CN114192079B - Magnetic hollow polymer microsphere and preparation method and application thereof - Google Patents
Magnetic hollow polymer microsphere and preparation method and application thereof Download PDFInfo
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- CN114192079B CN114192079B CN202111518224.8A CN202111518224A CN114192079B CN 114192079 B CN114192079 B CN 114192079B CN 202111518224 A CN202111518224 A CN 202111518224A CN 114192079 B CN114192079 B CN 114192079B
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Abstract
The invention relates to a magnetic hollow polymer microsphere and a preparation method and application thereof. The preparation method comprises the steps of preparing hollow polymer microspheres with uniform particle size, compounding the hollow microspheres and superparamagnetic nano particles and functionally modifying the surfaces of the hollow microspheres. The magnetic hollow polymer microsphere has the advantages of good surface hydrophilicity, small folded density, high magnetic responsiveness, high magnetic reaction speed and long suspension time in water dispersion, and is suitable for the field of detection.
Description
Technical Field
The invention relates to the field of polymer microsphere materials, in particular to a magnetic hollow polymer microsphere and a preparation method and application thereof.
Background
The magnetic microsphere is a micron/nanometer level sphere with magnetic responsiveness, and can be applied to the detection field such as the in vitro diagnosis field. When the magnetic microspheres are used, the spheres are generally dispersed in an aqueous solution to prepare an aqueous dispersion, the magnetic microspheres are orderly assembled and enriched in the aqueous dispersion under an external magnetic field, and the magnetic microspheres can be uniformly dispersed after the external magnetic field is removed. The magnetic microspheres are formed by assembling polymers or silane and superparamagnetic nano particles, and can be divided into core-shell type, dispersion type and multi-interlayer type from the assembling mode, the magnetic microspheres are generally solid spheres, have high integral folding density, are easy to rapidly settle in a water phase, have slow response under the action of a magnetic field, have low magnetic substance occupation ratio and poor magnetic attraction performance.
The polymer microspheres with hollow structures are expected to reduce the density of the microspheres. The polymer hollow microspheres are generally prepared by a hard template method or a soft template method, and hollow microspheres with different inner hole forms and shell thicknesses can be obtained by selecting different preparation steps and process conditions. The hard template method generally uses a solid ball as an internal cavity template, and performs a post-hollowing treatment after a polymer shell is modified on the surface, such as etching or extracting a main body component of a ball core, so as to obtain the polymer hollow microsphere. For example, after synthesizing silicon spheres, a polymer shell layer is modified on the surface of the silicon spheres, and hollow polymer microspheres can be obtained after hydrofluoric acid etching and kernel removal. The soft template method forms two phases into a liquid drop ball by mainly using an amphiphilic surfactant, and the hollow polymer microspheres can be obtained by simply cleaning the surface modified polymer layer. The polymer hollow microsphere is functionally modified, functional components are modified in the polymer hollow microsphere or on the surface of the polymer hollow microsphere, and the polymer hollow microsphere is hopeful to obtain special properties such as magnetic, optical, thermal, force or chemical response and the like, so that the functional hollow polymer microsphere is obtained.
Disclosure of Invention
In view of the defects of the prior art, the first object of the present invention is to provide a magnetic hollow polymer microsphere, which has good surface hydrophilicity, small reduced density, high magnetic content, good magnetic responsiveness, fast magnetic reaction speed and long suspension time in an aqueous dispersion. The second objective of the present invention is to provide a method for preparing the magnetic hollow polymer microsphere, which can effectively prepare the magnetic hollow polymer microsphere of the present invention. The third purpose of the present invention is to provide the application of the magnetic hollow polymer microsphere, wherein the magnetic hollow polymer microsphere does not lose signals due to sedimentation in detection use.
In order to achieve the first object of the present invention, the present invention provides a magnetic hollow polymer microsphere, which comprises a hollow polymer microsphere, a magnetic nanoparticle and a hydrophilic modification layer, wherein the magnetic nanoparticle is located in an inner cavity of the hollow polymer microsphere, and the hydrophilic modification layer covers the outer wall of the hollow polymer microsphere.
