulsion droplets within the cavities are then solidified in situ to prepare heterogeneous core-shell microparticles. Furthermore, by adjusting the parameters of the preparation method, the particle shape and size, as well as the number of particles embedded in the shell, can be effectively controlled. The microparticles exhibit good monodispersity, adjustable size, and diverse morphologies. The preparation method effectively regulates the particle shape, size, and number of particles embedded in the shell. This solves the problem that existing droplet microfluidic technologies cannot prepare complex-structured heterogeneous microparticles and struggle to effectively control particle shape, size, and the number of embedded particles.

[0034] In a specific embodiment of the present invention, the method for preparing the continuous phase fluid is as follows: for thermosetting microspheres, PVA solution and sodium alginate are provided, and sodium alginate is dissolved in PVA solution to obtain a continuous phase fluid; for photocurable microspheres, F127 and sodium alginate are provided, and sodium alginate and F127 are dissolved in deionized water to obtain a continuous phase fluid.

[0035] In a specific embodiment of the present invention, the mass fraction of sodium alginate in the continuous phase fluid is 0.5%-5.0%.

[0036] In a specific embodiment of the present invention, the sodium alginate used in the continuous phase fluid is sodium alginate with a viscosity of 15-25 cP.

[0037] In a specific embodiment of the present invention, the method for preparing the intermediate phase fluid is as follows: For photocurable microspheres, a photoinitiator and a prepolymer monomer are provided, and the photoinitiator is dissolved in the prepolymer monomer to obtain an intermediate phase fluid; For thermosetting microspheres, PDMS prepolymer A and PDMS curing agent B are provided; the two are mixed evenly to obtain an intermediate phase fluid.

[0038] In a specific embodiment of the present invention, PDMS prepolymer A and PDMS curing agent B in the mesophase fluid are preferably mixed in a volume ratio of 1:4 to 1:10.

[0039] PDMS prepolymer A is the polymer bulk and has a relatively viscous texture; PDMS curing agent B has a low viscosity. PDMS curing agent B is used to cure PDMS prepolymer A and adjust the viscosity of the mixture.

[0040] In a specific embodiment of the present invention, the photoinitiator is selected from free radical photoinitiators, such as any one of 2-Hydroxy-2-methylpropiophenone (1173), Irgacure 184, and Irgacure 907.

[0041] In a specific embodiment of the present invention, the prepolymer monomers of the mesophase fluid include, but are not limited to, one or more of epoxy acrylate, polyurethane acrylate, polyester acrylate, and pure acrylate.

[0042] In a specific embodiment of the present invention, for thermosetting microspheres, the innermost phase fluid is an aqueous PVA solution; for photocurable microspheres, the innermost phase is deionized water or contains any one or more of PVA, gelatin, polymer monomers, EGDA, acrylamide, crosslinking agent MBA, and initiator 2959.

[0043] In a specific embodiment of the present invention, when the innermost phase fluid is an aqueous PVA solution, the preparation method is to dissolve PVA in deionized water under heating conditions to obtain a PVA solution.

[0044] In a specific embodiment of the present invention, the mass fraction of the PVA solution is 2%.

[0045] In a specific embodiment of the present invention, please refer to Figure 1 The specific operation of obtaining the preset component involves providing a microfluidic device and a receiving liquid phase; injecting the continuous phase fluid, intermediate phase fluid, and innermost phase fluid into different inlets of the microfluidic device to generate a mixed emulsion flow in the device; introducing the mixed emulsion flow into the receiving liquid phase through the outlet of the microfluidic device, whereby the mixed emulsion flow crosslinks to form a fiber gel network; and solidifying the mixed emulsion in the fiber gel network in situ to obtain the preset component.

[0046] In a specific embodiment of the present invention, the operation of dissolving the pre-formed component specifically involves dissolving the fiber gel network in the pre-formed component with sodium citrate solution, and then washing it with deionized water to obtain the finished product.

[0047] In a specific embodiment of the present invention, the receiving phase is a calcium chloride solution. Specifically, the receiving phase is preferably an aqueous solution of calcium chloride.

