CN117736361A - Functionalized magnetic microsphere and preparation method and application thereof - Google Patents
Functionalized magnetic microsphere and preparation method and application thereof Download PDFInfo
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- CN117736361A CN117736361A CN202311494092.9A CN202311494092A CN117736361A CN 117736361 A CN117736361 A CN 117736361A CN 202311494092 A CN202311494092 A CN 202311494092A CN 117736361 A CN117736361 A CN 117736361A
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- 239000004005 microsphere Substances 0.000 title claims abstract description 233
- 238000002360 preparation method Methods 0.000 title abstract description 10
- 229920000642 polymer Polymers 0.000 claims abstract description 114
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims abstract description 48
- SZVJSHCCFOBDDC-UHFFFAOYSA-N ferrosoferric oxide Chemical compound O=[Fe]O[Fe]O[Fe]=O SZVJSHCCFOBDDC-UHFFFAOYSA-N 0.000 claims abstract description 45
- 239000000178 monomer Substances 0.000 claims abstract description 35
- 239000000377 silicon dioxide Substances 0.000 claims abstract description 24
- 239000002245 particle Substances 0.000 claims abstract description 21
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- 230000005415 magnetization Effects 0.000 claims abstract description 14
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- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 74
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- 239000000243 solution Substances 0.000 claims description 56
- 239000011259 mixed solution Substances 0.000 claims description 32
- XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Substances [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 28
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- BAUYGSIQEAFULO-UHFFFAOYSA-L iron(2+) sulfate (anhydrous) Chemical compound [Fe+2].[O-]S([O-])(=O)=O BAUYGSIQEAFULO-UHFFFAOYSA-L 0.000 claims description 4
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- PGTLVXOZIGEXJA-UHFFFAOYSA-M sodium;2-phenylethenesulfonate;styrene Chemical compound [Na+].C=CC1=CC=CC=C1.[O-]S(=O)(=O)C=CC1=CC=CC=C1 PGTLVXOZIGEXJA-UHFFFAOYSA-M 0.000 description 6
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 5
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- GVGUFUZHNYFZLC-UHFFFAOYSA-N dodecyl benzenesulfonate;sodium Chemical compound [Na].CCCCCCCCCCCCOS(=O)(=O)C1=CC=CC=C1 GVGUFUZHNYFZLC-UHFFFAOYSA-N 0.000 description 4
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- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 2
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- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- CQEYYJKEWSMYFG-UHFFFAOYSA-N butyl acrylate Chemical compound CCCCOC(=O)C=C CQEYYJKEWSMYFG-UHFFFAOYSA-N 0.000 description 2
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- USHAGKDGDHPEEY-UHFFFAOYSA-L potassium persulfate Chemical compound [K+].[K+].[O-]S(=O)(=O)OOS([O-])(=O)=O USHAGKDGDHPEEY-UHFFFAOYSA-L 0.000 description 2
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- JQXYBDVZAUEPDL-UHFFFAOYSA-N 2-methylidene-5-phenylpent-4-enoic acid Chemical compound OC(=O)C(=C)CC=CC1=CC=CC=C1 JQXYBDVZAUEPDL-UHFFFAOYSA-N 0.000 description 1
- PQSQBXGSIRXRFL-UHFFFAOYSA-N 2-methylpropanamide;dihydrochloride Chemical compound Cl.Cl.CC(C)C(N)=O PQSQBXGSIRXRFL-UHFFFAOYSA-N 0.000 description 1
- JLBJTVDPSNHSKJ-UHFFFAOYSA-N 4-Methylstyrene Chemical compound CC1=CC=C(C=C)C=C1 JLBJTVDPSNHSKJ-UHFFFAOYSA-N 0.000 description 1
- LBSXSAXOLABXMF-UHFFFAOYSA-N 4-Vinylaniline Chemical compound NC1=CC=C(C=C)C=C1 LBSXSAXOLABXMF-UHFFFAOYSA-N 0.000 description 1
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 1
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 1
- 229910000013 Ammonium bicarbonate Inorganic materials 0.000 description 1
- 239000004342 Benzoyl peroxide Substances 0.000 description 1
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 1
- LZZYPRNAOMGNLH-UHFFFAOYSA-M Cetrimonium bromide Chemical compound [Br-].CCCCCCCCCCCCCCCC[N+](C)(C)C LZZYPRNAOMGNLH-UHFFFAOYSA-M 0.000 description 1
- 108010093096 Immobilized Enzymes Proteins 0.000 description 1
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 1
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- MNCGMVDMOKPCSQ-UHFFFAOYSA-M sodium;2-phenylethenesulfonate Chemical compound [Na+].[O-]S(=O)(=O)C=CC1=CC=CC=C1 MNCGMVDMOKPCSQ-UHFFFAOYSA-M 0.000 description 1
- XFTALRAZSCGSKN-UHFFFAOYSA-M sodium;4-ethenylbenzenesulfonate Chemical compound [Na+].[O-]S(=O)(=O)C1=CC=C(C=C)C=C1 XFTALRAZSCGSKN-UHFFFAOYSA-M 0.000 description 1
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Landscapes
- Soft Magnetic Materials (AREA)
Abstract
The invention belongs to the technical field of high polymer materials, and relates to a functionalized magnetic microsphere, a preparation method and application thereof. The functionalized magnetic microsphere takes a polymer microsphere as a core, a ferroferric oxide layer is formed on the surface of the polymer microsphere through in-situ magnetization, and a silicon dioxide shell is coated outside the ferroferric oxide layer. Wherein, the polymer microsphere is formed by polymerizing monomer I and monomer II; the pH of the polymer microsphere solution is adjusted to 5-8 before the surface of the polymer microsphere is magnetized. The functionalized magnetic microsphere has the characteristics of more uniform distribution of surface magnetic nano particles, uniform particle size, high magnetic content, high magnetic stability, quick magnetic response and rich surface functional groups.