According to the technical scheme, the magnetic hollow polymer microsphere mainly comprises a hollow polymer microsphere, magnetic nanoparticles and a hydrophilic modification layer, and the particle size of the magnetic hollow polymer microsphere can be 1-15 micrometers. The hollow polymer microspheres are hollowed relative to the core part of the solid microspheres, so that the reduced density of the microspheres can be reduced, the signal loss in detection application caused by rapid sedimentation of the microspheres in an aqueous dispersion under the action of gravity can be avoided, the using amount of the polymer can be reduced, the content of a magnetic material is relatively increased, and the magnetic responsiveness is improved. The magnetic nanoparticles have a nanoscale size, for example, the size can be 3-50 nm, and the magnetic nanoparticles can enter the hollow polymer microspheres, so that the magnetic nanoparticles are coated by the hollow polymer microspheres and are not easy to separate from the hollow polymer microspheres. The hydrophilic modification layer introduces abundant hydrophilic groups on the outer wall of the microsphere, so that the dispersibility of the magnetic hollow polymer microsphere in aqueous solution is improved, the microsphere is prevented from easily agglomerating, and surface functional groups can be provided for combining functional substances such as antigens or antibodies. The hollow polymer microsphere, the magnetic nano-particles and the hydrophilic modification layer are matched with each other, so that the hollow polymer microsphere has excellent suspension performance and magnetic response performance in a water dispersion phase. The hollow polymer microsphere is suitable for the detection field, and is particularly suitable for chemiluminescence immunoassay.
The further technical scheme is that the hydrophilic modification layer is crosslinked with the outer wall of the hollow polymer microsphere, and the hollow polymer microsphere and the hydrophilic modification layer prevent the magnetic nanoparticles from leaking from the inner cavity.
According to the technical scheme, in order to further adapt to complex detection environments in detection application, the hydrophilicity modification layer is crosslinked with the hollow polymer microspheres, so that the sealing property of the inner cavities of the microspheres is improved, the leakage of the magnetic nanoparticles is avoided, and the hollow magnetic microspheres can keep good performance in different detection environments.
The further technical proposal is that the magnetic hollow polymer microsphere has uniform grain diameter.
According to the technical scheme, the magnetic hollow polymer microsphere disclosed by the invention is uniform in particle size and low in particle size dispersion degree, and can better meet the application requirements in the fields of biological substance detection, separation and the like.
The further technical proposal is that the magnetic nano-particles are hydrophobic superparamagnetic nano-particles.
According to the technical scheme, the hydrophobic magnetic nanoparticles are further adopted, for example, the hydrophobic magnetic nanoparticles are obtained by modifying ferromagnetic substances with hydrophobic substances, so that the ferromagnetic substances can be protected, and the magnetic nanoparticles are prevented from being easily separated from the inner cavity of the hollow polymer microsphere and dispersed in water.
The hollow polymer microsphere is formed by copolymerizing a monofunctional monomer and a polyfunctional monomer.
According to the technical scheme, the hollow polymer microsphere can be formed by copolymerizing a monofunctional group monomer and a polyfunctional group monomer, has a certain crosslinking degree, and improves the strength and chemical stability of the hollow polymer microsphere.
The further technical proposal is that the hydrophilic modification layer is provided with hydrophilic groups which are at least one of amino, carboxyl and hydroxyl; the hydrophilic modification layer is connected with the outer wall of the hollow polymer microsphere through a covalent bond, and the covalent bond is an amido bond, an ester bond or a covalent bond formed by the reaction of an amino group, a carboxyl group or a hydroxyl group and an epoxy group.
According to the above technical scheme, the hydrophilic group of the hydrophilic modification layer of the present invention can be selected from the above common hydrophilic groups, and the hydrophilic modification layer can be prepared by using the existing chemical substances having these hydrophilic groups. The covalent bond connection mode of the hydrophilic modification layer and the hollow polymer microspheres can adopt the common connection bonds and can realize crosslinking by adopting conventional chemical reaction. The hydrophilic group can play a role in improving hydrophilicity and can also participate in crosslinking to realize covalent bond connection.
In order to achieve the second object of the present invention, the present invention provides a method for preparing magnetic hollow polymer microspheres according to any one of the above aspects, comprising the steps of:
the method comprises the following steps: preparing monodisperse linear polystyrene microspheres; activating linear polystyrene microspheres, mixing and swelling a monofunctional group monomer, a polyfunctional group monomer and the linear polystyrene microspheres, then carrying out emulsion copolymerization reaction, and removing the linear polystyrene microspheres after the reaction is finished to obtain hollow polymer microspheres;
step two: preparing magnetic nanoparticles; mixing the magnetic nanoparticles with the hollow polymer microspheres, and then washing off the magnetic nanoparticles on the surfaces of the hollow polymer microspheres to obtain coated microspheres with the magnetic nanoparticles in the inner cavities of the hollow polymer microspheres;
step three: when the hollow polymer microsphere has reactive groups, carrying out a crosslinking reaction on the hollow polymer microsphere and a hydrophilic polyfunctional compound; or when the hollow polymer microspheres do not have reactive groups, introducing the reactive groups on the hollow polymer microspheres, and then carrying out crosslinking reaction on the hollow polymer microspheres and the hydrophilic polyfunctional compound.
