Continuous preparation method of high-dispersity polyglycidyl methacrylate microspheres based on microfluidic technology

Abstract

The invention discloses a continuous preparation method of high-dispersity polyglycidyl methacrylate (PGMA) microspheres based on a microfluidic technology, and aims to solve the core difficulties that the system is unstable, the flow velocity range is limited, the particle size and morphology uniformity of the microspheres are difficult to accurately control and the like in the existing preparation process. According to the method, a dispersed phase system with dichloromethane as a core is constructed, micro-fluidic operation parameters are optimized, a staged ultraviolet light polymerization curing process is adopted, the method has the advantages of energy conservation, high efficiency and batch synthesis, and the prepared PGMA microspheres have the advantages of uniform particle size, regular morphology, controllable pore structure and abundant epoxy functional groups on the surface, so that the performance of the PGMA microspheres is greatly improved. The method has wide application prospects in the fields of protein separation, sewage treatment, drug delivery, biosensor construction and the like.

Description

Technical Field

[0001] This invention belongs to the field of organic materials technology and relates to a continuous preparation method of highly dispersible polyglycidyl methacrylate microspheres based on microfluidic technology. Background Technology

[0002] Micron-sized porous polymer microspheres, as a class of novel functional materials with excellent performance, have become a research hotspot in the field of polymer materials in recent years. Glycidyl methacrylate (GMA) is an ester compound containing both acrylate double bonds and epoxy groups, as shown in Formula 1. It is inexpensive, insoluble in water, readily soluble in organic solvents, and contains epoxy groups within its molecule. Its molecular structure contains highly reactive carbon-carbon double bonds, allowing it to polymerize other functional monomers and also undergo self-polymerization. Due to the high reactivity of the epoxy groups in its side chains, good hydrophilicity, biocompatibility, and non-toxicity, it has been widely used in chromatographic separation, industrial catalysis, and controlled-release carriers for biomaterials. Currently, researchers hope to prepare micron-sized polyglycidyl methacrylate (PGMA) microspheres with uniform particle size distribution and controllable surface properties by studying the influencing factors of microsphere shape, particle size, and pore size during polymerization. However, the preparation process of microspheres is complex and affected by various factors. How to accurately control particle size according to requirements remains a hot topic and a challenge in this field.

[0003]

[0004] Formula 1 Microfluidics is a technology that precisely controls and processes microscale fluids within microchannels (tens to hundreds of micrometers). Within these microchannels, immiscible dispersed and continuous phases are compressed or sheared at their interface to form droplets. Its advantages include precise control over microsphere size by varying the flow rates and ratios of the two phases, as well as the channel diameter; rapid mixing, reaction, and separation of microdroplets within the microchannel, effectively preventing cross-mixing between samples and significantly shortening reaction time; strong integration capabilities, facilitating the preparation of stable, uniform, and dispersed microspheres; and high sensitivity, accuracy, and repeatability. Based on these core advantages—precise size control, low contamination, high efficiency, speed, and high repeatability—microfluidics provides strong support for the large-scale preparation and cross-disciplinary applications of functional polymer microspheres.

[0005] To address the challenges of precise particle size control and poor morphological uniformity in existing PGMA microsphere preparation processes, this invention employs microfluidic technology to prepare monodisperse droplets containing photosensitive monomers. After being irradiated with ultraviolet light to initiate a polymerization and cross-linking reaction, the droplets rapidly solidify into shells, forming solid microspheres. Benefiting from the short and efficient solidification process, the prepared microspheres exhibit both uniform and stable morphology and consistent particle size. Furthermore, this process possesses energy-efficient and high-volume synthesis potential, making it widely applicable in fields such as protein separation, wastewater treatment, drug delivery, and biosensor construction. Summary of the Invention

[0006] The purpose of this invention is to overcome the problems existing in the preparation of polyglycidyl methacrylate (PGMA) microspheres using microfluidic technology, such as discontinuous preparation process, poor monodispersity (CV value) of microspheres, low curing efficiency, and difficulty in controlling internal structure. This invention provides a continuous preparation method for highly monodisperse PGMA microspheres based on microfluidic technology. This method achieves efficient, continuous, and stable preparation of PGMA microspheres with uniform particle size, regular morphology, and controllable pore size by constructing a dichloromethane-based dispersed phase system, optimizing microfluidic operating parameters, and employing a staged ultraviolet light polymerization and curing process.