[0048] In a specific embodiment of the present invention, the preparation method of the liquid phase is to dissolve anhydrous calcium chloride in deionized water to obtain the liquid phase solution.

[0049] In a specific embodiment of the present invention, the mass-volume fraction of calcium chloride in the liquid phase is 0.5%-10%.

[0050] In a specific embodiment of the present invention, please refer to Figure 1 The specific operation for obtaining the preset component involves providing a microfluidic device and a liquid phase solution: calcium chloride solution, a continuous phase fluid, an intermediate phase fluid, and an innermost phase fluid. The continuous phase fluid, intermediate phase fluid, and innermost phase fluid are injected into different inlets of the microfluidic device, forming a monodisperse polyemulsion in the collection tube of the microfluidic device. The output port of the microfluidic device is placed below the surface of the calcium chloride solution, causing the outflowing phase to crosslink in the calcium chloride solution to form calcium alginate fibers. The emulsion in the fiber cavities is then cured by heating or photocuring. The calcium alginate fiber gel network is dissolved with sodium citrate solution, and the resulting particles are washed with deionized water and dried for storage.

[0051] Secondly, the present invention also provides an irregularly shaped core-shell microparticle prepared by the aforementioned preparation method. The microparticle comprises an irregularly shaped shell and a predetermined number of particles embedded within the shell. Multiple particles are embedded within the shell, achieving a multi-particle configuration.

[0052] It is understood that the irregular core-shell microparticles of the present invention have an irregularly shaped outer shell, with multiple particles embedded inside, and the size and shape are controllable.

[0053] Most existing solid microparticles are simple spherical, ellipsoidal, rod-shaped, or spindle-shaped, making them difficult to apply in certain specific fields. The heteromorphic core-shell microparticles of this invention have a completely different morphology from existing solid microparticles, enabling them to have a wider range of applications in fields such as displays, sensing, microrobotics, and material capture and delivery.

[0054] In a specific embodiment of the present invention, the preset quantity is 1 to 20.

[0055] Thirdly, the present invention also provides an application based on the aforementioned preparation method, which adjusts the flow rate of the microfluidic device to regulate the size, shape, and number of particles embedded in the microparticle shell.

[0056] It is understandable that the application of the preparation method of this invention, by changing microfluidic control parameters such as the composition of each phase solution, flow rate conditions, and device structure to initially adjust the morphology of the complex emulsion mixture, and then through the sodium alginate-calcium ion gelation process in the contact liquid phase, the complex emulsion mixture will further deform and transform into a fiber cavity structure, thereby controlling the structure and morphology of the droplets encapsulated in the cavity. This method has a wide range of applications and strong advantages. Furthermore, by changing the conditions used to solidify the complex emulsion droplets in the fiber cavity, such as temperature, the final particle morphology and structure can be further controlled using the preparation method of this invention.

[0057] In a specific embodiment of the present invention, the flow rates of the continuous phase fluid, the dispersed phase fluid, and the innermost phase fluid in the microfluidic device are adjusted to regulate the size, shape, and number of particles embedded in the microparticle shell.

[0058] In a specific embodiment of the present invention, the method for adjusting the size, shape, and number of particles embedded in the microparticle shell is as follows: By adjusting the composition, flow rate, and device structure of each phase (continuous phase fluid, intermediate phase fluid, innermost phase fluid) solution, the size of the prepared complex emulsion droplets and the morphology of the emulsion in the transition tube can be controlled, thus obtaining the initial complex emulsion droplet template. During the sol-gel transformation process in hydrogel fiber molding, the morphology of the emulsion will undergo further deformation, thereby forming a heteromorphic complex emulsion template embedded in the fiber template; by in-situ curing the heteromorphic emulsion template, heteromorphic core-shell microparticles can be obtained. Furthermore, by adjusting the parameters and operating conditions of the solidified irregular emulsion template, such as temperature, the irregular composite emulsion template can be further controlled to obtain irregular core-shell particles with different morphologies.

[0059] In a specific embodiment of the present invention, the flow rate Q1 of the innermost phase fluid is 20~200 uL / h, the flow rate Q2 of the intermediate phase fluid is 200~800 uL / h, and the flow rate Q3 of the continuous phase fluid is 1000~8000 uL / h.