According to the technical scheme, the hollow polymer microspheres with good magnetic response, long suspension time, good dispersibility in water, no magnetic leakage and rich surface functional groups are prepared by the preparation of the hollow polymer microspheres with uniform particle size, the compounding of the hollow microspheres and the superparamagnetic nano particles, the shell treatment of the composite microspheres and the surface functional modification.
The further technical scheme is that in the step one: the monofunctional monomer is (methyl) acrylate or a derivative thereof, and the polyfunctional monomer is a multi (methyl) acrylate-based compound; or the monofunctional monomer is styrene or derivatives thereof, and the multifunctional monomer is divinylbenzene or derivatives thereof. The monofunctional monomer or the polyfunctional monomer may or may not have a reactive group other than an alkenyl group.
According to the technical scheme, the monofunctional monomer and the polyfunctional monomer, namely the cross-linking agent, can be of the types, the raw materials of the monomers are easy to obtain, and the polymerization reaction process is mature.
The further technical scheme is that in the first step, the preparation steps of the linear polystyrene microspheres are as follows: styrene monomer, azodiisobutyronitrile as initiator, polyvinyl pyrrolidone as stabilizer, ethanol and water as solvent are emulsion polymerized to prepare the monodisperse linear polystyrene microsphere.
According to the technical scheme, the linear polystyrene microspheres can be prepared in an emulsion polymerization mode to prepare the linear polystyrene microspheres with low particle size dispersity, so that the uniform particle size of the prepared hollow polymer microspheres is ensured. The particle size of the linear polystyrene microsphere can be 0.5-10 μm, and the monodisperse linear polystyrene microsphere with the required particle size can be obtained by selecting the raw material dosage, the reaction process conditions and the like.
The further technical scheme is that in the step one, the activated linear polystyrene microsphere comprises: and ultrasonically emulsifying and stirring the linear polystyrene microspheres, dibutyl phthalate and a sodium dodecyl sulfate aqueous solution to obtain the activated seed microsphere emulsion.
According to the technical scheme, the polystyrene microspheres can be activated before polymerization of the shell layer, so that the polystyrene microspheres are emulsified and dispersed, and subsequent process steps such as swelling are facilitated.
The further technical scheme is that in the step one, swelling comprises: the benzoyl peroxide initiator, the monofunctional group monomer, the polyfunctional group monomer, the dimethylbenzene and the lauryl sodium sulfate aqueous solution are ultrasonically emulsified, then mixed with the activated seed microsphere emulsion, and are swelled under stirring.
According to the technical scheme, the monofunctional monomer, the cross-linking agent and the pore-forming agent xylene can be added for swelling before the polymerization of the shell layer, the monofunctional monomer and the cross-linking agent are polymerized on the surface of the swollen monodisperse polystyrene microsphere, the uniform particle size can be kept, and the shell layer is separated from the core layer by polymerization after swelling, so that the core layer substances can be removed conveniently.
The further technical scheme is that in the step one, the emulsion copolymerization reaction comprises the following steps: and adding a polyvinylpyrrolidone aqueous solution into the emulsion obtained after swelling for copolymerization reaction.
According to the technical scheme, the shell layer can be prepared through emulsion polymerization, the dispersing agent is further added to improve the stability of emulsion droplets, and the preparation process is simple.
The further technical scheme is that in the step one, the removing of the linear polystyrene microspheres comprises the following steps: extracting the microspheres obtained by emulsion copolymerization with dichloroethane.
According to the technical scheme, the invention further adopts an extraction method to remove the linear polystyrene of the core layer material, thereby removing the linear polystyrene of the core layer and obtaining the hollow polymer microsphere.
The further technical scheme is that in the second step, the preparation steps of the magnetic nanoparticles are as follows: mixing ferric trichloride hexahydrate, ferrous sulfate heptahydrate, deionized water and concentrated ammonia water for reaction, and then adding alkoxy silane with hydrophobic groups for continuous reaction to obtain the hydrophobic superparamagnetic nano-particles.
