Preparation method of adjustable special-shaped microparticles
By using droplet microfluidics, a water-in-oil emulsion is formed and cross-linked and solidified in a microfluidic device using sodium alginate and surfactant fluids. This solves the problem of the difficulty in preparing irregularly shaped microparticles in the prior art, and realizes the monodispersity and morphological diversity of irregularly shaped microparticles, meeting the needs of cutting-edge research and application.
Patent Information
- Application Number
- CN202511881447.9
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-12-12
- Publication Date
- 2026-02-10
AI Technical Summary
Existing technologies struggle to prepare irregularly shaped microparticles with adjustable size, good monodispersity, and diverse morphologies. In particular, microfluidic devices require extremely high concentrations of initiators and can only prepare microparticles with simple, regular structures, which cannot meet the needs of cutting-edge research or potential applications.
Using droplet microfluidics, a water-in-oil emulsion was formed by preparing continuous and dispersed phases of sodium alginate and surfactant using a microfluidic device. The emulsion was then crosslinked in a calcium chloride solution to form a fiber gel network. Subsequently, the fibers were solidified and dissolved in situ, and various parameters were adjusted to prepare irregularly shaped microparticles.
This method enables the preparation of irregularly shaped microparticles with good monodispersity, adjustable size, and diverse morphology, enriching the methods for microparticle preparation and meeting the needs of cutting-edge research and potential applications.
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Figure CN121490682A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of microparticle preparation technology, specifically to a method for preparing tunable irregularly shaped microparticles. Background Technology
[0002] Microparticles, as advanced functional materials, have been widely used in drug delivery, tissue engineering, optical devices, biosensors, and model particles. The properties of microparticles are related to their size, structure, composition, and morphology. However, traditional methods such as emulsion polymerization, dispersion polymerization, and spray drying often result in microparticles with good dispersibility, 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.
[0003] Currently, technologies for manufacturing microparticles with size control, monodispersity, and multiple morphologies include droplet microfluidics, flowing photolithography microfluidics, electrohydrodynamic co-jetting, photolithography, imprinting based on soft photolithography, and micromolding. Among these, droplet microfluidics allows for precise control of multiple fluids at the microscale. Each heterogeneous phase or compartment in the generated droplet can serve as a template, and physical and chemical reactions can occur at or between the interfaces through polymerization, ionic crosslinking, and solvent evaporation, thereby transforming the droplet into solid microparticles. While these methods can flexibly adjust particle size and morphology, the morphological structures of the particles that can be prepared are very limited, and the preparation conditions are demanding. Microparticles polymerized in microfluidic devices require the particle template material to have an extremely fast solidification rate, which usually requires the addition of extremely high concentrations of slightly toxic initiators (typically greater than 10%), greatly limiting their subsequent applications. Furthermore, current methods can only prepare some simple, regular non-spherical particles, such as helical, spindle, and rod-shaped particles, which cannot meet the needs of some cutting-edge research or future potential applications. Therefore, new methods still need to be explored and developed to prepare some irregular microparticles with specific or biomimetic structures. Summary of the Invention
[0004] To address the shortcomings of existing technologies, this invention provides a method for preparing tunable, irregularly shaped microparticles. It utilizes droplet microfluidic technology to prepare microparticles with good monodispersity, adjustable size, and diverse morphologies, thereby further enriching and developing microparticle preparation methods.
[0005] To achieve the above objectives, the present invention adopts the following technical solution: This invention provides a method for preparing tunable irregularly shaped microparticles, comprising the following steps: Step 1: Prepare continuous phase and dispersed phase fluids Preparation of continuous phase fluid: Sodium alginate and surfactant are dissolved in a solvent to obtain the fluid, wherein the mass volume fraction of sodium alginate is 0.5-5% and the mass volume fraction of surfactant is 0.1-2%. Preparation of dispersed phase fluid: The dispersed phase fluid includes any one or more of the following forms: (1) Photoinitiated dispersed phase fluid: obtained by dissolving the photoinitiator in the prepolymer monomer; (2) Thermally initiated dispersed phase fluid: obtained by mixing PDMS prepolymer A with PDMS curing agent B; Preparation of the contacting liquid: Anhydrous calcium chloride is dissolved in deionized water to obtain the solution, wherein the mass-volume fraction of the calcium chloride is 0.5-10%. Step 2: Preparation of tunable irregular microparticles Dispersed phase fluid and continuous phase fluid are injected into different inlets of the microfluidic device to generate a monodisperse oil-in-water emulsion in the collection tube of the microfluidic device. The mixed flow of the oil-in-water emulsion is introduced into a calcium chloride solution through the outlet of the microfluidic device to rapidly crosslink and form fibers. The emulsion in the fiber cavity is then solidified in situ by light or heat. The fibers are then dissolved with sodium citrate solution and finally washed with deionized water and dried. Irregular particle morphology formation and its control strategy: (1) Adjusting the composition of each phase solution, the flow rate and the structure of the device to control the size of the prepared emulsion droplets and the morphology of the emulsion in the transition tube can yield the initial droplet template; (2) The morphology of the emulsion will undergo further deformation during the sol-gel transformation process in the hydrogel fiber forming process, thereby forming a heteromorphic emulsion template embedded in the fiber template. (3) The irregularly shaped emulsion template is cured in situ, and irregularly shaped particles are obtained after fiber dissolution and cleaning.
