TWI446924B - Manufacturing method of magnetic composite particles - Google Patents
Manufacturing method of magnetic composite particles Download PDFInfo
- Publication number
- TWI446924B TWI446924B TW101101902A TW101101902A TWI446924B TW I446924 B TWI446924 B TW I446924B TW 101101902 A TW101101902 A TW 101101902A TW 101101902 A TW101101902 A TW 101101902A TW I446924 B TWI446924 B TW I446924B
- Authority
- TW
- Taiwan
- Prior art keywords
- magnetic
- composite
- oil
- water
- ratio
- Prior art date
Links
- 230000005291 magnetic effect Effects 0.000 title claims description 181
- 238000004519 manufacturing process Methods 0.000 title claims description 25
- 239000011246 composite particle Substances 0.000 title description 3
- 239000002131 composite material Substances 0.000 claims description 186
- 239000006249 magnetic particle Substances 0.000 claims description 134
- 239000000243 solution Substances 0.000 claims description 92
- 239000011259 mixed solution Substances 0.000 claims description 91
- 239000002122 magnetic nanoparticle Substances 0.000 claims description 75
- 239000001913 cellulose Substances 0.000 claims description 74
- 229920002678 cellulose Polymers 0.000 claims description 74
- 239000002245 particle Substances 0.000 claims description 74
- 239000011859 microparticle Substances 0.000 claims description 68
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 57
- 238000000034 method Methods 0.000 claims description 52
- 229920003169 water-soluble polymer Polymers 0.000 claims description 51
- 239000003921 oil Substances 0.000 claims description 45
- 235000019198 oils Nutrition 0.000 claims description 45
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims description 44
- 235000010413 sodium alginate Nutrition 0.000 claims description 44
- 239000000661 sodium alginate Substances 0.000 claims description 44
- 229940005550 sodium alginate Drugs 0.000 claims description 44
- 238000002156 mixing Methods 0.000 claims description 29
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 24
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 19
- 239000000126 substance Substances 0.000 claims description 19
- 239000000463 material Substances 0.000 claims description 9
- 239000004094 surface-active agent Substances 0.000 claims description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 7
- 229910052799 carbon Inorganic materials 0.000 claims description 7
- 239000004848 polyfunctional curative Substances 0.000 claims description 7
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 claims description 4
- 150000001875 compounds Chemical class 0.000 claims description 3
- 235000015112 vegetable and seed oil Nutrition 0.000 claims description 3
- 229920001661 Chitosan Polymers 0.000 claims description 2
- 235000019483 Peanut oil Nutrition 0.000 claims description 2
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 2
- 235000019486 Sunflower oil Nutrition 0.000 claims description 2
- 235000005687 corn oil Nutrition 0.000 claims description 2
- 239000002285 corn oil Substances 0.000 claims description 2
- 239000010642 eucalyptus oil Substances 0.000 claims description 2
- 229940044949 eucalyptus oil Drugs 0.000 claims description 2
- 239000012208 gear oil Substances 0.000 claims description 2
- 239000010720 hydraulic oil Substances 0.000 claims description 2
- 239000010705 motor oil Substances 0.000 claims description 2
- 239000004006 olive oil Substances 0.000 claims description 2
- 235000008390 olive oil Nutrition 0.000 claims description 2
- 239000000312 peanut oil Substances 0.000 claims description 2
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 2
- 239000003549 soybean oil Substances 0.000 claims description 2
- 235000012424 soybean oil Nutrition 0.000 claims description 2
- 239000002600 sunflower oil Substances 0.000 claims description 2
- 229910052723 transition metal Inorganic materials 0.000 claims description 2
- 235000009754 Vitis X bourquina Nutrition 0.000 claims 1
- 235000012333 Vitis X labruscana Nutrition 0.000 claims 1
- 240000006365 Vitis vinifera Species 0.000 claims 1
- 235000014787 Vitis vinifera Nutrition 0.000 claims 1
- 239000012071 phase Substances 0.000 description 74
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N Iron oxide Chemical compound [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 description 62
- 229920000642 polymer Polymers 0.000 description 29
- 238000009826 distribution Methods 0.000 description 19
- 238000004458 analytical method Methods 0.000 description 16
- 238000003756 stirring Methods 0.000 description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 238000002360 preparation method Methods 0.000 description 14
- 210000004027 cell Anatomy 0.000 description 13
- 239000007788 liquid Substances 0.000 description 13
- 239000011238 particulate composite Substances 0.000 description 12
- XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Substances [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 11
- NDLPOXTZKUMGOV-UHFFFAOYSA-N oxo(oxoferriooxy)iron hydrate Chemical compound O.O=[Fe]O[Fe]=O NDLPOXTZKUMGOV-UHFFFAOYSA-N 0.000 description 10
- 239000000696 magnetic material Substances 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- 238000000576 coating method Methods 0.000 description 8
- -1 decane compound Chemical class 0.000 description 8
- 239000010419 fine particle Substances 0.000 description 8
- 125000000524 functional group Chemical group 0.000 description 8
- 239000010410 layer Substances 0.000 description 8
- DIOQZVSQGTUSAI-UHFFFAOYSA-N n-butylhexane Natural products CCCCCCCCCC DIOQZVSQGTUSAI-UHFFFAOYSA-N 0.000 description 8
- 238000006116 polymerization reaction Methods 0.000 description 8
- 238000000635 electron micrograph Methods 0.000 description 7
- 239000000203 mixture Substances 0.000 description 7
- 239000011248 coating agent Substances 0.000 description 6
- SZVJSHCCFOBDDC-UHFFFAOYSA-N ferrosoferric oxide Chemical compound O=[Fe]O[Fe]O[Fe]=O SZVJSHCCFOBDDC-UHFFFAOYSA-N 0.000 description 6
- 229910052742 iron Inorganic materials 0.000 description 6
- 239000011148 porous material Substances 0.000 description 6
- SGVYKUFIHHTIFL-UHFFFAOYSA-N 2-methylnonane Chemical compound CCCCCCCC(C)C SGVYKUFIHHTIFL-UHFFFAOYSA-N 0.000 description 5
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 5
- 229940072056 alginate Drugs 0.000 description 5
- 235000010443 alginic acid Nutrition 0.000 description 5
- 229920000615 alginic acid Polymers 0.000 description 5
- 239000008346 aqueous phase Substances 0.000 description 5
- 239000006185 dispersion Substances 0.000 description 5
- 239000007791 liquid phase Substances 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- 239000002861 polymer material Substances 0.000 description 5
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 4
- 239000004793 Polystyrene Substances 0.000 description 4
- 238000013019 agitation Methods 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 238000000975 co-precipitation Methods 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 239000000314 lubricant Substances 0.000 description 4
- 239000002923 metal particle Substances 0.000 description 4
- 239000000178 monomer Substances 0.000 description 4
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 239000000376 reactant Substances 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 3
- 239000000427 antigen Substances 0.000 description 3
- 102000036639 antigens Human genes 0.000 description 3
- 108091007433 antigens Proteins 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 239000011324 bead Substances 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- YCOZIPAWZNQLMR-UHFFFAOYSA-N heptane - octane Natural products CCCCCCCCCCCCCCC YCOZIPAWZNQLMR-UHFFFAOYSA-N 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- 229920002223 polystyrene Polymers 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- QRIMLDXJAPZHJE-UHFFFAOYSA-N 2,3-dihydroxypropyl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OCC(O)CO QRIMLDXJAPZHJE-UHFFFAOYSA-N 0.000 description 2
- GXDHCNNESPLIKD-UHFFFAOYSA-N 2-methylhexane Natural products CCCCC(C)C GXDHCNNESPLIKD-UHFFFAOYSA-N 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- VTLYFUHAOXGGBS-UHFFFAOYSA-N Fe3+ Chemical compound [Fe+3] VTLYFUHAOXGGBS-UHFFFAOYSA-N 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 2
- 150000001335 aliphatic alkanes Chemical class 0.000 description 2
- 239000000908 ammonium hydroxide Substances 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 229940098773 bovine serum albumin Drugs 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 229910017052 cobalt Inorganic materials 0.000 description 2
- 239000010941 cobalt Substances 0.000 description 2
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 2
- 239000000470 constituent Substances 0.000 description 2
- 239000011258 core-shell material Substances 0.000 description 2
- 239000008367 deionised water Substances 0.000 description 2
- 229910021641 deionized water Inorganic materials 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- DCAYPVUWAIABOU-UHFFFAOYSA-N hexadecane Chemical compound CCCCCCCCCCCCCCCC DCAYPVUWAIABOU-UHFFFAOYSA-N 0.000 description 2
- 238000003018 immunoassay Methods 0.000 description 2
- KUVMKLCGXIYSNH-UHFFFAOYSA-N isopentadecane Chemical compound CCCCCCCCCCCCC(C)C KUVMKLCGXIYSNH-UHFFFAOYSA-N 0.000 description 2
- CJBFZKZYIPBBTO-UHFFFAOYSA-N isotetradecane Natural products CCCCCCCCCCCC(C)C CJBFZKZYIPBBTO-UHFFFAOYSA-N 0.000 description 2
- HGEMCUOAMCILCP-UHFFFAOYSA-N isotridecane Natural products CCCCCCCCCCC(C)C HGEMCUOAMCILCP-UHFFFAOYSA-N 0.000 description 2
- 239000002105 nanoparticle Substances 0.000 description 2
- 229920005615 natural polymer Polymers 0.000 description 2
- 229910052759 nickel Inorganic materials 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- BGHCVCJVXZWKCC-UHFFFAOYSA-N tetradecane Chemical compound CCCCCCCCCCCCCC BGHCVCJVXZWKCC-UHFFFAOYSA-N 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- IIYFAKIEWZDVMP-UHFFFAOYSA-N tridecane Chemical compound CCCCCCCCCCCCC IIYFAKIEWZDVMP-UHFFFAOYSA-N 0.000 description 2
- 239000008158 vegetable oil Substances 0.000 description 2
- 229910000859 α-Fe Inorganic materials 0.000 description 2
- JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 description 1
- PTTPXKJBFFKCEK-UHFFFAOYSA-N 2-Methyl-4-heptanone Chemical compound CC(C)CC(=O)CC(C)C PTTPXKJBFFKCEK-UHFFFAOYSA-N 0.000 description 1
- CNPVJWYWYZMPDS-UHFFFAOYSA-N 2-methyldecane Chemical compound CCCCCCCCC(C)C CNPVJWYWYZMPDS-UHFFFAOYSA-N 0.000 description 1
- GTJOHISYCKPIMT-UHFFFAOYSA-N 2-methylundecane Chemical compound CCCCCCCCCC(C)C GTJOHISYCKPIMT-UHFFFAOYSA-N 0.000 description 1
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- CWYNVVGOOAEACU-UHFFFAOYSA-N Fe2+ Chemical compound [Fe+2] CWYNVVGOOAEACU-UHFFFAOYSA-N 0.000 description 1
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- NHTMVDHEPJAVLT-UHFFFAOYSA-N Isooctane Chemical compound CC(C)CC(C)(C)C NHTMVDHEPJAVLT-UHFFFAOYSA-N 0.000 description 1
- CERQOIWHTDAKMF-UHFFFAOYSA-M Methacrylate Chemical compound CC(=C)C([O-])=O CERQOIWHTDAKMF-UHFFFAOYSA-M 0.000 description 1
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical group NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 1
- 108091005461 Nucleic proteins Proteins 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 238000005054 agglomeration Methods 0.000 description 1
- 230000004520 agglutination Effects 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000007605 air drying Methods 0.000 description 1
- 125000003172 aldehyde group Chemical group 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 150000001718 carbodiimides Chemical class 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000007596 consolidation process Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000007334 copolymerization reaction Methods 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 239000000412 dendrimer Substances 0.000 description 1
- 229920000736 dendritic polymer Polymers 0.000 description 1
- 238000006193 diazotization reaction Methods 0.000 description 1
- JVSWJIKNEAIKJW-UHFFFAOYSA-N dimethyl-hexane Natural products CCCCCC(C)C JVSWJIKNEAIKJW-UHFFFAOYSA-N 0.000 description 1
- SNRUBQQJIBEYMU-UHFFFAOYSA-N dodecane Chemical compound CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 230000005294 ferromagnetic effect Effects 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 238000013467 fragmentation Methods 0.000 description 1
- 238000006062 fragmentation reaction Methods 0.000 description 1
- 239000008169 grapeseed oil Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000013537 high throughput screening Methods 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000003999 initiator Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- JEIPFZHSYJVQDO-UHFFFAOYSA-N iron(III) oxide Inorganic materials O=[Fe]O[Fe]=O JEIPFZHSYJVQDO-UHFFFAOYSA-N 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- VKPSKYDESGTTFR-UHFFFAOYSA-N isododecane Natural products CC(C)(C)CC(C)CC(C)(C)C VKPSKYDESGTTFR-UHFFFAOYSA-N 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 230000001050 lubricating effect Effects 0.000 description 1
- 238000007885 magnetic separation Methods 0.000 description 1
- 230000005389 magnetism Effects 0.000 description 1
- 239000007769 metal material Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- FQPSGWSUVKBHSU-UHFFFAOYSA-N methacrylamide Chemical compound CC(=C)C(N)=O FQPSGWSUVKBHSU-UHFFFAOYSA-N 0.000 description 1
- 239000000693 micelle Substances 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 229940094933 n-dodecane Drugs 0.000 description 1
- 239000002086 nanomaterial Substances 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 239000002096 quantum dot Substances 0.000 description 1
- 238000007670 refining Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 239000011265 semifinished product Substances 0.000 description 1
- 229910000077 silane Inorganic materials 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000010557 suspension polymerization reaction Methods 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
- RSJKGSCJYJTIGS-UHFFFAOYSA-N undecane Chemical compound CCCCCCCCCCC RSJKGSCJYJTIGS-UHFFFAOYSA-N 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
Landscapes
- Soft Magnetic Materials (AREA)
- Hard Magnetic Materials (AREA)
Description
本發明係有關於一種磁性微粒複合物的製作方法；特別是關於一種包含了控制溶液混合的步驟，以製造磁性微粒複合物的製作方法。 The present invention relates to a method for producing a magnetic particulate composite; and more particularly to a method for producing a magnetic particulate composite comprising the step of controlling the mixing of the solution.