Description
Technical Field
The invention belongs to the technical field of high polymer materials, and relates to a functionalized magnetic microsphere, a preparation method and application thereof.
Background
The magnetic polymer microsphere is a spherical magnetic material with the particle size of about hundreds of nanometers to several micrometers, which is formed by combining inorganic magnetic materials (iron, cobalt, nickel, oxides thereof and the like) with superparamagnetism and organic polymers. On the one hand, the magnetic microsphere has the functional characteristics of a polymer or a biological molecule, and the surface of the polymer microsphere can be provided with a plurality of functional groups through chemical reactions such as copolymerization, surface modification and the like, so that the magnetic microsphere is coupled with an antibody, an antigen or other biological molecules to realize the functions of specific biological recognition, molecular capture, release and the like. On the other hand, the magnetic material has superparamagnetism and sensitive magnetic responsiveness, can quickly respond under the condition of an externally applied magnetic field, and has the advantages of small energy consumption and simple and convenient operation. Therefore, the magnetic polymer microsphere is used as a novel functional polymer material, and has been widely focused and applied to nucleic acid extraction in biomedical fields such as drug loading, targeted therapy, nuclear magnetic resonance contrast agents, immobilized enzymes, separation and purification of biomolecules, in-vitro diagnosis and the like. In order to meet the application in the biomedical field, the magnetic polymer microsphere needs to meet the characteristics of good biocompatibility, high saturation magnetization, good spherical homogeneous structure, dispersion stability, low nonspecific adsorption, rich surface functional group content and the like.
The structure of the magnetic microsphere can be divided into four types of dispersion type, core-shell type, sandwich type and hollow type. The preparation methods of the synthetic magnetic polymer microspheres in the prior literature and patent are mature, and mainly comprise a dispersion polymerization method, a suspension polymerization method, an interface deposition method, a seed polymerization method and the like. The dispersion polymerization method can realize accurate control on the particle size and shape distribution of the prepared magnetic microsphere, but the magnetic microsphere prepared by the method has the defects of nonuniform quality, nonuniform particle size distribution, low magnetic content, few surface functional groups and the like. The suspension polymerization method or emulsion polymerization method is to disperse magnetic nano particles in a high molecular monomer or solution to form oil-in-water emulsion, and to carry out polymerization reaction in a suspension state to form microspheres. The method has the defects that the affinity between the high molecular material and the magnetic nano particles is poor, and the embedding efficiency is low due to the strong hydrophilicity of the magnetic nano particles when the monomers are polymerized. And a large number of magnetic particles are attached to the surface of the microsphere, so that the elution is difficult, and the biological activity of the bioactive substances during fixation or separation is influenced. The interface deposition method is to adsorb positively charged magnetic nanometer particles on the surface of negatively charged polymer microsphere by electrostatic action, and then coat a layer of polymer material on the surface. The method can realize functional modification of the magnetic microsphere by introducing different substances into the interface so as to adapt to different requirements. However, as each magnetic microsphere surface can only adsorb one layer of magnetic nano particles, the magnetic content of the magnetic beads is low, the stability of the method depends on the stability of interfaces, and the operation flow of some interface deposition methods is complex and the preparation cost is high. The seed polymerization method is to first swell seed microsphere in water solution containing monomer, initiator, stabilizer and surfactant and then to initiate polymerization via heating. However, the seed polymerization method comprises a plurality of experimental steps, the operation is complex, proper experimental conditions and technology are needed, and most of the magnetic microspheres prepared based on the seed polymerization method are of porous structures, the magnetic nanoparticles are deposited in the pore canal, the outer layer is coated with the functionalized polymer, and the magnetic beads prepared by the method have the risk of magnetic leakage and have reduced magnetic responsiveness. And because of the non-uniformity of the hydrophilicity and hydrophobicity of the polymer shell and the magnetic nano particles, the non-specific adsorption can be caused, so that the sensitivity of the magnetic microsphere is low, the extraction efficiency is low, and the detection error is large.
Although the application of the biological magnetic beads in the biomedical field is very wide, the problems of complex preparation method, low magnetic bead performance, higher import cost and the like still exist. The preparation technology of the imported brand magnetic beads and the application of the imported brand magnetic beads in the biomedical field are very mature, but the price of the imported brand magnetic beads is 5 to 6 times that of domestic magnetic beads, the core technology for preparing the magnetic beads is not mastered at present, and the prepared magnetic beads still have the defects of wide particle size distribution, weak magnetism, easiness in magnetic leakage, poor specificity, low degree of functionalization and the like. Therefore, it is necessary to develop a novel magnetic polymer microsphere which has the advantages of simple and convenient technological process operation, low raw material cost, uniform particle size, high magnetic content and rich surface functionalization.
Disclosure of Invention
Aiming at the technical problems of nonuniform particle size, poor magnetizing effect and weak surface functionalization of the existing magnetic beads, the invention provides the magnetic microsphere with high magnetic content, strong magnetic stability, uniform nanoparticle distribution and strong surface functionalization.
