CN115975252B - Preparation method of magnetic polymer microsphere with double-layer shell structure - Google Patents
Preparation method of magnetic polymer microsphere with double-layer shell structure Download PDFInfo
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- CN115975252B CN115975252B CN202310128133.6A CN202310128133A CN115975252B CN 115975252 B CN115975252 B CN 115975252B CN 202310128133 A CN202310128133 A CN 202310128133A CN 115975252 B CN115975252 B CN 115975252B
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- 239000004005 microsphere Substances 0.000 title claims abstract description 196
- 229920000642 polymer Polymers 0.000 title claims abstract description 165
- 238000002360 preparation method Methods 0.000 title claims abstract description 18
- 238000000034 method Methods 0.000 claims abstract description 56
- 239000000178 monomer Substances 0.000 claims abstract description 33
- 239000011248 coating agent Substances 0.000 claims abstract description 28
- 238000000576 coating method Methods 0.000 claims abstract description 28
- 239000002243 precursor Substances 0.000 claims abstract description 28
- 238000010992 reflux Methods 0.000 claims abstract description 27
- 238000005538 encapsulation Methods 0.000 claims abstract description 24
- 238000006116 polymerization reaction Methods 0.000 claims abstract description 17
- 238000001556 precipitation Methods 0.000 claims abstract description 17
- 239000003999 initiator Substances 0.000 claims abstract description 15
- 230000002209 hydrophobic effect Effects 0.000 claims abstract description 14
- 239000004793 Polystyrene Substances 0.000 claims abstract description 13
- 229920002223 polystyrene Polymers 0.000 claims abstract description 13
- 230000008961 swelling Effects 0.000 claims abstract description 13
- 230000009471 action Effects 0.000 claims abstract description 6
- 239000004094 surface-active agent Substances 0.000 claims abstract description 6
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- -1 amino, carboxyl Chemical group 0.000 claims description 34
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 33
- MYRTYDVEIRVNKP-UHFFFAOYSA-N 1,2-Divinylbenzene Chemical compound C=CC1=CC=CC=C1C=C MYRTYDVEIRVNKP-UHFFFAOYSA-N 0.000 claims description 20
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 19
- 238000006243 chemical reaction Methods 0.000 claims description 18
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 15
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 claims description 14
- 239000000243 solution Substances 0.000 claims description 14
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- 239000003431 cross linking reagent Substances 0.000 claims description 12
- 125000000524 functional group Chemical group 0.000 claims description 11
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 claims description 8
- ROOXNKNUYICQNP-UHFFFAOYSA-N ammonium persulfate Chemical compound [NH4+].[NH4+].[O-]S(=O)(=O)OOS([O-])(=O)=O ROOXNKNUYICQNP-UHFFFAOYSA-N 0.000 claims description 8
- 229920001477 hydrophilic polymer Polymers 0.000 claims description 8
- 239000004342 Benzoyl peroxide Substances 0.000 claims description 7
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 claims description 7
- 235000019400 benzoyl peroxide Nutrition 0.000 claims description 7
- VOZRXNHHFUQHIL-UHFFFAOYSA-N glycidyl methacrylate Chemical compound CC(=C)C(=O)OCC1CO1 VOZRXNHHFUQHIL-UHFFFAOYSA-N 0.000 claims description 7
- 229920001600 hydrophobic polymer Polymers 0.000 claims description 7
- ZIUHHBKFKCYYJD-UHFFFAOYSA-N n,n'-methylenebisacrylamide Chemical compound C=CC(=O)NCNC(=O)C=C ZIUHHBKFKCYYJD-UHFFFAOYSA-N 0.000 claims description 7
- 229960002089 ferrous chloride Drugs 0.000 claims description 6
- NMCUIPGRVMDVDB-UHFFFAOYSA-L iron dichloride Chemical compound Cl[Fe]Cl NMCUIPGRVMDVDB-UHFFFAOYSA-L 0.000 claims description 6
- CWYNVVGOOAEACU-UHFFFAOYSA-N Fe2+ Chemical class [Fe+2] CWYNVVGOOAEACU-UHFFFAOYSA-N 0.000 claims description 5
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 claims description 5
- DBCAQXHNJOFNGC-UHFFFAOYSA-N 4-bromo-1,1,1-trifluorobutane Chemical compound FC(F)(F)CCCBr DBCAQXHNJOFNGC-UHFFFAOYSA-N 0.000 claims description 4
- 239000004593 Epoxy Substances 0.000 claims description 4
- 229910001870 ammonium persulfate Inorganic materials 0.000 claims description 4
- STVZJERGLQHEKB-UHFFFAOYSA-N ethylene glycol dimethacrylate Substances CC(=C)C(=O)OCCOC(=O)C(C)=C STVZJERGLQHEKB-UHFFFAOYSA-N 0.000 claims description 4
- VKYKSIONXSXAKP-UHFFFAOYSA-N hexamethylenetetramine Chemical compound C1N(C2)CN3CN1CN2C3 VKYKSIONXSXAKP-UHFFFAOYSA-N 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- USHAGKDGDHPEEY-UHFFFAOYSA-L potassium persulfate Chemical compound [K+].[K+].[O-]S(=O)(=O)OOS([O-])(=O)=O USHAGKDGDHPEEY-UHFFFAOYSA-L 0.000 claims description 4
- 229920002818 (Hydroxyethyl)methacrylate Polymers 0.000 claims description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims description 3
- WOBHKFSMXKNTIM-UHFFFAOYSA-N Hydroxyethyl methacrylate Chemical compound CC(=C)C(=O)OCCO WOBHKFSMXKNTIM-UHFFFAOYSA-N 0.000 claims description 3
- 235000011114 ammonium hydroxide Nutrition 0.000 claims description 3
- SJMYWORNLPSJQO-UHFFFAOYSA-N tert-butyl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OC(C)(C)C SJMYWORNLPSJQO-UHFFFAOYSA-N 0.000 claims description 3
- HSOOIVBINKDISP-UHFFFAOYSA-N 1-(2-methylprop-2-enoyloxy)butyl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OC(CCC)OC(=O)C(C)=C HSOOIVBINKDISP-UHFFFAOYSA-N 0.000 claims description 2
- LCPVQAHEFVXVKT-UHFFFAOYSA-N 2-(2,4-difluorophenoxy)pyridin-3-amine Chemical compound NC1=CC=CN=C1OC1=CC=C(F)C=C1F LCPVQAHEFVXVKT-UHFFFAOYSA-N 0.000 claims description 2
- XRXANEMIFVRKLN-UHFFFAOYSA-N 2-hydroperoxy-2-methylbutane Chemical compound CCC(C)(C)OO XRXANEMIFVRKLN-UHFFFAOYSA-N 0.000 claims description 2
- RUMACXVDVNRZJZ-UHFFFAOYSA-N 2-methylpropyl 2-methylprop-2-enoate Chemical compound CC(C)COC(=O)C(C)=C RUMACXVDVNRZJZ-UHFFFAOYSA-N 0.000 claims description 2
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 claims description 2
- 229910002651 NO3 Inorganic materials 0.000 claims description 2
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 claims description 2
- 150000008064 anhydrides Chemical class 0.000 claims description 2
- 239000012298 atmosphere Substances 0.000 claims description 2
- QUZSUMLPWDHKCJ-UHFFFAOYSA-N bisphenol A dimethacrylate Chemical compound C1=CC(OC(=O)C(=C)C)=CC=C1C(C)(C)C1=CC=C(OC(=O)C(C)=C)C=C1 QUZSUMLPWDHKCJ-UHFFFAOYSA-N 0.000 claims description 2
- OIWOHHBRDFKZNC-UHFFFAOYSA-N cyclohexyl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OC1CCCCC1 OIWOHHBRDFKZNC-UHFFFAOYSA-N 0.000 claims description 2
- 239000011790 ferrous sulphate Substances 0.000 claims description 2
- 235000003891 ferrous sulphate Nutrition 0.000 claims description 2
- 239000004312 hexamethylene tetramine Substances 0.000 claims description 2
- 235000010299 hexamethylene tetramine Nutrition 0.000 claims description 2
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 claims description 2
- 229910000359 iron(II) sulfate Inorganic materials 0.000 claims description 2
- FQPSGWSUVKBHSU-UHFFFAOYSA-N methacrylamide Chemical compound CC(=C)C(N)=O FQPSGWSUVKBHSU-UHFFFAOYSA-N 0.000 claims description 2
- 239000011259 mixed solution Substances 0.000 claims description 2
- CHQMHPLRPQMAMX-UHFFFAOYSA-L sodium persulfate Substances [Na+].[Na+].[O-]S(=O)(=O)OOS([O-])(=O)=O CHQMHPLRPQMAMX-UHFFFAOYSA-L 0.000 claims description 2