磁性微粒於生物醫學領域的應用相當廣泛，其常應用於分離或篩選生物分子之相關技術。其中尤以磁性粒子複合物較為普及。磁性粒子複合物包含了磁性微粒結構，可經由以天然或合成之高分子修飾後，常有助於其維持穩定性與分散性、提升與生物分子如核酸或蛋白質的結合能力與特異性、降低生物毒性與提高生物相容性，以及增加水溶性之優勢。 Magnetic particles are widely used in the biomedical field and are commonly used in related technologies for isolating or screening biomolecules. Among them, magnetic particle composites are particularly popular. The magnetic particle composite contains a magnetic particle structure, which can be modified by a natural or synthetic polymer to help maintain stability and dispersibility, enhance binding ability and specificity with biomolecules such as nucleic acids or proteins, and reduce Biological toxicity and increased biocompatibility, as well as increased water solubility.
關於磁性粒子複合物於生物分子的分離技術之應用，一般常用於聯接蛋白質或抗體的磁性粒子複合物的粒徑自奈米級至微米級均具有其應用性。舉例而言，用於分離特定細胞的免疫性磁性粒子複合物，其係利用聯接於磁性粒子複合物的抗體與目標細胞表面的抗原結合，與磁性粒子複合物結合的細胞進而被吸附並滯留在外加磁場中，達到分離目標細胞的效果。其中，就每單位細胞中可結合之磁性粒子複合物的數量而言，微米級磁性粒子複合物雖然遠少於奈米級磁性粒子複合物，但就每單位細胞量所含之整體磁力而言，其具有較高的單位細胞磁力，因此所得的分離效果較佳。 Regarding the application of the magnetic particle composite to the separation technique of biomolecules, the particle size of the magnetic particle composite generally used for linking proteins or antibodies has its applicability from nanometer to micrometer. For example, an immunomagnetic particle complex for isolating a specific cell, which binds to an antigen on a surface of a target cell by an antibody coupled to the magnetic particle complex, and the cell bound to the magnetic particle complex is adsorbed and retained in the cell. In the external magnetic field, the effect of separating the target cells is achieved. Among them, in terms of the number of magnetic particle composites that can be combined per unit cell, although the micron-sized magnetic particle composite is much smaller than the nano-sized magnetic particle composite, the overall magnetic force per unit cell amount is It has a high unit cell magnetic force, so the resulting separation effect is better.
舉例言之，目前市售的微米級磁性微粒複合物產品及其功能特性如下：美國BD Bioscience公司產品：BD IMagnetTM磁性微粒，其粒徑大小約0.1-0.45微米，介於奈米與微米之間，此磁性微粒表面載有的單株抗體，可藉由磁性分離管吸附特定的細胞，進而分離之。挪威Dynal公司產品：Dynabeads®磁珠，其材質為聚苯乙烯(Polystyrene,PS)，粒徑大小約2.8微米，此磁珠聯接特定的抗體，可選擇性地吸附特定的細胞後，藉由提供 外加磁場分離細胞，再以酵素截切磁珠上的抗體與細胞表面的抗原結合處，取得特定的細胞。美國Seradyn公司產品：Sera-Mag®磁性顆粒，粒徑約為1微米。美國Polysciences,Inc.公司產品：BioMag®磁珠，其粒徑大小約1微米，核心由氧化鐵組成，外層則包覆了一層矽烷化合物(silane)而同樣為Polysciences,Inc.公司產品Estapor®超順磁微粒(superparamagnetic microsphcres)，係為粒徑大小從次微米至微米的磁性粒子複合物。 For example words, currently commercially available micron-sized magnetic particles and the composite product features are as follows: U.S. BD Bioscience Products: BD IMagnet TM magnetic fine particles having a particle diameter size of about 0.1 to 0.45 microns, between the nm and micron In the meantime, the monoclonal antibodies carried on the surface of the magnetic particles can be separated by adsorbing specific cells by a magnetic separation tube. Dynal products from Norway: Dynabeads® magnetic beads, made of polystyrene (PS), with a particle size of about 2.8 μm. This magnetic bead is attached to a specific antibody and can selectively adsorb specific cells. The cells are separated by a magnetic field, and the antibody is bound to the antigen on the cell surface by an enzyme to obtain a specific cell. US Seradyn products: Sera-Mag® magnetic particles with a particle size of approximately 1 micron. Polysciences, Inc., USA: BioMag® magnetic beads with a particle size of about 1 micron, the core consists of iron oxide, and the outer layer is coated with a layer of silane, which is also the product of Polysciences, Inc. Estapor®. Superparamagnetic microsphcres are magnetic particle composites with particle sizes ranging from submicron to micron.
除了習知的磁性微粒，超順磁(Super-paramagnetic)微粒也是相當受矚目的材料，其特性係僅於外加磁場的情況下才表現出磁性，反之則無，所以可藉調整外加磁場的加以控制超順磁微粒所表現出的磁性，可應用在與磁性有關之技術領域。 In addition to the conventional magnetic particles, super-paramagnetic particles are also quite attractive materials. Their characteristics are magnetic only when an external magnetic field is applied, and vice versa. Therefore, the external magnetic field can be adjusted. Controlling the magnetic properties exhibited by superparamagnetic particles can be applied to the technical field related to magnetism.
前述習知磁性粒子複合物的製作方法，一般可區分為兩種：其一為包覆性方法，係以磁性金屬物質做為中心核，再以高分子包覆其外形成外殼；另一為散佈性方法，係以磁性金屬物質均勻分散於高分子材料中，或將其填充於此高分子的孔洞。 The method for preparing the conventional magnetic particle composite can be generally divided into two types: one is a coating method, the magnetic metal material is used as a central core, and the outer layer is formed by coating the outer layer with the polymer; The dispersive method is a method in which a magnetic metal substance is uniformly dispersed in a polymer material or filled in a pore of the polymer.
關於上述之包覆性方法，通常是利用矽烷化合物包覆磁性金屬顆粒，形成粒徑約0.1-10微米的磁性粒子複合物，主要應用於免疫吸附技術；而非矽烷類化合物形成之高分子材料也可應用於包覆磁性金屬顆粒，形成磁性粒子複合物。美國專利第4,267,234號揭示了一種利用聚戊二醛高分子包覆磁性金屬顆粒，且此高分子上帶有醛基可聯接抗體或抗原。此專利亦揭示此高分子中可混入聚氯乙烯(polyvinylpyrrolidone,PVP)或甲基丙烯酸酯(methacrylamide)類的高分子或單體，增加其應用性。美國專利第4,554,088號則揭示了一種利用矽烷類高分子包覆四氧化三鐵(Fe3O4)顆粒後，再利用重氮化(diazotization)，或者以碳二亞胺(carbodiimide)或戊二醛(glutaraldehyde)等加以改質，進而製備磁性高分子微粒，其可聯接抗體並用於生化分離技術。美國專利第4,783,336號揭示一種利用聚丙烯醛高分子包覆四氧化三鐵顆粒的方法。美國專利第6,204,033號中揭示一種利用純 聚乙烯高分子包覆鐵磁或超順磁物質的方法。美國專利第4,452,773號與第4,795,698號中分別揭示一種利用天然高分子(例如葡聚醣)與牛血清蛋白(BSA)包覆四氧化三鐵的方法。中華民國發明專利第169427號亦揭示一種利用有機高分子聚苯乙烯或甲基丙烯酸酯做為殼層，並包覆磁性的氧化鐵型鐵酸鹽的方法。上揭專利均係利用高分子包覆磁性顆粒，故所形成的磁性粒子複合物的中心核均為磁性顆粒，而表面則為帶有反應官能基之高分子。 Regarding the above coating method, the magnetic metal particles are usually coated with a decane compound to form a magnetic particle composite having a particle diameter of about 0.1 to 10 μm, which is mainly applied to an immunoadsorption technique; a polymer material formed by a non-decane compound; It can also be applied to coating magnetic metal particles to form a magnetic particle composite. U.S. Patent No. 4,267,234 discloses the use of a polyglutaraldehyde polymer to coat magnetic metal particles with an aldehyde group attached to the antibody or antigen. This patent also discloses that a polymer or a monomer which can be mixed with polyvinylpyrrolidone (PVP) or methacrylamide can be added to the polymer to increase its applicability. U.S. Patent No. 4,554,088 discloses the use of a decane-based polymer coated with ferroferric oxide (Fe 3 O 4 ) particles, followed by diazotization, or with carbodiimide or pentane. The glutaraldehyde or the like is modified to prepare magnetic polymer microparticles which can be linked to an antibody and used for biochemical separation techniques. U.S. Patent No. 4,783,336 discloses a method of coating a ferroferric oxide particle with a polyacrylaldehyde polymer. A method of coating a ferromagnetic or superparamagnetic substance with a pure polyethylene polymer is disclosed in U.S. Patent No. 6,204,033. A method of coating ferroferric oxide with a bovine serum albumin (BSA) using a natural polymer (e.g., dextran) is disclosed in U.S. Patent Nos. 4,452,773 and 4,795,698, respectively. The Republic of China Invention Patent No. 169427 also discloses a method of using an organic high molecular polystyrene or methacrylate as a shell and coating a magnetic iron oxide type ferrite. The above patents all use magnetic particles coated with magnetic particles, so the central core of the magnetic particle composite formed is magnetic particles, and the surface is a polymer with reactive functional groups.