[0007] To achieve the above objectives, the present invention adopts the following technical solution: A continuous preparation method for highly monodisperse polyglycidyl methacrylate (PGMA) microspheres based on microfluidic technology, characterized by comprising the following steps: (1) Preparation of dispersed phase: Glycidyl methacrylate (GMA), crosslinking agent, pore-forming agent and photoinitiator are dissolved in a mixed solvent system with dichloromethane as the core, and stirred until homogeneous to obtain a dispersed phase; The GMA has a mass concentration of 20 wt% to 35 wt%; the crosslinking agent is at least one of ethylene glycol dimethacrylate (EGDMA), divinylbenzene (DVB), and N,N-methylenebisacrylamide (MBA), with a mass concentration of 5 wt% to 40 wt%. The porogen is at least one of dodecyl alcohol, n-octanol, and cyclohexanol, with a mass concentration of 1 wt% to 20 wt%; the photoinitiator is at least one of 2,2-dimethoxy-2-phenylacetophenone (BDK) and 2,4,6-trimethylbenzoyl-diphenylphosphine oxide (TPO), with a mass concentration of 1 wt% to 4 wt% of the total mass of the monomer and crosslinking agent; and the dichloromethane in the mixed solvent has a mass concentration of 30 wt% to 60 wt%. (2) Preparation of continuous phase: Polyvinyl alcohol and surfactant are dissolved in deionized water, heated and stirred until completely dissolved to obtain a continuous phase; The surfactant is at least one of Span 80, Tween 80, and sodium dodecyl sulfate (SDS), with a mass concentration of 1 wt% to 4 wt%. (3) High-throughput generation of monodisperse microdroplets: The syringe loaded with the continuous phase and the dispersed phase is fixed on the micro-injection pump. By precisely controlling the flow rate ratio of the continuous phase to 10 mL / h to 50 mL / h and the dispersed phase to 0.5 mL / h to 5 mL / h, the two phases are introduced into the flow-focusing microchannel. The continuous and stable generation of emulsion containing highly monodisperse microdroplets is achieved by utilizing the shearing effect of the continuous phase on the dispersed phase. (4) Staged UV polymerization curing and post-treatment: The emulsion containing highly monodisperse microdroplets flows through a transparent tube and is first rapidly cured in the 254 nm UV region, which rapidly crosslinks and shapes the surface of the microdroplets to form primary microspheres with complete spherical shells; then the primary microspheres undergo a deep crosslinking reaction in the 365 nm UV region to achieve the final curing of the polymer, thereby completing the formation and deep curing of microspheres in a single flow system; the cured product is filtered, washed and dried to obtain PGMA microspheres with high monodispersity and regular morphology. (5) The highly monodisperse polyglycidyl methacrylate (PGMA) microspheres prepared by this invention have broad application prospects in many fields such as protein separation, wastewater treatment, drug delivery, and biosensor construction due to their uniform particle size, regular morphology, controllable pore structure and abundant epoxy functional groups on the surface. Attached Figure Description