- BAUYGSIQEAFULO-UHFFFAOYSA-L iron(2+) sulfate (anhydrous) Chemical compound [Fe+2].[O-]S([O-])(=O)=O BAUYGSIQEAFULO-UHFFFAOYSA-L 0.000 claims 1
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 40
- 229910052742 iron Inorganic materials 0.000 description 33
- 239000000203 mixture Substances 0.000 description 26
- 239000007864 aqueous solution Substances 0.000 description 24
- 238000003756 stirring Methods 0.000 description 22
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
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- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 12
- 239000007853 buffer solution Substances 0.000 description 12
- IQFVPQOLBLOTPF-HKXUKFGYSA-L congo red Chemical compound [Na+].[Na+].C1=CC=CC2=C(N)C(/N=N/C3=CC=C(C=C3)C3=CC=C(C=C3)/N=N/C3=C(C4=CC=CC=C4C(=C3)S([O-])(=O)=O)N)=CC(S([O-])(=O)=O)=C21 IQFVPQOLBLOTPF-HKXUKFGYSA-L 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 238000002156 mixing Methods 0.000 description 9
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- 239000002105 nanoparticle Substances 0.000 description 8
- 238000002474 experimental method Methods 0.000 description 7
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- 239000002245 particle Substances 0.000 description 7
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical class [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 6
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 6
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 6
- 238000002835 absorbance Methods 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
- DOIRQSBPFJWKBE-UHFFFAOYSA-N dibutyl phthalate Chemical compound CCCCOC(=O)C1=CC=CC=C1C(=O)OCCCC DOIRQSBPFJWKBE-UHFFFAOYSA-N 0.000 description 6
- NAQMVNRVTILPCV-UHFFFAOYSA-N hexane-1,6-diamine Chemical compound NCCCCCCN NAQMVNRVTILPCV-UHFFFAOYSA-N 0.000 description 6
- 230000007062 hydrolysis Effects 0.000 description 6
- 238000006460 hydrolysis reaction Methods 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Chemical compound [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 description 6
- 239000000463 material Substances 0.000 description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 102000039446 nucleic acids Human genes 0.000 description 4
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- 150000007523 nucleic acids Chemical class 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
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- 239000000839 emulsion Substances 0.000 description 3
- 229910001448 ferrous ion Inorganic materials 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 230000003301 hydrolyzing effect Effects 0.000 description 3
- 238000001000 micrograph Methods 0.000 description 3
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- 239000012299 nitrogen atmosphere Substances 0.000 description 3
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
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- 239000004323 potassium nitrate Substances 0.000 description 3
- 235000010333 potassium nitrate Nutrition 0.000 description 3
- 238000001179 sorption measurement Methods 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
- 230000000975 bioactive effect Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 230000001276 controlling effect Effects 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 238000007720 emulsion polymerization reaction Methods 0.000 description 2
- 229920001480 hydrophilic copolymer Polymers 0.000 description 2
- SURQXAFEQWPFPV-UHFFFAOYSA-L iron(2+) sulfate heptahydrate Chemical compound O.O.O.O.O.O.O.[Fe+2].[O-]S([O-])(=O)=O SURQXAFEQWPFPV-UHFFFAOYSA-L 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 229910017604 nitric acid Inorganic materials 0.000 description 2
- 229920002454 poly(glycidyl methacrylate) polymer Polymers 0.000 description 2
- 230000002633 protecting effect Effects 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 239000002356 single layer Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000001132 ultrasonic dispersion Methods 0.000 description 2
- LDXJRKWFNNFDSA-UHFFFAOYSA-N 2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)-1-[4-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]piperazin-1-yl]ethanone Chemical compound C1CN(CC2=NNN=C21)CC(=O)N3CCN(CC3)C4=CN=C(N=C4)NCC5=CC(=CC=C5)OC(F)(F)F LDXJRKWFNNFDSA-UHFFFAOYSA-N 0.000 description 1
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- DEXFNLNNUZKHNO-UHFFFAOYSA-N 6-[3-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperidin-1-yl]-3-oxopropyl]-3H-1,3-benzoxazol-2-one Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C1CCN(CC1)C(CCC1=CC2=C(NC(O2)=O)C=C1)=O DEXFNLNNUZKHNO-UHFFFAOYSA-N 0.000 description 1
- JAWMENYCRQKKJY-UHFFFAOYSA-N [3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-ylmethyl)-1-oxa-2,8-diazaspiro[4.5]dec-2-en-8-yl]-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]methanone Chemical compound N1N=NC=2CN(CCC=21)CC1=NOC2(C1)CCN(CC2)C(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F JAWMENYCRQKKJY-UHFFFAOYSA-N 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 230000009920 chelation Effects 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 238000000151 deposition Methods 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 229940044631 ferric chloride hexahydrate Drugs 0.000 description 1
- SZVJSHCCFOBDDC-UHFFFAOYSA-N ferrosoferric oxide Chemical compound O=[Fe]O[Fe]O[Fe]=O SZVJSHCCFOBDDC-UHFFFAOYSA-N 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- NQXWGWZJXJUMQB-UHFFFAOYSA-K iron trichloride hexahydrate Chemical compound O.O.O.O.O.O.[Cl-].Cl[Fe+]Cl NQXWGWZJXJUMQB-UHFFFAOYSA-K 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 230000005415 magnetization Effects 0.000 description 1
- 150000002696 manganese Chemical class 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 230000001546 nitrifying effect Effects 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 238000012673 precipitation polymerization Methods 0.000 description 1
- 238000012113 quantitative test Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
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- 239000000126 substance Substances 0.000 description 1
- 238000006557 surface reaction Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
Landscapes
- Polymerisation Methods In General (AREA)
Abstract
The invention discloses a preparation method of magnetic polymer microspheres with double-layer shell structures, which comprises the following steps: the polystyrene seed microsphere is swelled in the first step under the action of a swelling agent and a surfactant, swelled in the second step under the action of a functional monomer, an initiator and the surfactant, and the functionalized porous polymer microsphere is prepared; preparing a magnetic polymer microsphere precursor by using the functionalized porous polymer microsphere as a template through a hydrothermal precipitation method; performing first polymerization encapsulation on the magnetic polymer microsphere precursor, and coating a hydrophobic coating on the surface of the magnetic polymer microsphere precursor by a reflux precipitation method, wherein the hydrophobic coating is a first shell of the magnetic polymer microsphere; performing second polymerization encapsulation on the magnetic polymer microsphere with the first shell, and coating a hydrophilic coating on the surface of the first shell by a reflux precipitation method, wherein the hydrophilic coating is the second shell of the magnetic polymer microsphere; thereby obtaining the magnetic polymer microsphere with a double-layer shell structure.