雖然上述之製作方法均可製得磁性粒子複合物，然而卻不易控制所製得之磁性粒子複合物的形狀與大小，造成微粒粒徑的分佈範圍較廣，且外觀形狀不規則，甚至有顆粒凝聚的現象，均可影響製得之磁性粒子複合物成品的磁性反應能力與含磁量，限制其應用性。 Although the above-mentioned manufacturing method can produce a magnetic particle composite, it is difficult to control the shape and size of the prepared magnetic particle composite, resulting in a wide distribution of particle size, irregular shape and even particles. The phenomenon of agglomeration can affect the magnetic reaction ability and magnetic content of the finished magnetic particle composite, and limit its applicability.
為了解決上述方法的問題，美國專利第5,320,944號揭示一種於聚苯乙烯高分子微粒表面包覆一層氧化型鐵、鈷、鎳類磁性物質的磁性高分子顆粒，其係應用於免疫分析。同樣地，為了解決上述問題，通常會採用另一種磁性粒子複合物的製作方法，即前述之散佈性磁性粒子複合物製作方法。此類方法通常是將磁性金屬物質均勻分散於高分子材料中，係利用高分子聚合用的單體與磁性材料均勻混合，或是將其填充至高分子材料的孔洞，經過聚合反應後製得磁性高分子微粒。例如，美國專利第4,454,234號揭示一種將丙烯酸胺(acrylamide)與亞甲基雙丙烯胺(N’N’-methylenebisacryl-amide)與磁性粒子(LaMn2Ge2)混合後於37℃下進行聚合反應，形成次微米磁性粒子複合物，之後將其進行改質，將高分子原有的酯基(ester group)改為羧基(carboxyl group)或酸性醯胺基(acid amide group)，再經催化反應後，可用於結合蛋白質。美國專利第4,358,388號揭示一種水包油式(oil in water)的懸浮聚合方法，將高分子材料單體、磁性金屬顆粒(三氧化四鐵)、起始劑與溶劑等均勻混合後，進一步乳化懸浮於有機相中，再將其加入水相中進行聚合，可形成磁性顆粒均勻分布於 其內部之磁性高分子微粒。 In order to solve the problem of the above method, U.S. Patent No. 5,320,944 discloses a magnetic polymer particle coated with a layer of oxidized iron, cobalt or nickel-based magnetic material on the surface of polystyrene polymer particles, which is applied to immunoassay. Similarly, in order to solve the above problems, another method of producing a magnetic particle composite, that is, the above-described method for producing a dispersed magnetic particle composite is generally employed. Such a method generally disperses a magnetic metal substance uniformly in a polymer material by uniformly mixing a monomer for polymer polymerization with a magnetic material, or filling it into a pore of a polymer material, and obtaining a magnetic property after polymerization. Polymer particles. For example, U.S. Patent No. 4,454,234 discloses the polymerization of acrylamide and N'N'-methylenebisacryl-amide with magnetic particles (LaMn 2 Ge 2 ) at 37 ° C. Forming a submicron magnetic particle composite, which is then modified to change the original ester group of the polymer to a carboxyl group or an acid amide group, followed by a catalytic reaction. After that, it can be used to bind proteins. U.S. Patent No. 4,358,388 discloses an oil-in-water suspension polymerization process in which a polymer material monomer, magnetic metal particles (ferric oxide), an initiator, and a solvent are uniformly mixed and further emulsified. The suspension is suspended in an organic phase, and then added to the aqueous phase for polymerization to form magnetic polymer particles in which magnetic particles are uniformly distributed.
此外，前述美國Seradyn公司的產品Sera-Mag®磁性顆粒所採用的製備方法則為另一種典型之磁性粒子複合物製作方法，其係於製備聚苯乙烯顆粒後，將其表面進行改質導入羧基之後，再包埋一層磁性物質於此顆粒表面，最後再以非苯乙烯類的高分子包覆(encapsulation)此顆粒，此種方法所製得的顆粒可稱作磁性核殼粒子(core-shell)。 In addition, the preparation method of the Sera-Mag® magnetic particles of the aforementioned US Seradyn company is another typical magnetic particle composite preparation method, which is characterized in that after preparing polystyrene particles, the surface thereof is modified and introduced into the carboxyl group. Thereafter, a layer of magnetic material is embedded on the surface of the particle, and finally the particle is encapsulated with a non-styrene polymer. The particle obtained by this method may be referred to as a magnetic core shell (core-shell). ).
又一種類似散佈性製作方法的做法為：先製作大小均一的球形高分子微粒後，再將磁性材料均勻分散於高分子顆粒的內部，或是填充於高分子的孔洞中，或甚至塗佈於高分子表面形成一層磁性材料層。例如，美國專利第4,654,276號揭示一種利用甲基丙烯酸(methyl methacrylate,MMA)與甲基丙烯縮水甘油酯(glyceryl methacrylate,GMA)等各式不同的單體，合成出多孔性的微米高分子顆粒，再將用於生成四氧化三鐵的二價鐵(Fe(II))與三價鐵(Fe(III))的鹽類，或用於製備其他種類的磁性顆粒所需之材料，與多孔性微米高分子顆粒均勻混合，之後再加入氫氧化銨(NH4OH)並加熱，使得磁性顆粒生成於高分子的孔隙中，並接合於此孔隙內。然而，由於此種方法是利用不同單體合成之多孔性微米高分子顆粒，其所能形成的奈米磁性顆粒含量不盡相同，一般而言含量約為5-20%。 Another method similar to the dispersive production method is: firstly, the spherical polymer microparticles of uniform size are prepared, and then the magnetic material is uniformly dispersed in the interior of the polymer particles, or filled in the pores of the polymer, or even coated. A layer of magnetic material is formed on the surface of the polymer. For example, U.S. Patent No. 4,654,276 discloses the use of methacrylic acid (MMA) and glyceryl methacrylate (GMA) to synthesize porous micron polymer particles. a salt of divalent iron (Fe(II)) and ferric iron (Fe(III)) used to form ferroferric oxide, or a material required for preparing other kinds of magnetic particles, and porosity The micron high molecular particles are uniformly mixed, and then ammonium hydroxide (NH 4 OH) is added and heated, so that the magnetic particles are formed in the pores of the polymer and joined into the pores. However, since this method is a porous micron-sized polymer particle synthesized by using different monomers, the content of nano magnetic particles which can be formed is not the same, and the content is generally about 5-20%.
類似前述美國專利第4,654,276號所揭示的製作方法雖可製得形狀與粒徑大小分佈範圍狹窄，且品質不錯的磁性粒子複合物，惟組成微粒磁性物質係於高分子微粒中的孔隙內反應生成，因而造成其製造與應用層面的侷限性。例如，磁性物質的前驅物及相關的反應試劑必須能擴散進入到高分子微粒內，並彼此接觸才可能會發生反應，進而產生磁性物質。此外，此種方法可採用的磁性物質種類，以及磁性粒子複合物中所含有的磁性物質總量(單位顆粒體積下之磁性物質量)都有其侷限，以致磁性粒子複合物成品的磁性量有其上限。 The magnetic particle composite having a narrow shape and particle size distribution and good quality can be obtained by the production method disclosed in the above-mentioned U.S. Patent No. 4,654,276, but the magnetic material composed of the microparticles is formed in the pores of the polymer microparticles. , thus causing limitations in its manufacturing and application levels. For example, the precursor of the magnetic substance and the related reaction reagent must be able to diffuse into the polymer particles and contact with each other to react, thereby generating a magnetic substance. In addition, the type of magnetic substance that can be used in such a method, and the total amount of magnetic substances contained in the magnetic particle composite (the mass of the magnetic substance per unit volume) have limitations, so that the magnetic quantity of the finished magnetic particle composite has Its upper limit.
綜上所述，目前製造磁性粒子複合物的方法多半需要利用複雜的化學 聚合反應或需添加各種界面活性劑，進而侷限了可使用的磁性金屬種類與高分子種類，連帶限制了磁性粒子複合物成品之應用性；此外，製作磁性粒子複合物的過程中必須進行複雜化學聚合反應，使得磁性粒子複合物在材質的改變與量產上，存有相當大的技術問題與成本負擔，實為此技術領域亟待克服的問題。 In summary, most of the current methods for fabricating magnetic particle composites require the use of complex chemistry. Polymerization or the addition of various surfactants, which limits the types of magnetic metals and polymers that can be used, which limits the applicability of the finished magnetic particle composites; in addition, complex chemistry must be performed in the process of making magnetic particle composites. The polymerization reaction causes the magnetic particle composite to have considerable technical problems and cost burdens in the material change and mass production, which is an urgent problem to be overcome in the technical field.