[0008] Figure 1 This is a schematic diagram of the microfluidic device used in the embodiments of the present invention; Figure 2 Optical microscope images and particle size distribution diagrams of the PGMA droplets prepared in Example 1; Figure 3 Optical microscope images and particle size distribution diagrams of the PGMA droplets prepared in Example 2; Figure 4 Optical microscope images and particle size distribution diagrams of the PGMA droplets prepared in Example 3; Figure 5 Optical microscope images and particle size distribution diagrams of the PGMA droplets prepared in Example 4; Figure 6 Optical microscope images and particle size distribution diagrams of the PGMA droplets prepared in Example 5; Figure 7 Optical microscope images and particle size distribution diagrams of the PGMA droplets prepared in Example 6; Figure 8Optical microscope images and particle size distribution diagrams of the cured PGMA microspheres prepared in Example 6; Figure 9 The image shows a scanning electron microscope (SEM) image of the PGMA microspheres prepared in Example 6. Figure 10 The image shows the infrared spectrum of the PGMA microspheres prepared in Example 6. Detailed Implementation

[0009] The following embodiments are given to specifically describe the present invention, but do not limit the invention. The scope of the invention is defined by the claims.

[0010] Example 1: A schematic diagram of the microfluidic device used in this invention is shown below. Figure 1 As shown.

[0011] 2.4 g of GMA, 1.6 g of EGDMA, 3 g of dodecanol, and 0.3 g of BDK were accurately weighed and dissolved in 3 g of dichloromethane at room temperature. After thorough stirring until all components were completely dissolved and uniformly dispersed, the solution was drawn into a syringe as the dispersed phase. 3 g of PVA was accurately weighed and added to 100 mL of deionized water. After heating and stirring until completely dissolved, a 3 wt% PVA solution was prepared and drawn into the syringe as the continuous phase. The syringe containing both the continuous and dispersed phases was fixed to a microinjection pump. The flow rate of the dispersed phase solution was set to 0.5 mL / h, and the flow rate of the continuous phase solution was set to 10 mL / h. Both phases were introduced into a flow-focusing microchannel. Utilizing the shearing effect of the continuous phase on the dispersed phase, continuous and stable microdroplets were generated. The resulting droplets are shown in the figure. Figure 2 As shown, its average particle size is calculated to be 185 μm.

[0012] Example 2: 4.2 g of GMA, 2.8 g of EGDMA, 1.5 g of dodecanol, and 0.3 g of BDK were accurately weighed and dissolved in 1.5 g of dichloromethane at room temperature. After thorough stirring until all components were completely dissolved and uniformly dispersed, the solution was drawn into a syringe as the dispersed phase. 3 g of PVA was accurately weighed and added to 100 mL of deionized water. After heating and stirring until completely dissolved, a 3 wt% PVA solution was prepared and drawn into the syringe as the continuous phase. The syringe containing both the continuous and dispersed phases was fixed to a microinjection pump. The flow rate of the dispersed phase solution was set to 0.5 mL / h, and the flow rate of the continuous phase solution was set to 10 mL / h. Both phases were introduced into a flow-focusing microchannel. Utilizing the shearing effect of the continuous phase on the dispersed phase, continuous and stable microdroplets were generated. The resulting droplets are shown in the figure. Figure 3 As shown, the average particle size was calculated to be 159 μm, and the CV value was 4.75%.

[0013] In Examples 1 and 2, the effect of adjusting the ratio of dodecyl alcohol to dichloromethane on the uniformity of microsphere size was investigated. As the ratio decreased, the droplet size became more uniform, but a few droplets with non-uniform sizes still remained.

[0014] Example 3: 2.4 g of GMA, 1.6 g of EGDMA, 0.5 g of dodecanol, and 0.3 g of BDK were accurately weighed and dissolved in 5.5 g of dichloromethane at room temperature. After thorough stirring until all components were completely dissolved and uniformly dispersed, the solution was drawn into a syringe as the dispersed phase. 3 g of PVA was accurately weighed and added to 100 mL of deionized water. After heating and stirring until completely dissolved, a 3 wt% PVA solution was prepared and drawn into a syringe as the continuous phase. The syringe containing both the continuous and dispersed phases was fixed to a microinjection pump. The flow rate of the dispersed phase solution was set to 1 mL / h, and the flow rate of the continuous phase solution was set to 30 mL / h. Both phases were introduced into a flow-focusing microchannel. Utilizing the shearing effect of the continuous phase on the dispersed phase, continuous and stable microdroplets were generated. The resulting droplets are shown in the figure. Figure 4 As shown, the average particle size was calculated to be 113 μm, and the CV value was 3.30%.

