CN111393574A - Magnetic microsphere with functional groups on surface and preparation method and application thereof - Google Patents
Magnetic microsphere with functional groups on surface and preparation method and application thereof Download PDFInfo
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Abstract
The invention relates to a magnetic microsphere with functional groups on the surface, a preparation method and application thereof, wherein the method comprises the steps of carrying out surface modification treatment on a polymer microsphere to obtain a modified microsphere, and preparing magnetic nano particles with functional groups on the surfaces, dispersing and mixing the magnetic nano particles and the magnetic nano particles in a solvent, adjusting the pH value of the solution to ensure that the surfaces of the modified microspheres and the magnetic nano particles are charged oppositely, adsorbing the magnetic nano particles on the surfaces of the modified microspheres to form composite microspheres, and then forming a polymer layer with the functional groups on the surfaces of the composite microspheres by using functional monomers on the surfaces of the composite microspheres in the presence of a surfactant by taking the composite microspheres as cores to obtain the magnetic microspheres.
Description
Technical Field
The invention belongs to the field of material chemical industry, and relates to a magnetic microsphere with functional groups on the surface, a preparation method and application thereof.
Background
The magnetic microsphere is a novel nano material, is the most widely cited core raw material in the field of in vitro diagnosis, and is a spherical magnetic material with the grain diameter of about several hundred nanometers to several micrometers, which is formed by combining an inorganic magnetic material and an organic polymer, on one hand, functional groups can be introduced into the surface of the magnetic microsphere, and the magnetic microsphere is coupled with antibodies, antigens or other biomolecules, and the quantitative analysis of a target object is realized by an immunoreaction and a high-sensitivity detection means; on the other hand, because the magnetic microspheres have convenient magnetic field control characteristics, when the magnetic microspheres are used as carriers to replace the traditional multi-well plate or other solid phase carriers, and are combined with various immunoassay signal marking means (such as immunoassay labeling methods such as enzyme-linked immunosorbent assay, chemiluminescence assay, fluorescence assay or immunoassay PCR assay) to realize rapid, automatic and multi-flux assay. Therefore, for the magnetic microspheres of the carrier or the signal marking material applied to in vitro separation and disease diagnosis, the magnetic microspheres have the characteristics of good spherical homogeneous structure, higher specific saturation magnetization, abundant functional groups on the surface, good biocompatibility, dispersion stability, lower non-specific adsorption property and the like, so that the sensitivity and consistency of detection can be ensured.
At present, the preparation methods of magnetic microspheres mainly include emulsion polymerization, dispersion polymerization, suspension polymerization, seed polymerization, and the like, and most of the magnetic microspheres prepared by other methods except seed polymerization have the defects of uneven particle size distribution, low magnetic content, few surface functional groups, and the like. The seed polymerization method has the advantages of uniform particle size distribution, uniform magnetic content, rich surface functional groups and the like, and is a main production method adopted by production enterprises with larger market share at present. Most of the magnetic microspheres prepared by the seed polymerization method are porous structures, iron oxide or ferroferric oxide is used as a magnetic core and deposited in a pore channel, and the outer layer is coated with a functional polymer. The magnetic microsphere prepared by the method has a pore channel structure, so that the deposited magnetic microsphere has the possibility of exudation, and in addition, due to the existence of the pore channel, the surface hydrophilicity and hydrophobicity are inconsistent, so that nonspecific adsorption is caused, and the problems of large in vitro diagnosis error, high background value, low sensitivity and the like are caused.
CN101085874A discloses a hydrophilic polymer magnetic microsphere, a preparation method and application thereof. Dispersing superparamagnetism Fe by using polar organic solvent such as formamide3O4Magnetic powder is used for preparing magnetic fluid, the magnetic fluid and hydrophilic monomers are mixed to form a polymerization phase, the polymerization phase is dispersed in hydrophobic organic solvent containing a stabilizer under stirring to form a suspension phase, and polymerization is initiated to prepare hydrophilic polymer magnetic microspheres.
CN103012828A discloses a preparation method of polymer iron oxide microspheres, which comprises the following steps: (1) preparing porous polymer microspheres in advance; (2) synthesizing iron oxide nano particles in the polymer microspheres obtained in the step (1) by adopting a coprecipitation method to obtain polymer/iron oxide composite microspheres; (3) coating silicon dioxide on the surface of the polymer ferric oxide microsphere obtained in the step (2) to prepare a magnetic microsphere; the polymer iron oxide microspheres obtained by the scheme have the problem of inconsistent surface hydrophilicity and hydrophobicity.
Therefore, it is imperative to develop a novel method for preparing magnetic microspheres, which has uniform particle size distribution, high magnetic content and abundant surface functional groups.
Disclosure of Invention
The invention aims to provide a magnetic microsphere with functional groups on the surface and a preparation method and application thereof, the method comprises the steps of carrying out surface modification treatment on a polymer microsphere to obtain a modified microsphere, preparing magnetic nanoparticles with functional groups on the surface, dispersing and mixing the modified microsphere and the magnetic nanoparticles in a solvent, adjusting the pH value of the solution to ensure that the surfaces of the modified microsphere and the magnetic nanoparticles are oppositely charged, adsorbing the magnetic nanoparticles on the surface of the modified microsphere to form a composite microsphere, forming a polymer layer with the functional groups on the surface of the composite microsphere by taking the composite microsphere as a core and a functional monomer in the presence of a surfactant to obtain the magnetic microsphere, the method effectively solves the problems of magnetic leakage and uneven surface hydrophilic and hydrophobic property in the traditional magnetic microsphere preparation process, the obtained magnetic microsphere has uniform particle size, high magnetic content and good consistency, the surface functional groups are abundant.