為解決前述習知技術既存之問題，本發明之主要目的係在於提供一種包含了控制油水界面張力步驟，用以製造磁性微粒複合物。此磁性微粒複合物之製作方法，包含有下列步驟：(1)提供磁性奈米粒子；(2)提供水溶性高分子，將此水溶性高分子溶解於水以形成水溶性高分子溶液；(3)將此磁性奈米粒子與此水溶性高分子溶液以一重量比例之比值均勻混合形成第一混合溶液；(4)提供分散相溶液，且將此分散相溶液與此第一混合溶液以一體積比例之比值在一轉速下以旋轉攪拌方式均勻混合形成第二混合溶液，其中此體積比例之比值介於1至40之間，此轉速介於200rpm至14000rpm之間，且由於此分散相溶液與此第一混合溶液互不相溶，因此此分散相溶液與此第一混合溶液形成界面，且此界面具有界面張力值介於0.1mN/m至50mN/m之間；以及(5)加入硬化劑於此第二混合溶液以製得此磁性微粒複合物，此磁性微粒複合物的粒徑大小介於10微米至70微米之間，且此磁性微粒複合物具有磁性量介於14emu/g至42emu/g之間。 In order to solve the problems of the prior art described above, it is a primary object of the present invention to provide a step of controlling the interfacial tension of oil and water for producing a magnetic particulate composite. The method for preparing the magnetic particle composite comprises the steps of: (1) providing magnetic nanoparticles; (2) providing a water-soluble polymer, and dissolving the water-soluble polymer in water to form a water-soluble polymer solution; 3) uniformly mixing the magnetic nanoparticle with the water-soluble polymer solution in a ratio by weight to form a first mixed solution; (4) providing a dispersed phase solution, and dispersing the dispersed phase solution with the first mixed solution The ratio of the volume ratio is uniformly mixed by agitation at a rotation speed to form a second mixed solution, wherein the ratio of the volume ratio is between 1 and 40, and the rotation speed is between 200 rpm and 14000 rpm, and due to the dispersed phase The solution is incompatible with the first mixed solution, so the dispersed phase solution forms an interface with the first mixed solution, and the interface has an interfacial tension value between 0.1 mN/m and 50 mN/m; and (5) The magnetic microparticle composite is prepared by adding a hardener to the second mixed solution, the magnetic microparticle composite having a particle size ranging from 10 micrometers to 70 micrometers, and the magnetic microparticle composite having a magnetic property of 14 emu/ g to 42 Between emu/g.
本發明之另一目的係在於提供一種可控制油水界面張力進而控制磁性微粒複合物粒徑，並可依使用需求調整磁性量而製得具有多樣化磁性量之 磁性微粒複合物的製作方法。 Another object of the present invention is to provide a diversified magnetic quantity by controlling the oil-water interfacial tension and controlling the particle size of the magnetic microparticle composite, and adjusting the magnetic quantity according to the needs of use. A method of producing a magnetic microparticle composite.
本發明之又一目的係在於提供一種磁性微粒複合物之製作方法，此方法可控制前述的磁性奈米粒子與水溶性高分子溶液相互混合的重量比例之比值，並依照此體積比例之比值，將兩者均勻混合形成第一混合溶液。由於磁性微粒複合物之磁性量取決於其磁性奈米粒子之含量，因此，此方法藉由控制前述的磁性奈米粒子與水溶性高分子溶液的重量比例之比值，控制此製作方法所製得的磁性微粒複合物之磁性量。 Another object of the present invention is to provide a method for preparing a magnetic microparticle composite, which can control the ratio of the weight ratio of the magnetic nanoparticle and the water-soluble polymer solution to each other, and according to the ratio of the volume ratio, The two were uniformly mixed to form a first mixed solution. Since the magnetic amount of the magnetic microparticle composite depends on the content of the magnetic nanoparticle, the method is controlled by controlling the ratio of the weight ratio of the magnetic nanoparticle to the water-soluble polymer solution. The magnetic amount of the magnetic particle composite.
本發明之再一目的係在於提供一種磁性微粒複合物之製作方法，此方法可控制前述的分散相溶液與第一混合溶液相互混合的體積比例之比值，並依照此體積比例之比值，將兩者進行定量配製與混合程序；此方法同時藉由旋轉攪拌方式提供並控制一特定的轉速，在此轉速之下，將前述的分散相溶液與第一混合溶液進行混合程序。因此，此方法藉由控制前述的體積比例之比值以及轉速，達成控制磁性微粒複合物粒徑之目的。 A further object of the present invention is to provide a method for preparing a magnetic microparticle composite, which can control the ratio of the volume ratio of the above-mentioned dispersed phase solution to the first mixed solution, and according to the ratio of the volume ratio, The quantitative preparation and mixing procedure is carried out; this method simultaneously provides and controls a specific rotation speed by means of rotary stirring, at which the aforementioned dispersion phase solution is mixed with the first mixed solution. Therefore, this method achieves the purpose of controlling the particle size of the magnetic particulate composite by controlling the ratio of the aforementioned volume ratio and the number of revolutions.
本發明之再一目的係在於提供一種製造程序簡易、成本較低且可製出多樣化的微粒產品之磁性微粒複合物的製作方法。 Still another object of the present invention is to provide a method for producing a magnetic particulate composite which is simple in manufacturing process, low in cost, and capable of producing a plurality of particulate products.
為了達成上述目的，本發明主要是藉由控制磁性微粒複合物中磁性奈米粒子之含量，控制成品之磁性量；同時，本發明更進一步利用膠體溶液「二相不互溶」之原理，並採用了可控制油水界面張力之步驟，藉由控制二種不互溶之液體相之間的界面張力，製造出具有特定粒徑、粒徑分布範圍狹窄且均勻以及具有多樣化磁性量的磁性微粒複合物。 In order to achieve the above object, the present invention mainly controls the magnetic quantity of the finished product by controlling the content of the magnetic nano particles in the magnetic particle composite; meanwhile, the present invention further utilizes the principle of "two-phase immiscible" of the colloidal solution, and adopts The step of controlling the interfacial tension of the oil-water interface, by controlling the interfacial tension between the two immiscible liquid phases, to produce a magnetic particle composite having a specific particle size, a narrow and uniform particle size distribution range, and a diverse magnetic quantity. .
為使本發明之目的、技術特徵及優點，能更為相關技術領域人員所了解並得以實施本發明，在此配合所附圖式於後續之說明書闡明本發明之技術特徵與實施方式，並列舉較佳實施例，並根據實施例提出相對應的實驗例進一步說明。以下文中所對照之圖式，係表達與本發明特徵有關之示意， 並未亦不需要依據實際情形完整繪製，合先敘明。 The present invention will be understood by those skilled in the art, and the present invention will be described in the following description in conjunction with the accompanying drawings. The preferred embodiment is further illustrated by the corresponding experimental examples according to the embodiments. The drawings referred to below are indicative of the features associated with the features of the invention. It does not need to be completely drawn according to the actual situation.
由於本發明揭露了一種磁性微粒複合物之製作方法，方法中所使用之磁性奈米粒子及水溶性高分子之製備原理，以及磁性微粒複合物之外觀、粒徑與磁性量之測量方法，已為相關技術領域具有通常知識者所能明瞭，故以下文中之說明，不再作完整描述。 The present invention discloses a method for preparing a magnetic microparticle composite, a preparation principle of the magnetic nanoparticle and the water-soluble polymer used in the method, and a method for measuring the appearance, particle diameter and magnetic quantity of the magnetic microparticle composite. It will be apparent to those skilled in the relevant art, and the description below will not be fully described.
請參考圖1，係根據本發明所提出之第一較佳實施例，為一種磁性微粒複合物製作方法步驟流程圖，以下據此步驟流程依序說明： Please refer to FIG. 1 , which is a flow chart of a method for fabricating a magnetic particle composite according to a first preferred embodiment of the present invention.
步驟S11：首先，提供磁性奈米粒子。可應用於本發明之磁性奈米粒子，只要是具有磁性或超順磁特性之磁性奈米粒子均可使用，其種類與製備方式於本發明中並未加以限制。可選用市售已製備完成的磁性奈米粒子成品或是半成品，或者可以自行製備磁性奈米粒子。 Step S11: First, magnetic nanoparticles are provided. The magnetic nanoparticles which can be applied to the present invention can be used as long as they are magnetic nanoparticles having magnetic or superparamagnetic properties, and the kind and preparation method thereof are not limited in the present invention. Commercially prepared finished magnetic nanoparticles or semi-finished products may be used, or magnetic nanoparticles may be prepared by themselves.
磁性奈米粒子之所以具備磁性係因其組成之元素含有不成對電子，例如，當磁性奈米粒子成分中的化合物元素組成含有鐵、鈷、鎳等元素時，通常會表現磁性性質，且若將這些元素與其他元素結合時，則能形成具備不同特性的磁性材料，衍生出不同的應用價值。而本發明中所指之磁性奈米粒子係包含了符合化學式為：FexMy(VIA)z之化合物，化學式中M為內過渡金屬元素，VIA為VIA族元素；x、y、z則分別代表了一特定數值，其中x為不小於0之數值，y、z則為非零正數。 Magnetic nanoparticles have magnetic properties because their constituent elements contain unpaired electrons. For example, when a compound element composition of a magnetic nanoparticle component contains an element such as iron, cobalt, or nickel, it usually exhibits magnetic properties. When these elements are combined with other elements, magnetic materials with different characteristics can be formed, resulting in different application values. The magnetic nanoparticle referred to in the present invention comprises a compound according to the chemical formula: Fe x M y (VIA) z , wherein M is an internal transition metal element, VIA is a VIA group element; and x, y, z are Represents a specific value, where x is a value not less than 0, and y and z are non-zero positive numbers.
利用化學共沉法製得之含有四氧化三鐵的磁性奈米粒子，製造磁性微粒複合物為例，其係利用習知的化學共沉法製備四氧化三鐵磁性奈米粒子，先將各項含有鐵離子之反應物，以特定莫耳比例混合，接著以旋轉攪拌方法，在特定轉速下旋轉攪拌混合反應物，使其充分混合，並適時加入催化劑，幫助反應的進行；接著，再以氫氧化鈉(NaOH)或氫氧化銨(NH4OH)等鹼性物質調整反應物之反應環境的pH值至適當值(例如pH值=12)之後，提供一特定溫度，使其在此溫度下充分反應並生成沉澱物，最後再以離心方式取得此沉澱物，即可獲得特定大小(粒徑範圍介於10奈米至100奈米) 並具有磁性的四氧化三鐵磁性奈米粒子。 The magnetic nanoparticle containing triiron tetroxide prepared by the chemical co-precipitation method is used as an example to prepare a magnetic microparticle composite, which is prepared by a conventional chemical co-precipitation method for preparing ferroferric oxide magnetic nanoparticles. The reactant containing iron ions is mixed at a specific molar ratio, and then the mixture is stirred and stirred at a specific rotation speed by a rotary stirring method, thoroughly mixed, and a catalyst is added at a proper time to assist the reaction; then, hydrogen is further added. An alkaline substance such as sodium hydroxide (NaOH) or ammonium hydroxide (NH 4 OH) adjusts the pH of the reaction environment of the reactant to an appropriate value (for example, pH = 12) to provide a specific temperature at which the temperature is maintained. The precipitate is sufficiently reacted, and finally the precipitate is obtained by centrifugation to obtain a ferroferric oxide magnetic nanoparticle having a specific size (particle size ranging from 10 nm to 100 nm) and having magnetic properties.