[0006] For example, the mass-volume fraction of the sodium alginate is any one of 1%, 1.5%, 2%, 2.5%, 3% and 4% or a value between two of them.
[0007] For example, the mass-volume fraction of the surfactant is any one of 0.1%, 1%, 2%, or a value between two of them.
[0008] Preferably, the surfactant is selected from any one or more of F127, sodium dodecyl sulfate, sodium carboxymethyl cellulose, and polyvinyl alcohol.
[0009] Preferably, the viscosity of the sodium alginate is any one of 4-12 cP, 15-25 cP, and >2000 cP.
[0010] Preferably, the photoinitiator has a volume fraction of 1%.
[0011] Preferably, the photoinitiator is selected from 2-hydroxy-2-methylphenylacetone (1173), or any one of other ultraviolet photoinitiators such as Irgacure 184, Irgacure 907, Bis(2,4,6-trimethylbenzoyl)-phenylphosphine oxide, and Diphenyl(2,4,6-trimethylbenzoyl)phosphine oxide.
[0012] Preferably, the prepolymer monomer is ETPTA.
[0013] Preferably, the volume ratio of PDMS prepolymer A to PDMS curing agent B is 1:10.
[0014] Preferably, the preparation process of the photoinitiated dispersed phase fluid is as follows: after mixing the prepolymer monomer and the functionalized material, a photoinitiator is added.
[0015] Preferably, when the functionalized material is 4-cyano-4'-pentylbiphenyl (5CB), it is mixed with ETPTA at a volume ratio of 1:4, and then 1% (V / V) of photoinitiator is added.
[0016] Preferably, the functionalized material has a mass-volume fraction of 0.25-1 wt%.
[0017] Preferably, the functionalized material is selected from any one or more of Pt nanoparticles and Fe3O4 nanoparticles. Preferably, the preparation process of the photoinitiated dispersed phase fluid is as follows: mixing the initiator, vegetable oil and prepolymer monomer.
[0018] Preferably, the vegetable oil is corn oil.
[0019] Preferably, the volume ratio of the vegetable oil to the prepolymer monomer is 1:1.
[0020] Preferably, the process of preparing the dispersed phase fluid is replaced by: the dispersed phase fluid comprising an inner oil phase 1 and an inner oil phase 2; the inner oil phase 1 is selected from any one or more of fluorocarbon oil FC40, fluorocarbon oil HFE7500, fluorocarbon oil HFE7500 containing 5% HFE7500 Surf surfactant, silicone oil for oil bath, and light mineral oil; the inner oil phase 2 is obtained by dissolving a photoinitiator in a prepolymer monomer.
[0021] Preferably, in step 2, the flow rate of the continuous phase fluid is 1000~3000 μL / h.
[0022] For example, in step 2, the flow rate of the continuous phase fluid is any one of 1000 μL / h, 1500 μL / h, 1600 μL / h, 2000 μL / h, 3000 μL / h, or a value between two of them.
[0023] Preferably, in step 2, the flow rate of the dispersed phase fluid is 100~1000 μL / h.
[0024] For example, in step 2, the flow rate of the dispersed phase fluid is any one of 100 μL / h, 200 μL / h, 250 μL / h, 300 μL / h, 350 μL / h, 400 μL / h, 500 μL / h, 600 μL / h, 700 μL / h, 800 μL / h, or 1000 μL / h, or a value between two of them.
[0025] Preferably, the calcium chloride solution has a mass-volume fraction of 2%.
[0026] Preferably, the sodium citrate solution has a mass-volume fraction of 1%.
[0027] Preferably, the microfluidic device collection tube is connected to a transition tube, which is a glass capillary tube with a length of 1-2 cm and an inner diameter of 350-550 μm; or, the transition tube is a conical glass capillary tube with a length of 1-2 cm and an inner diameter of 100-200 μm at the conical opening; or, the transition tube is a square glass tube or an equilateral triangular glass tube.