In order to achieve the purpose, the invention adopts the following technical scheme:
in a first aspect, the present invention provides a method for preparing magnetic microspheres with functional groups on the surface, comprising the following steps:
(1) carrying out surface modification treatment on the polymer microspheres to obtain modified microspheres with charges on the surfaces;
(2) preparing magnetic nanoparticles with functional groups on the surfaces;
(3) dispersing and mixing the modified microspheres obtained in the step (1) and the magnetic nanoparticles obtained in the step (2) in a solvent, and adjusting the pH value to enable the magnetic nanoparticles to be adsorbed on the surfaces of the modified microspheres to obtain composite microspheres;
(4) and (4) dispersing the composite microspheres obtained in the step (3) in a solvent, adding a surfactant and a functional monomer, and carrying out polymerization reaction to obtain the magnetic microspheres with functional groups on the surfaces.
The preparation method of the magnetic microsphere comprises the steps of carrying out surface modification treatment on a polymer microsphere to obtain a modified microsphere, enabling the surface of the modified microsphere to be charged, preparing magnetic nanoparticles with functional groups on the surface, dispersing and mixing the modified microsphere and the polymer microsphere in a solvent, adjusting pH to enable the magnetic nanoparticles and the modified microsphere to have opposite charges, and enabling the magnetic nanoparticles to be adsorbed on the surface of the modified microsphere to obtain a composite microsphere; then under the action of a surfactant, the functional monomer is subjected to polymerization reaction on the surface of the composite microsphere to form a magnetic microsphere with functional groups on the surface; the surfactant is added, and the hydrophilicity and hydrophobicity of the surface of the microsphere can be changed.
Preferably, the polymer microspheres in step (1) include any one of polystyrene microspheres, polymethyl methacrylate microspheres, polyglycidyl methacrylate microspheres, polyacrylic acid microspheres, agarose microspheres, dextran microspheres, or chitosan microspheres, or a combination of at least two of them, and the combination exemplarily includes a combination of polystyrene microspheres and polymethyl methacrylate microspheres, or a combination of polyglycidyl methacrylate microspheres and polyacrylic acid microspheres, or the like.
Preferably, the preparation method of the polymeric microspheres in step (1) comprises any one of dispersion polymerization, emulsion polymerization, soap-free emulsion polymerization or miniemulsion polymerization.
Preferably, the method of the surface modification treatment in step (1) is a chemical method.
Preferably, the surface modification treatment method in step (1) includes nitration reaction or reduction reaction of nitro group.
The reduction of the nitro group here means that the nitration is carried out first and then the reduction is carried out.
Preferably, the surface of the modified microsphere obtained after the surface of the polymer microsphere is subjected to nitration reaction has positive charges.
Preferably, the surface of the modified microsphere has positive charges after the reduction reaction of the nitro group on the surface of the polymer microsphere.
The modified microsphere surface has positive charges, which means the charge species on the surface of the modified microsphere under neutral conditions.
Preferably, the method for performing surface modification treatment on the polymer microspheres by using nitration reaction comprises performing surface treatment on the polymer microspheres by using a mixed solution of sulfuric acid and nitric acid to obtain modified microspheres with charges on the surfaces.
Preferably, the mixed solution of sulfuric acid and nitric acid is obtained by mixing sulfuric acid and nitric acid.
Preferably, the nitric acid has a concentration of 60-70%, such as 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, or the like, preferably 65-68%.
Preferably, the concentration of the sulfuric acid is 94-96%, such as 94.5%, 95%, or 95.5%, etc.
The concentrations of nitric acid and sulfuric acid mentioned above are both referred to as mass concentrations.
Preferably, the mixing ratio (volume ratio) of the sulfuric acid and the nitric acid is 10:1 to 1:10, for example, 9:1, 8:1, 7:1, 6:1, 5:1, 4:1, 3:1, 2:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, or the like.
Preferably, the method for surface treatment of the polymer microspheres by using the mixed solution of sulfuric acid and nitric acid comprises cooling the mixed solution of sulfuric acid and nitric acid to 8-12 ℃, for example, 9 ℃, 10 ℃ or 11 ℃, and then adding the polymer microspheres, mixing, and cooling to obtain the modified microspheres with hydrophilic surfaces.
The mixed solution of sulfuric acid and nitric acid is obtained by mixing sulfuric acid and nitric acid, and heat is generated in the mixing process, so that the temperature of the mixed acid needs to be reduced to the range before the surface modification treatment, and the subsequent surface modification process is facilitated.
Preferably, the time for mixing after adding the polymeric microspheres is after the temperature is raised to 45-55 deg.C, such as 46 deg.C, 47 deg.C, 48 deg.C, 49 deg.C, 50 deg.C, 51 deg.C, 52 deg.C, 53 deg.C or 54 deg.C, etc., and stirring is continued for 1-3h, such as 1.5h, 2h or 2.5h, etc.
Preferably, the stirring rate is 150-250r/min, such as 160r/min, 170r/min, 180r/min, 190r/min, 200r/min, 210r/min, 220r/min, 230r/min or 240r/min, etc.
Preferably, the method of cooling after the polymer microspheres are added and mixed is to add ice water.
Preferably, after the temperature is reduced, solid-liquid separation and washing are further carried out, so that the modified microspheres are obtained.
Preferably, the magnetic nanoparticles in step (2) have a particle size of 5-200nm, such as 10nm, 30nm, 50nm, 80nm, 100nm, 120nm, 150nm, 180nm, or the like.
Preferably, the material of the magnetic nanoparticles includes any one of ferroferric oxide, ferric oxide or a ferro-manganese compound or a combination of at least two of the ferroferric oxide, the ferric oxide or the ferro-manganese compound, and the combination exemplarily includes a combination of the ferroferric oxide and the ferric oxide, a combination of the ferro-manganese compound and the ferroferric oxide, a combination of the ferric oxide and the ferro-manganese compound, and the like, and is preferably ferroferric oxide and/or ferric oxide.