[0060] For specific microfluidic devices and solution systems: by reasonably matching the flow rates of the innermost phase fluid, intermediate phase fluid and continuous phase fluid, the size and shape of microparticles, as well as the number of embedded particles, can be adjusted.

[0061] In a specific embodiment of the present invention, the number of particles embedded in a monodisperse particle is adjusted by regulating the flow rate of the continuous phase fluid.

[0062] Specifically, the higher the continuous phase velocity, the fewer the number of embedded particles. That is, the number of embedded particles increases as the continuous phase velocity decreases.

[0063] In a specific embodiment of the present invention, functional particles are added to the mesophase fluid to adjust the specific functions of the microparticles.

[0064] In specific embodiments of the present invention, functional particles include, but are not limited to, thermosensitive particles, color-changing particles, magnetic particles, fluorescent particles, and catalytic particles.

[0065] Example 1: Preparation of irregularly shaped particles using PDMS-encapsulated PVA irregularly shaped multiple emulsions (1) Preparation of continuous phase fluid, dispersed phase fluid, innermost phase fluid, and wetted phase fluid Preparation of continuous phase fluid: PVA is dissolved in deionized water under heating conditions to prepare a PVA solution with a mass volume fraction of 2%. Sodium alginate with a viscosity of 15-25 cP is added and dissolved to obtain a continuous phase fluid with a mass volume fraction of 2% sodium alginate in the continuous phase fluid.

[0066] Preparation of mesophase fluid: Mix PDMS prepolymer A and PDMS curing agent B at a volume ratio of 1:10 to obtain mesophase fluid.

[0067] Preparation of the innermost phase fluid: Under heating conditions, PVA is dissolved in deionized water to prepare a PVA solution with a mass-volume fraction of 2%, which is the innermost phase fluid.

[0068] Preparation of the wetted phase: Dissolve anhydrous calcium chloride in deionized water to obtain the wetted phase solution. The mass-volume fraction of calcium chloride in the wetted phase solution is 2%.

[0069] (2) Preparation of fiber-confined microparticles Example 1-1 Using a conventional two-stage re-emulsification apparatus, the flow rate of the innermost phase fluid is Q1 = 50 uL / h, the flow rate of the intermediate phase fluid is Q2 = 500 uL / h, and the flow rate of the continuous phase fluid is Q3 = 5000 uL / h.

[0070] Monodisperse polyemulsions were formed in the collection tube of the microfluidic device. The output port (inner diameter 500 μm) of the microfluidic device was placed below the surface of a 2% (w / v) calcium chloride solution, allowing the outflowing emulsions to crosslink in the calcium chloride solution to form calcium alginate fibers with embedded polyemulsions. The emulsions in the fiber cavities were then heated and solidified. The calcium alginate fibers were dissolved in a 1% sodium citrate solution, and the resulting particles were washed with deionized water and dried for storage.

[0071] Examples 1-2 The experimental procedure is the same as in Example 1-1, except that a 1 cm long circular transition tube (with an inner diameter of 300 μm) is connected to the outlet end of the output tube, and the flow rates are Q1=50 uL / h, Q2=500 uL / h, and Q3=4000 uL / h.

[0072] Examples 1-3 The experimental procedure is the same as in Examples 1-2, except that the flow rates are Q1=100 uL / h, Q2=400 uL / h, and Q3=4000 uL / h.

[0073] Examples 1-4 The experimental steps are the same as in Examples 1-2, except that the flow rates are Q1=100 uL / h, Q2=400 uL / h, and Q3=2200 uL / h.

[0074] Examples 1-5 The experimental procedure is the same as in Examples 1-2, except that the flow rates are Q1=100 uL / h, Q2=400 uL / h, and Q3=1000 uL / h.

[0075] The morphology of the microparticles prepared in Examples 1-1 was observed using optical microscopy and scanning electron microscopy. The prepared PDMS-encapsulated PVA irregularly shaped particles are as follows: Figure 2 As shown, the particles undergo partial deformation during the heating and curing process, and the particles eventually exhibit a comma-shaped appearance from a specific perspective.