The invention aims to provide a functionalized magnetic microsphere, which takes a polymer microsphere as a core, a ferroferric oxide layer is formed on the surface of the polymer microsphere through in-situ magnetization, and a silicon dioxide shell is coated outside the ferroferric oxide layer.
In the functionalized magnetic microsphere, the polydispersity index of the functionalized magnetic microsphere is less than 0.1.
In the functionalized magnetic microsphere, the particle size of the polymer microsphere is 0.2-10 mu m.
In the functionalized magnetic microsphere, the polymer microsphere is formed by polymerizing monomer I and monomer II.
Preferably, the polymer microsphere is prepared by the following steps: and dissolving the monomer I, the monomer II and the emulsifier in an ethanol/water mixed solution, stirring under a nitrogen atmosphere, adding an initiator, and then heating and polymerizing to obtain the polymer microsphere.
The mixed solution is stirred for a period of time under nitrogen atmosphere, and oxygen in the reaction system can be removed. Most of the polymer microspheres are realized through free radical reaction of monomers, firstly, an initiator is added, the initiator is decomposed at a proper temperature to generate two free radicals, the monomers are added to the tail end of a polymer chain through the free radicals, the polymer chain is continuously transferred and prolonged, and finally, the high-molecular polymer is formed. Wherein the nitrogen atmosphere removes oxygen because oxygen blocks the polymerization of free radicals. In the copolymerization system, the functional monomer provides specific functional groups, and the polymer microsphere with various surface functional groups has wide application in the fields of biology, medical analysis, protein synthesis, chromatography, coating and the like.
Preferably, the monomer one and the monomer two are independently selected from one or more of styrene, methyl styrene, para-aminostyrene, acrylic acid, methacrylic acid, methyl methacrylate, glycidyl methacrylate, butyl acrylate, acrylamide, maleic acid and sodium styrenesulfonate. The polymer microsphere provided by the invention has the advantages that the surfaces of the monomer I and the monomer II selected by the polymer microsphere are provided with a plurality of functional groups, the functional groups comprise but are not limited to carboxyl, sulfonic acid groups, amino groups and the like, so that the surface of the polymer microsphere obtained by synthesis is rich in the functional groups, a large number of binding sites are provided for iron ions and ferrous ions in the subsequent magnetizing process, the complexing of the iron ions, the ferrous ions and the polymer microsphere is more complete and stable, the magnetizing quantity of the surface of the polymer microsphere is improved, and the magnetizing is more uniform.
Further preferably, the high molecular polymer microspheres comprise one or more of poly (styrene-acrylic acid), poly (styrene-methacrylic acid), poly (styrene-butyl acrylate-acrylic acid), poly (styrene-methyl methacrylate-acrylic acid), poly (styrene-sodium styrene sulfonate).
In the functionalized magnetic microsphere, the crosslinking ratio of the monomer I to the high polymer microsphere is 20-99%, and the crosslinking ratio of the monomer II to the high polymer microsphere is 1-20%.
Preferably, the emulsifier is one or more of sodium dodecyl sulfate, sodium dodecyl benzene sulfonate, sodium octyl sulfonate and cetyltrimethylammonium bromide.
Preferably, the mass of the emulsifier is 0-0.5% of the total mass of the monomers. The particle size of the microsphere is controlled by controlling the dosage of the emulsifier.
Preferably, the volume ratio of ethanol to water in the ethanol/water mixture is (0:1) - (0.2:1).
Preferably, the stirring under nitrogen atmosphere can be carried out by any stirring mode, including mechanical stirring, and the mechanical stirring speed is 200-500r/min.
Preferably, the initiator is one or more of potassium persulfate, ammonium persulfate, benzoyl peroxide, azobisisobutyronitrile, and 2, 2-azobis (2-methylpropionamide) dihydrochloride.
Preferably, the mass of the initiator is 0.5 to 1% of the total mass of the monomers.
Preferably, the polymerization reaction temperature is 70-90℃and the reaction time is 8-24 hours.
In the functionalized magnetic microsphere, the pH of the polymer microsphere solution is adjusted to 5-8 before the surface of the polymer microsphere is magnetized. Before magnetizing, the pH value of the polymer microsphere solution is regulated to change the functional groups on the surface of the polymer microsphere into ionic states, so that the groups on the surface of the microsphere can capture iron ions and ferrous ions in the mixed solution in the magnetizing process, the magnetic content and the magnetic stability of the magnetic microsphere are improved, and the magnetic nanoparticles on the surface of the microsphere can be distributed more uniformly.
In the functionalized magnetic microsphere, the magnetization amount of the ferroferric oxide layer formed by magnetization on the surface of the polymer microsphere reaches more than 40 weight percent.
Preferably, the magnetization amount of the polymer microsphere surface to form the ferroferric oxide layer is 50wt% or more.
Preferably, the ferroferric oxide layer is formed by magnetizing the surface of the polymer microsphere by the following steps: taking a polymer microsphere solution, and firstly adjusting the pH value of the polymer microsphere solution to 5-8; under nitrogen atmosphere, adding ferric ion solution mixed by ferric salt and ferrous salt, stirring, regulating pH value to 7-11, heating until the ferric ion and ferrous ion hydrolyze, nucleate and complex on the surface of polymer microsphere, magnetically separating, cleaning to obtain magnetic polymer microsphere, and storing in water.