Preferably, the functional group on the surface of the magnetic nanoparticle in step (2) includes any one of carboxyl, amino, hydroxyl, alkyl or thiol, or a combination of at least two of them, and the combination illustratively includes a combination of carboxyl and amino, a combination of hydroxyl and alkyl, or a combination of thiol and carboxyl, and the like.
The surface of the magnetic nano-particle comprises the group, so that the surface charge property of the magnetic nano-particle can be changed, the charge density is increased, the pH is adjusted, the modified microsphere and the magnetic nano-particle generate electrostatic interaction, the magnetizing process is completed, and the magnetic content and consistency of the prepared magnetic microsphere are improved.
Preferably, the preparation method of the magnetic nanoparticles in step (2) includes a hydrothermal synthesis method or a coprecipitation method.
Preferably, the preparation method of the magnetic nanoparticles in step (2) includes adding ammonia water into a solution containing ferric salt and ferrous salt, reacting, and then adding a surface functional group compound to obtain the magnetic nanoparticles.
Preferably, the molar ratio of the ferric salt to the ferrous salt in the solution containing the ferric salt and the ferrous salt is 10:1 to 1:10, such as 9:1, 8:1, 7:1, 6:1, 5:1, 4:1, 3:1, 2:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8 or 1: 9.
Preferably, the ammonia is added in an amount such that the pH of the solution is ≧ 12, e.g., 12.1, 12.4, 12.8, or 13, or the like.
Preferably, the ratio of the surface functional group compound to the molar amount of elemental iron in the solution containing the ferric and ferrous salts is < 1, such as 0.8, 0.85, 0.9 or 0.95, etc.
Preferably, the surface functional group compound comprises any one of sodium citrate, polyethylene glycol or oleic acid or a combination of at least two thereof, preferably sodium citrate.
Preferably, the surface functional group compound is sodium citrate, and the surface of the magnetic nanoparticle is negatively charged.
The charge species referred to herein refers to charge species under neutral conditions.
Preferably, the preparation method of the magnetic nanoparticles comprises the following steps:
(a) adding a trivalent ferric salt into water, introducing inert gas, and adding a divalent ferric salt to obtain a solution containing the trivalent ferric salt and the divalent ferric salt;
(b) heating the solution in the step (a), stirring, adding ammonia water, then adding a surface functional group compound, and continuously stirring to obtain the magnetic nanoparticles.
Preferably, the temperature of heating in step (b) is 85-95 deg.C, such as 86 deg.C, 87 deg.C, 88 deg.C, 89 deg.C, 90 deg.C, 91 deg.C, 92 deg.C, 93 deg.C or 94 deg.C.
Preferably, the stirring rate in step (b) is 250-350r/min, such as 260r/min, 270r/min, 280r/min, 290r/min, 300r/min, 310r/min, 320r/min, 330r/min or 340r/min, etc.
Preferably, the stirring in step (b) is continued for a period of 1-3h, e.g. 1.5h, 2h or 2.5h, etc.
Preferably, the stirring in step (b) is further followed by cooling, solid-liquid separation and washing.
Preferably, the method for solid-liquid separation is magnetic adsorption separation.
Preferably, the detergent for washing is water.
Preferably, the amount of the magnetic nanoparticles added in step (3) is in excess. The excessive amount refers to the adding amount of the magnetic nanoparticles is larger than the adsorption amount of the modified microsphere surface to the magnetic nanoparticles.
Preferably, the solvent in step (3) is water.
Preferably, the pH adjustment in step (3) is in the range of 2 to 9, such as 3, 4, 5, 6, 7 or 8, etc., preferably 2 to 4.
Preferably, the step (3) further comprises shaking adsorption after adjusting the pH.
Preferably, the time of the oscillating adsorption is 1-3h, such as 1.5h, 2h or 2.5 h.
Preferably, the shaking adsorption is followed by solid-liquid separation and water washing.
Preferably, the surfactant of step (4) is an ionic surfactant.
Preferably, the surfactant in step (4) includes any one of sodium oleate, CTAB, SDS or sodium dodecyl benzene sulfonate or a combination of at least two thereof, and the combination exemplarily includes a combination of sodium oleate and CTAB or a combination of SDS and sodium dodecyl benzene sulfonate, and the like.
Preferably, the functional monomer in step (4) is a monomer having a functional group and/or a double bond.
Preferably, the functional monomer in step (4) includes any one of acrylic acid, methacrylic acid, glycidyl methacrylate, methyl acrylate or ethyl acrylate, or a combination of at least two thereof, and the combination illustratively includes a combination of methacrylic acid and glycidyl methacrylate, or a combination of methyl acrylate and ethyl acrylate, or the like.
Preferably, the surfactant is added in step (4) in the form of a surfactant solution.
Preferably, the solvent of the surfactant solution is water.
Preferably, the pH of the surfactant solution is 5.5-6.5, such as 5.6, 5.7, 5.8, 5.9, 6, 6.1, 6.2, 6.3, or 6.4, and the like.
The pH value of the surfactant solution is adjusted to be within the range before the surfactant solution is added, so that the dissociation of the magnetic nanoparticles on the surface of the modified microspheres caused by the addition of the surfactant can be avoided, and the obtained magnetic microspheres are ensured to have high magnetic content.
Preferably, step (4) further comprises adding an initiator before adding the functional monomer.
Preferably, the initiator comprises any one of potassium persulfate, AIBN, or BPO, or a combination of at least two of potassium persulfate and AIBN, a combination of BPO and potassium persulfate, a combination of AIBN and BPO, or the like, as examples.
Preferably, the mass ratio of the functional monomer added in the step (4) to the composite microspheres is 1 (0.5-2), such as 1:0.6, 1:1 or 1: 1.5.