步驟S12：接著，提供一水溶性高分子，將水溶性高分子溶解於水以形成一水溶性高分子溶液。在此步驟S12中，製備水溶性高分子溶液所需要之水溶性高分子，本發明對其種類並無特別的限制，各種來源的水溶性高分子，只要其可完全溶解於水或是水溶液中，均可用於製備此水溶性高分子溶液，譬如由纖維素、幾丁聚醣、海藻酸納、聚乙烯醇等水溶性高分子所形成的水溶性高分子溶液，均適用於此步驟S12，形成各項水溶性高分子溶液，並以其製作磁性微粒複合物。 Step S12: Next, a water-soluble polymer is provided, and the water-soluble polymer is dissolved in water to form a water-soluble polymer solution. In this step S12, a water-soluble polymer required for preparing a water-soluble polymer solution is prepared. The present invention is not particularly limited in its kind, and the water-soluble polymer of various sources can be completely dissolved in water or an aqueous solution as long as it is completely soluble in water or an aqueous solution. The water-soluble polymer solution can be used for preparing the water-soluble polymer solution, for example, a water-soluble polymer solution formed of a water-soluble polymer such as cellulose, chitosan, sodium alginate or polyvinyl alcohol, and is applicable to the step S12. Each of the water-soluble polymer solutions is formed, and a magnetic particle composite is produced therefrom.
步驟S13：再接著，將磁性奈米粒子與水溶性高分子溶液以一重量比例之比值均勻混合形成第一混合溶液。在此步驟S13中，可根據使用者的需求依照選用特定之水溶性高分子並依照步驟S12製備水溶性高分子溶液之後，將其與依照步驟S11所提供之磁性奈米粒子進行混合。將磁性奈米粒子與水溶性高分子溶液以特定重量比例之比值定量配製，並均勻混合，所形成之混合液即為第一混合溶液。 Step S13: Next, the magnetic nanoparticle and the water-soluble polymer solution are uniformly mixed at a ratio of a weight ratio to form a first mixed solution. In this step S13, a water-soluble polymer solution can be prepared according to the user's requirements according to the selection of the specific water-soluble polymer and in accordance with step S12, and then mixed with the magnetic nanoparticles provided in accordance with step S11. The magnetic nanoparticle and the water-soluble polymer solution are quantitatively prepared in a specific weight ratio, and uniformly mixed, and the resulting mixture is the first mixed solution.
此步驟S13所指的重量比例之比值係為「磁性奈米粒子與水溶性高分子溶液的重量比例之比值」，此重量比例之比值應大於0並且小於或等於1。且通常此重量比例之比值係介於0.1至1之間，意即在此步驟S13中，定量配製第一混合溶液時，所使用的磁性奈米粒子與水溶性高分子溶液之重量比例之比值(w/w)須介於1：1至1：10之間，換言之，即所使用的磁性奈米粒子的重量須小於或等於水溶性高分子溶液的重量。 The ratio of the weight ratio referred to in this step S13 is "the ratio of the weight ratio of the magnetic nanoparticle to the water-soluble polymer solution", and the ratio of the weight ratio should be greater than 0 and less than or equal to 1. And usually the ratio of the weight ratio is between 0.1 and 1, which means that in this step S13, the ratio of the weight ratio of the magnetic nanoparticle to the water-soluble polymer solution used when the first mixed solution is quantitatively prepared (w/w) must be between 1:1 and 1:10, in other words, the weight of the magnetic nanoparticles used must be less than or equal to the weight of the water-soluble polymer solution.
於上述步驟S13中，磁性奈米粒子本身的磁性量，以及磁性奈米粒子與水溶性高分子溶液之重量比例之比值，係為決定磁性微粒複合物最終磁性量的關鍵因素，在前述的磁性奈米粒子與水溶性高分子溶液的重量比例之比值範圍內，此比值可依需求調整成預設之值，使磁性微粒複合物之磁性量隨此重量比例之比值而變化。因此，使用者可依各種需求或是因應磁性微粒複合物後續之用途，調整磁性微粒複合物之磁性量，此舉除了可提供 一種有效利用磁性微粒複合物之方法，讓此磁性微粒複合物應用更加廣泛外，並可進一步降低生產或購買磁性奈米粒子之成本，提高此磁性微粒複合物之生產與應用效益。 In the above step S13, the ratio of the magnetic quantity of the magnetic nanoparticle itself and the weight ratio of the magnetic nanoparticle to the water-soluble polymer solution is a key factor for determining the final magnetic amount of the magnetic microparticle composite, and the magnetic property is as described above. Within the ratio of the ratio of the weight ratio of the nanoparticle to the water-soluble polymer solution, the ratio can be adjusted to a predetermined value according to the demand, and the magnetic amount of the magnetic particulate composite varies with the ratio of the weight ratio. Therefore, the user can adjust the magnetic quantity of the magnetic particle composite according to various needs or in response to the subsequent use of the magnetic particle composite, in addition to providing A method for effectively utilizing magnetic particle composites allows the magnetic particle composite to be applied more widely, and can further reduce the cost of producing or purchasing magnetic nano particles, and improve the production and application efficiency of the magnetic particle composite.
於此步驟S13中可採用的混合方式未有特殊限制，可選用旋轉攪拌、震盪混合或其他混合方式，只要能達到均勻混合之效果即可適用於此步驟S13，製備第一混合溶液。 The mixing mode which can be employed in this step S13 is not particularly limited, and rotary stirring, shaking mixing or other mixing means may be selected, and as long as the effect of uniform mixing can be achieved, the first mixed solution can be prepared by applying to the step S13.
步驟S14：再接著，提供一分散相溶液，且將分散相溶液與第一混合溶液以一體積比例之比值在一轉速下以旋轉攪拌方式均勻混合形成第二混合溶液。此步驟S14係應用了油水「二相不互溶」之原理，敘述如後。 Step S14: Next, a dispersed phase solution is provided, and the ratio of the dispersed phase solution to the first mixed solution in a volume ratio is uniformly mixed by agitation at a rotation speed to form a second mixed solution. In this step S14, the principle of "two phases are not mutually soluble" of oil and water is applied, and the description is as follows.
一般而言，在膠體溶液中含有兩種不同相態的物質時，其一係分散相，另一係連續相，其中分散相是由微小的粒子或液滴所組成，遍佈在整個連續相中。本發明所述的「二相不互溶」是指一種液體與另一種液體之間不互溶的狀態。習知的「二相不互溶」中的二種液體相通常是指有機相與水相，若將二者加以混合，並配合不同的混合條件與方法，如混合速率或混合溫度等，則在混合的過程中會產生不同的分散形式，譬如在旋轉攪拌混合的情況下，其中一相係以液滴形式分散在另一相中，而以液滴存在的一相係為分散相，另一則為連續相。 In general, when a colloidal solution contains two different phase states, one is a dispersed phase and the other is a continuous phase in which the dispersed phase is composed of tiny particles or droplets throughout the continuous phase. . The "two-phase immiscible" as used in the present invention means a state in which one liquid is immiscible with another liquid. The two liquid phases in the conventional "two-phase immiscible" generally refer to the organic phase and the aqueous phase. If the two are mixed and combined with different mixing conditions and methods, such as mixing rate or mixing temperature, Different dispersion forms are produced during the mixing process, such as in the case of rotary agitation mixing, in which one phase is dispersed as droplets in the other phase, and one phase in which the droplets are present is the dispersed phase, and the other is It is a continuous phase.
針對前述之有機相與水相的分散形式，依此分散形式所處的狀態可區分為兩類：(1)水相分散在有機相中稱為「油中水」W/O(water in oil)型態；(2)有機相分散在水相中則為「水中油」O/W(oil in water)型態。而本發明所指之「二相不互溶」係特別指一種使用油相與水相構成的油水混合系統，其油水二相不互溶的特性。關於油水不互溶之特性及原理，係熟習此領域技術人員所熟知，因此簡要敘述如後，俾利於闡明本發明之特徵。 In view of the above-mentioned dispersion form of the organic phase and the aqueous phase, the state in which the dispersed form is located can be classified into two types: (1) the aqueous phase is dispersed in the organic phase, which is called "water in oil" W/O (water in oil) (2) The organic phase is dispersed in the water phase and is the "oil in water" type. The term "two-phase immiscible" as used in the present invention refers specifically to an oil-water mixing system comprising an oil phase and an aqueous phase, the oil-water two-phase being immiscible. The nature and principle of the incompatibility of oil and water are well known to those skilled in the art, and therefore, a brief description will be made to clarify the features of the present invention.
就熱力學的角度而言，一個系統能否處於熱力學的穩定狀態，取決於此系統的自由能(△G)是否處於最低值。其中自由能可用內能(△U)與亂度(△S)表示為：△G=△U-T△S，其中T為絕對溫度。因此前述系統的內 能與亂度也間接成為判別系統穩定的指標。 From a thermodynamic point of view, whether a system is in a thermodynamically stable state depends on whether the free energy (ΔG) of the system is at its lowest value. The free energy can be expressed as internal energy (ΔU) and disorder (ΔS) as: ΔG=ΔU-TΔS, where T is the absolute temperature. Therefore within the aforementioned system The ability and chaos also indirectly become an indicator of the stability of the system.
就液相而言，不同種類的液體本身具有不同的「表面張力」，亦即液體表面分子所受各方向的力不均衡時(內聚力大於對空氣的附著力)，而使得液面收縮成最小表面積的力。而當不同種類的液體A與液體B互相混合或互相接觸時，會因液體具有表面張力之特性，於不同液相之間形成一「界面張力」(γ)。又此界面張力大小與不同液相間的接觸面積(△A)大小相關，故關於本發明所述的油水混合系統，經計算後可得前述之系統的內能(△U)趨近於γ△A，其關係如下式所示△G=γ△A-T△S。 In the liquid phase, different kinds of liquids themselves have different "surface tension", that is, when the forces on the surface of the liquid are unbalanced in all directions (cohesion is greater than the adhesion to air), and the liquid surface shrinks to a minimum. The force of the surface area. When different kinds of liquid A and liquid B are mixed with each other or contact each other, an "interfacial tension" (γ) is formed between different liquid phases due to the surface tension property of the liquid. Moreover, the magnitude of the interfacial tension is related to the contact area (ΔA) between different liquid phases. Therefore, with respect to the oil-water mixing system of the present invention, the internal energy (ΔU) of the aforementioned system is obtained to be close to γ. ΔA, the relationship is as follows: ΔG = γ ΔAT ΔS.
由此可知，雖然油水不互溶的特性可增加油水混合系統的亂度，然而油相和水相之間的界面張力遠大於T△S，因此，其自由能幾乎完全取決於γ△A，致使油水混合系統常存有多餘的能量，處於不安定的狀態，這也是在一般情況下油水共存時通常會互相分離，成為不互溶的兩相的原因，也因此過去常採用添加界面活性劑的方式使兩相形成微胞(micelle)的方式，使其充分穩定混合。 It can be seen that although the oil-water-immiscible property can increase the chaos of the oil-water mixing system, the interfacial tension between the oil phase and the water phase is much larger than TΔS, and therefore, the free energy depends almost entirely on γΔA, resulting in Oil-water mixing systems often have excess energy and are in an unstable state. This is also the reason why oil and water usually coexist in the normal state and become mutually insoluble two phases. Therefore, in the past, surfactants were often added. The two phases are formed into a micelle in such a manner that they are sufficiently stably mixed.
