Method for preparing magnetic polymer microspheres
Through the coupling reaction between functionalized polymer microspheres and silane-modified magnetic nanoparticles, the problem of easy shedding and poor dispersion of magnetic particles in magnetic polymer microspheres is solved, and the stable binding and efficient surface functionalization of magnetic nanoparticles are achieved, meeting the requirements of the field of biological detection.
Patent Information
- Application Number
- CN202510073784.9
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-01-17
- Publication Date
- 2025-05-13
AI Technical Summary
In the prior art, when preparing magnetic polymer microspheres, magnetic particles are prone to fall off, have poor dispersion, and the magnetic content is uncontrollable, making it difficult to achieve surface functionalization.
The magnetic nanoparticles modified with functionalized polymer microspheres are coupled through functional groups to form covalent bonds, so that the magnetic Fe3O4 nanoparticles are closely bound to the polymer microspheres, and the magnetic content is increased through multiple couplings.
The stable bonding of magnetic nanoparticles is achieved, and the magnetic leakage is reduced by avoiding the magnetic properties and the magnetic leakage is less than 10ppm, ensuring the dispersion and particle size controllability of magnetic polymer microspheres, and facilitating subsequent surface modification.
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Figure CN119972020A_ABST
Abstract
Description
Technical Field
[0001] The invention relates to a method for preparing magnetic polymer microspheres. Background Art
[0002] Magnetic polymer microspheres have attracted widespread attention due to their magnetic effect and biocompatibility, and have shown broad application prospects in many fields. Magnetic polymer microspheres not only have superparamagnetism, can quickly move and separate under the action of an external magnetic field, but can also be modified with various functional groups on the surface, and then combined with various functional substances. As a labeling carrier, magnetic polymer microspheres have important application value in biological detection fields such as immunoassay, nucleic acid extraction, cell sorting, biosensors and biochips.
[0003] Magnetic polymer microspheres refer to functional microspheres with spherical morphology formed by combining inorganic magnetic particles with organic polymer materials through a certain method. They combine the advantages of easy processing and good flexibility of polymer materials with the advantages of superparamagnetism and high mechanical properties of magnetic particles. The methods for combining inorganic magnetic particles with organic polymer materials can generally be divided into physical methods and chemical methods: the physical method is to make polymer microspheres and magnetic particles collide by high-speed airflow impact or high-speed grinding, and rely on physical action to achieve the combination of the two. This method has the advantages of being convenient, fast and low cost, but has high requirements for equipment, and the subsequent magnetic particles are prone to fall off, resulting in a decrease in magnetism; the chemical methods mainly include embedding method, monomer polymerization method and in-situ method. Among them, the in-situ method is to generate magnetic particles in situ on the surface or inside of the polymer microsphere mother core. This method has the advantages of controllable microsphere particle size and high magnetic content, but has the defects of uncontrollable magnetic content, poor dispersibility and difficulty in surface functionalization. Summary of the invention
[0004] Purpose of the invention: The purpose of the present invention is to provide a method for preparing magnetic polymer microspheres, wherein the magnetic particles on the magnetic microspheres prepared by the method are not easy to fall off, have good dispersibility, have functional groups on the surface, and the magnetic leakage is less than 10ppm.
[0005] Technical solution: The method for preparing magnetic polymer microspheres described in the present invention is specifically: functionalized polymer microspheres and silane-modified magnetic nanoparticles are coupled through functional group reaction to obtain magnetic polymer microspheres; wherein the functional groups modified with the functionalized polymer microspheres are functional groups that can react with silane-modified magnetic nanoparticles.
[0006] Wherein, the functional groups modified on the functionalized polymer microspheres are amino, vinyl, epoxy, benzyl chloride, carboxyl, carbonyl, acyl chloride, isocyanate or hydroxyl.
[0007] Wherein, the mixing mass ratio of the functionalized polymer microspheres and the silane-modified magnetic nanoparticles is 1:1-8.
[0008] The reaction temperature is 60-90°C and the reaction time is 4-24h.