[0028] The beneficial effects of this invention are: In the preparation method of the irregularly shaped microparticles of the present invention, sodium alginate aqueous phase is used as continuous phase, and a monodisperse oil-in-water emulsion is prepared by microfluidic technology. The mixed flow of the oil-in-water emulsion enters the calcium chloride solution through the outlet of the microfluidic device, wherein the outlet of the microfluidic device is slightly immersed below the surface of the calcium chloride solution. Calcium ions diffuse from the outside to the inside under the driving force of the concentration difference and rapidly crosslink with alginate ions in the continuous phase to form a fiber gel network structure. The formed fiber cavities encapsulate the oil-in-water emulsion, and then the emulsion in the fiber cavities is solidified in situ. Then, the calcium alginate fibers are dissolved using sodium citrate solution. After washing and separation, microparticles with rich morphologies can be obtained. The morphology of the microparticles can be controlled by controlling the parameters in the preparation process. Attached Figure Description
[0029] Figure 1 This is a schematic diagram illustrating the preparation of the irregularly shaped microparticles of the present invention.
[0030] Figure 2 Optical photographs and scanning electron microscope images of irregularly shaped microparticles prepared by controlling the flow rate of the dispersed phase in Example 1 of this invention.
[0031] Figure 3 This is a graph showing the characteristic length and width variations of irregularly shaped microparticles prepared by controlling the flow rate of the dispersed phase in Example 1 of the present invention.
[0032] Figure 4 Optical photographs and scanning electron microscope images of the preparation of irregularly shaped microparticles by adjusting the viscosity of sodium alginate in Example 2 of this invention.
[0033] Figure 5 Optical photographs and scanning electron microscope images of the preparation of irregularly shaped microparticles by controlling surfactants in a continuous phase in Example 3 of the present invention.
[0034] Figure 6 Optical photographs and scanning electron microscope images of the preparation of irregularly shaped microparticles by adjusting the sodium alginate concentration in Example 4 of this invention.
[0035] Figure 7 Optical photographs and scanning electron microscope images of irregularly shaped microparticles prepared from doped functionalized materials in Example 5 of this invention.
[0036] Figure 8 This is a schematic diagram illustrating the addition of a transition tube at the outlet end of the single emulsion device to regulate droplet size according to the present invention.
[0037] Figure 9 Optical photographs and scanning electron microscope images of irregularly shaped microparticles prepared by adding transition tubes with different inner diameters to the collection tube of the microfluidic device in Embodiment 6 of the present invention.
[0038] Figure 10 Optical photographs and scanning electron microscope images of irregularly shaped microparticles were prepared by adding square and triangular transition tubes to the collection tube of the microfluidic device in Embodiment 7 of the present invention.
[0039] Figure 11 Optical photographs and scanning electron microscope images of the irregularly shaped microparticles prepared under different conditions in Example 8 of the present invention.
[0040] Figure 12 For the use of this invention Schematic diagram of Janus droplet preparation using a modular device.
[0041] Figure 13 For use in Embodiment 9 of the present invention Optical photographs and scanning electron microscope images of irregularly shaped microparticles prepared by a novel device.
[0042] Figure 14 Optical photographs and scanning electron microscope images of the irregularly shaped microparticles prepared in Example 10 of this invention. Detailed Implementation
[0043] To enable those skilled in the art to better understand the technical solution of the invention, the invention will be further described in detail below with reference to specific embodiments.
[0044] The mass-volume fraction described in this invention is: when 1g of solute is placed in 100ml of solvent, the mass-volume ratio is 1.0%.
[0045] Example 1: Adjusting the particle size by changing the dispersed phase flow rate (1) Preparation of continuous phase and dispersed phase fluids Preparation of continuous phase fluid: Dissolve sodium alginate (viscosity specification 15-25 cP) in deionized water, with a sodium alginate mass-volume fraction of 2%, and add surfactant F127, with a surfactant mass-volume fraction of 1% in the continuous phase fluid; Preparation of dispersed phase fluid: Dispersed phase fluid is obtained by dissolving the photoinitiator 2-hydroxy-2-methylphenylpropanone in the prepolymer monomer ethoxylated trimethylolpropane triacrylate (ETPTA). The content of 2-hydroxy-2-methylphenylpropanone (1173) in the dispersed phase fluid is 1% (V / V). Preparation of the contacting liquid: Anhydrous calcium chloride is dissolved in deionized water to obtain the solution, wherein the mass-volume fraction of the calcium chloride is 2%. (2) Preparation of tunable heteromorphic microparticles like Figure 1 As shown, a monodisperse oil-in-water emulsion was formed in the collection tube of the microfluidic device using a 450 μm collection tube. The flow rate of the continuous phase fluid was maintained at Q2 = 1500 μL / h, and the flow rates of the dispersed phase fluid were Q1 at 200, 400, 600, 800, and 1000 μL / h, respectively. 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 solidified in situ. The calcium alginate fibers were dissolved in a 1 wt% sodium citrate solution, and the resulting particles were washed with deionized water and dried for storage.