Description
Technical Field
The invention relates to a preparation method of a magnetic polymer microsphere with a double-layer shell structure.
Background
The magnetic polymer microsphere not only has the characteristics of non-toxicity and superparamagnetism of the magnetic inorganic nano particles, but also has the characteristics of polarity, biocompatibility, easy surface functionalization and the like of the polymer, and has wide application in a plurality of fields, in particular biological detection and in-vitro diagnostic reagents. The magnetic microsphere for diagnostic reagent is required to have uniform particle size, fast magnetic response, good suspension property and low nonspecific adsorption to biomacromolecule such as protein, nucleic acid, etc.
Among the disclosed methods for preparing magnetic polymer microspheres, the template method has the advantages of high process stability, uniform product particle size, strong magnetic responsiveness, multifunctional surface and the like, and becomes the mainstream preparation method of commercial magnetic polymer microspheres. Patent document US8038987B2 discloses a preparation method of coated magnetic polymer particles, which uses nitrified porous polystyrene microspheres as a template, and then coprecipitates ferric salt and manganese salt into the porous microspheres to prepare the magnetic polymer microspheres. Similarly, patent document US20170218095 discloses a three-step procedure for producing superparamagnetic polymer microspheres, synthesizing low molecular weight polystyrene microsphere seeds by emulsion polymerization, then swelling and crosslinking to obtain porous crosslinked polystyrene microspheres, finally nitrifying benzene rings in the microspheres with a mixture of sulfuric acid and nitric acid, and then using the nitrified microspheres with ammonia (25%) and ferrous sulfate heptahydrate for the subsequent magnetizing step. In the above magnetizing process, the adsorption, deposition and centrifugation operations have to be repeated in a laborious and time-consuming manner in order to deposit as many iron nanoparticles as possible in the nitrified microspheres. Also, each 5g of dry polystyrene microspheres is nitrified, consuming 125mL of a mixture of concentrated nitric acid and concentrated sulfuric acid, which causes serious environmental problems. Most importantly, the free iron nano particles and the iron ions generated by the free iron nano particles are always present in a reaction system, so that the practical application effect of the product microsphere is limited.
In order to further solve the above problems, researchers have further explored the surface encapsulation process of magnetic polymer microspheres. Patent document CN108467461a discloses a preparation method of surface carboxyl core-shell superparamagnetism microsphere, firstly preparing polyglycidyl methacrylate microsphere by emulsion polymerization, then preparing large-size monodisperse porous polyglycidyl methacrylate microsphere by one-step seed swelling polymerization, then preparing monodisperse superparamagnetism microsphere in situ by ferric salt deposition-alkaline coprecipitation method, and finally carrying out surface carboxyl modification on the magnetic microsphere by distillation precipitation polymerization. The method performs polymer encapsulation on the surface of the magnetic microsphere and completes functional modification at the same time. However, in the encapsulation process, the monomer used is a hydrophilic monomer such as methacrylic acid or acrylic acid, and the single-layer hydrophilic copolymer coating obtained by distillation, precipitation and polymerization in acetonitrile has very limited improvement on the stability of the product microsphere. Patent document US5814687a discloses a method for testing magnetic polymer microsphere iron ion leakage comprising: almost no superparamagnetic substance was present near the surface of the magnetic polymer microspheres, and the amount of metal dissolved in the solvent must be 10mg/L or less when 1g of the magnetic polymer microspheres were immersed in 10mL of water at 70℃for 2 hours. Experiments prove that after the magnetic polymer microsphere prepared by the method disclosed in the patent document CN108467461A is treated by the steps, the iron ion quantity dissolved in the solvent is far more than 10mg/L, namely the problem of iron ion leakage still exists.
Disclosure of Invention
The invention aims to: the invention aims to provide a preparation method of magnetic polymer microspheres without free iron nano particles and without iron ion leakage.
The technical scheme is as follows: the invention relates to a preparation method of a magnetic polymer microsphere with a double-layer shell structure, which specifically comprises the following steps:
(1) The polystyrene seed microsphere is swelled in the first step under the action of a swelling agent and a surfactant, swelled in the second step under the action of a functional monomer, an initiator and the surfactant, and the functionalized porous polymer microsphere is prepared; the first swelling can make the polymer molecular chain softer, so that the functional monomer can be better dissolved into the molecular chain during the second swelling, and the functional monomer is used for the second chelation reaction with iron ions;
(2) Preparing a magnetic polymer microsphere precursor by using the functionalized porous polymer microsphere as a template through a hydrothermal precipitation method; the mass ratio of the ferrous ions to the microspheres is limited, and the reaction is carried out in an ethylene glycol system, so that the ferrous ions in the reaction system are all captured and chelated by the functional groups on the surface of the sphere, and the generated ferroferric oxide can be all adsorbed in the interior and pores of the microspheres without free iron ions in the system;
(3) Performing first polymerization encapsulation on the magnetic polymer microsphere precursor, and coating a hydrophobic polymer coating on the surface of the magnetic polymer microsphere precursor by a reflux precipitation method, wherein the hydrophobic polymer coating is a first shell of the magnetic polymer microsphere; the thickness of the obtained hydrophobic polymer coating is 10-60 nm by controlling the mass ratio of the hydrophobic monomer to the microsphere, and the property of low activity of the hydrophobic layer plays a role in protecting the microsphere, so that the leakage of iron ions in the microsphere can be effectively prevented;
(4) Performing second polymerization encapsulation on the magnetic polymer microsphere with the first shell, and coating a hydrophilic polymer coating on the surface of the first shell by a reflux precipitation method, wherein the hydrophilic polymer coating is the second shell of the magnetic polymer microsphere; the thickness of the hydrophilic polymer coating is 15-25 nm, and if the hydrophilic thickness is too high, the microspheres are adhered to each other; the magnetic polymer microsphere with a double-layer shell structure is obtained.