然而，本發明基於上述油水混合系統中油水不互溶之特徵，提供一種無須添加界面活性劑的步驟之磁性微粒複合物的製作方法，包含以下步驟：(1)提供磁性奈米粒子；(2)提供水溶性高分子，將此水溶性高分子溶解於水以形成水溶性高分子溶液；(3)將磁性奈米粒子與水溶性高分子溶液以一重量比例之比值均勻混合形成第一混合溶液；(4)提供分散相溶液，且將此分散相溶液與第一混合溶液以一體積比例之比值在一轉速下以旋轉攪拌方式均勻混合形成第二混合溶液；以及(5)加入硬化劑於此第二混合溶液以製得磁性微粒複合物。 However, the present invention is based on the feature that the oil-water immiscible in the oil-water mixing system described above, and provides a method for preparing a magnetic particle composite without the step of adding a surfactant, comprising the steps of: (1) providing magnetic nanoparticles; (2) Providing a water-soluble polymer, the water-soluble polymer is dissolved in water to form a water-soluble polymer solution; (3) uniformly mixing the magnetic nanoparticles and the water-soluble polymer solution in a ratio of a weight ratio to form a first mixed solution (4) providing a dispersed phase solution, and uniformly mixing the dispersed phase solution and the first mixed solution in a volume ratio at a rotational speed in a rotational stirring manner to form a second mixed solution; and (5) adding a hardening agent to This second mixed solution is used to produce a magnetic particulate composite.
此步驟S14係應用了前述的油水「二相不互溶」之特徵，意即油水混 合時即產生了一界面張力，而此步驟S14係藉由調整「分散相溶液與第一混合溶液之體積比例之比值」，操作並控制油水界面張力。 In this step S14, the above-mentioned oil-water "two-phase non-miscible" feature is applied, which means that the oil and water are mixed. At the same time, an interfacial tension is generated, and in step S14, the oil-water interfacial tension is operated and controlled by adjusting the ratio of the volume ratio of the dispersed phase solution to the first mixed solution.
而在初步定量混合分散相溶液與第一混合溶液之後，接著採用旋轉攪拌的方式將分散相溶液與第一混合溶液進行混合的動作，因而形成了第二混合溶液，而此第二混合溶液同時提供了一種油水混合系統，可用以實施本發明所述之磁性微粒複合物之製作，且可藉此達成控制磁性微粒複合物的粒徑之目的。 After the preliminary quantitative mixing of the dispersed phase solution and the first mixed solution, the action of mixing the dispersed phase solution with the first mixed solution is then carried out by means of rotational stirring, thereby forming a second mixed solution, and the second mixed solution is simultaneously An oil-water mixing system is provided for carrying out the production of the magnetic particulate composite of the present invention, and thereby achieving the purpose of controlling the particle size of the magnetic particulate composite.
接著，進一步說明步驟S14中「分散相溶液與第一混合溶液之體積比例之比值」、「旋轉攪拌之轉速」與「磁性微粒複合物之粒徑」之實施範圍與相互關係。 Next, the execution range and the relationship between the "ratio of the volume ratio of the dispersed phase solution to the first mixed solution", the "rotational rotational speed" and the "particle diameter of the magnetic fine particle composite" in the step S14 will be further described.
本發明所指之分散相溶液與第一混合溶液之體積比例之比值介於1至40之間，意即在此步驟S14中，定量配製第二混合溶液時，所使用的分散相溶液與第一混合溶液之體積比例介於1：1至40：1之間，換言之，即所使用的分散相溶液的體積須大於或等於第一混合溶液的體積。 The ratio of the volume ratio of the dispersed phase solution to the first mixed solution referred to in the present invention is between 1 and 40, that is, in the step S14, when the second mixed solution is quantitatively prepared, the dispersed phase solution and the used The volume ratio of a mixed solution is between 1:1 and 40:1, in other words, the volume of the dispersed phase solution used must be greater than or equal to the volume of the first mixed solution.
至於此步驟S14中「旋轉攪拌之轉速」，意指使用旋轉攪拌方式混合分散相溶液與第一混合溶液，定量配製第二混合溶液時，此旋轉攪拌之轉速是可以依照需求而調整的，且此轉速可影響於第二混合溶液中所形成之磁性微粒複合物之粒徑，此轉速介於200rpm至14000rpm之間，而在實際應用上，大於1000rpm以上的轉速較容易造成磁性微粒複合物之顆粒變形或碎裂，可能影響其品質，因此，此轉速更佳值係介於600rpm至1000rpm之間。 As for the "rotational stirring rotation speed" in the step S14, it means that when the second mixed solution is quantitatively prepared by mixing the dispersed phase solution and the first mixed solution by the rotary stirring method, the rotation speed of the rotary stirring can be adjusted according to the demand, and The rotation speed may affect the particle size of the magnetic particle composite formed in the second mixed solution, and the rotation speed is between 200 rpm and 14000 rpm, and in practical applications, the rotation speed of more than 1000 rpm is more likely to cause the magnetic particle composite. The deformation or fragmentation of the particles may affect its quality, so a better value for this speed is between 600 rpm and 1000 rpm.
此步驟S14指出知分散相溶液泛指與第一混合溶液不互溶之液體或溶液，可為機械油，包括用於潤滑、冷卻和密封機械裝置摩擦部分的潤滑劑，可以是礦物性潤滑劑、植物性潤滑劑或人工合成潤滑劑，諸如：真空幫浦油、矽油、機油、齒輪油、液壓油等；植物油，包括以壓榨、溶劑萃取方式或更進一步煉製生產之植物油，諸如：大豆油、葡萄籽油、葵花子油、 花生油、橄欖油、玉米油等；或高碳數烷類，包括含碳數介於5至17的液態烷類，諸如：碳數為6~16之正烷，如正己烷、正庚烷、正辛烷、正壬烷、正癸烷、正十一烷、正十二烷、正十三烷、正十四烷、正十五烷、正十六烷；或碳數為6~16之異烷，如異己烷、異庚烷、異辛烷、異壬烷、異癸烷、異十一烷、異十二烷、異十三烷、異十四烷、異十五烷、異十六烷或甲苯等，只要此分散相溶液是與第一混合溶液不互溶之油類物質，其界面張力均落於上述之界面張力範圍內(0.1mN/m至50mN/m)，可供達成控制此界面張力的目標即可做為分散相溶液，故本發明對分散相之種類不加以限制。 This step S14 indicates that the dispersed phase solution generally refers to a liquid or solution that is immiscible with the first mixed solution, and may be a mechanical oil, including a lubricant for lubricating, cooling, and sealing the friction portion of the mechanical device, which may be a mineral lubricant, Vegetable lubricants or synthetic lubricants such as vacuum pump oil, eucalyptus oil, engine oil, gear oil, hydraulic oil, etc.; vegetable oils, including vegetable oils produced by pressing, solvent extraction or further refining, such as: soybean oil Grape seed oil, sunflower oil, Peanut oil, olive oil, corn oil, etc.; or high carbon number alkane, including liquid alkanes having a carbon number of 5 to 17, such as n-hexane having a carbon number of 6 to 16, such as n-hexane, n-heptane, N-octane, n-decane, n-decane, n-undecane, n-dodecane, n-tridecane, n-tetradecane, n-pentadecane, n-hexadecane; or a carbon number of 6-16 Isoalkane, such as isohexane, isoheptane, isooctane, isodecane, isodecane, isoundecane, isododecane, isotridecane, isotetradecane, isopentadecane, iso-decane Hexane or toluene, etc., as long as the dispersed phase solution is an oil substance which is immiscible with the first mixed solution, the interfacial tension falls within the above interfacial tension range (0.1 mN/m to 50 mN/m), and is available for The target for controlling the interfacial tension can be used as a dispersed phase solution, so the present invention does not limit the kind of the dispersed phase.
由於此步驟S14中，分散相溶液與此第一混合溶液互不相溶，因此前述之分散相溶液與前述之第一混合溶液形成有一界面，且此界面具有一界面張力值介於0.1mN/m至50mN/m之間。換言之，將前述之分散相溶液與前述之第一混合溶液混合形成第二混合溶液時，同時提供了一界面張力，此界面張力係代表了前述之第二混合溶液(即前述之油水混合系統)中的能量狀態，而此界面張力因此成為此第二混合溶液中決定物質分散情狀態之關鍵因素之一，進而影響後續於第二混合溶液中形成之磁性微粒複合物之粒徑。 Since the dispersed phase solution and the first mixed solution are incompatible with each other in the step S14, the foregoing dispersed phase solution forms an interface with the first mixed solution, and the interface has an interfacial tension value of 0.1 mN/ m to 50 mN/m. In other words, when the foregoing dispersed phase solution is mixed with the first mixed solution to form a second mixed solution, an interfacial tension is provided, and the interfacial tension represents the aforementioned second mixed solution (ie, the aforementioned oil-water mixing system). The state of energy in the interfacial tension thus becomes one of the key factors determining the state of dispersion of the substance in the second mixed solution, thereby affecting the particle size of the magnetic particle composite formed in the second mixed solution.
步驟S15：最後，加入一硬化劑於第二混合溶液以製得此磁性微粒複合物。在此步驟S15中，係配合第二混合溶液中的成分添加了特定之硬化劑，使第二混合溶液中的組成磁性微粒複合物的分子間產生凝集、交聯、膠結、聚合、鍵結、固化或固結等現象，進而製得多樣化的磁性微粒複合物產品。根據以上步驟S11至S15步驟所所製得之磁性微粒複合物，其粒徑大小介於10微米至70微米之間，且此磁性微粒複合物具有之磁性量介於14emu/g至42emu/g之間。 Step S15: Finally, a hardener is added to the second mixed solution to prepare the magnetic particulate composite. In this step S15, a specific hardener is added to the components in the second mixed solution to cause agglutination, cross-linking, cementation, polymerization, bonding, and intermolecular formation of the constituent magnetic particle composites in the second mixed solution. Curing or consolidation, etc., to produce a variety of magnetic particle composite products. The magnetic particle composite prepared according to the above steps S11 to S15 has a particle size ranging from 10 micrometers to 70 micrometers, and the magnetic microparticle composite has a magnetic amount ranging from 14 emu/g to 42 emu/g. between.
請繼續參考圖1，繼續針對此步驟S14指出的「分散相溶液與第一混合溶液之體積比例之比值」(為利於說明，以下稱為「V油/V水」)與「界面張力」進行說明。步驟S14中，V油/V水、界面張力值以及旋轉攪拌之轉 速，均係控制所形成磁性微粒複合物的粒徑的主要因素。其中V油/V水的較佳值係介於2至20，更佳值係介於3至10之間，且粒徑隨V油/V水的提高而增加；界面張力的較佳值係介於2mN/m至40mN/m，更佳值係介於5mN/m至30mN/m；轉速的較佳值係介於400rpm至1200rpm。 Please continue to refer to FIG. 1 to continue the "ratio of the volume ratio of the dispersed phase solution to the first mixed solution" (for the sake of explanation, hereinafter referred to as "V oil / V water") and "interfacial tension" for the step S14. Description. In step S14, the V oil/V water, the interfacial tension value, and the rotation of the rotation agitation The speed is the main factor controlling the particle size of the formed magnetic particle composite. The preferred value of V oil/V water is between 2 and 20, and the preferred value is between 3 and 10, and the particle size increases with the increase of V oil/V water; the preferred value of interfacial tension is It is between 2 mN/m and 40 mN/m, and more preferably between 5 mN/m and 30 mN/m; a preferred value for the rotational speed is between 400 rpm and 1200 rpm.