[0046] The morphology of the fibers and microparticles prepared in this embodiment was observed using an optical microscope and a scanning electron microscope, as shown in Figure 2. Data analysis is as follows: Figure 3 As shown in the figure, the length and width of the prepared particles increase significantly with the increase of the dispersed phase flow rate. Therefore, the size and morphology of the irregularly shaped microparticles can be controlled by adjusting the dispersed phase flow rate.
[0047] Example 2: Preparation of microparticles of different shapes by controlling the viscosity of sodium alginate (1) Preparation of continuous phase and dispersed phase fluids Preparation of continuous phase fluid: Sodium alginate with viscosity grades of 4-12 cP, 15-25 cP and >2000 cP were dissolved in deionized water, with a mass volume fraction of 2% for each type of sodium alginate. Surfactant F127 was added to each type of fluid, with a mass volume fraction of 1% for the surfactant in the continuous phase fluid.
[0048] Preparation of dispersed phase fluid: Dispersed phase fluid is obtained by dissolving the photoinitiator 2-hydroxy-2-methylphenylpropanone (1173) in the prepolymer monomer ethoxylated trimethylolpropane triacrylate (ETPTA). The content of 2-hydroxy-2-methylphenylpropanone (1173) in the dispersed phase fluid is 1% (V / V). Preparation of the contacting liquid: Anhydrous calcium chloride is dissolved in deionized water to obtain the solution, wherein the mass-volume fraction of the calcium chloride is 2%. (2) Preparation of tunable heteromorphic microparticles Using a monodisperse oil-in-water emulsion device with a collection tube of 450 μm, the flow rate of the continuous phase fluid was maintained at Q2 = 1500 μL / h, and the flow rate of the dispersed phase fluid was Q1 = 250 μL / h. A monodisperse oil-in-water emulsion was formed in the collection tube of the microfluidic device. The outlet 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 solidified in situ. The calcium alginate fibers were dissolved with a 1 wt% sodium citrate solution, and the resulting particles were washed with deionized water and dried for storage.
[0049] The morphology of the microparticles prepared in this embodiment was observed using optical microscopy and scanning electron microscopy, as shown in Figure 4. It can be seen that as the viscosity of sodium alginate increases, the length of the prepared particles increases, successively changing from spherical to cylindrical, and then to rod-shaped. Therefore, by controlling the viscosity of sodium alginate, microparticles with different morphologies can be obtained.
[0050] Example 3: Preparation of microparticles with different morphologies by changing the surfactant in the continuous phase (1) Preparation of continuous phase and dispersed phase fluids Preparation of continuous phase fluids: Dissolve sodium alginate with a viscosity of 15-25 cP in deionized water. The mass volume fraction of sodium alginate is 2%. Add different surfactants (0% mass volume fraction, 0.1% F127, 0.1% sodium dodecyl sulfate (SDS), and 0.1% sodium carboxymethyl cellulose (CMC-Na) to obtain four types of continuous phase fluids. Preparation of dispersed phase fluid: Dispersed phase fluid is obtained by dissolving the photoinitiator 2-hydroxy-2-methylphenylpropanone in the prepolymer monomer ethoxylated trimethylolpropane triacrylate (ETPTA). The content of 2-hydroxy-2-methylphenylpropanone in the dispersed phase fluid is 1% (V / V). Preparation of the contacting liquid: Anhydrous calcium chloride is dissolved in deionized water to obtain the solution, wherein the mass-volume fraction of the calcium chloride is 2%. (2) Preparation of tunable heteromorphic microparticles Using a monodisperse oil-in-water emulsion device with a collection tube of 450 μm, the flow rate of the dispersed phase fluid is Q1 = 350 μL / h, and the flow rate of the continuous phase fluid is Q2 = 1000 μL / h. A monodisperse oil-in-water emulsion is formed in the collection tube of the microfluidic device. The outlet of the microfluidic device is 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 is then solidified in situ. The calcium alginate fibers are dissolved with a 1 wt% sodium citrate solution, and the resulting particles are washed with deionized water and dried for storage.
[0051] The morphology of the microparticles prepared in this embodiment is as follows: Figure 5 As shown, when sodium carboxymethyl cellulose (CMC-Na) is used as a surfactant, the particles are approximately hamburger-shaped; when sodium dodecyl sulfate is used as a surfactant, the particles are approximately date-shaped; and when F127 is used as a surfactant, the particles are apple-shaped. Therefore, by controlling the type and concentration of surfactants in the continuous phase fluid, microparticles with different morphologies can be obtained.
[0052] Example 4: Preparation of microparticles with different morphologies by changing the concentration of sodium alginate (1) Preparation of continuous phase and dispersed phase fluids Preparation of continuous phase fluids: Sodium alginate with a viscosity of 15-25 cP was dissolved in deionized water at different mass volume fractions (1.0%, 1.5%, 2%, 2.5%, 3% and 4%), and surfactant F127 was added to each to obtain six kinds of continuous phase fluids, in which the mass volume fraction of surfactant was 1% in each case.