[0009] Wherein, the functionalized polymer microspheres are functionalized porous polymer microspheres, functionalized porous hyper-crosslinked polymer microspheres, hydrogel hollow microspheres with a cavity structure or functionalized smooth polymer microspheres.
[0010] Among them, after the functionalized polymer microspheres and the silane-modified magnetic nanoparticles are coupled through a functional group reaction, based on the coupled first layer of magnetic nanoparticles, a second layer of magnetic nanoparticles is coupled to the first layer of magnetic nanoparticles through a functional group reaction. In this way, magnetic polymer microspheres coupled with multiple layers of magnetic nanoparticles are obtained.
[0011] The silane-modified magnetic nanoparticles are prepared by the following method: dispersing the magnetic nanoparticles in an ethanol aqueous solution, adding a silane coupling agent thereto, adjusting the pH of the system to 7 to 9, heating the reaction, magnetically separating and washing to obtain the silane-modified magnetic nanoparticles.
[0012] Wherein, the particle size of the magnetic nanoparticles is 5 to 100 nm.
[0013] Wherein, the reaction temperature is 20-60°C, and the reaction time is 12-48h.
[0014] The content of the surface functional groups of the silane-modified magnetic nanoparticles is 0.1-1 mmol / g; the surface functional groups of the silane-modified magnetic nanoparticles are amino, epoxy, thiol, isocyanate or vinyl.
[0015] The particle size of the magnetic nanoparticles is 5-100 nm; the particle size of the magnetic polymer microspheres is 0.8-6 μm, and the coefficient of variation is about 0.01-0.5, indicating that the particle size of the magnetic polymer microspheres prepared by the present invention is uniform.
[0016] Beneficial effects: Compared with the prior art, the present invention has the following significant advantages: the method of the present invention uses porous / hollow / smooth polymer microspheres as the core, adopts the coupling magnetization method to combine the magnetic Fe3O4 nanoparticles with the polymer microspheres by forming covalent bonds, and can achieve the desired magnetic content by multiple couplings for multi-layer magnetization. While achieving controllable magnetic content, it effectively avoids the magnetic nanoparticles from falling off the surface of the microspheres, and the magnetic leakage is less than 10ppm, thereby meeting the requirements of the field of biological detection, and does not require cumbersome encapsulation steps and can be used directly; at the same time The magnetic nanoparticles prepared by the method of the present invention can also ensure that the magnetic nanoparticles are evenly distributed on the surface of the polymer microspheres, and are not easy to agglomerate on the surface of the polymer microspheres, thereby ensuring the controllability and dispersibility of the particle size of the magnetic polymer microspheres; in addition, the magnetic Fe3O4 nanoparticles are evenly distributed on the surface of the porous polymer microspheres, and because they have been modified with reactive functional groups, they are conducive to the subsequent surface modification of the magnetic polymer microspheres; and the free Fe3O4 nanoparticles in the reaction system are quite different from the magnetic polymer spheres in particle size, and the separation of the two can be easily achieved by subsequent centrifugal operation. BRIEF DESCRIPTION OF THE DRAWINGS
[0017] Figure 1 This is a scanning electron microscope image of the porous polymer microspheres prepared in Example 1;
[0018] Figure 2 This is a scanning electron microscope image of the magnetic polymer microspheres prepared in Example 1;
[0019] Figure 3 The scanning electron microscope image of the porous hyper-crosslinked polymer microspheres prepared in Example 2;
[0020] Figure 4 This is a scanning electron microscope image of the hydrogel hollow microspheres prepared in Example 3;
[0021] Figure 5 This is a scanning electron microscope image of the smooth polymer microspheres prepared in Example 4;