此外，在步驟S15之後可進一步加上一步驟S16(圖中未示)，步驟S16為一種沖洗步驟，係使用異丙醇或甲醇類組成的沖洗液來沖洗完成步驟S15後所製得之磁性微粒複合物。本發明對於此沖洗步驟所使用的沖洗液之溶劑種類、溶劑組成以及沖洗時間次數與時間不加以限制，例如可使用不同濃度的甲醇、異丙醇或是含有甲醇異與異丙醇之混合液，進行沖洗步驟。 In addition, a step S16 (not shown) may be further added after the step S15, and the step S16 is a rinsing step of rinsing the magnetic material obtained after the step S15 is completed by using a rinsing liquid composed of isopropyl alcohol or methanol. Microparticle composite. The present invention does not limit the solvent type, solvent composition, and the number of times and time of the rinsing liquid used in the rinsing step. For example, different concentrations of methanol, isopropyl alcohol or a mixture containing methanol and isopropanol may be used. , carry out the rinsing step.
最後，在步驟S16之後可再進一步加上一步驟S17(圖中未示)，步驟S17為一乾燥步驟，本發明對於乾燥程序所採用的方法也不加以限制，例如可以採用加熱烘乾或自然風乾等方式，將磁性微粒複合物加以乾燥。 Finally, after step S16, a step S17 (not shown) may be further added, and step S17 is a drying step. The method used in the drying process of the present invention is not limited, for example, heating drying or natural The magnetic particulate composite is dried by air drying or the like.
基於上述實施例可得知，本發明之磁性微粒複合物之製作方法所使用的磁性奈米粒子和水溶性高分子溶液的組合十分多元，可選用多種磁性奈米粒子與多種水溶性高分子溶液進行混合，以形成所述之第一混合液，進而製作多元化的磁性微粒複合物產品。 Based on the above examples, it can be seen that the combination of the magnetic nano particles and the water-soluble polymer solution used in the method for producing the magnetic microparticle composite of the present invention is very diverse, and various magnetic nanoparticles and various water-soluble polymer solutions can be selected. Mixing is carried out to form the first mixed liquid, thereby producing a plurality of magnetic particulate composite products.
再者，因本發明之磁性微粒複合物之製作方法可控制磁性微粒複合物之磁性量，故可依照使用者對於磁性微粒複合物的應用需求(如降低生物毒性、提高生物分子相容性、提高生物應用性、提升磁性結合之專一性等)，提升或減低磁性微粒複合物之磁性量，製得多樣性磁性量之磁性微粒複合物，除可增加應用效益外，亦可減少不必之材料浪費或達成減少生產成本之效。 Furthermore, since the magnetic particle composite of the present invention can control the magnetic quantity of the magnetic particle composite, it can be used according to the user's application requirements for the magnetic particle composite (eg, reducing biological toxicity, improving biomolecular compatibility, Improve the bioavailability, enhance the specificity of magnetic bonding, etc., increase or decrease the magnetic quantity of the magnetic particle composite, and obtain a magnetic particle composite with a variety of magnetic quantities, in addition to increasing the application efficiency, and also reducing unnecessary materials. Waste or achieve the effect of reducing production costs.
為使本發明具備更廣泛之用途，熟習本技術領域之技藝者，可根據本發明記載之技術內容得知，本發明之磁性微粒複合物之製作方法除了可採用磁性奈米粒子外，亦可依照不同用途，選用微米粒子或非磁性奈米粒子，譬如碳球、量子點、瑩光分子或枝狀分子(dendrimer)等微粒型產品取代， 但不僅限於此。 In order to make the present invention more widely used, those skilled in the art can know from the technical content described in the present invention that the magnetic particle composite of the present invention can be produced by using magnetic nanoparticles. Depending on the application, microparticles or non-magnetic nanoparticles, such as carbon spheres, quantum dots, fluorescent molecules or dendrimers, may be used instead. But it is not limited to this.
同理，熟習本技術領域之技藝者，可進一步根據用途，對於本發明所述之磁性微粒複合物以習知的化學改質方法進行化學改質，導入官能基(例如胺基、羥基、醯基、羰基等)至此磁性微粒複合物表面。或者是以習知方法將帶有官能基之分子或材料單層披覆或多層披覆至此磁性微粒複合物外層。 Similarly, those skilled in the art can further chemically modify the magnetic microparticle composite according to the present invention by a known chemical modification method according to the use, and introduce a functional group (for example, an amine group, a hydroxyl group, a hydrazine). Base, carbonyl, etc.) to the surface of the magnetic particle composite. Alternatively, a single layer of a molecule or material having a functional group may be coated or multilayered to the outer layer of the magnetic particle composite in a conventional manner.
而熟習本技術領域之技藝者，可經由詳閱本發明記載之技術內容而了解，欲將官能基導入本發明所述之磁性微粒複合物，亦可在本發明之磁性微粒複合物之製作方法中，加入預設官能基共聚合之步驟，用以獲得具備有預設官能基之磁性微粒複合物。而對於前文提及之官能基的種類並未有特別的限制。 Those skilled in the art can understand that the functional group is introduced into the magnetic particle composite of the present invention, and the magnetic particle composite of the present invention can also be produced by the technical contents described in the present invention. In the step of adding a predetermined functional group copolymerization, a magnetic particle composite having a predetermined functional group is obtained. There is no particular limitation on the types of functional groups mentioned above.
此外，本發明之磁性微粒複合物的製作方法，其係搭配磁性奈米粒子與水溶性高分子使用。此磁性奈米粒子為事先選定或製備而得，因此可選用的種類廣泛，故可選擇高磁性量或較低磁性量的磁性奈米物質作為磁性奈米粒子；又因此製作方法係可根據使用者需求，調整磁性奈米粒子與水溶性高分子溶液之重量比例之比值，控制磁性微粒複合物之磁性量，因此，配合使用上述步驟(1)至步驟(5)之製作方法，搭配使用各種磁性奈米粒子與水溶性高分子故可製得多種磁性量的磁性微粒複合物，且此磁性微粒複合物具有一磁性量介於14emu/g至42emu/g之間。 Further, the method for producing a magnetic fine particle composite of the present invention is used in combination with magnetic nanoparticles and a water-soluble polymer. The magnetic nano particles are selected or prepared in advance, so that a wide variety of materials can be selected, so that a magnetic nano-material having a high magnetic quantity or a low magnetic quantity can be selected as the magnetic nano-particles; The ratio of the weight ratio of the magnetic nanoparticle to the water-soluble polymer solution is adjusted to control the magnetic amount of the magnetic microparticle composite. Therefore, the preparation method of the above steps (1) to (5) is used in combination with various methods. The magnetic nanoparticle and the water-soluble polymer can produce a plurality of magnetic magnetic composites having a magnetic amount, and the magnetic microparticle composite has a magnetic amount of between 14 emu/g and 42 emu/g.
而本發明不同於習知技藝之處在於，習知之磁性微粒複合物製備過程中為了均勻混合高分子溶液及磁性粒子，通常採用添加界面活性劑的方法來達到穩定混合材料的目標，並且常使用複雜且昂貴的化學聚合反應，才得以產出磁性微粒複合物；然而本發明則採用了較簡易的控制油水界面張力的步驟，達成均勻混合並控制磁性微粒複合物粒徑之目的，同時減低了生產成本。 However, the present invention is different from the prior art in that in order to uniformly mix the polymer solution and the magnetic particles in the preparation process of the conventional magnetic particle composite, a method of adding a surfactant is generally used to achieve the goal of stabilizing the mixed material, and is often used. The complex and expensive chemical polymerization reaction can produce the magnetic particle composite; however, the present invention adopts a relatively simple step of controlling the interfacial tension of the oil-water to achieve uniform mixing and control of the particle size of the magnetic particle composite, and at the same time reduces Cost of production.
此外，本發明所述之磁性微粒複合物除了具有磁性外，其表面亦可進 一步鍵結不同的官能基，或者以物理性及化學性方法修飾，使其具備廣泛的用途與高度的經濟價值。可應用生物檢測方法或臨床檢測分析(例如，免疫分析、化學發光分析、放射線分析)、生物醫學研究以及高通量篩檢技術(high-throughput screening)等。 In addition, the magnetic particle composite of the present invention may have a surface in addition to being magnetic. Different functional groups are bonded in one step, or modified by physical and chemical methods, so that they have a wide range of uses and high economic value. Bioassay methods or clinical assays (eg, immunoassays, chemiluminescence assays, radioactivity analysis), biomedical research, and high-throughput screening can be applied.
為進一步說明本發明第一較佳實施例所述之磁性微粒複合物製備方法，請參考下列二個實驗例： In order to further illustrate the preparation method of the magnetic microparticle composite according to the first preferred embodiment of the present invention, please refer to the following two experimental examples:
首先，為了取得磁性奈米粒子，先行以下述之化學共沉法製備氧化鐵磁性奈米粒子：先將二價及三價鐵離子以莫耳比1：2之比例混合，以300rpm之轉速進行旋轉攪拌，並以1M NaOH溶液調整反應物之pH值至12，之後於60℃下使其反應1小時後，再以高轉速離心後取其黑色沉澱物，並加入去離子水使其分散，藉此製備具有磁性的氧化鐵磁性奈米粒子(四氧化三鐵)，其平均粒經約為10奈米。 First, in order to obtain magnetic nanoparticles, the iron oxide magnetic nanoparticles are prepared by the following chemical co-precipitation method: first, the divalent and trivalent iron ions are mixed at a molar ratio of 1:2, and the rotation speed is 300 rpm. Rotate and stir, adjust the pH of the reactants to 12 with 1M NaOH solution, then react at 60 ° C for 1 hour, then centrifuge at high speed, then take the black precipitate and add deionized water to disperse it. Thereby, magnetic iron oxide magnetic nanoparticles (ferric oxide) having magnetic properties of about 10 nm were prepared.
在製備氧化鐵磁性奈米粒子同時，提供了纖維素水溶性高分子，並將其於低溫環境下，溶解在含有6%的氫氧化鈉與4%的尿素水溶液中，形成一纖維素水溶性高分子溶液。 In the preparation of iron oxide magnetic nanoparticles, a cellulose water-soluble polymer is provided, which is dissolved in a solution containing 6% sodium hydroxide and 4% urea in a low temperature environment to form a cellulose water-soluble. Polymer solution.