According to the technical scheme, the preparation method of the magnetic nanoparticles can be characterized in that the ferromagnetic particles are prepared firstly, and then the hydrophobic group alkoxy silane is used for coating the ferromagnetic particles, so that the ferromagnetic particles can be protected, and the agglomeration phenomenon of the ferromagnetic particles is reduced.
The further technical scheme is that in the second step, the mixing of the magnetic nanoparticles and the hollow polymer microspheres comprises: ultrasonically mixing the hollow polymer microspheres, the magnetic nanoparticles and tetrahydrofuran, standing, and removing the tetrahydrofuran in the reaction solution after the standing is finished.
According to the technical scheme, the good solvent of the hydrophobic part of the nano magnetic particles can be used for carrying out mixed adsorption on the hollow polymer microspheres and the magnetic nanoparticles, so that the magnetic nanoparticles can enter the inner cavity of the hollow polymer microspheres more easily, and the magnetic nanoparticles can be attached to the inner cavity wall of the inner cavity of the hollow polymer microspheres better after tetrahydrofuran in reaction liquid is removed in modes such as evaporation and the like.
The further technical scheme is that in the second step, the washing away of the magnetic nanoparticles on the outer wall of the hollow polymer microsphere comprises: the hollow polymeric microspheres were washed multiple times with anhydrous methanol.
According to the technical scheme, the magnetic nanoparticles on the outer wall of the hollow polymer microsphere can be removed in a cleaning mode, the magnetic nanoparticles in the inner cavity of the hollow polymer microsphere are reserved, and the magnetic nanoparticles are prevented from being separated in the using process of the magnetic hollow polymer microsphere.
The further technical scheme is that in the step one, the monofunctional group monomer is (methyl) acrylate with epoxy group; in the third step, the hydrophilic polyfunctional group compound is a polyamino compound; the cross-linking reaction of the hollow polymer microsphere and the hydrophilic polyfunctional compound comprises the following steps: dispersing the hollow polymer microspheres in a sodium dodecyl sulfate aqueous solution, and adding a polyamino compound to react to obtain the amino modified magnetic hollow polymer microspheres.
According to the technical scheme, the hollow polymer microsphere can be prepared by adopting a monofunctional monomer with a reactive group, and the reactive group such as an epoxy group can directly react with a hydrophilic polyfunctional compound to carry out crosslinking, so that the hollow polymer microsphere is further sealed, and a hydrophilic modification layer is formed.
The further technical scheme is that in the step one, the monofunctional group monomer is styrene or a derivative thereof without a reactive group; in step three, the introduction of reactive groups on the hollow polymeric microspheres includes: dispersing hollow polymer microspheres in an organic solvent, adding anhydrous aluminum chloride and chloracetyl chloride for reaction, and introducing chloracyl on the hollow polymer microspheres; the hydrophilic polyfunctional compound is a polyamino compound; the cross-linking reaction of the hollow polymer microsphere and the hydrophilic polyfunctional compound comprises the following steps: dispersing the hollow polymer microspheres introduced with reactive groups in isopropanol, and adding a polyamino compound for reaction to obtain amino-modified magnetic hollow polymer microspheres.
According to the technical scheme, the invention can also adopt a monofunctional group monomer with a reactive group to prepare the hollow polymer microsphere, introduce the reactive group through chemical reaction after preparing the hollow polymer microsphere, and then react with a hydrophilic polyfunctional compound to form a hydrophilic modification layer. For example, in the case of styrene-type crosslinked hollow polymer microspheres, after chloroacetylation, chlorine may be reacted with a hydrophilic polyfunctional compound.
In order to achieve the third object of the present invention, the present invention provides the use of the magnetic hollow polymer microsphere according to any one of the above aspects or the magnetic hollow polymer microsphere prepared by the preparation method according to any one of the above aspects in detection or substance separation.
According to the technical scheme, the magnetic hollow polymer microsphere has the advantages of good magnetic response, long suspension time, good dispersibility in water, no magnetic leakage, rich surface functional groups and the like, and is suitable for application in detection or substance separation.
Drawings
FIG. 1 is a schematic diagram of a preparation process of an embodiment of the preparation method of the magnetic hollow polymer microsphere of the present invention.
FIG. 2 is an image of an aqueous dispersion of magnetic hollow polymer microspheres prepared in example 6 of the present invention under an optical microscope.