[0015] Example 4: 3 g of GMA, 0.8 g of EGDMA, 0.2 g of dodecanol, and 0.3 g of BDK were accurately weighed and dissolved in 6 g of dichloromethane at room temperature. After thorough stirring until all components were completely dissolved and uniformly dispersed, the solution was drawn into a syringe as the dispersed phase. 3 g of PVA was accurately weighed and added to 100 mL of deionized water. After heating and stirring until completely dissolved, a 3 wt% PVA solution was prepared and drawn into a syringe as the continuous phase. The syringe containing both the continuous and dispersed phases was fixed to a microinjection pump. The flow rate of the dispersed phase solution was set to 3 mL / h, and the flow rate of the continuous phase solution was set to 40 mL / h. Both phases were introduced into a flow-focusing microchannel. Utilizing the shearing effect of the continuous phase on the dispersed phase, continuous and stable microdroplets were generated. The resulting droplets are shown in the figure. Figure 5 As shown, its average particle size is calculated to be 82 μm.

[0016] In Examples 3 and 4, considering that the addition of dodecanol would lead to an increase in the viscosity of the oil phase, it is speculated that reducing the viscosity of the oil phase and increasing the flow rate of the aqueous phase could effectively optimize the uniformity of the droplets and further reduce the particle size.

[0017] Example 5: 3 g of GMA, 0.8 g of EGDMA, 0.2 g of n-octanol, and 0.3 g of BDK were accurately weighed and dissolved in 6 g of dichloromethane at room temperature. After thorough stirring until all components were completely dissolved and uniformly dispersed, the solution was drawn into a syringe as the dispersed phase. 3 g of PVA was accurately weighed and added to 100 mL of deionized water. After heating and stirring until completely dissolved, a 3 wt% PVA solution was prepared and drawn into a syringe as the continuous phase. The syringe containing both the continuous and dispersed phases was fixed to a microinjection pump. The flow rate of the dispersed phase solution was set to 3 mL / h, and the flow rate of the continuous phase solution was set to 40 mL / h. Both phases were introduced into a flow-focusing microchannel. Utilizing the shearing effect of the continuous phase on the dispersed phase, continuous and stable microdroplets were generated. The resulting droplets are shown in the figure. Figure 6 As shown, the average particle size was calculated to be 76 μm, and the CV value was 4.12%.

[0018] In Example 5, since dodecanol tends to solidify in winter, it cannot dissolve sufficiently and disperse uniformly in the solvent. Therefore, dodecanol was replaced with n-octanol, which has a lower freezing point and can effectively reduce the viscosity of the dispersed phase, thereby promoting the stable formation of microspheres.

[0019] Example 6: 3 g of GMA, 0.8 g of EGDMA, 0.2 g of n-octanol, and 0.3 g of BDK were accurately weighed and dissolved in 6 g of dichloromethane at room temperature. After thorough stirring until all components were completely dissolved and uniformly dispersed, the solution was drawn into a syringe as the dispersed phase. 3 g of PVA was accurately weighed and added to 100 mL of deionized water. After heating and stirring until completely dissolved, 0.5 g of Tween 80 was added to the system, and stirring continued until homogeneous. This solution was then drawn into a syringe as the continuous phase. The syringe containing both the continuous and dispersed phases was fixed to a microinjection pump. The flow rate of the dispersed phase solution was set to 3 mL / h, and the flow rate of the continuous phase solution was set to 40 mL / h. Both phases were introduced into a flow-focusing microchannel. Utilizing the shearing effect of the continuous phase on the dispersed phase, continuous and stable microdroplets were generated. The resulting droplets are shown in the figure. Figure 7 As shown, the calculated average particle size is 79 μm, the CV value is 3.26%, the particle size distribution is concentrated, and the monodispersity is good. Then, the droplets obtained under these conditions were subjected to staged UV polymerization and curing followed by post-treatment to obtain PGMA microspheres, as shown... Figure 8 As shown, the average particle size is calculated to be 49 μm, and the monodispersity is well maintained.