Further preferably, the mass of the polymer microspheres is 0.1-2.0g.
Further preferably, the pH of the polymer microsphere solution is adjusted to a pH of 5 to 8 using ammonia or hydrochloric acid.
Further preferably, fe in the iron ion solution 2+ And Fe (Fe) 3+ The molar ratio is (1:1) - (1:3).
Further preferably, the iron ion solution is mechanically stirred after being added, the mechanical stirring speed is 200-600r/min, and the stirring time is 1-12h. Mechanical agitation can affect the reaction.
Further preferably, after the addition of the iron ion solution, the pH is adjusted to 7-11 using ammonia or sodium hydroxide.
It is further preferred that the nucleation temperature of the ferroferric oxide is 70-90 ℃ and the reaction time is 0.5-3h.
The functionalized magnetic microsphere is coated with a silicon dioxide shell, so that the surface of the magnetic polymer microsphere is modified with a large number of hydroxyl groups.
Specifically, the method comprises the following steps of coating a silicon dioxide shell outside a ferroferric oxide layer: dispersing the magnetic polymer microsphere in ethanol/water mixed solution, adding ammonia water after ultrasonic mixing, continuing ultrasonic, adding tetraethoxysilane, and mechanically stirring to obtain the sandwich polymer microsphere/ferroferric oxide layer/silicon dioxide shell functionalized magnetic microsphere.
Preferably, the magnetic polymer microspheres are dispersed in an ethanol/water mixed solution, and the volume ratio of ethanol to water is (1:1) - (1:5).
Preferably, the volume of ammonia water added is 0.01-10mL.
Preferably, ethyl orthosilicate is added in a volume of 0.1-10mL.
Preferably, the temperature of the mechanical stirring is 30-50 ℃ and the time is 5-24h. Ammonia is added to make the reaction system alkaline, tetraethyl orthosilicate is hydrolyzed into silicon dioxide under alkaline condition at the temperature, and the silicon dioxide is coated on the surface of the magnetic polymer microsphere.
The invention also aims at providing a preparation method of the functionalized magnetic microsphere, which comprises the following steps:
(1) Dissolving a monomer I, a monomer II and an emulsifier in an ethanol/water mixed solution, stirring under a nitrogen atmosphere, adding an initiator, heating and polymerizing to obtain polymer microspheres, cleaning, and preserving in water;
(2) Taking a polymer microsphere solution, and firstly adjusting the pH value of the polymer microsphere solution to 5-8; adding ferric ion solution mixed by ferric salt and ferrous salt under nitrogen atmosphere, stirring, then adjusting the pH value to 7-11, heating, hydrolyzing, nucleating and complexing ferric ion and ferrous ion on the surface of polymer microspheres, magnetically separating, cleaning to obtain magnetic polymer microspheres, and storing in water;
(3) Dispersing the magnetic polymer microspheres in an ethanol/water mixed solution, adding ammonia water after ultrasonic mixing, continuing ultrasonic, adding tetraethoxysilane, and mechanically stirring at room temperature to obtain the sandwich polymer microspheres/ferroferric oxide layer/silicon dioxide shell functionalized magnetic microspheres.
It is still another object of the present invention to provide the use of the functionalized magnetic microsphere as described above for extracting nucleic acids.
The particle size of the functionalized magnetic microsphere is 600-700nm, and the functionalized magnetic microsphere has the advantages of large specific surface area, good suspension property and the like. And because the magnetic microsphere surface contains abundant silicon hydroxyl groups, nucleic acid can be reversibly captured and released in an acidic/alkaline environment. Therefore, the functionalized magnetic microsphere can be widely applied to nucleic acid extraction.
The specific extraction process comprises the following steps: adding lysate to plasma to separate tissue protein from DNA, adding magnetic beads to capture DNA, separating by external magnetic field, and eluting with eluent to obtain purified DNA.
Compared with the prior art, the invention has the following advantages:
1. the functionalized magnetic microsphere is a sandwich microsphere, which sequentially comprises a polymer microsphere, a ferroferric oxide layer and a silicon dioxide shell from inside to outside, wherein the polymer microsphere is synthesized by using two or more monomers through one-step reaction, and a polymer template is not required to be formed first by a conventional seed method or a swelling method, so that the synthesis method is simple, a large number of binding sites can be provided for iron ions and ferrous ions in the monomers in the subsequent magnetizing process, the complexing of the iron ions, the ferrous ions and the polymer microsphere is more complete and stable, the magnetizing quantity of the surface of the polymer microsphere is improved, and the magnetizing is more uniform.
2. The pH value of the polymer microsphere solution is firstly adjusted before the functionalized magnetic microsphere is magnetized to form the ferroferric oxide, the functional groups on the surface of the polymer microsphere are changed into ionic states, the groups on the surface of the microsphere can capture iron ions and ferrous ions in the mixed solution more easily in the magnetizing process, the magnetic content and the magnetic stability of the magnetic microsphere are improved more favorably, and the magnetic nanoparticles on the surface of the microsphere can be distributed more uniformly.
3. The magnetic nanoparticles on the surface of the functionalized magnetic microsphere have the characteristics of more uniform distribution, uniform particle size, high magnetic content, quick magnetic response and rich surface functional groups, can extract nucleic acid with higher quality, and lays a foundation for subsequent research. And the problems of inconsistent hydrophilicity and hydrophobicity and easy magnetic leakage existing on the surface of the magnetic microsphere are also solved. The synthesis method of the functionalized magnetic microsphere is simple, low in cost and high in yield.