[0022] Figure 6 The curves showing the change of magnetic saturation intensity and magnetic leakage of magnetic polymer microspheres prepared by multi-layer magnetic bonding in Example 5;
[0023] Figure 7 This is a scanning electron microscope image of the magnetic polymer microspheres prepared in Comparative Example 1. DETAILED DESCRIPTION
[0024] Example 1
[0025] The method for preparing magnetic polymer microspheres of the present invention comprises the following steps:
[0026] (1) Synthesis of functionalized porous polymer microspheres: First, 30 mL of isopropanol and 20 mL of deionized water were added to a three-necked flask, and then 4.5 mL of styrene, 0.9 g of polyvinyl pyrrolidone and 0.20 g of azobisisobutyronitrile were added thereto. The reaction was heated to 75 °C under nitrogen protection for 12 h. After the reaction, the microspheres were centrifuged and washed with deionized water to obtain polystyrene seed microspheres with a particle size of about 1 μm. 5 mL of cyclohexyl acetate and 2.4 mL of dibutyl phthalate were added to 50 mL of an aqueous solution containing 0.1 g of sodium dodecyl sulfate, and then 0.3 g of polystyrene was added thereto. The ethylene seed microspheres were ultrasonically emulsified and transferred to a three-necked flask and swollen at room temperature for 12 hours; then 3 mL of ethylene glycol dimethacrylate, 1 mL of methyl methacrylate, 2 mL of glycidyl methacrylate and 0.24 g of azobisisobutyronitrile were added to 50 mL of an aqueous solution containing 0.1 g of sodium dodecyl sulfate and ultrasonically emulsified; the emulsion was added to the reaction solution after swelling for 12 hours and continued to swell for 6 hours; finally, the reaction was carried out at 70°C for 16 hours under the protection of a nitrogen atmosphere, and after the reaction, the porous polymer microspheres were washed by centrifugation with ethanol to obtain a BET specific surface area of 154.75 m 2 / g, pore size distribution is 1~16nm (see Figure 1 ); the coefficient of variation of porous polymer microspheres is 0.014;
[0027] (2) Add 5.5 g of ferrous chloride tetrahydrate and 9 g of ferric chloride hexahydrate to 50 mL of distilled water, mix them evenly with ultrasound, transfer them to a three-necked flask, stir them mechanically at a speed of 1000 rpm to make them disperse quickly and evenly, then raise the temperature to 70°C and stir them continuously for 1 hour, then quickly add 8 mL of ammonia water to the system, and react for 0.5 hour. After the product is cooled, separate it by magnetic attraction, wash it with deionized water 3 to 4 times until it is neutral, and dry it in an oven to obtain black Fe3O4 powder; add 1 g of Fe3O4 powder to a mixture of 90 mL of ethanol and 40 mL of deionized water, mix them evenly with ultrasound, transfer them to a 250 mL three-necked flask, add 3 mL of ammonia water and 3 mL of aminopropyltriethoxysilane under mechanical stirring at 500 rpm, react them at 50°C for 24 hours, separate them by magnetic attraction with ethanol, and wash them three times to obtain silane-modified magnetic Fe3O4 particles, the surface amino functional group content of the magnetic Fe3O4 particles is 0.375 mmol / g;
[0028] (3) 0.1 g of the functionalized porous polymer microspheres of step (1) and 0.1 g of the aminopropyltriethoxysilane-modified Fe3O4 particles of step (2) were dispersed in 30 ml of ethanol, transferred to a 50 mL three-necked flask, mechanically stirred at 200 rpm, and then the temperature was raised to 70°C for reaction for 24 h; after the reaction, the free modified Fe3O4 particles were easily washed away by centrifugation with ethanol to obtain magnetic polymer microspheres. According to the standard detection method, 0.1 g of the microspheres were soaked in 10 mL of deionized water (70°C) for 2 h, and the magnetic leakage was measured by o-phenanthroline spectrophotometry to be 7.9 ppm. According to the standard detection method, the magnetic leakage of 0.1 g of magnetic microspheres after soaking in 10 mL of deionized water (70°C) for 2 h was 7.9 ppm.
[0029] pass Figure 2 It can be seen that the magnetic polymer microspheres prepared in Example 1 have good dispersibility and uniformity, and the coefficient of variation of the magnetic polymer microspheres is about 0.018.