As a preferred technical scheme of the invention, the preparation method of the magnetic microsphere comprises the following steps:
preparing polymer microspheres;
(II) carrying out nitration reaction or reduction reaction of nitro on the surface of the polymer microsphere prepared in the step (I);
(III) preparing magnetic nanoparticles with functional groups on the surface, which comprises adding trivalent ferric salt into water, introducing inert gas, and adding divalent ferric salt to obtain a solution containing trivalent ferric salt and divalent ferric salt; then heating the solution to 85-95 ℃, stirring at 250-350r/min, adding ammonia water, then adding a surface functional group compound, and continuously stirring for 1-3h to obtain the magnetic nanoparticles;
(IV) ultrasonically dispersing the modified microspheres in the step (II) in water, adding the magnetic nanoparticles obtained in the step (III), adjusting the pH value to 2-9, and oscillating for adsorption to obtain composite microspheres;
(V) dispersing the composite microspheres in the step (IV) in water, adding an initiator and a surfactant solution, heating to 55-65 ℃, adding a functional monomer, continuously stirring for 10-14h, heating to 70-80 ℃, continuously stirring for 10-14h, performing solid-liquid separation, and washing with water to obtain the magnetic microspheres.
In a second aspect, the invention provides a magnetic microsphere with functional groups on the surface, which is prepared by the method of the first aspect, and the magnetic microsphere is a three-layer core-shell structure and comprises a polymer microsphere located in a core, a magnetic nanoparticle layer located in an intermediate layer, and a polymer layer with functional groups located in a shell.
Preferably, the diameter of the polymeric microspheres is 0.1-5 μm, such as 0.5 μm, 1 μm, 2 μm, 3 μm, or 4 μm.
In a third aspect, the present invention provides a use of the magnetic microsphere having functional groups on the surface thereof according to the second aspect, for any one of immunodiagnosis, protein separation or cell screening.
Compared with the prior art, the invention has the following beneficial effects:
(1) the preparation method of the magnetic microsphere comprises the steps of carrying out surface modification on a polymer microsphere, preparing magnetic nanoparticles with functional groups on the surface, mixing the polymer microsphere and the magnetic nanoparticles, adjusting the pH value to ensure that the surfaces of the polymer microsphere and the magnetic nanoparticles are oppositely charged, adsorbing the magnetic nanoparticles on the surface of the polymer microsphere to obtain a composite microsphere, and forming a polymer layer with the functional groups on the surface of the composite microsphere by using the composite microsphere as a core through polymerization of functional monomers in the presence of a surfactant, namely the magnetic microsphere is prepared;
(2) the method solves the problems of magnetic flux leakage and uneven surface hydrophilicity and hydrophobicity in the traditional magnetic microsphere preparation process.
Drawings
FIG. 1 shows the composite microsphere after the magnetic nanoparticles and the modified microsphere have reacted in example 1 of the present invention.
Detailed Description
The technical solution of the present invention is further explained by the following embodiments. It should be understood by those skilled in the art that the examples are only for the understanding of the present invention and should not be construed as the specific limitations of the present invention.
Example 1
The preparation method of the magnetic microsphere comprises the following steps:
the method comprises the following steps:
(a) adding 500m of L deionized water and 50m of L styrene into a 1L three-necked bottle, introducing nitrogen at room temperature, and stirring for 10 minutes at the rotating speed of 200 r/min;
(b) adding 1.0g of potassium persulfate into 50ml of deionized water, and dissolving by ultrasonic waves;
(c) pouring the potassium persulfate solution in the step (b) into the solution in the step (a), heating to 80 ℃, stirring for 24 hours at the rotating speed of 200r/min, and obtaining polystyrene microspheres;
the grain diameter of the prepared polystyrene microsphere is about 700 nanometers;
(II) carrying out nitration reaction on the surface of the polymer microsphere prepared in the step (I), and specifically comprising the following steps:
(a') mixing 900g of 95% concentrated sulfuric acid with 300g of 65% concentrated nitric acid to prepare a solution A, and cooling to 10 ℃;
(B ') adding 30g of the prepared polystyrene microspheres into the solution A in the step (a'), continuously stirring, and stirring for 2 hours at 200r/min when the temperature is raised to 50 ℃ to obtain a solution B;
(c ') adding ice water into the solution B in the step (B'), reducing the temperature to be below 10 ℃, then carrying out centrifugal separation on the nitrated polystyrene microspheres, and repeatedly washing the microspheres with deionized water to obtain hydrophilic modified microspheres with the surfaces subjected to nitration reaction;
(III) the preparation of the magnetic nano-particles with functional groups on the surfaces specifically comprises the following steps:
adding 30.6g of ferric chloride hexahydrate into 475m L deionized water, introducing nitrogen, stirring for dissolving, adding 11.5g of ferrous chloride tetrahydrate, heating to 90 ℃, adjusting the stirring speed to 300r/min, quickly adding 36m L ammonia water, adding 102m L sodium citrate solution (32.5g of solid sodium citrate monohydrate) after 5 minutes, stirring for 2 hours at 90 ℃, cooling to room temperature, enabling a magnet to be adsorbed, adding deionized water, and repeatedly washing to obtain magnetic nanoparticles with a large amount of negative charges on the surface;
(IV) the modified microspheres are magnetized, a method for mixing the modified microspheres and the magnetic nanoparticles is adopted, and the method specifically comprises the following steps:
adding 11.2g of modified microspheres into 112m L deionized water, performing ultrasonic dispersion, adding excessive sodium citrate modified magnetic nanoparticles, adjusting the pH to 3 with hydrochloric acid, performing vibration adsorption for 2 hours, performing centrifugal separation, removing the non-adsorbed magnetic nanoparticles on the upper layer, and repeatedly washing with deionized water to obtain modified microspheres with magnetic nanoparticles adsorbed on the surfaces;
(V) preparing the polymer layer with the functional groups on the surface, which specifically comprises the following steps:
adding 2g of modified microspheres with magnetic nanoparticles adsorbed on the surface into 2000m L deionized water for dispersion, then adding 0.03g of potassium persulfate and a surfactant solution (CTAB), wherein the concentration of the CTAB in the added solution is 0.05% (w/v), the pH value of the CTAB solution is adjusted to 6.0 in advance, then raising the temperature to 60 ℃, after stabilization, slowly adding 2g of methacrylic acid into the solution, the mass ratio of the methacrylic acid to the modified microspheres is 1:1, stirring the mixture at 60 ℃ for 12 hours, raising the temperature to 75 ℃, continuing stirring the mixture for 12 hours at the rotating speed of 200r/min, adsorbing the mixture by using a magnet, discarding supernatant, and washing the mixture by using deionized water for several times to obtain the magnetic microspheres with carboxyl groups modified on the surfaces.