[0076] A circular transition tube with an inner diameter of 300 μm and a length of 1 cm is connected to the outlet end of the output tube. See the schematic diagram. Figure 3 .

[0077] Furthermore, the particles prepared in Examples 1-2 to 1-5 were observed using an optical microscope and a scanning electron microscope, see [reference]. Figure 4 (In the figure, a~d represent Examples 1-2 to Examples 1-5 respectively).

[0078] Please refer to the following: Figure 4 As shown in a~d, the prepared particles become slender after adding a conical-circular transition tube with an inner diameter of 300 μm.

[0079] By changing the flow rate of each phase in Examples 1-2 to 1-5, the number of particles embedded in the shell can be controllably adjusted. Please continue to refer to... Figure 4 In section a~b, with a fixed continuous phase flow velocity of 4000 μL / h, by increasing the inner phase flow velocity and decreasing the intermediate phase flow velocity, the irregularly shaped particles can be transformed from a "1-pack-1" structure to a "1-pack-2" structure. Please refer to further details. Figure 4 In the b~d section, it can be found that when the flow rates of the inner phase and the intermediate phase are fixed at 100 uL / h and 400 uL / h respectively, as the flow rate of the continuous phase decreases from 4000 uL / h to 1000 uL / h, the prepared irregularly shaped particles successively exhibit the structures of "1-packing-2", "1-packing-3", and "1-packing-4".

[0080] Example 2: Preparation of irregularly shaped particles using ETPTA-in-water irregular emulsion (1) Preparation of continuous phase fluid, dispersed phase fluid, and innermost phase fluid Preparation of continuous phase fluid: Dissolve sodium alginate with a viscosity of (15-25 cP) in deionized water, and add surfactant F127 to obtain continuous phase fluid. The mass volume fraction of sodium alginate in continuous phase fluid is 2%, and the mass volume fraction of surfactant is 1%.

[0081] Preparation of intermediate phase fluid: Dissolve the photoinitiator 2-hydroxy-2-methylphenylacetone (1173) in (3) ethoxylated trimethylolpropane triacrylate, the photoinitiator content is 1% (V / V), and mix evenly to obtain the intermediate phase fluid.

[0082] Preparation of the innermost phase fluid: Deionized water is used as the innermost phase fluid.

[0083] (2) Preparation of fiber-confined microparticles Example 2-1 A two-stage re-emulsification device with an output port inner diameter of 400 μm was used. The flow rate of the innermost phase fluid was Q1 = 100 μL / h, the flow rate of the intermediate phase fluid was Q2 = 400 μL / h, and the flow rate of the continuous phase fluid was Q3 = 1500 μL / h, forming a monodisperse re-emulsion in the collection tube of the microfluidic device. The output port of the microfluidic device was placed below the surface of a 2% (w / v) calcium chloride solution, causing the outflowing phase to crosslink in the calcium chloride solution to form calcium alginate fibers. The irregular emulsion in the fiber cavities was then photocured. The calcium alginate fibers were dissolved in a 1% sodium citrate solution, and the resulting particles were washed with deionized water and dried for storage.

[0084] Example 2-2 The experimental procedure is the same as in Example 2-1, except that the flow rates are Q1=50 uL / h, Q2=300 uL / h, and Q3=2000 uL / h.

[0085] Example 2-3 The experimental procedure is the same as in Example 2-1, except that the flow rates are Q1=100 uL / h, Q2=400 uL / h, and Q3=3000 uL / h.

[0086] The fibers and particles prepared in Examples 2-1 to 2-3 were tested using optical microscopy and scanning electron microscopy. (See [link to relevant documentation]). Figure 5 (In the figure, a~c represent Examples 2-1 to 2-3 respectively).

[0087] See Figure 5 In the figure, the size and shape of particles a~c have changed, indicating that the particle size and shape can be adjusted by changing the flow rate ratio. When the flow rate is Q1=100 uL / h, Q2=400 uL / h, and Q3=1500 uL / h, the resulting irregularly shaped particles are cavitary, large, cap-shaped particles. Figure 5 a); When the flow rate is Q1=50 uL / h, Q2=300 uL / h, and Q3=2000 uL / h, the resulting irregularly shaped particles are slender, cap-shaped particles with cavities ( Figure 5When the flow rates are Q1 = 100 uL / h, Q2 = 400 uL / h, and Q3 = 3000 uL / h, the resulting irregularly shaped particles are spherical particles with cavities. Figure 5 c). It can be seen that the morphology of the final irregular microparticles can be flexibly changed by adjusting the flow rates of the inner phase, intermediate phase, and continuous phase.