Drawings
FIG. 1 is a scanning electron microscope image of the polymer microspheres of example 1;
FIG. 2 is a scanning electron microscope image of the magnetic polymer microsphere in example 1;
FIG. 3 is a scanning electron microscope image of the functionalized magnetic microspheres of example 1;
FIG. 4 is a graph showing the particle size distribution of functionalized magnetic microspheres of example 1;
FIG. 5 is a graph of saturation magnetization of magnetic polymer microspheres and functionalized magnetic microspheres of example 1;
FIG. 6 is a thermogravimetric analysis of the functionalized magnetic microspheres of example 1;
FIG. 7 is an EDS spectrum of the functionalized magnetic microsphere of example 1;
FIG. 8 is a scanning electron microscope image of the magnetic microspheres of comparative example 1;
FIG. 9 is a scanning electron microscope image of the magnetic microspheres of comparative example 2.
Detailed Description
The technical solution of the present invention will be further described by means of specific examples and drawings, it being understood that the specific examples described herein are only for aiding in understanding the present invention and are not intended to be limiting. And the drawings described herein are for illustration purposes only and are not intended to limit the scope of the present disclosure. Unless otherwise indicated, all materials used in the examples of the present invention are those commonly used in the art, and all methods used in the examples are those commonly used in the art.
Example 1
18g of styrene, 1g of acrylic acid and 0.05g of sodium dodecyl benzene sulfonate are weighed, dissolved in a mixed solution of 100ml of water and 20ml of ethanol, nitrogen is introduced, deoxygenated for 1h under a nitrogen atmosphere under stirring at a speed of 500r/min, then 0.2g of ammonium persulfate is added, the mixed solution is immersed in a 70-oil bath, and the mixed solution is mechanically stirred at a speed of 500r/min and reacted for 24h. After the reaction is finished, the obtained polymer microsphere is centrifugally washed by deionized water for 3 times and then dispersed in water to obtain the poly (styrene-acrylic acid) microsphere with carboxylated surface, wherein a scanning electron microscope image of the poly (styrene-acrylic acid) microsphere is shown as a graph in figure 1, and the polymer microsphere synthesized by using the monomer has uniform particle size as can be seen from the graph in figure 1.
5g of the above surface carboxylated poly (styrene-acrylic acid) microspheres were weighed in a beaker, sonicated in a mixed solution of 50ml water and 50ml ethanol, and the pH of the solution was adjusted to 7.5 with ammonia. 2.5g of ferric chloride and 3g of ferrous chloride tetrahydrate are weighed and dissolved in 10ml of deionized water to obtain an iron ion solution, the iron ion solution is added into the polymer solution, and the polymer solution is mechanically stirred for 1h at 500r/min under the nitrogen atmosphere. Then ammonia water is slowly added dropwise to adjust the pH of the solution to 10, and the temperature is raised to 80 ℃ after the completion of the dropwise addition to react for 2 hours. After the reaction is finished, magnetic microspheres are separated out, and are alternately washed by ethanol and water for 3 times, so that poly (styrene-acrylic acid)/ferroferric oxide magnetic microspheres, namely magnetic polymer microspheres, with the magnetization reaching more than 40 weight percent are obtained. The scanning electron microscope image of the poly (styrene-acrylic acid)/ferroferric oxide magnetic microsphere is shown in figure 2, and the figure 2 shows that the ferroferric oxide magnetic microsphere with very uniform surface magnetic nanoparticle distribution is obtained in the embodiment.
1g of the poly (styrene-acrylic acid)/ferroferric oxide magnetic microsphere is weighed in a beaker, dispersed in a mixed solution of 20mL of ethanol and 100mL of water, evenly mixed by ultrasonic, added with 5mL of ammonia water, mechanically stirred for 0.5h at 300r/min, added with 2mL of tetraethyl orthosilicate, and mechanically stirred for 6h at 30 ℃. After the reaction is finished, magnetic microspheres are separated out, and the magnetic microspheres are alternately washed with ethanol and water for 3 times to obtain hydroxylated poly (styrene-acrylic acid)/ferroferric oxide/silicon dioxide magnetic microspheres, namely the functionalized magnetic microspheres.
A scanning electron microscope image of poly (styrene-acrylic acid)/ferroferric oxide/silica magnetic microspheres (i.e., functionalized magnetic microspheres) in this example is shown in fig. 3. From fig. 3, a clear silica shell can be observed, demonstrating successful silica coating.
In this example, the poly (styrene-acrylic acid)/ferroferric oxide/silicon dioxide magnetic microsphere (i.e. functionalized magnetic microsphere) passes the laser particle size analyzer test, and the result is shown in fig. 4, and the particle size distribution range of the functionalized magnetic microsphere of the invention is very narrow, the polydispersity index is less than 0.1, which indicates that the microsphere particle size has good uniformity.
The saturation magnetization of poly (styrene-acrylic acid)/ferroferric oxide magnetic microspheres (i.e., magnetic polymer microspheres) and poly (styrene-acrylic acid)/ferroferric oxide/silica magnetic microspheres (i.e., functionalized magnetic microspheres) in this example is shown in fig. 5. As can be seen from FIG. 5, the saturation magnetization of the magnetic polymer microsphere reaches 22.98emu/g, and the saturation magnetization of the functionalized magnetic microsphere coated with silicon reaches 22.52emu/g.