In the embodiment, a scanning electron microscope image of the modified microsphere after magnetization is shown in fig. 1, and as can be seen from fig. 1, the magnetic nanoparticles are uniformly coated on the surface of the modified microsphere, so that the composite microsphere has high magnetic content and good consistency. Thus, in this embodiment, the surface of the polymer microsphere is modified by nitration reaction to obtain a modified microsphere, the surface of the modified microsphere has positive charges, and meanwhile, the surface of the magnetic nanoparticle modified by sodium citrate has a large amount of negative charges. In the embodiment, in the preparation process of the polymer layer with functional groups on the surface, a large number of magnetic nanoparticles with negative charges are adsorbed on the surface of the composite microsphere, the functional monomer methacrylic acid has a hydrophobic effect and is difficult to approach, the ionic surfactant CTAB is added in the embodiment, so that the contact between the functional monomer and the surface of the composite microsphere is promoted, the polymerization reaction is carried out, and the obtained magnetic microsphere has a large number of functional groups on the surface.
Example 2
This example differs from example 1 in that the sodium citrate solution was replaced with an equal volume of polyethylene glycol solution (the molar amount of polyethylene glycol in the polyethylene glycol solution was the same as the sodium citrate in the sodium citrate solution described above) in step (iii), and the other conditions were exactly the same as in example 1.
Example 3
This example differs from example 1 in that the equimolar amount of methacrylic acid in step (V) was replaced with ethyl acrylate, and the other conditions were exactly the same as in example 1.
Example 4
This example differs from example 1 in that the equal volume of CTAB solution was replaced by a sodium oleate solution (the molar amount of sodium oleate in the sodium oleate solution is the same as the molar amount of CTAB in the CTAB solution) and the other conditions are exactly the same compared to example 1.
Example 5
This example differs from example 1 in that the volume of CTAB solution was replaced by an equal volume of sodium dodecylbenzenesulfonate solution (the molar amount of sodium dodecylbenzenesulfonate in the sodium dodecylbenzenesulfonate solution is the same as the molar amount of CTAB in the CTAB solution), and the other conditions were exactly the same as in example 1.
Example 6
The preparation method of the magnetic microsphere comprises the following steps:
the preparation method of the polymethyl methacrylate microspheres by adopting a soap-free emulsion polymerization method comprises the following steps:
(a) adding 500m of L deionized water and 50m of L methyl methacrylate into a 1L three-necked bottle, introducing nitrogen at room temperature, and stirring for 10 minutes at the rotating speed of 200 r/min;
(b) adding 1.0g of potassium persulfate into 50ml of deionized water, and dissolving by ultrasonic waves;
(c) pouring the potassium persulfate solution in the step (b) into the solution in the step (a), heating to 85 ℃, stirring for 24 hours at the rotating speed of 200r/min, and obtaining polymethyl methacrylate microspheres;
the grain size of the prepared polymethyl methacrylate microsphere is 1 mu m;
(II) carrying out nitration reaction on the surface of the polymer microsphere prepared in the step (I), and specifically comprising the following steps:
(a') mixing 900g of 95% concentrated sulfuric acid with 300g of 65% concentrated nitric acid to prepare a solution A, and cooling to 10 ℃;
(B ') adding 30g of the prepared polymethyl methacrylate microspheres into the solution A in the step (a'), continuously stirring, and stirring for 2 hours at 200r/min when the temperature is raised to 50 ℃ to obtain a solution B;
(c ') adding ice water into the solution B in the step (B'), reducing the temperature to be below 10 ℃, then carrying out centrifugal separation on the nitrated polymethyl methacrylate microspheres, and repeatedly washing with deionized water to obtain hydrophilic modified microspheres with the surfaces subjected to nitration reaction;
(III) the preparation of the magnetic nano-particles with functional groups on the surfaces specifically comprises the following steps:
adding 30.6g of ferric chloride hexahydrate into 475m L deionized water, introducing nitrogen, stirring for dissolving, adding 11.5g of ferrous chloride tetrahydrate, heating to 85 ℃, adjusting the stirring speed to 300r/min, quickly adding 36m L ammonia water, adding 102m L sodium citrate solution (32.5g of solid sodium citrate monohydrate) after 5 minutes, stirring for 3 hours at 85 ℃, cooling to room temperature, enabling a magnet to be adsorbed, adding deionized water, and repeatedly washing to obtain magnetic nanoparticles with a large amount of negative charges on the surface;
(IV) the modified microspheres are magnetized, a method for mixing the modified microspheres and the magnetic nanoparticles is adopted, and the method specifically comprises the following steps:
adding 11.2g of modified microspheres into 112m L deionized water, performing ultrasonic dispersion, adding excessive sodium citrate modified magnetic nanoparticles, adjusting the pH to 4 with hydrochloric acid, performing vibration adsorption for 2 hours, performing centrifugal separation, removing the non-adsorbed magnetic nanoparticles on the upper layer, and repeatedly washing with deionized water to obtain modified microspheres with magnetic nanoparticles adsorbed on the surfaces;
(V) preparing the polymer layer with the functional groups on the surface, which specifically comprises the following steps:
adding 2g of modified microspheres with magnetic nanoparticles adsorbed on the surface into 2000m L of deionized water for dispersion, then adding 0.05g of potassium persulfate and a surfactant solution (CTAB), wherein the concentration of the CTAB in the added solution is 0.03% (w/v), the pH value of the CTAB solution is adjusted to 6 in advance, then raising the temperature to 65 ℃, after stabilization, slowly adding 4g of methacrylic acid into the solution, the mass ratio of the methacrylic acid to the modified microspheres with magnetic nanoparticles adsorbed on the surface is 2:1, stirring the mixture at 65 ℃ for 12 hours, raising the temperature to 75 ℃, continuing stirring the mixture for 12 hours at the rotating speed of 200r/min, adsorbing the mixture by using a magnet, discarding supernatant, and washing the mixture for several times by using deionized water to obtain the magnetic microspheres with carboxyl groups modified on the surface.