[0088] Example 3: Preparation of irregularly shaped particles using ETPTA-soybean oil mixed-phase water-encapsulated double emulsion (1) Preparation of continuous phase and dispersed phase fluids Preparation of continuous phase fluid: Dissolve sodium alginate with a viscosity of (15-25 cP) in deionized water, and add surfactant F127 to obtain continuous phase fluid. The mass volume fraction of sodium alginate in continuous phase fluid is 2%, and the mass volume fraction of surfactant is 1%.

[0089] Preparation of the mesophase fluid: (3) ethoxylated trimethylolpropane triacrylate and edible soybean oil are mixed at a volume ratio of 3:1. Photoinitiator 2-hydroxy-2-methylphenylacetone and polyglycerol-6 polyricinoleate (PGPR) are added. The photoinitiator content is 1% (V / V) and the PGPR content is 2% (W / V). The mesophase fluid is obtained by mixing evenly.

[0090] Preparation of the innermost phase fluid: Deionized water is the innermost phase fluid.

[0091] (2) Preparation of fiber-confined microparticles Example 3-1 A two-stage re-emulsification device with an output port inner diameter of 500 μm was used. The flow rate of the innermost phase fluid was Q1 = 100 μL / h, the flow rate of the intermediate phase fluid was Q2 = 400 μL / h, and the flow rate of the continuous phase fluid was Q3 = 2000 μL / h, forming a monodisperse re-emulsion in the collection tube of the microfluidic device. The output port of the microfluidic device was placed below the surface of a 2% (w / v) calcium chloride solution, causing the outflowing phase to crosslink in the calcium chloride solution to form calcium alginate fibers. The emulsion in the fiber cavities was then immediately photocured. The calcium alginate fibers were dissolved in a 1% sodium citrate solution, and the resulting particles were washed with deionized water and dried for storage.

[0092] Example 3-2 The experimental procedure is the same as in Example 3-1, except that the generated calcium alginate fiber is left to stand for 10 minutes before the emulsion in the fiber cavity is lightly cured.

[0093] Optical photographs and scanning electron microscope images, such as Figure 6 As shown in the scanning electron microscope image, the surface of the directly photocured particles is smooth. Figure 6 a) The surface of particles that are left to stand and then light-cured is rough and has depressions. Figure 6 b). The reason for this difference is that during the standing process, the soybean oil and ETPTA in the re-emulsion oil phase will undergo phase separation and become a heterogeneous solution, thus forming a discontinuous and rough structure during curing.

[0094] Example 4: Preparation of irregularly shaped particles using ETPTA-encapsulated PVA-AM double emulsion (1) Preparation of continuous phase and dispersed phase fluids Preparation of continuous phase fluid: Dissolve sodium alginate with a viscosity of (15-25 cP) in deionized water, and add surfactant F127 to obtain continuous phase fluid. The mass volume fraction of sodium alginate in continuous phase fluid is 2%, and the mass volume fraction of surfactant is 1%.

[0095] Preparation of intermediate phase fluid: Dissolve the photoinitiator 2-hydroxy-2-methylphenylacetone (1173) in (3) ethoxylated trimethylolpropane triacrylate, the photoinitiator content is 1% (V / V), and mix evenly to obtain the intermediate phase fluid.

[0096] Preparation of the innermost phase fluid: Prepare a 2% PVA solution, add acrylamide (1M), crosslinking agent N,N'-methylenebisacrylamide (0.02M), and photoinitiator 2-hydroxy-2-methyl-1-[4-(2-hydroxyethoxy)phenyl]-1-propanone (2959) (0.01M), mix well to obtain the innermost phase fluid.