[0053] Preparation of dispersed phase fluid: Dispersed phase fluid is obtained by dissolving the photoinitiator 2-hydroxy-2-methylphenylpropanone (1173) in the prepolymer monomer ethoxylated trimethylolpropane triacrylate (ETPTA). The content of 2-hydroxy-2-methylphenylpropanone in the dispersed phase fluid is 1% (V / V). Preparation of the contacting liquid: Anhydrous calcium chloride is dissolved in deionized water to obtain the solution, wherein the mass-volume fraction of the calcium chloride is 2%. (2) Preparation of tunable heteromorphic microparticles Using a monodisperse oil-in-water emulsion device with a collection tube of 450 μm, the flow rate of the dispersed phase fluid is Q1 = 300 μL / h, and the flow rate of the continuous phase fluid is Q2 = 1000 μL / h. A monodisperse oil-in-water emulsion is formed in the collection tube of the microfluidic device. The outlet of the microfluidic device is 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 is then solidified in situ. The calcium alginate fibers are dissolved with a 1 wt% sodium citrate solution, and the resulting particles are washed with deionized water and dried for storage.
[0054] The morphology of the microparticles prepared in this embodiment was observed using an optical microscope and a scanning electron microscope, such as... Figure 6 As shown, the prepared particles change from spherical to cylindrical shapes with increasing sodium alginate concentration. Therefore, by adjusting the sodium alginate concentration, microparticles with different morphologies can be obtained.
[0055] Example 5: Adding functional materials to the dispersed phase to regulate the morphology of microparticles Example 5-1: (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, with a mass-volume fraction of 2% for all sodium alginate. Add surfactant F127 to obtain the continuous phase fluid, with a mass-volume fraction of 1% for the surfactant. Preparation of dispersed phase fluid: The prepolymer monomer ethoxylated trimethylolpropane triacrylate (ETPTA) and the liquid crystal material 4-cyano-4'-pentylbiphenyl (5CB) are mixed at a volume ratio of 4:1. The photoinitiator 2-hydroxy-2-methylphenylpropanone (1173) is added to the mixture at a volume fraction of 1% (V / V) and stirred until homogeneous to obtain the dispersed phase fluid. Preparation of the contacting liquid: Anhydrous calcium chloride is dissolved in deionized water to obtain the solution, wherein the mass-volume fraction of the calcium chloride is 2%. (2) Preparation of tunable heteromorphic microparticles Using a monodisperse oil-in-water emulsion device with a collection tube of 450 μm, the flow rate of the dispersed phase fluid is Q1 = 300 μL / h, and the flow rate of the continuous phase fluid is Q2 = 1500 μL / h. A monodisperse oil-in-water emulsion is formed in the collection tube of the microfluidic device. The outlet of the microfluidic device is placed below the surface of a 2% (w / v) calcium chloride solution, so that the outflowing phase crosslinks in the calcium chloride solution to form calcium alginate fibers. The emulsion in the fiber cavity is then solidified in situ. The calcium alginate fibers are dissolved with a 1 wt% sodium citrate solution, and the resulting particles are washed with deionized water and dried for storage.
[0056] Example 5-2: The experimental steps are the same as in Example 5-1, except that a single emulsion device with a collection tube of 350 μm is used, the dispersed phase fluid is doped with 0.25 wt% Pt nanoparticles (<50 nm), the flow rate of the dispersed phase fluid is Q1=400 μL / h, and the flow rate of the continuous phase fluid is Q2=1500 μL / h.
[0057] Example 5-3: The experimental steps are the same as in Example 5-1, except that the dispersed phase fluid is doped with 1 wt% Fe3O4 nanoparticles (<50 nm), the flow rate of the dispersed phase fluid is Q1=100 μL / h, and the flow rate of the continuous phase fluid is Q2=3000 μL / h.
[0058] Example 5-4: The experimental steps are the same as in Example 5-1, except that a single emulsion device with a collection tube of 400 μm is used. The dispersed phase fluid is simultaneously doped with 1 wt% Pt nanoparticles (<50 nm) and 1 wt% Fe3O4 nanoparticles (<50 nm) by mass volume fraction. The flow rate of the dispersed phase fluid is Q1 = 500 μL / h, and the flow rate of the continuous phase fluid is Q2 = 1500 μL / h.
[0059] The morphology of the microparticles prepared in this embodiment was observed using an optical microscope and a scanning electron microscope, such as... Figure 7 As shown, the microparticles prepared from doped liquid crystal materials are shaped like teacups; the doped Pt nanoparticles are spherical; and the microparticles doped with Fe3O4 have rough surfaces. Therefore, by adding different functional materials to the dispersed phase, microparticles with different morphologies can be obtained.