The thermogravimetric analysis of the poly (styrene-acrylic acid)/ferroferric oxide/silica magnetic microspheres (i.e., functionalized magnetic microspheres) of this example is shown in fig. 6. From fig. 6, it can be derived that the magnetic content of the functionalized magnetic microsphere of the present invention is 42%.
The EDS spectra of poly (styrene-acrylic acid)/ferroferric oxide/silica magnetic microspheres (i.e., functionalized magnetic microspheres) in this example are shown in fig. 7. From fig. 7, it can be derived that silica was successfully modified on the surface of the magnetic polymer microsphere in this example.
Example 2
Weighing 20g of styrene, 1g of methyl methacrylate, 1g of acrylic acid and 0.05g of sodium dodecyl sulfate, dissolving in a mixed solution of 100ml of water and 20ml of ethanol, introducing nitrogen to deoxidize for 1h, adding 0.2g of ammonium bicarbonate, immersing the mixed solution in an oil bath at 70 ℃, mechanically stirring at a speed of 500r/min, and reacting for 24h. After the reaction, the obtained polymer microspheres are centrifugally washed by deionized water for 3 times and then dispersed in water to obtain the poly (styrene-methyl methacrylate-acrylic acid) microspheres with carboxylated surfaces.
5g of the poly (styrene-methyl methacrylate-acrylic acid) microsphere is weighed into a beaker, dispersed in a mixed solution of 50ml of water and 50ml of ethanol by ultrasonic, and a certain amount of ammonia water is added to adjust the pH of the solution to 7.5. 3g of ferric chloride and 6g of ferrous chloride tetrahydrate are weighed and dissolved in 10ml of deionized water to obtain an iron ion solution, the iron ion solution is added into the polymer solution, and the polymer solution is mechanically stirred for 4 hours at 500r/min under the nitrogen atmosphere. Adding sodium hydroxide to regulate the pH value of the solution to 10, dispersing by ultrasonic wave, dripping into the system, heating to 90 ℃ and reacting for 1h. After the reaction is finished, magnetic microspheres are separated magnetically, and are alternately washed with ethanol and water for 3 times to obtain poly (styrene-methyl methacrylate-acrylic acid)/ferroferric oxide magnetic microspheres.
0.5g of the poly (styrene-methyl methacrylate-acrylic acid)/ferroferric oxide magnetic microsphere is weighed and placed in a beaker, dispersed in a mixed solution of 10ml of ethanol and 50ml of water, evenly mixed by ultrasonic, added with 2.5ml of ammonia water, mechanically stirred for 0.5h at 300r/min, added with 1ml of tetraethyl orthosilicate, and mechanically stirred for 6h at 30 ℃. After the reaction is finished, magnetic microspheres are separated out, and are alternately washed with ethanol and water for 3 times to obtain hydroxylated poly (styrene-methyl methacrylate-acrylic acid)/ferroferric oxide/silicon dioxide magnetic microspheres, namely the functionalized magnetic microspheres.
Example 3
4.5g of styrene, 0.25g of butyl acrylate, 0.25g of acrylic acid and 0.05g of sodium dodecyl benzene sulfonate are weighed and dissolved in a mixed solution of 25ml of water and 5ml of ethanol, nitrogen is introduced to deoxidize for 1h, 0.04g of ammonium persulfate is added, the mixed solution is immersed in an oil bath at 70 ℃ and mechanically stirred at a speed of 300r/min, and the reaction is carried out for 12h. After the reaction, the obtained polymer microsphere is centrifugally washed by deionized water for 3 times, and then dispersed in water, so as to obtain the poly (styrene-butyl acrylate-acrylic acid) microsphere with carboxylated surface.
1g of the poly (styrene-butyl acrylate-acrylic acid) microsphere is weighed into a beaker, dispersed in a mixed solution of 10ml of water and 10ml of ethanol by ultrasonic, and a certain amount of ammonia water is added to adjust the pH of the solution to 7.5. 0.6g of ferric chloride and 1.2g of ferrous chloride tetrahydrate are weighed and dissolved in 3ml of deionized water to obtain an iron ion solution, the iron ion solution is added into the polymer solution, and the polymer solution is mechanically stirred for 3 hours at 300r/min under the nitrogen atmosphere. Adding sodium hydroxide to regulate the pH of the solution to about 10, dispersing by ultrasonic, dripping into the system, heating to 90 ℃ and reacting for 1h. After the reaction is finished, magnetic microspheres are separated magnetically, and are alternately washed with ethanol and water for 3 times to obtain poly (styrene-butyl acrylate-acrylic acid)/ferroferric oxide magnetic microspheres.
0.5g of the poly (styrene-butyl acrylate-acrylic acid)/ferroferric oxide magnetic microsphere is weighed and placed in a beaker, dispersed in a mixed solution of 20ml of ethanol and 50ml of water, evenly mixed by ultrasonic, added with 2.5ml of ammonia water, mechanically stirred for 0.5h, added with 1ml of tetraethyl orthosilicate, and mechanically stirred for 6h at 30 ℃. After the reaction is finished, magnetic microspheres are separated out, and are alternately washed with ethanol and water for 3 times to obtain hydroxylated poly (styrene-butyl acrylate-acrylic acid)/ferroferric oxide/silicon dioxide magnetic microspheres, namely the functionalized magnetic microspheres.