[0020] In Example 6, to address the issue of a large number of small-diameter secondary particles in the prepared droplets, a surfactant was introduced into the continuous phase to reduce the interfacial tension between the two phases, optimize the interfacial behavior during the dispersion process of the dispersed phase, thereby improving the phenomenon of excessive small-diameter particles and enhancing the uniformity of the microsphere particle size distribution. This invention, based on microfluidic technology, achieves controllable adjustment and stable preparation of PGMA microspheres by synergistically controlling key parameters such as dispersed phase composition, pore-forming agent type and content, and the flow rates of the continuous and dispersed phases. The method offers mild preparation conditions, good repeatability, and produces microspheres with a concentrated particle size distribution, high monodispersity, and a continuously adjustable particle size range, making it suitable for applications requiring various microsphere sizes.

Claims

1. A continuous preparation method for highly dispersible polyglycidyl methacrylate (PGMA) microspheres based on microfluidic technology, characterized in that, Includes the following steps: (1) Preparation of dispersed phase: Glycidyl methacrylate (GMA), crosslinking agent, pore-forming agent and photoinitiator are dissolved in a mixed solvent system with dichloromethane as the core, and stirred until homogeneous to obtain a dispersed phase; The GMA has a mass concentration of 20 wt% to 35 wt%; the crosslinking agent is at least one of ethylene glycol dimethacrylate (EGDMA), divinylbenzene (DVB), and N,N-methylenebisacrylamide (MBA), with a mass concentration of 5 wt% to 40 wt%. The porogen is at least one of dodecyl alcohol, n-octanol, and cyclohexanol, with a mass concentration of 1 wt% to 20 wt%; the photoinitiator is at least one of 2,2-dimethoxy-2-phenylacetophenone (BDK) and 2,4,6-trimethylbenzoyl-diphenylphosphine oxide (TPO), with a mass concentration of 1 wt% to 4 wt% of the total mass of the monomer and crosslinking agent; and the dichloromethane in the mixed solvent has a mass concentration of 30 wt% to 60 wt%. (2) Preparation of continuous phase: Polyvinyl alcohol and surfactant are dissolved in deionized water, heated and stirred until completely dissolved to obtain a continuous phase; The surfactant is at least one of Span 80, Tween 80, and sodium dodecyl sulfate (SDS), with a mass concentration of 1 wt% to 4 wt%. (3) High-throughput generation of monodisperse microdroplets: The syringe loaded with the continuous phase and the dispersed phase is fixed on the micro-injection pump. By precisely controlling the flow rate ratio of the continuous phase to 10 mL / h to 50 mL / h and the dispersed phase to 0.5 mL / h to 5 mL / h, the two phases are introduced into the flow-focusing microchannel. The continuous and stable generation of emulsion containing highly monodisperse microdroplets is achieved by utilizing the shearing effect of the continuous phase on the dispersed phase. (4) Staged UV polymerization curing and post-treatment: The emulsion containing highly monodisperse microdroplets flows through a transparent tube and is first rapidly pre-cured in the 254 nm UV region, so that the surface of the microdroplets is rapidly cross-linked and shaped to form primary microspheres with complete spherical shells; then the primary microspheres undergo a deep cross-linking reaction in the 365 nm UV region to achieve the final curing of the polymer, thereby completing the microsphere forming and deep curing in a single flow system; the cured product is filtered, washed and dried to obtain highly monodisperse PGMA microspheres.

2. The method according to claim 1, characterized in that: The precise flow rate control and flow-focusing microchannel described in step (3) work together to ensure that the PGMA microspheres prepared by a single microfluidic unit have high monodispersity while maintaining high throughput.

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