FIG. 3 is a scanning electron microscope image of an aqueous dispersion of magnetic hollow polymeric microspheres prepared in example 7 of the present invention.
FIG. 4 is an SEM photograph of the magnetic hollow polymer microspheres prepared in example 7 of the present invention.
FIG. 5 is a photograph showing an example of magnetic response of magnetic hollow polymeric microspheres in an aqueous dispersion of the magnetic hollow polymeric microspheres prepared in example 7 of the present invention.
The present invention will be described in further detail with reference to the drawings and the detailed description.
Detailed Description
Example 1
Synthesizing linear polystyrene microspheres:
a500 mL three-necked flask was charged with 7.5g of polyvinylpyrrolidone K-30, 0.4g of azobisisobutyronitrile, 136g of absolute ethanol, 10g of styrene and 30g of deionized water. And (3) assembling a stirrer, stirring at 300rpm for 30min, uniformly dispersing, introducing nitrogen to remove oxygen for 30min, heating to 70 ℃, polymerizing for 24h, centrifugally separating the product, and washing with anhydrous methanol for 5 times to obtain the linear polystyrene microspheres with the particle size of 1.2 mu m, wherein the yield is about 7 g.
Example 2
Preparation of hollow poly (glycidyl methacrylate-ethylene glycol dimethacrylate) microspheres:
2g of the 1.2 μm linear polystyrene microspheres obtained in example 1, 4g of dibutyl phthalate and 40g of an aqueous solution containing 0.25 wt.% of sodium lauryl sulfate were added to a 100mL beaker and sonicated for 30min to give an emulsion which was slowly stirred at 35 ℃ for 24h to give activated seed microspheres. After activation, 0.4g of benzoyl peroxide, 20g of glycidyl methacrylate, 12g of ethylene glycol dimethacrylate, 14g of xylene and an aqueous solution containing 0.25 wt.% of sodium dodecyl sulfate were added to a 500mL beaker and subjected to ultrasonic emulsification for 30min to obtain a white emulsion. The white emulsion is added into activated seed microspheres, and slowly stirred for 24 hours at the temperature of 35 ℃ for swelling. After swelling, 200g of an aqueous solution containing 5 wt.% of polyvinylpyrrolidone is added, nitrogen is introduced to remove oxygen for 30min, and then the temperature is raised to 80 ℃ for polymerization for 24 h. The product was dispersed in 200g of dichloroethane after centrifugal separation, and linear polystyrene was extracted for 48h with a Soxhlet extractor. The subsequent product was subjected to centrifugal separation, washed 5 times with anhydrous methanol, and vacuum-dried at room temperature for 12 hours to obtain 2.8 μm hollow P (GMA-co-EGDMA) microspheres with uniform particle size and a yield of about 20 g.
Example 3
Preparation of hollow poly (styrene-divinylbenzene) microspheres:
this example is substantially the same as example 2 except that monofunctional monomer glycidyl methacrylate is replaced by styrene of equal mass and polyfunctional monomer crosslinker ethylene glycol dimethacrylate is replaced by divinylbenzene of equal mass. About 20g of 2.8 μm hollow P (St-co-DVB) microspheres of uniform particle size were prepared.
Example 4
Synthesis of hydrophobic superparamagnetic nanoparticles:
adding 40g of ferric trichloride hexahydrate, 40g of ferrous sulfate heptahydrate, 200g of deionized water and 100g of concentrated ammonia water into a 500mL three-neck flask, heating to 70 ℃ under the protection of nitrogen, reacting for 30min, then adding 20g of gamma- (methacryloyloxy) propyl trimethoxy silane at a time, continuing to perform heat preservation reaction for 1.5h, performing magnetic separation on a final product, washing with anhydrous methanol for 5 times, and finally performing vacuum drying at room temperature for 12h to obtain about 17g of hydrophobic superparamagnetic nanoparticles.
Example 5
Compounding hollow polymer microspheres and magnetic nanoparticles:
10g of the hollow polymer microspheres prepared in example 2 or example 3, 2g of the hydrophobic superparamagnetic nanoparticles prepared in example 5 and 200g of tetrahydrofuran were added into a 1L eggplant-shaped bottle, and the mixture was ultrasonically mixed for 30min and then allowed to stand for 24 h. And after timing is finished, removing the solvent in the reaction solution by rotary evaporation to obtain dark brown magnetic microsphere mixture solid powder. And dispersing and cleaning the product in absolute methanol for 4 times, carrying out magnetic attraction separation, and finally carrying out vacuum drying at room temperature for 12 hours to obtain about 10g of coated magnetic microspheres with surface magnetic nanoparticles washed away.