In this embodiment, the polymer microspheres are replaced with polymethyl methacrylate microspheres, and after the polymer microspheres are subjected to modification treatment according to the present invention and are magnetized with magnetic microspheres having functional groups on the surfaces under a specific pH condition, the magnetic microspheres obtained therefrom have high magnetic content and good consistency, and subsequently functional monomers are adsorbed and polymerized on the surfaces of the magnetic nanoparticle layers under the action of a surfactant to obtain polymer layers having functional groups, and the obtained magnetic nanoparticles have high surface functional group content.
Comparative example 1
This comparative example differs from example 1 in that the operation in step (II) was not carried out, and the other conditions were exactly the same as in example 1.
In the comparative example, the polymer microsphere is not subjected to surface modification treatment, and in the magnetizing process, the adsorption quantity of the magnetic nanoparticles on the surface of the polymer microsphere is small, and the consistency is poor.
Comparative example 2
This comparative example differs from example 1 in that no sodium citrate solution was added in step (III) and the other conditions were exactly the same as in example 1.
In the comparative example, the surface of the magnetic nano-particle is not provided with functional groups, and the magnetic nano-particle has less adsorption quantity on the surface of the polymer microsphere and poor consistency in the magnetizing process.
Comparative example 3
This comparative example differs from example 1 in that no surfactant solution was added in step (V) and the other conditions were exactly the same as in example 1.
In the comparative example, a surfactant is not added in the magnetizing process, and as a large number of magnetic nanoparticles with negative charges are adsorbed on the surface of the modified microsphere, the functional monomer cannot be adsorbed on the surface of the composite microsphere, and a polymer layer with functional groups cannot be formed.
The applicant declares that the above description is only a specific embodiment of the present invention, but the scope of the present invention is not limited thereto, and it should be understood by those skilled in the art that any changes or substitutions that can be easily conceived by those skilled in the art within the technical scope of the present invention are within the scope and disclosure of the present invention.
Claims (10)
1. A preparation method of magnetic microspheres with functional groups on the surfaces is characterized by comprising the following steps:
(1) carrying out surface modification treatment on the polymer microspheres to obtain modified microspheres with charges on the surfaces;
(2) preparing magnetic nanoparticles with functional groups on the surfaces;
(3) dispersing and mixing the modified microspheres obtained in the step (1) and the magnetic nanoparticles obtained in the step (2) in a solvent, and adjusting the pH value to enable the magnetic nanoparticles to be adsorbed on the surfaces of the modified microspheres to obtain composite microspheres;
(4) and (4) dispersing the composite microspheres obtained in the step (3) in a solvent, adding a surfactant and a functional monomer, and carrying out polymerization reaction to obtain the magnetic microspheres with functional groups on the surfaces.
2. The method of claim 1, wherein the polymer microspheres of step (1) comprise any one or a combination of at least two of polystyrene microspheres, polymethyl methacrylate microspheres, polyglycidyl methacrylate microspheres, polyacrylic acid microspheres, agarose microspheres, dextran microspheres, or chitosan microspheres;
preferably, the preparation method of the polymeric microspheres in step (1) comprises any one of dispersion polymerization, emulsion polymerization, soap-free emulsion polymerization or miniemulsion polymerization;
preferably, the method of the surface modification treatment in the step (1) is a chemical method;
preferably, the surface modification treatment method in the step (1) comprises nitration reaction or reduction reaction of nitro;
preferably, the surface of the modified microsphere obtained after the surface of the polymer microsphere is subjected to nitration reaction has positive charges;
preferably, the surface of the modified microsphere has positive charges after the reduction reaction of the nitro group on the surface of the polymer microsphere.
3. The method of claim 2, wherein the surface modification treatment of the polymer microsphere by nitration comprises surface treatment of the polymer microsphere with a mixture of sulfuric acid and nitric acid to obtain a modified microsphere with charges on the surface;
preferably, the method for surface treatment of the polymer microspheres by using the mixed solution of sulfuric acid and nitric acid comprises cooling the mixed solution of sulfuric acid and nitric acid to 8-12 ℃, adding the polymer microspheres, mixing, and cooling to obtain modified microspheres with hydrophilic surfaces;
preferably, the time for mixing after adding the polymer microspheres is that after the temperature is raised to 45-55 ℃, the stirring is continued for 1-3 h;
preferably, the stirring speed is 150-;
preferably, the method of cooling after the polymer microspheres are added and mixed is to add ice water;
preferably, after the temperature is reduced, solid-liquid separation and washing are further carried out, so that the modified microspheres are obtained.