[0030] Example 2
[0031] The method for preparing magnetic polymer microspheres of the present invention specifically comprises the following steps:
[0032] (1) Synthesis of functionalized porous hyper-crosslinked polymer microspheres: First, 0.12 g of azobisisobutyronitrile was weighed and dissolved in 100 mL of a mixed solvent of acetonitrile and toluene (volume ratio of 8:1). Then, 2.4 mL of divinylbenzene, 4 mL of p-chloromethylstyrene and 1.6 mL of acrylic acid were added thereto. Nitrogen was introduced for 30 minutes for deoxygenation. Then, the microspheres were immersed in an oil bath at 85°C for 2 to 4 hours. After the reaction, the microspheres were washed by centrifugation with ethanol and water and dried to obtain polymer microspheres with a particle size of about 2 μm. 2 g of the dried polymer microspheres were taken and dispersed in 40 mL The mixture was swollen in 1,2-dichloroethane with magnetic stirring for 12 h, then placed in a 45°C oil bath, and then 40 mL of 1,2-dichloroethane dispersed with 6 g of anhydrous ferric chloride was added. After reacting for 5 h, the temperature was raised to 80°C and the reaction was continued for 19 h. The obtained product was filtered and then extracted with a Soxhlet extractor for 24 h. Finally, it was vacuum dried to obtain functionalized porous hyper-crosslinked polymer microspheres with a BET specific surface area of 882.8 m 2 / g, pore size distribution is 0.8~23nm (see Figure 3 );
[0033] (2) In 60 mL of ethylene glycol, 3 g of ferric chloride hexahydrate, 4 g of sodium acetate and 1 g of polyethylene glycol (10000) were added, ultrasonically homogenized, and transferred to a 100 mL three-necked flask. The temperature was then raised to 160 ° C for reaction for 24 h. After the product was cooled, it was separated by magnetic attraction, washed with ethanol and deionized water, and dried in an oven to obtain black Fe3O4 powder; 1 g of Fe3O4 powder was added to a mixture of 90 mL of ethanol and 40 mL of deionized water, and transferred to a 250 mL three-necked flask after ultrasonic dispersion. Under mechanical stirring at 500 rpm, 3 mL of ammonia water and 3 mL of aminopropyltriethoxysilane were added, and the reaction was carried out at 50 ° C for 24 h. After the reaction, it was separated by magnetic attraction with ethanol and washed three times to obtain silane-modified magnetic Fe3O4 particles. The content of amino functional groups on the surface of the magnetic Fe3O4 particles was 0.392 mmol / g;
[0034] (3) 0.1 g of the functionalized porous hyper-crosslinked polymer microspheres of step (1) and 0.1 g of the aminopropyltriethoxysilane-modified Fe3O4 particles of step (2) were dispersed in 30 mL of dichloromethane, transferred to a 50 mL three-necked flask, mechanically stirred at a speed of 200 rpm, and then the temperature was raised to 70°C for reaction for 24 h; after the reaction, the free modified Fe3O4 particles were easily washed away by centrifugation with ethanol to obtain magnetic polymer microspheres with a magnetic leakage of 7.3 ppm.