Example 6
Surface modification of P (GMA-co-EGDMA) magnetic microspheres:
about 10g of the composite magnetic hollow polymer microspheres obtained by the procedure of example 5 from P (GMA-co-EGDMA) prepared in example 2 were dispersed in 500mL of an aqueous solution containing 0.25 wt.% sodium dodecyl sulfate, uniformly mixed by high-speed stirring for 30min, added with 10g of polyethyleneimine (molecular weight: about 2000), transferred to a 1L three-necked flask, and heated to 80 ℃ with rapid stirring for 12h reaction. And performing magnetic attraction separation on the product, washing for 5 times, and finally dispersing in a small amount of deionized water to obtain the 2.8-micron amino-modified magnetic hollow polymer microspheres with uniform particle size.
Example 7
Surface modification of P (St-co-DVB) magnetic microspheres:
about 10g of the composite magnetic hollow polymer microspheres obtained from P (St-co-DVB) obtained in example 3 by the procedure of example 5 was dispersed in 400g of carbon tetrachloride, and 20g of anhydrous aluminum chloride and 15g of chloroacetyl chloride were added and reacted at 75 ℃ for 24 hours under reflux. The product was magnetically separated and washed 5 times with anhydrous methanol. After separating out product microspheres, dispersing the product microspheres in 500mL of isopropanol, adding 20g of ethylenediamine, uniformly dispersing, and then heating to 70 ℃ for reaction for 12 hours. And magnetically separating the product, washing with anhydrous methanol for 5 times, and finally performing vacuum drying at room temperature for 12 hours to obtain the amino-modified magnetic hollow polymer microspheres with uniform particle sizes of 2.8 mu m.
As shown in fig. 1, in the preparation method of the above embodiment, the monodisperse uniform-particle-size linear polystyrene microsphere 1 is prepared as a template, so as to ensure uniform particle size of the prepared magnetic hollow polymer microsphere. Then, the linear polystyrene microspheres 1 are activated, monomers, a cross-linking agent and a pore-forming agent xylene are added, the linear polystyrene microspheres slowly swell, then polymerization is carried out, a monomer and cross-linking agent copolymer shell layer is formed, the monomers, the cross-linking agent and the pore-forming agent are uniform and single-phase before polymerization, the pore-forming agent and a polymer are subjected to phase separation after polymerization to form a core-shell structure, meanwhile, the linear polystyrene microspheres and the linear polystyrene are positioned in a core layer after the xylene swells, and the core layer is easily removed through cleaning and extraction, so that the hollow polymer microspheres 2 are obtained. And then mixing and adsorbing the hollow polymer microspheres 2 and the hydrophobic nano magnetic particles 3 in a solvent, washing to remove the nano magnetic particles 3 on the outer walls of the hollow polymer microspheres 2, and reserving the nano magnetic particles 3 in the inner cavities of the hollow polymer microspheres 2 to obtain the magnetic hollow polymer microspheres. The outer wall of the magnetic hollow polymer microsphere is provided with reactive groups such as epoxy groups, or reactive groups such as chloroacetyl groups which are covalently connected with the polymer are introduced through reaction, and the reactive groups are reacted with hydrophilic polyfunctional compounds to form a hydrophilic modification layer 4, wherein the hydrophilic modification layer 4 not only has the functions of introducing the hydrophilic groups into the outer wall of the microsphere and improving the dispersibility of the magnetic hollow polymer microsphere in water solution, but also has the function of secondary crosslinking of a shell layer to seal holes on the microsphere wall, so that the internal environment of the microsphere is stable, and no magnetic nano-particles leak.
As shown in fig. 2 to 3, the above embodiment can produce micron-sized magnetic hollow polymer microspheres, and the magnetic hollow polymer microspheres have uniform particle size. By adjusting the raw material dosage, the technological condition parameters and the like in the preparation method of the linear polystyrene microspheres 1, the monodisperse linear polystyrene microspheres 1 with different particle sizes can be obtained, and further the magnetic hollow polymer microspheres with different particle sizes can be obtained. As shown in fig. 4, the magnetic hollow polymer microsphere prepared in the above example has a hollow internal structure and a copolymer shell layer with a certain thickness of the monomer and the crosslinking agent.