[0060] Example 6: Adding a transition tube at the outlet end to control the morphology of microparticles Example 6-1: (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, with a mass-volume fraction of 2% for all sodium alginate. Add surfactant F127 to obtain the continuous phase fluid, with a mass-volume fraction of 1% for the surfactant in the continuous phase fluid. Preparation of dispersed phase fluid: Dispersed phase fluid is obtained by dissolving the photoinitiator 2-hydroxy-2-methylphenylpropanone (1173) in the prepolymer monomer ethoxylated trimethylolpropane triacrylate (ETPTA). The content of 2-hydroxy-2-methylphenylpropanone in the dispersed phase fluid is 1% (V / V). Preparation of the contacting liquid: Anhydrous calcium chloride is dissolved in deionized water to obtain the solution, wherein the mass-volume fraction of the calcium chloride is 2%. (2) Preparation of tunable heteromorphic microparticles The effect of adding glass tubes of different inner diameters at the outlet end on the preparation of microparticles was investigated. A schematic diagram of the apparatus is shown below. Figure 8 Using a monodisperse oil-in-water emulsion device with a collection tube of 450 μm, the flow rate of the dispersed phase fluid was Q1 = 700 μL / h, and the flow rate of the continuous phase fluid was Q2 = 1500 μL / h. A monodisperse oil-in-water emulsion was formed in the collection tube of the microfluidic device. The outlet 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 cavity was then solidified in situ. The calcium alginate fibers were dissolved with a 1 wt% sodium citrate solution, and the resulting particles were washed with deionized water and dried for storage.
[0061] Example 6-2: The experimental procedure is the same as in Example 6-1, except that a glass capillary tube with a length of 1 cm and an inner diameter of 350 μm is connected to the outlet end of the collection tube as a second-stage transition tube.
[0062] Example 6-3: The experimental procedure is the same as in Example 6-1, except that a glass capillary tube with a length of 1 cm and an inner diameter of 450 μm is connected to the outlet end of the collection tube.
[0063] Example 6-4: The experimental procedure is the same as in Example 6-1, except that a glass capillary tube with a length of 1 cm and an inner diameter of 550 μm is connected to the outlet end of the collection tube.
[0064] Example 6-5: The experimental procedure is the same as in Example 6-1, except that a 2 cm long, tapered glass capillary tube with an inner diameter of 200 μm is connected to the outlet end of the collection tube.
[0065] Example 6-6: The experimental procedure is the same as in Example 6-1, except that a 2 cm long, 100 μm inner diameter conical glass capillary tube is connected to the outlet end of the collection tube.
[0066] The morphology of the microparticles prepared in this embodiment was observed using an optical microscope and a scanning electron microscope, such as... Figure 9 As shown, the particles are round and flat when connected to a 350μm glass tube, become distinctly frustum-shaped when connected to a 550μm glass tube, and are rod-shaped when connected to a conical tube. Therefore, by adding different glass tubes at the outlet end, microparticles with different morphologies can be obtained.
[0067] Example 7: Preparation of microparticles by adding an irregularly shaped transition tube at the outlet end. Example 7-1: The experimental procedure is the same as in Example 6-1, except that the flow rate of the dispersed phase fluid is Q1=200 μL / h and the flow rate of the continuous phase fluid is Q2=1000 μL / h.
[0068] Example 7-2: The experimental procedure is the same as in Example 7-1, except that a square glass tube with a length of 1 cm, a cross-sectional length of 400 μm, and a width of 200 μm is connected to the outlet end of the collection tube.
[0069] Example 7-3: The experimental procedure is the same as in Example 7-1, except that a 1 cm long, equilateral triangular glass tube with a cross-sectional side length of 200 μm is connected to the outlet end of the collection tube.
[0070] The morphology of the microparticles prepared in this embodiment was observed using an optical microscope and a scanning electron microscope, such as... Figure 10 As shown, when connected to a square glass tube, the particles have a distinct quadrilateral outline, while when connected to a triangular tube, the particles exhibit a rounded triangular structure.
[0071] Example 8 Preparation of thermally initiated curable microspheres Example 8-1: (1) Preparation of continuous phase and dispersed phase fluids Preparation of continuous phase fluid: Prepare a 2% (w / v) polyvinyl alcohol (PVA) solution, add sodium alginate with a viscosity of 15-25 cP, and dissolve to obtain a continuous phase fluid. The mass-volume fraction of sodium alginate in the continuous phase fluid is 2%. Preparation of dispersed phase fluid: Mix PDMS prepolymer A (polymer monomer) and PDMS curing agent B at a volume ratio of 1:10 to obtain the dispersed phase fluid. Preparation of the contacting liquid: Anhydrous calcium chloride is dissolved in deionized water to obtain the solution, wherein the mass-volume fraction of the calcium chloride is 2%. (2) Preparation of tunable heteromorphic microparticles Using a monodisperse oil-in-water emulsion device with a collection tube of 450 μm, the flow rate of the dispersed phase fluid was Q1 = 600 μL / h, and the flow rate of the continuous phase fluid was Q2 = 3000 μL / h. A monodisperse oil-in-water emulsion was formed in the collection tube of the microfluidic device. The outlet 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 fibers were then heated at 65 °C to solidify the emulsion. The calcium alginate fibers were dissolved in a 1 wt% (w / v) sodium citrate solution, and the resulting particles were washed with deionized water and dried for storage.