[0035] Example 3
[0036] The method for preparing magnetic polymer microspheres of the present invention comprises the following steps:
[0037] (1) Synthesis of functionalized hydrogel hollow microspheres: First, 0.12 g of azobisisobutyronitrile was weighed and dissolved in a mixed solvent of 100 mL of acetonitrile and ethanol, and then 6 mL of methacrylic acid was added thereto. Nitrogen was introduced for 30 minutes for deoxygenation, and then the mixture was immersed in an oil bath at 80 to 100° C. for reaction for 0.5 to 3 hours. After precipitation polymerization, a mixed solution consisting of 1 mL of methacrylic acid and 0.25 mL of divinylbenzene was added to the reaction system and reacted for 1 to 3 hours. After the reaction, the mixture was centrifuged and washed with ethanol and water to remove the non-crosslinked polymethacrylic acid core, thereby obtaining hollow microspheres of poly(divinylbenzene-methacrylic acid) (see Figure 4 );
[0038] (2) In 50 mL of dibenzyl ether, 2 g of ferric acetylacetonate, 3.6 g of oleic acid, 3.6 g of oleylamine and 4.5 g of 1,2-hexadecanediol were added, and the mixture was uniformly dispersed by ultrasonication and then transferred to a 100 mL three-necked flask. The temperature was then raised to 200 °C for reaction for 2 h. After the product was cooled, it was separated by magnetic attraction, washed with ethanol for 3 to 4 times, and dried in an oven to obtain black Fe3O4 powder. In 150 mL of dichloromethane, 1 g of Fe3O4 powder was added, and the mixture was uniformly dispersed by ultrasonication and then transferred to a 250 mL three-necked flask. Under mechanical stirring at 500 rpm, 3 mL of ammonia water and 3 mL of isocyanatepropyltriethoxysilane were added, and the mixture was reacted at 50 °C for 24 h. After the reaction, the mixture was separated by magnetic attraction and washed three times with dichloromethane to obtain silane-modified magnetic Fe3O4 particles. The content of isocyanate functional groups on the surface of the magnetic Fe3O4 particles was 0.253 mmol / g.
[0039] (3) 0.1 g of the functionalized hydrogel hollow microspheres prepared in step (1) and 0.1 g of the silane-modified Fe3O4 particles prepared in step (2) were dispersed in 30 mL of dichloromethane, transferred to a 50 mL three-necked flask, mechanically stirred at a speed of 200 rpm, and then the temperature was raised to 70°C for reaction for 24 h; after the reaction, the free modified Fe3O4 particles were easily washed away by centrifugation with ethanol to obtain magnetic polymer microspheres with a magnetic leakage of 6.3 ppm.
[0040] Example 4
[0041] The method for preparing magnetic polymer microspheres of the present invention comprises the following steps:
[0042] (1) Synthesis of microspheres: First, 4 mL of glycidyl methacrylate and 0.5 g of PVP-K30 were dissolved in a 30 mL mixed solvent of water and ethanol, and then 0.12 g of azobisisobutyronitrile was added. After uniform dispersion, the mixture was transferred to a three-necked flask, and nitrogen was introduced for 30 minutes for deoxygenation. Then, the temperature was raised to 75°C for reaction for 12 hours. After the reaction, the mixture was washed by centrifugation with ethanol to obtain smooth poly(glycidyl methacrylate) microspheres (see Figure 5 );
[0043] (2) Add 5.5 g of ferrous chloride tetrahydrate and 9 g of ferric chloride hexahydrate to 50 mL of distilled water, mix them evenly with ultrasound, transfer them to a three-necked flask, stir them mechanically at a speed of 1000 rpm to make them disperse quickly and evenly, then raise the temperature to 70°C and stir them continuously for 1 hour, then quickly add 8 mL of ammonia water to the system, and react for 0.5 hour. After the product is cooled, separate it by magnetic attraction, wash it with deionized water 3 to 4 times until it is neutral, and dry it in an oven to obtain black Fe3O4 powder; add 1 g of Fe3O4 powder to a mixture of 90 mL of ethanol and 40 mL of deionized water, mix them evenly with ultrasound, transfer them to a 250 mL three-necked flask, add 3 mL of ammonia water and 3 mL of aminopropyltriethoxysilane under mechanical stirring at 500 rpm, react them at 50°C for 24 hours, separate them by magnetic attraction with ethanol, and wash them three times to obtain silane-modified magnetic Fe3O4 particles, the surface amino functional group content of the magnetic Fe3O4 particles is 0.375 mmol / g;
[0044] (3) Disperse 0.1 g of the poly(glycidyl methacrylate) microspheres prepared in step (1) and 0.1 g of the aminopropyltriethoxysilane-modified Fe3O4 particles prepared in step (2) in 30 ml of ethanol, transfer the mixture to a 50 ml three-necked flask, stir the mixture mechanically at 200 rpm, and then raise the temperature to 70°C to react for 24 h. After the reaction, centrifuge the mixture with ethanol to easily wash away the free modified Fe3O4 particles, and obtain magnetic polymer microspheres with a magnetic leakage of 8.4 ppm.