[0097] (2) Preparation of fiber-confined microparticles A two-stage re-emulsification device with an output port inner diameter of 400 μm was used. The flow rate of the innermost phase fluid was Q1 = 50 μL / h, the flow rate of the intermediate phase fluid was Q2 = 250 μL / h, and the flow rate of the continuous phase fluid was adjustable within the range of Q3 = 1800 μL / h, forming a monodisperse re-emulsion in the collection tube of the microfluidic device. The output port of the microfluidic device was placed below the surface of a 2% (w / v) calcium chloride solution, allowing the outflowing phase to crosslink in the calcium chloride solution to form calcium alginate fibers. The emulsion in the fiber cavities was then photocured. The calcium alginate fibers were dissolved in a 1% sodium citrate solution, and the resulting particles were washed with deionized water and dried for storage.

[0098] like Figure 7 As shown in Figure a, the optical photograph of this embodiment demonstrates the successful preparation of irregularly shaped microparticles containing internal hydrogel particles. Acrylamide undergoes photopolymerization to form internal hydrogel particles, resulting in a distinct core-shell structure in the prepared microspheres.

[0099] Example 5: Preparation of irregularly shaped particles using ETPTA-encapsulated PVA-EGDA double emulsion The experimental steps of Example 5 are the same as those of Example 4. The difference is that the innermost phase fluid is prepared first. In Example 5, 2% PVA solution is prepared first, and 20% (V / V) polyethylene glycol diacrylate and photoinitiator 2-hydroxy-2-methyl-1-[4-(2-hydroxyethoxy)phenyl]-1-propanone (2959) (0.02M) are added and mixed evenly to obtain the innermost phase fluid.

[0100] The optical photographs and scanning electron microscope images of the microparticles prepared in this embodiment are as follows: Figure 7 As shown in b, polyethylene glycol diacrylate undergoes photopolymerization to form internal hydrogel particles, giving the prepared microspheres a distinct core-shell structure.

[0101] Example 6: Preparation of irregularly shaped particles using ETPTA-encapsulated PVA-Gel double emulsion (1) Preparation of continuous phase and dispersed phase fluids Preparation of continuous phase fluid: Sodium alginate is dissolved in deionized water with a mass volume fraction of 2%. Surfactant F127 is added to obtain the continuous phase fluid with a mass volume fraction of 1%.

[0102] Preparation of intermediate phase fluid: Dissolve the photoinitiator 2-hydroxy-2-methylphenylpropanone (1173) in (3) ethoxylated trimethylolpropane triacrylate, mix evenly to obtain the dispersed phase fluid, the content of 2-hydroxy-2-methylphenylpropanone in the dispersed phase fluid is 1% (V / V).

[0103] Preparation of the innermost phase fluid: Prepare a gelatin solution with a mass volume fraction of 1% (W / V), add PVA, dissolve and stir evenly to obtain the innermost phase fluid, with a PVA mass volume fraction of 0.5% (W / V).

[0104] Preparation of the receiving phase: Dissolve anhydrous calcium chloride in deionized water to obtain the receiving phase solution, store at 0℃ for later use, and the calcium chloride content in the receiving phase solution is 2% (W / V).

[0105] (2) Preparation of fiber-confined microparticles Example 6-1 Using a two-stage re-emulsification device with an output port inner diameter of 400 μm, the flow rates of the innermost phase fluid were Q1 = 400 μL / h, the intermediate phase fluid Q2 = 400 μL / h, and the outermost phase fluid Q3 = 3500 μL / h, forming a monodisperse water-in-oil-in-water emulsion in the collection tube of the microfluidic device. The output port of the microfluidic device was placed below the surface of a 2% (w / v) calcium chloride solution at 0°C, causing the effluent phase to crosslink in the calcium chloride solution to form calcium alginate fibers. The emulsion in the fiber cavities was then photocured in situ. The calcium alginate fibers were dissolved in a 1% sodium citrate solution, and the resulting particles were washed with deionized water and dried for storage.

[0106] Example 6-2 The experimental procedure is the same as in Example 6-1, except that the continuous phase fluid flow rate is 2000 uL / h.

[0107] Example 6-3 The experimental procedure is the same as in Example 6-1, except that the continuous phase fluid flow rate is 1800 uL / h.