Based on different application scenes, the magnetic polymer microsphere with the second shell is placed in one or more solutions of sulfuric acid, sodium hydroxide, ethylenediamine, ammonia water or anhydride, and the reaction is carried out for 1 to 24 hours at the temperature of 30 to 120 ℃ to obtain the magnetic polymer microsphere with different functional groups on the surface. Different practical application scenes have different requirements on the types of the functional groups on the surfaces of the magnetic polymer microspheres, and the magnetic polymer microspheres can be grafted with different bioactive molecules such as proteins, nucleic acids and the like through the different functional groups on the surfaces of the magnetic polymer microspheres.
Wherein in the step (1), the functional monomer is a monomer with one or more functional groups of amino, carboxyl, epoxy or hydroxyl; the functional groups on the surface of the functionalized porous polymer microsphere are at least two of amino, carboxyl, epoxy or hydroxyl.
In the step (2), the hydrothermal precipitation method specifically comprises the following steps: dispersing functionalized porous polymer microspheres, ferrous compounds, hexamethylenetetramine and nitrate in a mixed solution of water and glycol, and reacting for 0.5-6 h at 50-150 ℃ in an inert atmosphere; the ferrous compound is ferrous chloride and/or ferrous sulfate; the mass ratio of the functionalized porous polymer microsphere to the ferrous compound is 1:3-3:1.
In the step (3), the first polymerization encapsulation is performed by a reflux precipitation method specifically comprises: dispersing the magnetic polymer microsphere precursor, hydrophobic monomer, cross-linking agent and initiator in acetonitrile, and carrying out reflux reaction for 0.5-6 h at 50-150 ℃.
Wherein the hydrophobic monomer is one or more of styrene, methyl methacrylate, isobutyl methacrylate or cyclohexyl methacrylate; the cross-linking agent is one or more of divinylbenzene, ethylene glycol dimethacrylate and N, N' -methylene bisacrylamide, and the adding amount of the cross-linking agent is 1-25% of the mass of the hydrophobic monomer; the initiator is one or more of azodiisobutyronitrile, benzoyl peroxide, potassium persulfate or ammonium persulfate, and the addition amount of the initiator is 0.2-10% of the mass of the hydrophobic monomer; the mass ratio of the hydrophobic monomer to the magnetic polymer microsphere precursor is 1: 3-10: 1.
in the step (4), the second polymerization encapsulation is performed by a reflux precipitation method specifically comprises: dispersing the magnetic polymer microsphere with the first shell, hydrophilic monomer, cross-linking agent and initiator in acetonitrile, and carrying out reflux reaction for 0.5-6 h at 50-150 ℃.
Wherein the hydrophilic monomer is one or more of glycidyl methacrylate, hydroxyethyl methacrylate, methacrylic acid, tert-butyl methacrylate or methacrylamide; the cross-linking agent is one or more of divinylbenzene, ethylene glycol dimethacrylate, butanediol dimethacrylate, bisphenol A dimethacrylate or N, N' -methylene bisacrylamide, and the adding amount of the cross-linking agent is 1-25% of the mass of the hydrophilic monomer; the initiator is one or more of azodiisobutyronitrile, benzoyl peroxide, tertiary amyl hydroperoxide, potassium persulfate, sodium persulfate or ammonium persulfate, and the addition amount of the initiator is 0.2-10% of the mass of the hydrophilic monomer; the mass ratio of the hydrophilic monomer to the magnetic polymer microsphere with the first shell is 1: 3-10: 1.
the magnetic polymer microsphere prepared by the method has uniform and controllable particle size and high magnetic content (not less than 18 weight percent), and can lead ferrous ions in a reaction system to be completely captured and chelated by functional groups on the surface of a sphere through the coordination of multi-functional groups while having high magnetic content, thereby avoiding the generation of free iron nano particles; meanwhile, the problem that iron ions are easy to leak in the practical application process of the magnetic polymer microsphere is solved through the hydrophobic-hydrophilic double-layer shell structure, wherein the hydrophobic polymer coating of the inner layer has effective fixing and protecting effects on the iron nano particles; the outer hydrophilic polymer coating has functional characteristics, and realizes the specific adsorption of the magnetic polymer microsphere to biological macromolecules such as proteins, nucleic acids and the like.
The beneficial effects are that: compared with the prior art, the invention has the following remarkable advantages: in the magnetization process of the porous polymer microsphere, the generation of free iron nano particles is avoided by the synergistic effect of a hydrothermal precipitation method and the polyfunctional groups on the surface of the microsphere; the encapsulation of the hydrophobic-hydrophilic double-layer shell structure solves the problem of iron ion leakage of the magnetic polymer microsphere in the practical application process; according to the practical application scene, the controllable and diversified functional groups on the surface of the magnetic polymer microsphere can be realized by regulating and controlling the types of the functional monomers in the polymerization process of the second shell, and the grafting of bioactive molecules such as proteins, nucleic acids and the like is facilitated.
Drawings
FIGS. 1A and B are a scanning electron microscope image and a transmission electron microscope image, respectively, of the functionalized porous polymer microspheres prepared in example 1;
FIGS. 2A and B are scanning electron microscope images of the magnetic polymer microsphere precursor prepared in example 1 at different magnifications;
fig. 3 a and B are sem images of the magnetic polymer microsphere with the second shell prepared in example 1 at different magnifications.
Detailed Description
The technical scheme of the invention is further described below with reference to the accompanying drawings.