As shown in FIG. 5, the magnetic hollow polymer microspheres prepared in the above examples have good suspension property and magnetic response property. The magnetic hollow polymer microspheres can be dispersed in water to form stable magnetic hollow polymer microsphere water dispersion, and the magnetic hollow polymer microspheres are not easy to settle in the water phase when placed for a long time, so that signals cannot be lost due to settlement in detection and use. The magnetic hollow microspheres also have the advantage of high magnetic reaction speed, and the enrichment can be completed within 20s after the magnetic field is applied. Therefore, the magnetic hollow polymer microsphere is suitable for the detection field, such as the detection of biological substances, and is particularly suitable for a chemiluminescence immunoassay scene.
Finally, it should be emphasized that the above-described embodiments are merely preferred examples of the invention, which is not intended to limit the invention. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (9)
1. A magnetic hollow polymer microsphere is characterized by comprising a hollow polymer microsphere, magnetic nanoparticles and a hydrophilic modification layer, wherein the magnetic nanoparticles enter an inner cavity of the hollow polymer microsphere to obtain a coated microsphere with the magnetic nanoparticles positioned in the inner cavity of the hollow polymer microsphere, and the hydrophilic modification layer covers the outer wall of the hollow polymer microsphere;
the core portion of the hollow polymeric microspheres is removed to form the internal cavity;
the outer wall of the hollow polymer microsphere is provided with an epoxy group or chloroacetyl covalently connected with a polymer is introduced through reaction, the epoxy group or the chloroacetyl reacts with a polyamino compound to form the hydrophilic modification layer crosslinked with the outer wall of the hollow polymer microsphere, and the hollow polymer microsphere and the hydrophilic modification layer prevent the magnetic nanoparticles from leaking from the inner cavity.
2. The magnetic hollow polymeric microsphere of claim 1, wherein:
the magnetic hollow polymer microspheres have uniform particle size;
the magnetic nanoparticles are hydrophobic superparamagnetic nanoparticles;
the hollow polymer microsphere is formed by copolymerizing a monofunctional group monomer and a polyfunctional group monomer.
3. The method for preparing magnetic hollow polymer microspheres according to claim 1 or 2, characterized by comprising the steps of:
the method comprises the following steps: preparing monodisperse linear polystyrene microspheres; activating the linear polystyrene microspheres, mixing and swelling a monofunctional group monomer, a polyfunctional group monomer and the linear polystyrene microspheres, and then carrying out emulsion copolymerization reaction, and removing the linear polystyrene microspheres after the reaction is finished to obtain hollow polymer microspheres;
step two: preparing magnetic nanoparticles; mixing the magnetic nanoparticles with the hollow polymer microspheres, and then washing away the magnetic nanoparticles on the outer walls of the hollow polymer microspheres to obtain coated microspheres with the magnetic nanoparticles in the inner cavities of the hollow polymer microspheres;
step three: when the hollow polymer microspheres have epoxy groups, carrying out a crosslinking reaction on the hollow polymer microspheres and a polyamino compound; or when the hollow polymer microspheres do not have reactive groups, introducing chloroacetyl groups on the hollow polymer microspheres, and then carrying out a crosslinking reaction on the hollow polymer microspheres and a polyamino compound.
4. The method according to claim 3, wherein in the first step:
the monofunctional monomer is (methyl) acrylate or a derivative thereof, and the multifunctional monomer is a multi (methyl) acrylate-based compound; or the monofunctional monomer is styrene or a derivative thereof, and the multifunctional monomer is divinylbenzene or a derivative thereof;
the monofunctional monomer or the polyfunctional monomer may or may not have a reactive group other than an alkenyl group.
5. The method according to claim 3, wherein in the first step:
the preparation steps of the linear polystyrene microsphere are as follows: styrene monomer, azodiisobutyronitrile as initiator, polyvinylpyrrolidone as stabilizer, ethanol and water as solvent are emulsion polymerized to prepare the monodisperse linear polystyrene microsphere;
activating the linear polystyrene microspheres comprises: ultrasonically emulsifying and stirring the linear polystyrene microspheres, dibutyl phthalate and a sodium dodecyl sulfate aqueous solution to obtain an activated seed microsphere emulsion;
the swelling comprises: ultrasonically emulsifying a benzoyl peroxide initiator, the monofunctional group monomer, the polyfunctional group monomer, xylene and a sodium dodecyl sulfate aqueous solution, mixing with an activated seed microsphere emulsion, and swelling under stirring;
the emulsion copolymerization reaction comprises the following steps: adding a polyvinylpyrrolidone aqueous solution into the emulsion obtained after swelling for copolymerization reaction;
removing the linear polystyrene microspheres comprises: extracting the microspheres obtained by emulsion copolymerization with dichloroethane.