Example 4
25g of styrene and 1.25g of sodium p-styrenesulfonate are weighed, dissolved in 150ml of water, fully mixed, deoxygenated by introducing nitrogen for 1h, added with 0.25g of potassium persulfate, immersed in an oil bath at 70 ℃ and mechanically stirred, and reacted for 8h. After the reaction, the obtained polymer microsphere is centrifugally washed by deionized water for 3 times, and then dispersed in water, so as to obtain the poly (styrene-sodium styrene sulfonate) microsphere with carboxylated surface.
2.5g of the poly (styrene-sodium styrene sulfonate) microspheres are weighed into a beaker, dispersed into a mixed solution of 25ml of water and 25ml of ethanol by ultrasonic, and a certain amount of ammonia water is added to adjust the pH of the solution to 7.5. 1.5g of ferric chloride and 3g of ferrous chloride tetrahydrate are weighed and dissolved in 10ml of deionized water to obtain an iron ion solution, the iron ion solution is added into the polymer solution, and the polymer solution is mechanically stirred for 4 hours at 500r/min under the nitrogen atmosphere. Adding sodium hydroxide to regulate the pH of the solution to about 10, dispersing by ultrasonic, dripping into the system, heating to 90 ℃ and reacting for 1h. After the reaction is finished, magnetic microspheres are separated magnetically, and are alternately washed with ethanol and water for 3 times to obtain poly (styrene-sodium styrenesulfonate)/ferroferric oxide magnetic microspheres.
1g of the poly (styrene-sodium styrenesulfonate)/ferroferric oxide magnetic microsphere is weighed and placed in a beaker, dispersed in a mixed solution of 40ml of ethanol and 100ml of water, evenly mixed by ultrasonic, added with 5ml of ammonia water, mechanically stirred for 0.5h, added with 2ml of tetraethyl orthosilicate, and mechanically stirred for 6h at 30 ℃. After the reaction is finished, magnetic microspheres are separated out, and are alternately washed with ethanol and water for 3 times to obtain hydroxylated poly (styrene-sodium styrenesulfonate)/ferroferric oxide/silicon dioxide magnetic microspheres, namely the functionalized magnetic microspheres.
Example 5
9g of styrene, 0.5g of glycidyl methacrylate, 0.5g of acrylic acid and 0.1g of sodium dodecyl benzene sulfonate are weighed and dissolved in a mixed solution of 50ml of water and 20ml of ethanol, nitrogen is introduced to deoxidize for 1h, 0.08g of ammonium persulfate is added, the mixed solution is immersed in an oil bath at 70 ℃ and mechanically stirred at a speed of 400r/min, and the reaction is carried out for 10h. After the reaction, the obtained polymer microspheres are centrifugally washed by deionized water for 3 times and then dispersed in water to obtain the poly (styrene-glycidyl methacrylate-acrylic acid) microspheres with carboxylated surfaces.
1g of the poly (styrene-glycidyl methacrylate-acrylic acid) microsphere is weighed into a beaker, dispersed in a mixed solution of 10ml of water and 10ml of ethanol by ultrasonic, and added with a certain amount of ammonia water to adjust the pH of the solution to 7.5. 0.6g of ferric chloride and 1.2g of ferrous chloride tetrahydrate are weighed and dissolved in 3ml of deionized water to obtain an iron ion solution, the iron ion solution is added into the polymer solution, and the polymer solution is mechanically stirred for 2 hours at 300r/min under the nitrogen atmosphere. Adding sodium hydroxide to regulate the pH of the solution to about 10, dispersing by ultrasonic, dripping into the system, heating to 90 ℃ and reacting for 1h. After the reaction is finished, magnetic microspheres are separated magnetically, and are alternately washed with ethanol and water for 3 times to obtain poly (styrene-glycidyl methacrylate-acrylic acid)/ferroferric oxide magnetic microspheres.
0.5g of the poly (styrene-glycidyl methacrylate-acrylic acid)/ferroferric oxide magnetic microsphere is weighed and placed in a beaker, dispersed in a mixed solution of 20ml of ethanol and 50ml of water, evenly mixed by ultrasonic, added with 2.5ml of ammonia water, mechanically stirred for 0.5h, added with 1ml of tetraethyl orthosilicate, and mechanically stirred for 6h at 30 ℃. After the reaction is finished, magnetic microspheres are separated out, and are alternately washed with ethanol and water for 3 times to obtain hydroxylated poly (styrene-glycidyl methacrylate-acrylic acid)/ferroferric oxide/silicon dioxide magnetic microspheres, namely the functionalized magnetic microspheres.
Comparative example 1
Firstly, synthesizing monodisperse ferroferric oxide magnetic nano particles, dispersing the monomer I, the monomer II, the magnetic nano particles and the emulsifier in an ethanol/water mixed solution as in the embodiment 1, stirring under nitrogen atmosphere, adding an initiator, heating and polymerizing to obtain magnetic polymer microspheres, cleaning and storing in water.
The magnetic microsphere prepared in the comparative example 1 is prepared by synthesizing ferroferric oxide, adding ferroferric oxide in the first step, namely adding two monomers, and coating magnetic particles by coating, but the magnetic particles are difficult to coat and have low magnetic content due to wide microsphere particle size distribution caused by incompatibility between inorganic particles and organic monomers. The scanning electron microscope image of the magnetic microsphere prepared in comparative example 1 is shown in fig. 8. From fig. 8, it can be derived that: TEM particle size distribution of the magnetic polymer microspheres prepared by direct coating is wide, and a large amount of non-coated ferroferric oxide exists in the background.