Example 1
The invention relates to a preparation method of a magnetic polymer microsphere with a double-layer shell structure, which specifically comprises the following steps:
(1) Synthesis of functionalized porous polymer microspheres: firstly, uniformly mixing the materials in a 50mL three-neck flask with the mass ratio of 3:2, then adding 0.375g of polyvinylpyrrolidone, 2.5mL of styrene and 0.04g of azodiisobutyronitrile into the mixture, and heating the mixture to 75 ℃ under the protection of nitrogen for reaction for 12 hours to obtain polystyrene seed microspheres with the particle size of about 1 mu m; 0.6mL of toluene and 1.8mL of dibutyl phthalate are added into 30mL of aqueous solution containing 0.05g of sodium dodecyl sulfate, ultrasonic emulsification is carried out, and 0.1g of polystyrene seed microsphere is added into the aqueous solution to be swelled for 12 hours at room temperature; 2.5mL of methyl methacrylate, 0.5mL of divinylbenzene, 0.5mL of glycidyl methacrylate and 0.12g of benzoyl peroxide were added to a 30mL aqueous solution containing 0.05g of sodium dodecyl sulfate, and the mixture was phacoemulsified; adding the emulsion into the reaction liquid after swelling for 12 hours, and continuing swelling for 6 hours; finally, carrying out polymerization reaction for 16h at 70 ℃ under the protection of nitrogen atmosphere to obtain porous polymer microspheres; hydrolyzing 1g of porous polymer microspheres with 50mL of 10wt% sodium hydroxide aqueous solution at 60 ℃ for 8 hours, washing with distilled water to be neutral after the hydrolysis is finished, and condensing and refluxing with 50mL of 0.2mol/L sulfuric acid aqueous solution at 80 ℃ for 4 hours to obtain functionalized porous polymer microspheres;
(2) Preparation of magnetic polymer microsphere precursor: 40mL of water, 10mL of ethylene glycol and 0.16g of functionalized porous polymer microspheres are respectively weighed and added into a 100mL three-neck flask with mechanical stirring, and the mechanical stirring rotation speed is 200rpm, so that the functionalized porous polymer microspheres are uniformly dispersed; then 0.08g ferrous chloride tetrahydrate, 0.5g hexamethylenediamine and 0.1g potassium nitrate are added into the three-neck flask in sequence, fully stirred for 15min under the protection of nitrogen, the water bath temperature is increased to 80 ℃, the stirring rotation speed is adjusted to 500rpm, and the reaction lasts for 1h; washing the obtained black product in a magnetic field with distilled water for a plurality of times, and vacuum drying to obtain a magnetic polymer microsphere precursor;
(3) Polymeric encapsulation of the first housing: 1g of the magnetic polymer microsphere precursor is weighed, dispersed in 150mL of acetonitrile by ultrasonic, and added into a 250mL four-neck flask with a reflux device; then 2g of methyl methacrylate, 0.2g of divinylbenzene and 0.05g of azodiisobutyronitrile are weighed and sequentially added into a four-neck flask, the four-neck flask with a reflux device is transferred into a water bath, the water bath temperature is set to 110 ℃, and the reaction lasts for 4 hours; washing the product in a magnetic field with distilled water for several times to obtain magnetic polymer microspheres with a first shell; the thickness of the first shell is 60nm;
(4) Polymeric encapsulation of the second housing: 1g of the magnetic polymer microsphere with the first shell is weighed, dispersed in 150mL of acetonitrile by ultrasonic, and added into a 250mL four-neck flask with a reflux device; weighing 4g of methacrylic acid, 1g of glycidyl methacrylate, 1g of N, N' -methylene bisacrylamide and 0.25g of azodiisobutyronitrile, performing ultrasonic dispersion to dissolve the materials, and adding the materials into a four-necked flask; transferring the four-neck flask with the reflux device into a water bath, setting the water bath temperature to 93 ℃, and reacting for 4 hours; washing the product in a magnetic field with distilled water for several times to obtain magnetic polymer microspheres with a second shell; the thickness of the second shell is 23nm;
hydrolysis of magnetic Polymer microspheres: 1g of the magnetic polymer microsphere with the second shell is weighed, dispersed in 100mL of 10wt% sulfuric acid aqueous solution by ultrasonic, hydrolyzed at 80 ℃ for 3 hours, and the hydrolyzed product is washed with distilled water for several times in a magnetic field to obtain the hydrolyzed magnetic polymer microsphere.
Quantitative experiments on iron ion leakage: 1g of the hydrolyzed magnetic polymer microsphere is weighed, dispersed in 30mL of water, and stirred continuously for 2 hours in a water bath at 70 ℃. After the stirring is finished, taking out the magnetic polymer microspheres, mixing the magnetic polymer microspheres with 40mL of water, 1mL of 25wt% hydrochloric acid aqueous solution and 3mL of hydroxylamine hydrochloride with the concentration of 100mg/L, continuously stirring the mixture for 1 to 2 hours in a water bath at the temperature of 70 ℃, then cooling the mixture to room temperature, adding a small piece of Congo red test paper, dropwise adding a saturated sodium acetate solution until the Congo red test paper just turns red, adding 5mL of buffer solution (the buffer solution is diluted to 100mL by water after 40g of acetic acid and 50mL of glacial acid) and 2mL of o-phenanthroline solution, developing the color for 15 minutes after uniformly stirring, using a 10mm cuvette to carry out blank zeroing, measuring absorbance at the position of 510nm, and comparing the free iron ion content in the system through a standard curve.
Example 2
The invention relates to a preparation method of a magnetic polymer microsphere with a double-layer shell structure, which specifically comprises the following steps:
(1) Synthesis of functionalized porous polymer microspheres: firstly, uniformly mixing the materials in a 50mL three-neck flask with the mass ratio of 3:2, then adding 0.375g of polyvinylpyrrolidone, 2.5mL of styrene and 0.04g of azodiisobutyronitrile into the mixture, and heating the mixture to 75 ℃ under the protection of nitrogen for reaction for 12 hours to obtain polystyrene seed microspheres with the particle size of about 1 mu m; 0.6mL of toluene and 1.8mL of dibutyl phthalate are added into 30mL of aqueous solution containing 0.05g of sodium dodecyl sulfate, ultrasonic emulsification is carried out, and 0.1g of polystyrene seed microsphere is added into the aqueous solution to be swelled for 12 hours at room temperature; 2.5mL of methyl methacrylate, 0.5mL of divinylbenzene, 0.5mL of glycidyl methacrylate and 0.12g of benzoyl peroxide were added to a 30mL aqueous solution containing 0.05g of sodium dodecyl sulfate, and the mixture was phacoemulsified; adding the emulsion into the reaction liquid after swelling for 12 hours, and continuing swelling for 6 hours; finally, carrying out polymerization reaction for 16h at 70 ℃ under the protection of nitrogen atmosphere to obtain porous polymer microspheres; hydrolyzing 1g of porous polymer microspheres with 50mL of 10wt% sodium hydroxide aqueous solution at 60 ℃ for 8 hours, washing with distilled water to be neutral after the hydrolysis is finished, and condensing and refluxing with 50mL of 0.2mol/L sulfuric acid aqueous solution at 80 ℃ for 4 hours to obtain functionalized porous polymer microspheres;
(2) Preparation of magnetic polymer microsphere precursor: 40mL of water, 10mL of ethylene glycol and 0.1g of functionalized porous polymer microspheres are respectively weighed and added into a 100mL three-neck flask with mechanical stirring, and the mechanical stirring rotation speed is 200rpm, so that the functionalized porous polymer microspheres are uniformly dispersed; then 0.08g ferrous chloride tetrahydrate, 0.5g hexamethylenediamine and 0.1g potassium nitrate are added into the three-neck flask in sequence, fully stirred for 15min under the protection of nitrogen, the water bath temperature is increased to 80 ℃, the stirring rotation speed is adjusted to 500rpm, and the reaction lasts for 1h; washing the obtained black product in a magnetic field with distilled water for a plurality of times, and vacuum drying to obtain a magnetic polymer microsphere precursor;