[0045] Example 5
[0046] The surface of the magnetic polymer microspheres prepared in Example 1 is amino-functionalized magnetic Fe3O4 particles, and the subsequent magnetization is carried out by the reaction of amino groups with epoxy groups:
[0047] (1) Preparation of epoxy-functionalized magnetic Fe3O4 particles: 5.5 g of ferrous chloride tetrahydrate and 9 g of ferric chloride hexahydrate were added to 50 mL of distilled water, and the mixture was homogenized by ultrasonication. The mixture was transferred to a three-necked flask and mechanically stirred at a speed of 1000 rpm to make it quickly and evenly dispersed. The temperature was then raised to 70 °C and stirred for 1 h. 8 mL of ammonia water was then quickly added to the system. The reaction lasted for 0.5 h. After the product was cooled, it was separated by magnetic attraction, washed with deionized water for 3 to 4 times until it was neutral, and dried in an oven to obtain black Fe3O4 powder. 1 g of Fe3O4 was added to a mixture of 90 mL of ethanol and 40 mL of deionized water. Fe3O4 powder was ultrasonically dispersed and transferred to a 250 mL three-necked flask. Under mechanical stirring at 500 rpm, 3 mL of ammonia water and 3 mL of glycidyloxypropyltrimethoxysilane (γ-glycidyloxypropyltrimethoxysilane) were added. The mixture was reacted at 50°C for 24 h. After the reaction, the mixture was separated by magnetic absorption with ethanol and washed three times to obtain silane-modified magnetic Fe3O4 particles. The content of epoxy functional groups on the surface of the magnetic Fe3O4 particles was 0.298 mmol / g.
[0048] (2) Second layer magnetization: 0.1 g of the magnetic polymer microspheres prepared in Example 1 and 0.1 g of epoxy-functionalized magnetic Fe3O4 particles were dispersed in 30 mL of ethanol, transferred to a 50 mL three-necked flask, mechanically stirred at 200 rpm, and then the temperature was raised to 70° C. and reacted for 24 h; after the reaction, the mixture was centrifuged with ethanol to obtain the second layer of magnetic polymer microspheres;
[0049] (3) Magnetizing the third layer: repeat step (2), except that the magnetic polymer microspheres prepared in Example 1 are replaced by the magnetic polymer microspheres of the second magnetization layer obtained in step (2), and the epoxy-functionalized magnetic Fe3O4 particles are replaced by amino-functionalized magnetic Fe3O4 particles; specifically: 0.1 g of the magnetic polymer microspheres of the second magnetization layer in step (2) and 0.1 g of Fe3O4 particles modified with aminopropyltriethoxysilane are dispersed in 30 ml of ethanol, transferred to a 50 mL three-necked flask, mechanically stirred at a speed of 200 rpm, and then the temperature is raised to 70°C for reaction for 24 hours; after the reaction, the ethanol is centrifuged to obtain the magnetic polymer microspheres of the third magnetization layer;
[0050] (4) Preparing the fourth magnetic layer: repeat step (2), disperse 0.1 g of the magnetic polymer microspheres prepared in step (3) and 0.1 g of the epoxy-functionalized magnetic Fe3O4 particles prepared in step (1) in 30 mL of ethanol, transfer the mixture to a 50 mL three-necked flask, stir the mixture at a speed of 200 rpm, and then raise the temperature to 70°C and react for 24 h; after the reaction, centrifuge the mixture with ethanol to obtain the fourth magnetic polymer microspheres;
[0051] (5) Fifth magnetization layer: repeat step (2), disperse 0.1 g of the fourth magnetization layer of magnetic polymer microspheres in step (4) and 0.1 g of aminopropyltriethoxysilane-modified Fe3O4 particles in 30 ml of ethanol, transfer to a 50 mL three-necked flask, stir mechanically at a speed of 200 rpm, and then raise the temperature to 70°C to react for 24 hours; after the reaction, centrifuge with ethanol to obtain the fifth magnetization layer of magnetic polymer microspheres.