Comparative example 2
This comparative example differs from example 1 only in that the pH of the solution was not adjusted to 7.5 using ammonia water at the time of magnetization, i.e., the polymer microspheres were ultrasonically dispersed in an ethanol/water mixed solution and the iron ion solution was directly added. The SEM image of the magnetic microspheres obtained in this comparative example is shown in the left diagram of fig. 9, and the SEM image of the functionalized magnetic microspheres obtained in example 1 is shown in the right diagram of fig. 9. The comparison can be carried out to obtain that the surface magnetic ions of the functionalized magnetic microsphere prepared by adjusting the pH value are full when the magnetic microsphere is magnetized, and the magnetic content and the magnetic response are greatly improved.
In conclusion, the functionalized magnetic microsphere has the characteristics of simple synthesis method, high magnetic flux on the surface of the polymer microsphere, more uniform distribution of the surface magnetic nanoparticles, uniform particle size, high magnetic content, high magnetic stability, quick magnetic response and rich surface functional groups.
The various aspects, embodiments, features of the invention are to be considered as illustrative in all respects and not restrictive, the scope of the invention being indicated only by the appended claims. Other embodiments, modifications, and uses will be apparent to those skilled in the art without departing from the spirit and scope of the claimed invention.
In the preparation method of the invention, the sequence of each step is not limited to the listed sequence, and the sequential change of each step is also within the protection scope of the invention without the inventive labor for the person skilled in the art. Furthermore, two or more steps or actions may be performed simultaneously.
Finally, it should be noted that the specific embodiments described herein are merely illustrative of the invention and are not limiting of the invention's embodiments. Those skilled in the art may make various modifications or additions to the described embodiments or substitutions in a similar manner, and need not and cannot fully practice all of the embodiments. While these obvious variations and modifications, which come within the spirit of the invention, are within the scope of the invention, they are to be construed as being without departing from the spirit of the invention.
Claims (10)
1. The functional magnetic microsphere is characterized in that the functional magnetic microsphere takes a polymer microsphere as a core, a ferroferric oxide layer is formed on the surface of the polymer microsphere through in-situ magnetization, and a silicon dioxide shell is coated outside the ferroferric oxide layer.
2. The functionalized magnetic microsphere of claim 1, wherein the polydispersity index of the functionalized magnetic microsphere is less than 0.1.
3. The functionalized magnetic microsphere according to claim 1, wherein the polymer microsphere has a particle size of 0.2 to 10 μm.
4. The functionalized magnetic microsphere of claim 1, 2 or 3, wherein the polymer microsphere is formed by polymerizing monomer one and monomer two, and the polymer microsphere is prepared by the following steps: and dissolving the monomer I, the monomer II and the emulsifier in an ethanol/water mixed solution, stirring under a nitrogen atmosphere, adding an initiator, and then heating and polymerizing to obtain the polymer microsphere.
5. A functionalized magnetic microsphere according to claim 1, 2 or 3, characterized in that the pH of the polymer microsphere solution is adjusted to 5-8 before the surface of the polymer microsphere is magnetized.
6. The functionalized magnetic microsphere according to claim 1, 2 or 3, wherein the amount of magnetization forming the ferroferric oxide layer on the surface of the polymer microsphere is 40wt% or more.
7. The functionalized magnetic microsphere of claim 6, wherein the polymer microsphere surface is magnetized to form the ferroferric oxide layer by: taking a polymer microsphere solution, and firstly adjusting the pH value of the polymer microsphere solution to 5-8; under nitrogen atmosphere, adding ferric ion solution mixed by ferric salt and ferrous salt, stirring, regulating pH value to 7-11, heating until the ferric ion and ferrous ion hydrolyze, nucleate and complex on the surface of polymer microsphere, magnetically separating, cleaning to obtain magnetic polymer microsphere, and storing in water.
8. The functionalized magnetic microsphere of claim 7, wherein Fe in the iron ion solution 2+ And Fe (Fe) 3+ The molar ratio is (1:1) - (1:3).
9. A method of preparing the functionalized magnetic microsphere of claim 1, comprising the steps of:
(1) Dissolving a monomer I, a monomer II and an emulsifier in an ethanol/water mixed solution, stirring under a nitrogen atmosphere, adding an initiator, heating and polymerizing to obtain polymer microspheres, cleaning, and preserving in water;
(2) Taking a polymer microsphere solution, and firstly adjusting the pH value of the polymer microsphere solution to 5-8; adding ferric ion solution mixed by ferric salt and ferrous salt under nitrogen atmosphere, stirring, then adjusting the pH value to 7-11, heating, hydrolyzing, nucleating and complexing ferric ion and ferrous ion on the surface of polymer microspheres, magnetically separating, cleaning to obtain magnetic polymer microspheres, and storing in water;
(3) Dispersing the magnetic polymer microspheres in an ethanol/water mixed solution, adding ammonia water after ultrasonic mixing, continuing ultrasonic, adding tetraethoxysilane, and mechanically stirring at room temperature to obtain the sandwich polymer microspheres/ferroferric oxide layer/silicon dioxide shell functionalized magnetic microspheres.
10. Use of the functionalized magnetic microsphere of claim 1 for extracting nucleic acid.
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