6. The production method according to any one of claims 3 to 5, characterized in that in the step two:
the preparation steps of the magnetic nanoparticles are as follows: mixing ferric trichloride hexahydrate, ferrous sulfate heptahydrate, deionized water and concentrated ammonia water for reaction, and then adding alkoxysilane with a hydrophobic group for continuous reaction to obtain hydrophobic superparamagnetic nanoparticles;
mixing the magnetic nanoparticles with the hollow polymeric microspheres comprises: ultrasonically mixing the hollow polymer microspheres, the magnetic nanoparticles and tetrahydrofuran, standing, and removing the tetrahydrofuran in a reaction solution after the mixture is finished;
washing away the magnetic nanoparticles on the surface of the hollow polymeric microspheres comprises: the hollow polymeric microspheres were washed multiple times with anhydrous methanol.
7. The production method according to any one of claims 3 to 5, characterized in that:
in the first step, the monofunctional monomer is (meth) acrylate with an epoxy group;
in the third step, the cross-linking reaction of the hollow polymer microspheres and the polyamino compound comprises: and dispersing the hollow polymer microspheres in a sodium dodecyl sulfate aqueous solution, and adding a polyamino compound to react to obtain the amino-modified magnetic hollow polymer microspheres.
8. The production method according to any one of claims 3 to 5, characterized in that in the step three:
in the first step, the monofunctional monomer is styrene or a derivative thereof without a reactive group;
in the third step, introducing a chloroacetyl group onto the hollow polymeric microspheres comprises: dispersing the hollow polymer microspheres in an organic solvent, adding anhydrous aluminum chloride and chloroacetyl chloride for reaction, and introducing chloroacetyl onto the hollow polymer microspheres;
the cross-linking reaction of the hollow polymer microspheres and the polyamino compound comprises the following steps: dispersing the hollow polymer microspheres introduced with the chloroacetyl in isopropanol, and adding a polyamino compound for reaction to obtain the amino-modified magnetic hollow polymer microspheres.
9. Use of magnetic hollow polymeric microspheres in detection or substance separation, characterized in that the magnetic hollow polymeric microspheres are magnetic hollow polymeric microspheres according to claim 1 or 2, or magnetic hollow polymeric microspheres prepared by the preparation method according to any one of claims 3 to 8.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH10195152A (en) * | 1996-12-27 | 1998-07-28 | Kazunori Kataoka | Core-shell microsphere and its production |
| CN1468898A (en) * | 2003-07-02 | 2004-01-21 | 北京倍爱康生物技术股份有限公司 | Prepn of super-paramagnetic polymer microsphere |
| CN102008925A (en) * | 2010-12-17 | 2011-04-13 | 天津大学 | Method for preparing inorganic/organic composite microspheres |
| CN109627370A (en) * | 2018-12-13 | 2019-04-16 | 中国科学院长春应用化学研究所 | The preparation method of a kind of nitrogen-containing functional group polyalcohol stephanoporate microballoons |
| CN111205581A (en) * | 2020-02-28 | 2020-05-29 | 雅邦绿色过程与新材料研究院南京有限公司 | Novel surface carboxylation method of magnetic microspheres |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH10195152A (en) * | 1996-12-27 | 1998-07-28 | Kazunori Kataoka | Core-shell microsphere and its production |
| CN1468898A (en) * | 2003-07-02 | 2004-01-21 | 北京倍爱康生物技术股份有限公司 | Prepn of super-paramagnetic polymer microsphere |
| CN102008925A (en) * | 2010-12-17 | 2011-04-13 | 天津大学 | Method for preparing inorganic/organic composite microspheres |
| CN109627370A (en) * | 2018-12-13 | 2019-04-16 | 中国科学院长春应用化学研究所 | The preparation method of a kind of nitrogen-containing functional group polyalcohol stephanoporate microballoons |
| CN111205581A (en) * | 2020-02-28 | 2020-05-29 | 雅邦绿色过程与新材料研究院南京有限公司 | Novel surface carboxylation method of magnetic microspheres |
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