[0072] Example 8-2: The experimental procedure is the same as in Example 8-1, except that a 2cm long, coarse conical transition tube (with an inner diameter of 200 μm) is connected to the outlet end.
[0073] Example 8-3: The experimental procedure is the same as in Example 8-1, except that a 2cm long thin conical transition tube (with an inner diameter of 100 μm) is connected to the outlet end.
[0074] The morphology of the microparticles prepared in this embodiment was observed using an optical microscope and a scanning electron microscope, such as... Figure 11 As shown, in Example 8-1, the particles are approximately comma-shaped; when connected to a coarse conical transition tube (with an inner diameter of 200 μm), the particles are relatively rounded ellipsoids; when connected to a fine conical transition tube (with an inner diameter of 100 μm), the particles are approximately elongated.
[0075] Example 9 Utilizing Preparing Janus microparticles using a novel device Example 9-1: (1) Preparation of continuous phase and dispersed phase fluids Preparation of continuous phase fluid: Dissolve sodium alginate with a viscosity specification of (15-25 cP) in deionized water, and add surfactant F127 to obtain the continuous phase fluid. The mass volume fraction of sodium alginate in the continuous phase fluid is 2%, and the mass volume fraction of surfactant is 1%. Oil phase 1 in the dispersed phase: Fluorocarbon oil FC40 is oil phase 1.
[0076] Preparation of the inner oil phase 2 of the dispersed phase: Dissolve the photoinitiator 2-hydroxy-2-methylphenylpropanone (1173) in the prepolymer monomer ethoxylated trimethylolpropane triacrylate (ETPTA) to obtain the inner oil phase 2 of the dispersed phase. The content of 2-hydroxy-2-methylphenylpropanone in the inner oil phase 2 of the dispersed phase is 1% (V / V).
[0077] 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%.
[0078] (2) Preparation of tunable heteromorphic microparticles like Figure 12 As shown, using a Janus apparatus, the flow rate of oil phase 1 is Q1 = 300 uL / h, the flow rate of oil phase 2 is Q2 = 300 uL / h, and the flow rate of the continuous phase fluid is Q3 = 1600 uL / h, forming a monodisperse emulsion in the collection tube of the microfluidic device. The outlet of the microfluidic device is 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 is then photocured. The calcium alginate fibers are dissolved with a 1 wt% sodium citrate solution, and the resulting particles are washed with deionized water and ethanol and then dried and stored.
[0079] Example 9-2: The experimental steps and fluid flow rate are the same as in Example 9-1, except that fluorocarbon oil HFE7500 is used as oil phase 1.
[0080] Example 9-3: The experimental steps and fluid flow rate are the same as in Example 9-1, except that fluorocarbon oil HFE7500 containing 5% HFE7500 Surf surfactant is used as oil phase 1.
[0081] Example 9-4: The experimental steps and fluid flow rate are the same as in Example 9-1, except that silicone oil for oil bath is used as oil phase 1.
[0082] Example 9-5: The experimental steps and fluid flow rate are the same as in Example 9-1, except that light mineral oil is used as oil phase 1.
[0083] The morphology of the microparticles prepared in this embodiment was observed using an optical microscope and a scanning electron microscope, such as... Figure 13 As shown, hat-shaped, drum-shaped, and various concave particles were obtained.
[0084] Example 10: Preparation of granules using ETPTA and corn oil blend (1) Preparation of continuous phase and dispersed phase fluids Preparation of continuous phase fluid: Dissolve sodium alginate with a viscosity specification of (15-25 cP) in deionized water, and add surfactant F127 to obtain the continuous phase fluid. The mass volume fraction of sodium alginate in the continuous phase fluid is 2%, and the mass volume fraction of surfactant is 1%. Preparation of dispersed phase fluid: Mix corn oil and prepolymer monomer ethoxylated trimethylolpropane triacrylate (ETPTA) at a volume ratio of 1:1, then add 1% (V / V) of photoinitiator and stir until homogeneous to obtain dispersed phase fluid.
[0085] 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%.
[0086] (2) Preparation of tunable heteromorphic microparticles Using a monodisperse emulsion device, the flow rate of the dispersed phase fluid is Q1 = 500 uL / h, and the flow rate of the continuous phase fluid is Q2 = 2000 uL / h, forming a monodisperse emulsion in the collection tube of the microfluidic device. The outlet of the microfluidic device is 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 is then photocured. The calcium alginate fibers are dissolved in a 1 wt% sodium citrate solution, and the resulting particles are washed with deionized water and ethanol and then dried and stored.