(3) Polymeric encapsulation of the first housing: 1g of the magnetic polymer microsphere precursor is weighed, dispersed in 150mL of acetonitrile by ultrasonic, and added into a 250mL four-neck flask with a reflux device; then weighing 1g of methyl methacrylate, 1g of styrene, 0.2g of divinylbenzene and 0.05g of azodiisobutyronitrile, sequentially adding the mixture into a four-neck flask, transferring the four-neck flask with a reflux device into a water bath, setting the water bath temperature to 110 ℃, and reacting for 4 hours; washing the product in a magnetic field with distilled water for several times to obtain magnetic polymer microspheres with a first shell; the thickness of the first shell is 10nm;
(4) Polymeric encapsulation of the second housing: 1g of the magnetic polymer microsphere with the first shell is weighed, dispersed in 150mL of acetonitrile by ultrasonic, and added into a 250mL four-neck flask with a reflux device; weighing 4g of hydroxyethyl methacrylate, 1g of tert-butyl methacrylate, 1g of N, N' -methylene bisacrylamide and 0.25g of azobisisobutyronitrile, performing ultrasonic dispersion to dissolve the components, and adding the components into a four-necked flask; transferring the four-neck flask with the reflux device into a water bath, setting the water bath temperature to 93 ℃, and reacting for 4 hours; washing the product in a magnetic field with distilled water for several times to obtain magnetic polymer microspheres with a second shell; the thickness of the second shell is 21nm;
hydrolysis of magnetic Polymer microspheres: 1g of the magnetic polymer microsphere with the second shell is weighed, dispersed in 100mL of 10wt% sulfuric acid aqueous solution by ultrasonic, hydrolyzed at 80 ℃ for 3 hours, and the hydrolyzed product is washed with distilled water for several times in a magnetic field to obtain the hydrolyzed magnetic polymer microsphere.
Quantitative experiments on iron ion leakage: 1g of the hydrolyzed magnetic polymer microsphere is weighed, dispersed in 30mL of water, and stirred continuously for 2 hours in a water bath at 70 ℃. After the stirring is finished, taking out the magnetic polymer microspheres, mixing the magnetic polymer microspheres with 40mL of water, 1mL of 25wt% hydrochloric acid aqueous solution and 3mL of hydroxylamine hydrochloride with the concentration of 100mg/L, continuously stirring the mixture for 1 to 2 hours in a water bath at the temperature of 70 ℃, then cooling the mixture to room temperature, adding a small piece of Congo red test paper, dropwise adding a saturated sodium acetate solution until the Congo red test paper just turns red, adding 5mL of buffer solution (the buffer solution is diluted to 100mL by water after 40g of acetic acid and 50mL of glacial acid) and 2mL of o-phenanthroline solution, developing the color for 15 minutes after uniformly stirring, using a 10mm cuvette to carry out blank zeroing, measuring absorbance at the position of 510nm, and comparing the free iron ion content in the system through a standard curve.
Example 3
The invention relates to a preparation method of a magnetic polymer microsphere with a double-layer shell structure, which specifically comprises the following steps:
(1) Synthesis of functionalized porous polymer microspheres: firstly, uniformly mixing the materials in a 50mL three-neck flask with the mass ratio of 3:2, then adding 0.375g of polyvinylpyrrolidone, 2.5mL of styrene and 0.04g of azodiisobutyronitrile into the mixture, and heating the mixture to 75 ℃ under the protection of nitrogen for reaction for 12 hours to obtain polystyrene seed microspheres with the particle size of about 1 mu m; 0.6mL of toluene and 1.8mL of dibutyl phthalate are added into 30mL of aqueous solution containing 0.05g of sodium dodecyl sulfate, ultrasonic emulsification is carried out, and 0.1g of polystyrene seed microsphere is added into the aqueous solution to be swelled for 12 hours at room temperature; 2.5mL of methyl methacrylate, 0.5mL of divinylbenzene, 0.5mL of glycidyl methacrylate and 0.12g of benzoyl peroxide were added to a 30mL aqueous solution containing 0.05g of sodium dodecyl sulfate, and the mixture was phacoemulsified; adding the emulsion into the reaction liquid after swelling for 12 hours, and continuing swelling for 6 hours; finally, carrying out polymerization reaction for 16h at 70 ℃ under the protection of nitrogen atmosphere to obtain porous polymer microspheres; hydrolyzing 1g of porous polymer microspheres with 50mL of 10wt% sodium hydroxide aqueous solution at 60 ℃ for 8 hours, washing with distilled water to be neutral after the hydrolysis is finished, and condensing and refluxing with 50mL of 0.2mol/L sulfuric acid aqueous solution at 80 ℃ for 4 hours to obtain functionalized porous polymer microspheres;
(2) Preparation of magnetic polymer microsphere precursor: 40mL of water, 10mL of ethylene glycol and 0.16g of functionalized porous polymer microspheres are respectively weighed and added into a 100mL three-neck flask with mechanical stirring, and the mechanical stirring rotation speed is 200rpm, so that the functionalized porous polymer microspheres are uniformly dispersed; then 0.08g ferrous chloride tetrahydrate, 0.5g hexamethylenediamine and 0.1g potassium nitrate are added into the three-neck flask in sequence, fully stirred for 15min under the protection of nitrogen, the water bath temperature is increased to 80 ℃, the stirring rotation speed is adjusted to 500rpm, and the reaction lasts for 1h; washing the obtained black product in a magnetic field with distilled water for a plurality of times, and vacuum drying to obtain a magnetic polymer microsphere precursor;
(3) Polymeric encapsulation of the first housing: 1g of the magnetic polymer microsphere precursor is weighed, dispersed in 150mL of acetonitrile by ultrasonic, and added into a 250mL four-neck flask with a reflux device; then 2g of methyl methacrylate, 0.2g of divinylbenzene and 0.05g of azodiisobutyronitrile are weighed and sequentially added into a four-neck flask, the four-neck flask with a reflux device is transferred into a water bath, the water bath temperature is set to 110 ℃, and the reaction lasts for 4 hours; washing the product in a magnetic field with distilled water for several times to obtain magnetic polymer microspheres with a first shell; the thickness of the first shell is 20nm;
(4) Polymeric encapsulation of the second housing: 1g of the magnetic polymer microsphere with the first shell is weighed, dispersed in 150mL of acetonitrile by ultrasonic, and added into a 250mL four-neck flask with a reflux device; 8g of methacrylic acid, 2g of glycidyl methacrylate, 2g of N, N' -methylene bisacrylamide and 0.5g of azodiisobutyronitrile are weighed, dispersed by ultrasonic to be dissolved and then added into a four-necked flask; transferring the four-neck flask with the reflux device into a water bath, setting the water bath temperature to 93 ℃, and reacting for 4 hours; washing the product in a magnetic field with distilled water for several times to obtain magnetic polymer microspheres with a second shell; the thickness of the second shell is 15nm;
hydrolysis of magnetic Polymer microspheres: 1g of the magnetic polymer microsphere with the second shell is weighed, dispersed in 100mL of 10wt% sulfuric acid aqueous solution by ultrasonic, hydrolyzed at 80 ℃ for 3 hours, and the hydrolyzed product is washed with distilled water for several times in a magnetic field to obtain the hydrolyzed magnetic polymer microsphere.