[0108] Optical photographs and scanning electron microscope images of the microparticles prepared in this embodiment are as follows: Figure 8 As shown, changing the flow rate of the continuous phase fluid can produce monodisperse particles of one-pack-one, one-pack-two, and one-pack-three types, respectively. Furthermore, under low temperature conditions, the internal gelatin undergoes gelation and solidification, resulting in microparticles with a typical core-shell structure. Figure 8 b4).

[0109] The fibers prepared in Example 6-2 were allowed to stand for 5 minutes and then photocured. Optical photographs of the fibers and particles are shown below. Figure 9 As shown in Figure a, the two emulsions in the inner phase fused due to the lack of immediate photocuring, resulting in ellipsoidal, one-pack-one-particle shapes. Changing the temperature of the calcium chloride solution in Example 6-2, i.e., using 2% (w / v) calcium chloride at 24°C as the wetted phase, and immediately photocuring the resulting fibers, yielded the following... Figure 9 As shown in b, there are spherical core-shell particles. From the above, it can be seen that the temperature of the receiving liquid and the curing operation conditions both affect the stability of the core-shell emulsion and its final morphology within the fiber. This not only causes the two emulsions in the inner phase to fuse into a single droplet, but also alters the final morphology of the core-shell particles.

[0110] In addition, the two-particle pack prepared in Example 6-2 was used to load Chlorella, such as Figure 10 As shown in Figure a, because the internal phase contains a gelatin solution, the gelatin solidifies upon cooling, making it impossible to directly load Chlorella. Gelatin has heat-melting properties, such as... Figure 10 First, the particles are washed with hot water. Figures b2 and b3 are optical photographs and scanning electron microscope images after washing, respectively. Figure b4 shows an optical photograph of the particles loaded with Chlorella after washing, which shows that Chlorella has been loaded into the particles.

[0111] Example 7: Preparation of irregularly shaped particles using ETPTA-coated PVA-AM-NIPAM or PVA-AM-NIPAM-Agar co-emulsions doped with thermochromic particles. (1) Preparation of continuous phase and dispersed phase fluids Example 7-1 Preparation of continuous phase fluid: Sodium alginate is dissolved in deionized water with a mass volume fraction of 2%. Surfactant F127 is added to obtain the continuous phase fluid with a mass volume fraction of 1%.

[0112] Preparation of intermediate phase fluid: Dissolve the photoinitiator 2-hydroxy-2-methylphenylpropanone (1173) in (3) ethoxylated trimethylolpropane triacrylate, then add thermosensitive color-changing (from blue to yellow at 31℃) microparticles, mix evenly to obtain the dispersed phase fluid, the content of 2-hydroxy-2-methylphenylpropanone in the dispersed phase fluid is 1% (V / V), and the content of temperature-responsive color-changing microparticles is 0.5% (W / V).

[0113] Preparation of the innermost phase fluid: Prepare a 2% PVA solution, add acrylamide (1M), N-isopropylacrylamide (1M), crosslinking agent N,N'-methylenebisacrylamide (0.02M), and photoinitiator 2-hydroxy-2-methyl-1-[4-(2-hydroxyethoxy)phenyl]-1-propanone (0.01M), and mix thoroughly to obtain the innermost phase fluid.

[0114] (2) Preparation of fiber-confined microparticles Using a two-stage re-emulsification device with an output port inner diameter of 400 μm, the flow rates of the innermost phase fluid were Q1 = 50 μL / h, the intermediate phase fluid Q2 = 250 μL / h, and the continuous phase fluid Q3 = 1800 μL / h, forming a monodisperse water-in-oil-in-water emulsion in the collection tube of the microfluidic device. The output port of the microfluidic device was placed below the surface of a 2% (w / v) calcium chloride solution, causing the outflowing phase to crosslink in the calcium chloride solution to form calcium alginate fibers. The emulsion in the fiber cavities was then photocured in situ. The calcium alginate fibers were dissolved with a 1% sodium citrate solution, and the resulting particles were washed with deionized water and dried for storage.

[0115] Example 7-2 The experimental procedure is the same as in Example 7-1, except that agar is added to the innermost phase fluid in Example 7-1, with an agar content of 0.5% (W / V).