[0087] The morphology of the microparticles prepared in this embodiment was observed using an optical microscope and a scanning electron microscope, such as... Figure 14 As shown, the obtained particles are clearly black and white under an optical microscope, and scanning electron microscopy reveals that one part is a porous hemisphere, while the other part is smaller and more porous.
[0088] The above are merely preferred embodiments of the present invention. It should be noted that the above preferred embodiments should not be considered as limitations on the present invention, and the scope of protection of the present invention should be determined by the scope defined in the claims. For those skilled in the art, several improvements and modifications can be made without departing from the spirit and scope of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.
Claims
1. A method for preparing tunable irregularly shaped microparticles, characterized in that, Includes the following steps: Step 1: Prepare continuous phase and dispersed phase fluids Preparation of continuous phase fluid: Sodium alginate and surfactant are dissolved in a solvent to obtain the fluid, wherein the mass volume fraction of sodium alginate is 0.5-5% and the mass volume fraction of surfactant is 0.1-2%. Preparation of dispersed phase fluid: The dispersed phase fluid includes any one or more of the following forms: (1) Photoinitiated dispersed phase fluid: obtained by dissolving the photoinitiator in the prepolymer monomer; (2) Thermally initiated dispersed phase fluid: obtained by mixing PDMS prepolymer A with PDMS curing agent B; Preparation of the contacting liquid: Anhydrous calcium chloride is dissolved in deionized water to obtain the solution, wherein the mass-volume fraction of the calcium chloride is 0.5-10%. Step 2: Preparation of tunable irregular microparticles Dispersed phase fluid and continuous phase fluid are injected into different inlets of the microfluidic device to generate a monodisperse oil-in-water emulsion in the collection tube of the microfluidic device. The oil-in-water emulsion is introduced into calcium chloride solution through the outlet of the microfluidic device to rapidly crosslink and form fibers. The emulsion in the fiber cavity is then solidified in situ by light or heat. The fibers are then dissolved with sodium citrate solution and finally washed with deionized water and dried. Irregular particle morphology formation and its control strategy: (1) Adjusting the composition of each phase solution, the flow rate and the structure of the device to control the size of the prepared emulsion droplets and the morphology of the emulsion in the transition tube can yield the initial droplet template; (2) The morphology of the emulsion will undergo further deformation during the sol-gel transformation process in the hydrogel fiber forming process, thereby forming a heteromorphic emulsion template embedded in the fiber template. (3) The irregularly shaped emulsion template is cured in situ, and irregularly shaped particles are obtained after fiber dissolution and cleaning.
2. The preparation method according to claim 1, characterized in that, The surfactant is selected from any one or more of F127, sodium dodecyl sulfate, sodium carboxymethyl cellulose, and polyvinyl alcohol.
3. The preparation method according to claim 1, characterized in that, The viscosity of the sodium alginate is any one of 4-12 cP, 15-25 cP, and >2000 cP.
4. The preparation method according to claim 1, characterized in that, The preparation process of the photoinitiated dispersed phase fluid is as follows: after mixing the prepolymer monomer and functionalized material, a photoinitiator is added.
5. The preparation method according to claim 4, characterized in that, The functionalized material is selected from any one or more of 4-cyano-4'-pentylbiphenyl, Pt nanoparticles, and Fe3O4 nanoparticles.
6. The preparation method according to claim 1, characterized in that, The preparation process of the photoinitiated dispersed phase fluid is as follows: the initiator and vegetable oil are dissolved in the prepolymer monomer to obtain the solution.
7. The preparation method according to claim 1, characterized in that, The process of preparing the dispersed phase fluid is replaced by: the dispersed phase fluid includes an inner oil phase 1 and an inner oil phase 2; the inner oil phase 1 is selected from any one or more of fluorocarbon oil FC40, fluorocarbon oil HFE7500, fluorocarbon oil HFE7500 containing 5% HFE7500 Surf surfactant, silicone oil for oil bath, and light mineral oil; the inner oil phase 2 is obtained by dissolving a photoinitiator in a prepolymer monomer.
8. The preparation method according to claim 1, characterized in that, In step 2, the flow rate of the continuous phase fluid is 1000~3000 μL / h.
9. The preparation method according to claim 1, characterized in that, In step 2, the flow rate of the dispersed phase fluid is 100~1000 μL / h.
10. The preparation method according to claim 1, characterized in that, The microfluidic device's collection tube is connected to a transition tube, which is a glass capillary tube with a length of 1-2 cm and an inner diameter of 350-550 μm; or, the transition tube is a conical glass capillary tube with a length of 1-2 cm and an inner diameter of 100-200 μm at the conical opening; or, the transition tube is a square glass tube or an equilateral triangular glass tube.