4. The method according to any one of claims 1 to 3, wherein the magnetic nanoparticles in step (2) have a particle size of 5 to 200 nm;
preferably, the material of the magnetic nanoparticles comprises any one or a combination of at least two of ferroferric oxide, ferric oxide or a ferro-manganese compound, and is preferably ferroferric oxide and/or ferric oxide;
preferably, the functional group on the surface of the magnetic nanoparticle in step (2) includes any one or a combination of at least two of carboxyl, amino, hydroxyl, alkyl or sulfhydryl;
preferably, the preparation method of the magnetic nanoparticles in the step (2) comprises a hydrothermal synthesis method or a coprecipitation method;
preferably, the preparation method of the magnetic nanoparticles in the step (2) includes adding ammonia water into a solution containing ferric salt and ferrous salt to perform a reaction, and then adding a surface functional group compound to obtain the magnetic nanoparticles;
preferably, the molar ratio of the ferric salt to the ferrous salt in the solution containing the ferric salt and the ferrous salt is 10: 1-1: 10;
preferably, the adding amount of the ammonia water enables the pH value of the solution to be more than or equal to 12;
preferably, the ratio of the molar amount of the surface functional group compound to the iron element in the solution containing ferric salt and ferrous salt is less than 1;
preferably, the surface functional group compound comprises any one or a combination of at least two of sodium citrate, polyethylene glycol or oleic acid, preferably sodium citrate;
preferably, the surface functional group compound is sodium citrate, and the surface of the magnetic nanoparticle is negatively charged;
preferably, the preparation method of the magnetic nanoparticles comprises the following steps:
(a) adding a trivalent ferric salt into water, introducing inert gas, and adding a divalent ferric salt to obtain a solution containing the trivalent ferric salt and the divalent ferric salt;
(b) heating the solution in the step (a), stirring, adding ammonia water, then adding a surface functional group compound, and continuously stirring to obtain the magnetic nanoparticles;
preferably, the temperature of heating in step (b) is 85-95 ℃;
preferably, the stirring rate in step (b) is 250-350 r/min;
preferably, the stirring in step (b) is continued for 1 to 3 hours;
preferably, the stirring in the step (b) is continued, and then cooling, solid-liquid separation and washing are further included;
preferably, the solid-liquid separation method is magnetic adsorption separation;
preferably, the detergent for washing is water.
5. The method of any one of claims 1 to 4, wherein the solvent of step (3) is water;
preferably, the pH adjustment in step (3) is in the range of 2 to 9, preferably 2 to 4;
preferably, the step (3) further comprises shaking adsorption after adjusting the pH;
preferably, the oscillating adsorption time is 1-3 h;
preferably, the shaking adsorption is followed by solid-liquid separation and water washing.
6. The method of any one of claims 1-5, wherein the surfactant of step (4) is an ionic surfactant;
preferably, the surfactant in step (4) comprises any one of sodium oleate, CTAB, SDS or sodium dodecyl benzene sulfonate or a combination of at least two of the above;
preferably, the functional monomer in step (4) comprises any one or a combination of at least two of acrylic acid, methacrylic acid, glycidyl methacrylate, methyl acrylate or ethyl acrylate;
preferably, the surfactant is added in step (4) in the form of a surfactant solution;
preferably, the solvent of the surfactant solution is water;
preferably, the surfactant solution has a pH of 5.5 to 6.5;
preferably, the step (4) further comprises adding an initiator before adding the functional monomer;
preferably, the initiator comprises any one of potassium persulfate, AIBN or BPO, or a combination of at least two thereof;
preferably, the mass ratio of the functional monomer added in the step (4) to the composite microspheres is 1 (0.5-2).
7. The method according to any one of claims 1 to 6, characterized in that it comprises the steps of:
preparing polymer microspheres;
(II) carrying out nitration reaction or reduction reaction of nitro on the surface of the polymer microsphere prepared in the step (I);
(III) preparing magnetic nanoparticles with functional groups on the surface, which comprises adding trivalent ferric salt into water, introducing inert gas, and adding divalent ferric salt to obtain a solution containing trivalent ferric salt and divalent ferric salt; then heating the solution to 85-95 ℃, stirring at 250-350r/min, adding ammonia water, then adding a surface functional group compound, and continuously stirring for 1-3h to obtain the magnetic nanoparticles;
(IV) ultrasonically dispersing the modified microspheres in the step (II) in water, adding the magnetic nanoparticles obtained in the step (III), adjusting the pH value to 2-9, and oscillating for adsorption to obtain composite microspheres;
(V) dispersing the composite microspheres in the step (IV) in water, adding an initiator and a surfactant solution, heating to 55-65 ℃, adding a functional monomer, continuously stirring for 10-14h, heating to 70-80 ℃, continuously stirring for 10-14h, performing solid-liquid separation, and washing with water to obtain the magnetic microspheres.
8. The magnetic microsphere with functional groups on the surface, which is prepared by the method according to any one of claims 1 to 7, is characterized in that the magnetic microsphere is of a three-layer core-shell structure and comprises a polymer microsphere positioned in a core, a magnetic nanoparticle layer positioned in an intermediate layer and a polymer layer with functional groups positioned in a shell layer.
9. The magnetic microsphere of claim 8, wherein the polymeric microsphere has a diameter of 0.1 to 5 μm.
10. Use of magnetic microspheres with functional groups on their surface according to claim 8 or 9 for any of immunodiagnosis, protein separation or cell screening.