Quantitative experiments on iron ion leakage: 1g of the hydrolyzed magnetic polymer microsphere is weighed, dispersed in 30mL of water, and stirred continuously for 2 hours in a water bath at 70 ℃. After the stirring is finished, taking out the magnetic polymer microspheres, mixing the magnetic polymer microspheres with 40mL of water, 1mL of 25wt% hydrochloric acid aqueous solution and 3mL of hydroxylamine hydrochloride with the concentration of 100mg/L, continuously stirring the mixture for 1 to 2 hours in a water bath at the temperature of 70 ℃, then cooling the mixture to room temperature, adding a small piece of Congo red test paper, dropwise adding a saturated sodium acetate solution until the Congo red test paper just turns red, adding 5mL of buffer solution (the buffer solution is diluted to 100mL by water after 40g of acetic acid and 50mL of glacial acid) and 2mL of o-phenanthroline solution, developing the color for 15 minutes after uniformly stirring, using a 10mm cuvette to carry out blank zeroing, measuring absorbance at the position of 510nm, and comparing the free iron ion content in the system through a standard curve.
Comparative example 1 is a surface carboxyl core-shell superparamagnetic microsphere prepared by a method disclosed in CN108467461A
Quantitative experiments on iron ion leakage: 1g of surface carboxyl core-shell superparamagnetic microsphere is weighed and dispersed in 30mL of water, and the mixture is stirred continuously for 2 hours in a water bath at 70 ℃. After the stirring is finished, taking out the magnetic polymer microspheres, mixing the magnetic polymer microspheres with 40mL of water, 1mL of 25wt% hydrochloric acid aqueous solution and 3mL of hydroxylamine hydrochloride with the concentration of 100mg/L, continuously stirring the mixture for 1 to 2 hours in a water bath at the temperature of 70 ℃, then cooling the mixture to room temperature, adding a small piece of Congo red test paper, dropwise adding a saturated sodium acetate solution until the Congo red test paper just turns red, adding 5mL of buffer solution (the buffer solution is diluted to 100mL by water after 40g of acetic acid and 50mL of glacial acid) and 2mL of o-phenanthroline solution, developing the color for 15 minutes after uniformly stirring, using a 10mm cuvette to carry out blank zeroing, measuring absorbance at the position of 510nm, and comparing the free iron ion content in the system through a standard curve.
Comparative example 2
Comparative example 2 the preparation of magnetic polymer microspheres was substantially identical to that of example 3, the only difference being that comparative example 2 prepared a magnetic polymer microsphere precursor in step (2) by the co-precipitation method, the specific procedure for preparing a magnetic polymer microsphere precursor by the co-precipitation method being: respectively weighing 0.9g of ferrous chloride tetrahydrate, 1.4g of ferric chloride hexahydrate, 0.16g of functionalized porous polymer microsphere and 50mL of water, adding into a 100mL three-neck flask with mechanical stirring, quickly and uniformly dispersing the mixture at 1000rpm, then raising the temperature to 70 ℃ for stirring for 1h, quickly adding 8mL of ammonia water into the system, reacting for 0.5h, washing the obtained black product in a magnetic field with distilled water for a plurality of times, and vacuum drying to obtain the magnetic polymer microsphere precursor.
Quantitative experiments on iron ion leakage: 1g of the magnetic polymer microsphere prepared in comparative example 2 was weighed, dispersed in 30mL of water, and stirred continuously for 2 hours in a water bath at 70 ℃. After the stirring is finished, taking out the magnetic polymer microspheres, mixing the magnetic polymer microspheres with 40mL of water, 1mL of 25wt% hydrochloric acid aqueous solution and 3mL of hydroxylamine hydrochloride with the concentration of 100mg/L, continuously stirring the mixture for 1 to 2 hours in a water bath at the temperature of 70 ℃, then cooling the mixture to room temperature, adding a small piece of Congo red test paper, dropwise adding a saturated sodium acetate solution until the Congo red test paper just turns red, adding 5mL of buffer solution (the buffer solution is diluted to 100mL by water after 40g of acetic acid and 50mL of glacial acid) and 2mL of o-phenanthroline solution, developing the color for 15 minutes after uniformly stirring, using a 10mm cuvette to carry out blank zeroing, measuring absorbance at the position of 510nm, and comparing the free iron ion content in the system through a standard curve. Comparative example 3
Comparative example 3 the preparation of magnetic polymer microspheres was essentially identical to the process of example 3, the only difference being that comparative example 3 did not first polymerization encapsulate the magnetic polymer microsphere precursor, but rather encapsulation of the hydrophilic polymer coating was performed directly on the magnetic polymer microsphere precursor.
Quantitative experiments on iron ion leakage: 1g of the magnetic polymer microsphere prepared in comparative example 3 was weighed, dispersed in 30mL of water, and stirred continuously for 2 hours in a water bath at 70 ℃. After the stirring is finished, taking out the magnetic polymer microspheres, mixing the magnetic polymer microspheres with 40mL of water, 1mL of 25wt% hydrochloric acid aqueous solution and 3mL of hydroxylamine hydrochloride with the concentration of 100mg/L, continuously stirring the mixture for 1 to 2 hours in a water bath at the temperature of 70 ℃, then cooling the mixture to room temperature, adding a small piece of Congo red test paper, dropwise adding a saturated sodium acetate solution until the Congo red test paper just turns red, adding 5mL of buffer solution (the buffer solution is diluted to 100mL by water after 40g of acetic acid and 50mL of glacial acid) and 2mL of o-phenanthroline solution, developing the color for 15 minutes after uniformly stirring, using a 10mm cuvette to carry out blank zeroing, measuring absorbance at the position of 510nm, and comparing the free iron ion content in the system through a standard curve.