[0052] Figure 6 The magnetic saturation intensity and magnetic leakage variation curves of the magnetic polymer microspheres prepared by multi-layer magnetization show that the magnetic saturation intensity and magnetic leakage increase with the increase of the number of magnetizations, but the magnetic leakage is always less than 10ppm, indicating that the magnetic polymer microspheres obtained by multiple magnetizations have a high magnetic saturation intensity and a very low magnetic leakage.
[0053] Comparative Example 1
[0054] A method for preparing magnetic polymer microspheres comprises the following steps:
[0055] (1) Synthesis of porous polymer microspheres: First, 30 mL of isopropanol and 20 mL of deionized water were added to a three-necked flask, and then 4.5 mL of styrene, 0.9 g of polyvinyl pyrrolidone and 0.20 g of azobisisobutyronitrile were added thereto. The temperature was raised to 75°C under nitrogen protection for 12 h. After the reaction, the microspheres were centrifuged and washed with deionized water to obtain polystyrene seed microspheres with a particle size of about 1 μm. 5 mL of cyclohexyl acetate and 2.4 mL of dibutyl phthalate were added to 50 mL of an aqueous solution containing 0.1 g of sodium dodecyl sulfate, and then 0.3 g of polystyrene seed microspheres were added thereto. The microspheres were ultrasonically emulsified and transferred to a three-necked flask. The microspheres were swollen at room temperature for 12 h. Then, 50 mL of an aqueous solution containing 0.1 g of sodium dodecyl sulfate was added. 3mL ethylene glycol dimethacrylate, 1mL methyl methacrylate, 2mL glycidyl methacrylate and 0.24g azobisisobutyronitrile were added and ultrasonically emulsified; the emulsion was added to the reaction solution after swelling for 12h, and the swelling was continued for 6h; finally, the reaction was carried out at 70°C for 16h under the protection of nitrogen atmosphere, and after the reaction, the porous polymer microspheres were centrifuged and washed with ethanol and dried in an oven to obtain porous polymer microspheres; 1g of the porous polymer microspheres were hydrolyzed with 30mL, 5wt% sodium hydroxide aqueous solution at 80°C for 3h, and then condensed and refluxed with 30mL, 0.2mol / L sulfuric acid aqueous solution at 80°C for 4h, and after the hydrolysis was completed, the hydrolyzed porous polymer microspheres were washed with distilled water until neutral, and the BET specific surface area of the hydrolyzed porous polymer microspheres was 154.75m 2 / g, pore size distribution is 1~16nm;
[0056] (2) Add 5.5 g of ferrous chloride tetrahydrate and 9 g of ferric chloride hexahydrate to 50 mL of distilled water, mix them evenly with ultrasound, transfer them to a three-necked flask, stir them mechanically at a speed of 1000 rpm to make them disperse quickly and evenly, then raise the temperature to 70°C and stir them continuously for 1 hour, then quickly add 8 mL of ammonia water to the system, and react for 0.5 hour. After the product is cooled, separate it by magnetic attraction, wash it with deionized water 3 to 4 times until it is neutral, and dry it in an oven to obtain black Fe3O4 powder; add 1 g of Fe3O4 powder to a mixture of 90 mL of ethanol and 40 mL of deionized water, mix them evenly with ultrasound, transfer them to a 250 mL three-necked flask, add 3 mL of ammonia water and 3 mL of aminopropyltriethoxysilane under mechanical stirring at 500 rpm, react them at 50°C for 24 hours, separate them by magnetic attraction with ethanol, and wash them three times to obtain silane-modified magnetic Fe3O4 particles, the surface amino functional group content of the magnetic Fe3O4 particles is 0.375 mmol / g;
[0057] (3) 0.1 g of hydrolyzed porous polymer microspheres and 0.1 g of aminopropyltriethoxysilane-modified Fe3O4 particles were dispersed in 30 ml of ethanol and transferred to a 50 mL three-necked flask. The mechanical stirring speed was 200 rpm, and then the temperature was increased to 70°C for 24 h. After the end, the microspheres were centrifuged with ethanol to obtain magnetic polymer microspheres. The magnetic leakage was measured by o-phenanthroline spectrophotometry to be 89.3 ppm.