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112175150A (en) * | 2020-09-21 | 2021-01-05 | 南京赛纳宝纳米科技有限公司 | Novel preparation method of functionalized porous magnetic microspheres |
| CN113265379A (en) * | 2021-05-14 | 2021-08-17 | 厦门依加成科技有限公司 | Microsphere with functionalized spots on surface and preparation method and application thereof |
| CN113621113A (en) * | 2021-08-11 | 2021-11-09 | 天津博蕴纯化装备材料科技有限公司 | Alkenyl magnetic base ball and preparation method and application thereof |
| CN114057940A (en) * | 2021-12-02 | 2022-02-18 | 中山大学 | Biodegradable carbomer polymer microsphere with core-shell structure as well as preparation method and application thereof |
| CN115845816A (en) * | 2022-12-07 | 2023-03-28 | 中元汇吉生物技术股份有限公司 | Magnetic microsphere, preparation thereof and application thereof in mass spectrum sample desalting |
Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6103379A (en) * | 1994-10-06 | 2000-08-15 | Bar-Ilan University | Process for the preparation of microspheres and microspheres made thereby |
| CN1390863A (en) * | 2002-06-26 | 2003-01-15 | 天津大学 | Magnetic composite microsphere of molecular blot polymer and its suspemsion polymerization process for preparing it |
| US20060159962A1 (en) * | 2005-01-20 | 2006-07-20 | Luminex Corporation | Magnetic microspheres for use in fluorescence-based applications |
| CN106622172A (en) * | 2016-12-29 | 2017-05-10 | 天津博纳艾杰尔科技有限公司 | Preparation method of surface-functionalized, micron-sized, porous, paramagnetic and spherical resin particle |
| CN107245196A (en) * | 2017-06-22 | 2017-10-13 | 成都爱兴生物科技有限公司 | Multilayer assembles the preparation method of micron size polystyrene magnetic composite microsphere |
| CN108467461A (en) * | 2018-02-28 | 2018-08-31 | 苏州为度生物技术有限公司 | The preparation method of surface carboxyl groups nucleocapsid superparamagnetism microballoon |
| CN110396148A (en) * | 2019-08-05 | 2019-11-01 | 东南大学 | A kind of magnetic polystyrene microsphere and preparation method thereof |
| CN110734524A (en) * | 2018-07-18 | 2020-01-31 | 苏州为度生物技术有限公司 | Preparation method of cationic polymer modified magnetic shell-core microsphere |
-
2020
- 2020-03-31 CN CN202010241213.9A patent/CN111393574B/en active Active
Patent Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6103379A (en) * | 1994-10-06 | 2000-08-15 | Bar-Ilan University | Process for the preparation of microspheres and microspheres made thereby |
| CN1390863A (en) * | 2002-06-26 | 2003-01-15 | 天津大学 | Magnetic composite microsphere of molecular blot polymer and its suspemsion polymerization process for preparing it |
| US20060159962A1 (en) * | 2005-01-20 | 2006-07-20 | Luminex Corporation | Magnetic microspheres for use in fluorescence-based applications |
| US20160266103A1 (en) * | 2005-01-20 | 2016-09-15 | Luminex Corporation | Magnetic microspheres for use in fluorescence-based applications |
| CN106622172A (en) * | 2016-12-29 | 2017-05-10 | 天津博纳艾杰尔科技有限公司 | Preparation method of surface-functionalized, micron-sized, porous, paramagnetic and spherical resin particle |
| CN107245196A (en) * | 2017-06-22 | 2017-10-13 | 成都爱兴生物科技有限公司 | Multilayer assembles the preparation method of micron size polystyrene magnetic composite microsphere |
| CN108467461A (en) * | 2018-02-28 | 2018-08-31 | 苏州为度生物技术有限公司 | The preparation method of surface carboxyl groups nucleocapsid superparamagnetism microballoon |
| CN110734524A (en) * | 2018-07-18 | 2020-01-31 | 苏州为度生物技术有限公司 | Preparation method of cationic polymer modified magnetic shell-core microsphere |
| CN110396148A (en) * | 2019-08-05 | 2019-11-01 | 东南大学 | A kind of magnetic polystyrene microsphere and preparation method thereof |
Non-Patent Citations (3)
| Title |
|---|
| ZHANG BO，等: "Preparation and application of magnetic microsphere carriers", 《FRONTIERS OF CHEMICAL ENGINEERING IN CHINA》 * |
| 录华主编: "《精细化工概论》", 30 November 1999, 化学工业出版社 * |
| 谢玲玲: "聚苯乙烯微球的制备、功能化及其吸附BSA的性能研究", 《中国优秀硕士学位论文全文数据库医药卫生科技辑》 * |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112175150A (en) * | 2020-09-21 | 2021-01-05 | 南京赛纳宝纳米科技有限公司 | Novel preparation method of functionalized porous magnetic microspheres |
| CN113265379A (en) * | 2021-05-14 | 2021-08-17 | 厦门依加成科技有限公司 | Microsphere with functionalized spots on surface and preparation method and application thereof |
| CN113265379B (en) * | 2021-05-14 | 2022-04-29 | 厦门依加成科技有限公司 | Microsphere with functionalized spots on surface and preparation method and application thereof |
| WO2022236863A1 (en) * | 2021-05-14 | 2022-11-17 | 厦门依加成科技有限公司 | Microsphere having functionalized spot on surface, and preparation method and application of microsphere |
| CN113621113A (en) * | 2021-08-11 | 2021-11-09 | 天津博蕴纯化装备材料科技有限公司 | Alkenyl magnetic base ball and preparation method and application thereof |
| CN113621113B (en) * | 2021-08-11 | 2022-07-26 | 天津博蕴纯化装备材料科技有限公司 | Alkenyl magnetic base ball and preparation method and application thereof |
| CN114057940A (en) * | 2021-12-02 | 2022-02-18 | 中山大学 | Biodegradable carbomer polymer microsphere with core-shell structure as well as preparation method and application thereof |
| CN114057940B (en) * | 2021-12-02 | 2023-11-03 | 中山大学 | Biodegradable carbomer core-shell structure polymer microsphere and preparation method and application thereof |
| CN115845816A (en) * | 2022-12-07 | 2023-03-28 | 中元汇吉生物技术股份有限公司 | Magnetic microsphere, preparation thereof and application thereof in mass spectrum sample desalting |
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