[0116] like Figure 11 As shown, this embodiment successfully obtained two different core-shell shaped particles, each containing different hydrogel particles. Furthermore, optical photographs of the fibers and particles after photocuring clearly show thermosensitive color-changing particles doped on the particle surface; scanning electron microscope images of the cut shaped microparticles also reveal the internal hydrogel particle structure, which is not limited to the currently used hydrogel system.

[0117] The preparation method and application of the heteromorphic core-shell microparticles provided by the present invention have been described in detail above. Specific examples have been used to illustrate the principle and implementation of the present invention. The above description of the embodiments is only for the purpose of helping to understand the method and core idea of ​​the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made to the present invention without departing from the principle of the present invention, and these improvements and modifications also fall within the protection scope of the claims of the present invention.

Claims

1. A method for preparing heteromorphic core-shell microparticles, characterized in that, Includes the following steps: Continuous phase fluid, intermediate phase fluid, and innermost phase fluid were prepared separately. A complex emulsion mixture was prepared using a continuous phase fluid, an intermediate phase fluid, and an innermost phase fluid. The complex emulsion mixture was cross-linked to obtain a fiber gel network. The emulsion in the fiber gel network was solidified to obtain a pre-designed component. The fiber gel network in the pre-made component is dissolved, washed, and the finished product is obtained.

2. The method for preparing heteromorphic core-shell microparticles according to claim 1, characterized in that, The method for preparing the continuous phase fluid is as follows: for thermosetting microspheres, PVA solution and sodium alginate are provided, and sodium alginate is dissolved in PVA solution to obtain a continuous phase fluid; for photocurable microspheres, F127 and sodium alginate are provided, and sodium alginate and F127 are dissolved in deionized water to obtain a continuous phase fluid.

3. The method for preparing heteromorphic core-shell microparticles according to claim 2, characterized in that, In the continuous phase fluid, the mass fraction of sodium alginate is 0.5%-5.0%.

4. The method for preparing heteromorphic core-shell microparticles according to claim 1, characterized in that, The method for preparing the intermediate phase fluid is as follows: For photocurable microspheres, a photoinitiator and a prepolymer monomer are provided, and the photoinitiator is dissolved in the prepolymer monomer to obtain an intermediate phase fluid; For thermosetting microspheres, PDMS prepolymer A and PDMS curing agent B are provided; the two are mixed evenly to obtain an intermediate phase fluid.

5. The method for preparing heteromorphic core-shell microparticles according to claim 1, characterized in that, For thermosetting microspheres, the innermost phase fluid is an aqueous PVA solution; For photocurable microspheres, the innermost phase is deionized water or contains any one or more of PVA, gelatin, polymer monomers, EGDA, acrylamide, crosslinking agent MBA, and initiator 2959.

6. The method for preparing heteromorphic core-shell microparticles according to claim 1, characterized in that, The specific operation of obtaining the preset component involves providing a microfluidic device and a liquid phase; injecting the continuous phase fluid, intermediate phase fluid, and innermost phase fluid into different inlets of the microfluidic device to generate a mixed emulsion flow in the device; introducing the mixed emulsion flow into the liquid phase through the outlet of the microfluidic device, whereby the mixed emulsion flow crosslinks to form a fiber gel network. The complex emulsion in the fiber gel network is cured in situ to obtain the preset part.

7. The method for preparing heteromorphic core-shell microparticles according to claim 1, characterized in that, The specific operation of dissolving the pre-form involves dissolving the fiber gel network in the pre-form using sodium citrate solution, followed by washing with deionized water to obtain the finished product.

8. The method for preparing heteromorphic core-shell microparticles according to claim 1, characterized in that, The liquid phase is a calcium chloride solution.

9. A heteromorphic core-shell microparticle prepared by the preparation method according to any one of claims 1-8, characterized in that, The microparticles include: an irregularly shaped shell and a predetermined number of particles embedded in the shell.

10. The application of the method for preparing heteromorphic core-shell microparticles according to any one of claims 1-8, characterized in that, Adjusting the flow rate of the microfluidic device regulates the size, shape, and number of particles embedded in the microparticle shell.

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