[0058] Comparative Example 1: Porous polymer microspheres with negative charge after hydrolysis adsorb positively charged Fe3O4 particles ( Figure 7 ), by comparing the magnetic properties of Example 1 and Comparative Example 1, it can be clearly found that the magnetic leakage of the magnetic microspheres prepared in Example 1 is much smaller than that of Comparative Example 1, and is less than 10ppm, which meets the standards in the field of biological detection and can be used directly. At the same time, the magnetic particles prepared in Comparative Example 1 are unevenly dispersed on the surface of the microspheres, and the microspheres are difficult to disperse after agglomeration. Example 1 is magnetized by coupling, and the amino groups on the magnetic Fe3O4 particles react with the epoxy groups on the porous microspheres. After the reaction, the microspheres are uniformly wrapped by the magnetic Fe3O4 particles, so the surface is positively charged, and it is not easy to agglomerate. At the same time, the surface is functionalized while magnetizing, which is beneficial to subsequent applications.
Claims
1. A method for preparing magnetic polymer microspheres, characterized in that: Specifically, the functionalized polymer microspheres and the silane-modified magnetic nanoparticles are coupled through functional group reaction to obtain magnetic polymer microspheres; wherein the functional groups modified on the functionalized polymer microspheres are functional groups that can react with the silane-modified magnetic nanoparticles.
2. The method for preparing magnetic polymer microspheres according to claim 1, characterized in that: The functional groups modified on the functionalized polymer microspheres are amino, vinyl, epoxy, benzyl chloride, carboxyl, carbonyl, acyl chloride, isocyanate or hydroxyl.
3. The method for preparing magnetic polymer microspheres according to claim 1, characterized in that: The mixing mass ratio of the functionalized polymer microspheres to the silane-modified magnetic nanoparticles is 1:1-8.
4. The method for preparing magnetic polymer microspheres according to claim 1, characterized in that: The reaction temperature is 60-90°C and the reaction time is 4-24h.
5. The method for preparing magnetic polymer microspheres according to claim 1, characterized in that: The functionalized polymer microsphere is one of functionalized porous polymer microspheres, functionalized porous hyper-crosslinked polymer microspheres, hydrogel hollow microspheres with a cavity structure, or functionalized smooth polymer microspheres.
6. The method for preparing magnetic polymer microspheres according to claim 1, characterized in that: After the functionalized polymer microspheres and the silane-modified magnetic nanoparticles are coupled through a functional group reaction, based on the coupled first layer of magnetic nanoparticles, a second layer of magnetic nanoparticles is coupled to the first layer of magnetic nanoparticles through a functional group reaction. In this way, magnetic polymer microspheres coupled with at least one layer of magnetic nanoparticles are obtained.
7. The method for preparing magnetic polymer microspheres according to claim 1, characterized in that: The silane-modified magnetic nanoparticles are prepared by the following method: specifically, the magnetic nanoparticles are dispersed in an ethanol aqueous solution, a silane coupling agent is added thereto, the pH of the system is adjusted to 7-9, a temperature reaction is performed, magnetic separation and washing are performed, and the silane-modified magnetic nanoparticles are obtained.
8. The method for preparing magnetic polymer microspheres according to claim 7, characterized in that: The reaction temperature is 20-60° C., and the reaction time is 12-48 hours.
9. The method for preparing magnetic polymer microspheres according to claim 7, characterized in that: The functional groups modified on the surface of the silane-modified magnetic nanoparticles are amino, epoxy, mercapto, isocyanate or vinyl, and the content of the functional groups is 0.1-1 mmol / g.
10. The method for preparing magnetic polymer microspheres according to claim 7, characterized in that: The particle size of the magnetic nanoparticles is 5-100 nm; the particle size of the magnetic polymer microspheres is 0.8-6 μm, and the coefficient of variation is about 0.01-0.5.