TABLE 1 quantitative test results of iron ion leakage for magnetic Polymer microspheres
| Numbering device | Iron ion leakage (mg/L) | Magnetic content (mg/mg) |
| Example 1 | 8 | 18.9 |
| Example 2 | 5 | 25.6 |
| Example 3 | 2 | 28.4 |
| Comparative example 1 | 65 | 14.1 |
| Comparative example 2 | 230 | 33.2 |
| Comparative example 3 | 77 | 19.7 |
As shown in Table 1, the magnetic polymer microsphere prepared by the method has good monodispersity and high magnetic content, the iron ion leakage amount in the system is less than 10mg/L, and the encapsulation coating of the hydrophobic-hydrophilic double-layer shell structure has reliable stabilization effect on the magnetic polymer microsphere, so that the problem of iron ion leakage of the magnetic polymer microsphere in the practical application process is solved. The experimental results of comparative examples 1 and 3 show that the encapsulation effect of the single-layer hydrophilic copolymer coating on the magnetic polymer microspheres is far lower than that of a double-layer shell structure or even a combination encapsulation mode of a multi-layer shell structure.
Claims (10)
1. The preparation method of the magnetic polymer microsphere with the double-layer shell structure is characterized by comprising the following steps of:
(1) The polystyrene seed microsphere is swelled in the first step under the action of a swelling agent and a surfactant, swelled in the second step under the action of a functional monomer, an initiator and the surfactant, and the functionalized porous polymer microsphere is prepared;
(2) Preparing a magnetic polymer microsphere precursor by using the functionalized porous polymer microsphere as a template through a hydrothermal precipitation method;
(3) Performing first polymerization encapsulation on the magnetic polymer microsphere precursor, and coating a hydrophobic polymer coating on the surface of the magnetic polymer microsphere precursor by a reflux precipitation method, wherein the hydrophobic polymer coating is a first shell of the magnetic polymer microsphere;
(4) Performing second polymerization encapsulation on the magnetic polymer microsphere with the first shell, and coating a hydrophilic polymer coating on the surface of the first shell by a reflux precipitation method, wherein the hydrophilic polymer coating is the second shell of the magnetic polymer microsphere; the magnetic polymer microsphere with a double-layer shell structure is obtained.
2. The method for preparing the magnetic polymer microsphere with the double-layer shell structure according to claim 1, wherein the method comprises the following steps: based on different application scenes, the magnetic polymer microsphere with the second shell is placed in one or more solutions of sulfuric acid, sodium hydroxide, ethylenediamine, ammonia water or anhydride, and reacted for 1-24 hours at 30-120 ℃ to obtain the magnetic polymer microsphere with different functional groups on the surface.
3. The method for preparing the magnetic polymer microsphere with the double-layer shell structure according to claim 1, wherein the method comprises the following steps: in the step (1), the functional monomer is a monomer with one or more functional groups of amino, carboxyl, epoxy or hydroxyl; the functional groups on the surface of the functionalized porous polymer microsphere are one or more of amino, carboxyl, epoxy or hydroxyl.
4. The method for preparing the magnetic polymer microsphere with the double-layer shell structure according to claim 1, wherein the method comprises the following steps: in the step (2), the hydrothermal precipitation method specifically comprises the following steps: dispersing functionalized porous polymer microspheres, ferrous compounds, hexamethylenetetramine and nitrate in a mixed solution of water and glycol, and reacting for 0.5-6 h at 50-150 ℃ in an inert atmosphere; the ferrous compound is ferrous chloride and/or ferrous sulfate; the mass ratio of the functionalized porous polymer microsphere to the ferrous compound is 1:3-3:1.
5. The method for preparing the magnetic polymer microsphere with the double-layer shell structure according to claim 1, wherein the method comprises the following steps: in the step (3), the first polymerization encapsulation is performed by a reflow precipitation method specifically comprises: dispersing the magnetic polymer microsphere precursor, hydrophobic monomer, cross-linking agent and initiator in acetonitrile, and carrying out reflux reaction for 0.5-6 h at 50-150 ℃.
6. The method for preparing the magnetic polymer microsphere with the double-layer shell structure according to claim 5, wherein the method comprises the following steps: the thickness of the hydrophobic polymer coating is 10-60 nm.
7. The method for preparing the magnetic polymer microsphere with the double-layer shell structure according to claim 5, wherein the method comprises the following steps: the hydrophobic monomer is one or more of styrene, methyl methacrylate, isobutyl methacrylate or cyclohexyl methacrylate; the cross-linking agent is one or more of divinylbenzene, ethylene glycol dimethacrylate and N, N' -methylene bisacrylamide, and the adding amount of the cross-linking agent is 1-25% of the mass of the hydrophobic monomer; the initiator is one or more of azodiisobutyronitrile, benzoyl peroxide, potassium persulfate or ammonium persulfate, and the addition amount of the initiator is 0.2-10% of the mass of the hydrophobic monomer; the mass ratio of the hydrophobic monomer to the magnetic polymer microsphere precursor is 1: 3-10: 1.
8. the method for preparing the magnetic polymer microsphere with the double-layer shell structure according to claim 1, wherein the method comprises the following steps: in the step (4), the second polymerization encapsulation is performed by a reflow precipitation method specifically comprises: dispersing the magnetic polymer microsphere with the first shell, hydrophilic monomer, cross-linking agent and initiator in acetonitrile, and carrying out reflux reaction for 0.5-6 h at 50-150 ℃.
9. The method for preparing the magnetic polymer microsphere with the double-layer shell structure according to claim 8, wherein the method comprises the following steps: the thickness of the hydrophilic polymer coating is 15-25 nm.
10. The method for preparing the magnetic polymer microsphere with the double-layer shell structure according to claim 8, wherein the method comprises the following steps: the hydrophilic monomer is one or more of glycidyl methacrylate, hydroxyethyl methacrylate, methacrylic acid, tert-butyl methacrylate or methacrylamide; the cross-linking agent is one or more of divinylbenzene, ethylene glycol dimethacrylate, butanediol dimethacrylate, bisphenol A dimethacrylate or N, N' -methylene bisacrylamide, and the adding amount of the cross-linking agent is 1-25% of the mass of the hydrophilic monomer; the initiator is one or more of azodiisobutyronitrile, benzoyl peroxide, tertiary amyl hydroperoxide, potassium persulfate, sodium persulfate or ammonium persulfate, and the addition amount of the initiator is 0.2-10% of the mass of the hydrophilic monomer; the mass ratio of the hydrophilic monomer to the magnetic polymer microsphere with the first shell is 1: 3-10: 1.
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| 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 |
| CN114106254A (en) * | 2021-11-25 | 2022-03-01 | 东南大学 | Method for preparing functionalized magnetic polymer microspheres by miniemulsion polymerization method using porous microspheres as templates |
| CN114192079A (en) * | 2021-12-13 | 2022-03-18 | 广州光驭超材料有限公司 | Magnetic hollow polymer microsphere and preparation method and application thereof |
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| 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 |
| CN114106254A (en) * | 2021-11-25 | 2022-03-01 | 东南大学 | Method for preparing functionalized magnetic polymer microspheres by miniemulsion polymerization method using porous microspheres as templates |
| CN114192079A (en) * | 2021-12-13 | 2022-03-18 | 广州光驭超材料有限公司 | Magnetic hollow polymer microsphere and preparation method and application thereof |
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