接著，將上述製備得之氧化鐵磁性奈米粒子與纖維素水溶性高分子溶液，分別配製具有不同「氧化鐵磁性奈米粒子與纖維素水溶性高分子溶液重量比例之比值」(為利於說明，以下稱之為「W氧化鐵磁性奈米粒子/W纖維素」)且混合均勻的三種第一混合溶液：其一為W氧化鐵磁性奈米粒子/W纖維素為0.25時所製備的第一種第一混合溶液，稱作「樣品A」；其二為W氧化鐵磁性奈米粒子/W纖維素為0.5時所製備的第二種第一混合溶液，稱作「樣品B」；其三則為W氧化鐵磁性奈米粒子/W纖維素為1時所製備的第三種第一混合溶液，稱作「樣品C」。 Next, the iron oxide magnetic nanoparticles prepared above and the cellulose water-soluble polymer solution are respectively prepared to have different ratios of the weight ratio of the iron oxide magnetic nanoparticles to the cellulose water-soluble polymer solution (for the purpose of explanation) , hereinafter referred to as "W iron oxide magnetic nanoparticle / W cellulose") and uniformly mixed three first mixed solutions: one of which is prepared when W ferric oxide magnetic nanoparticles/W cellulose is 0.25 a first mixed solution, referred to as "Sample A"; and a second first mixed solution prepared when W ferric oxide magnetic nanoparticles/W cellulose is 0.5, referred to as "Sample B"; The third is a third first mixed solution prepared when W iron oxide magnetic nanoparticles/W cellulose is 1, and is referred to as "sample C".
接著，提供一油相作為分散相溶液，並分別將上述的樣品A、樣品B、 樣品C以旋轉攪拌方式在特定轉速下與分散相均勻混合，配製形成第二混合溶液，再來，加入硬化劑於此第二混合溶液以製得「纖維素磁性微粒複合物A」、「纖維素磁性微粒複合物B」、「纖維素磁性微粒複合物C」。將上述纖維素磁性微粒複合物A、纖維素磁性微粒複合物B與纖維素磁性微粒複合物C分別進行磁性量分析，分析結果請參閱圖2。圖2係本實驗例一中，採用上述三項纖維素磁性微粒複合物進行磁性量分析後所得之數據圖，以柱狀圖方式呈現。從圖2的柱狀圖可得知，纖維素磁性微粒複合物A磁性量約為12.5emu/g；纖維素磁性微粒複合物B磁性量24.6emu/g；纖維素磁性微粒複合物C磁性量42.7emu/g，三者的磁性量數據明顯呈現出纖維素磁性微粒複合物磁性量隨著W氧化鐵磁性奈米粒子/W纖維素的提高而增加的關係，且其中第一混合溶液之磁性量將影響最終製成之纖維素磁性微粒複合物之磁性量，且纖維素磁性微粒複合物磁性量隨著前述「氧化鐵磁性奈米粒子與纖維素水溶性高分子溶液重量比例之比值」而變化，且第一混合溶液之磁性量將影響最終製成之纖維素磁性微粒複合物之磁性量。 Next, an oil phase is provided as a dispersed phase solution, and the above sample A, sample B, Sample C is uniformly mixed with the dispersed phase at a specific rotation speed by a rotary stirring method to prepare a second mixed solution, and then a hardening agent is added to the second mixed solution to prepare "cellulose magnetic microparticle composite A" and "fiber". Fine magnetic particle composite B" and "cellulose magnetic particle composite C". The cellulose magnetic microparticle composite A, the cellulose magnetic microparticle composite B, and the cellulose magnetic microparticle composite C were each subjected to magnetic quantity analysis, and the analysis results are shown in Fig. 2 . Fig. 2 is a graph showing the data obtained by magnetic analysis of the above three cellulose magnetic microparticle composites in the first experimental example, which is presented in a histogram manner. It can be seen from the histogram of Fig. 2 that the magnetic quantity of the cellulose magnetic particle composite A is about 12.5 emu/g; the magnetic quantity of the cellulose magnetic particle composite B is 24.6 emu/g; the magnetic quantity of the cellulose magnetic particle composite C 42.7emu/g, the magnetic quantity data of the three showed that the magnetic properties of the cellulose magnetic microparticle composite increased with the increase of W ferrite magnetic nanoparticles/W cellulose, and the magnetic properties of the first mixed solution The amount will affect the magnetic quantity of the cellulose magnetic microparticle composite finally produced, and the magnetic quantity of the cellulose magnetic microparticle composite will follow the ratio of the weight ratio of the ferric oxide magnetic nanoparticle to the cellulose water soluble polymer solution. The change, and the amount of magnetic material of the first mixed solution will affect the magnetic amount of the finally produced cellulose magnetic particle composite.
同時，為了製作粒徑不同的纖維素磁性微粒複合物，取用W氧化鐵磁性奈米粒子/W纖維素為1時，配製而得之第一混合溶液，並使用了一油相做為分散相溶液，以旋轉攪拌方式，在轉速為800rpm下進行混合，配製具有不同「分散相溶液與第一混合溶液之體積比例之比值」(為利於說明，以下稱之為「V油/V水」)且混合均勻的四種第二混合溶液：其一為V油/V水為2時所製備的第一種第二混合溶液，稱作「樣品D」；其二為V油/V水為5時所製備的第二種第二混合溶液，稱作「樣品E」；其三為V油/V水為10時所製備的第三種第二混合溶液，稱作「樣品F」；最後為，V油/V水為20時所製備的第四種第二混合溶液，稱作「樣品G」。 Meanwhile, in order to produce a cellulose magnetic microparticle composite having different particle diameters, when the W ferric oxide magnetic nanoparticles/W cellulose is used, the first mixed solution is prepared and an oil phase is used as a dispersion. The phase solution is mixed by rotary stirring at a rotation speed of 800 rpm to prepare a ratio of the volume ratio of the dispersed phase solution to the first mixed solution (for convenience, hereinafter referred to as "V oil / V water"). And four uniformly mixed solutions: one is a first second mixed solution prepared when V oil/V water is 2, and is called "sample D"; the second is V oil / V water is The second second mixed solution prepared at 5 o'clock is called "sample E"; the third is the third second mixed solution prepared when V oil / V water is 10, which is called "sample F"; The fourth second mixed solution prepared when V oil/V water is 20 is referred to as "sample G".
接著，分別以上述四種第二混合溶液進行後續的製作步驟，也就是加入硬化劑(硬化劑種類可為醇或酮類，例如：甲醇、乙醇、丙醇、丁醇、異丙醇、異丁醇、丙酮、丁酮、異丁酮等)後，最形成四種纖維素磁性微 粒複合物，分別為「纖維素磁性微粒複合物D」、「纖維素磁性微粒複合物E」、「纖維素磁性微粒複合物F」與「纖維素磁性微粒複合物G」。最後，以異丙醇和甲醇溶液來沖洗此上述四項纖維素磁性微粒複合物，並加以烘乾後，即可製得纖維素磁性微粒複合物。 Then, the subsequent preparation steps are respectively performed by using the above four second mixed solutions, that is, the hardener is added (the type of the hardener may be an alcohol or a ketone, for example, methanol, ethanol, propanol, butanol, isopropanol, iso After the formation of butanol, acetone, methyl ethyl ketone, isobutyl ketone, etc., the most four types of cellulose magnetic micro The granular composites are "cellulose magnetic microparticle composite D", "cellulose magnetic microparticle composite E", "cellulose magnetic microparticle composite F", and "cellulose magnetic microparticle composite G", respectively. Finally, the above four cellulose magnetic microparticle composites are washed with a solution of isopropyl alcohol and methanol, and dried to obtain a cellulose magnetic microparticle composite.
請參考圖3、圖4、圖5與圖6，係使用電子顯微鏡分別觀察上述纖維素磁性微粒複合物D、E、F與G之照相圖，均顯示本實驗例一所製得之纖維素磁性微粒複合物外觀為球型且大小均勻。 Referring to FIG. 3, FIG. 4, FIG. 5 and FIG. 6, the photographic images of the above-mentioned cellulose magnetic microparticle composites D, E, F and G are respectively observed by an electron microscope, and the cellulose obtained in the first experimental example is shown. The magnetic particle composite has a spherical shape and a uniform size.
接著，為確認上述纖維素磁性微粒複合物D、E、F與G之粒徑大小，以習知的磁性微粒複合物粒徑測量方法，分析測定上述四種纖維素磁性微粒複合物之粒徑分布範圍。此分析結果請參閱圖7。圖7係本實驗例一中，採用上述四項樣品進行粒徑分布範圍分析後所得之數據圖，以柱狀圖方式呈現。從圖7的柱狀圖可得知，纖維素磁性微粒複合物D粒徑分布範圍介於10微米至20微米；纖維素磁性微粒複合物E粒徑分布範圍介於20微米至40微米；纖維素磁性微粒複合物F粒徑分布範圍介於30微米至50微米，纖維素磁性微粒複合物G粒徑分布範圍介於50微米至70微米。充分顯示了分散相溶液(油相)與第二混合溶液之間的「V油/V水」對於製得的影響了纖維素磁性微粒複合物之粒徑，顯示纖維素磁性微粒磁性量隨「V油/V水」而變化。 Next, in order to confirm the particle size of the cellulose magnetic microparticle composites D, E, F, and G, the particle diameter of the above four kinds of cellulose magnetic microparticle composites is analyzed and determined by a conventional magnetic particle composite particle diameter measuring method. distribution range. See Figure 7 for the results of this analysis. Fig. 7 is a data chart obtained by analyzing the particle size distribution range using the above four samples in the first experimental example, and presented in a histogram manner. It can be seen from the histogram of FIG. 7 that the cellulose magnetic particle composite D has a particle size distribution ranging from 10 micrometers to 20 micrometers; the cellulose magnetic microparticle composite E has a particle size distribution ranging from 20 micrometers to 40 micrometers; The magnetic particle composite F particle size distribution ranges from 30 micrometers to 50 micrometers, and the cellulose magnetic microparticle composite G particle size distribution ranges from 50 micrometers to 70 micrometers. It fully shows that the "V oil / V water" between the dispersed phase solution (oil phase) and the second mixed solution affects the particle size of the cellulose magnetic particle composite, and shows that the magnetic property of the cellulose magnetic particle is " V oil / V water" changes.
且根據上述之電子顯微鏡照相圖(第3-6圖)與粒徑分布範圍分析結果(圖7)，明顯呈現出纖維素磁性微粒複合物之粒徑隨V油/V水的提高而增加的關係。 According to the above-mentioned electron micrograph (Fig. 3-6) and the particle size distribution range analysis result (Fig. 7), it is apparent that the particle size of the cellulose magnetic particle composite increases with the increase of V oil/V water. relationship.
此外，為確認本實施例中，進行分散相溶液與第二混合溶液進行混合時，不同的旋轉攪拌之「轉速」對於纖維素磁性微粒複合物之粒徑大小的關係實施以下方法進行確認：首先，分散相溶液(油相)在V油/V水為10時，製備的第二混合溶液稱做「樣品H」，接著以定量之H分別以五種旋轉攪拌速度混合。 Further, in order to confirm that in the present embodiment, when the dispersed phase solution and the second mixed solution were mixed, the relationship between the "rotational speed" of the different rotational stirring and the particle size of the cellulose magnetic fine particle composite was confirmed by the following method: The dispersed phase solution (oil phase) was prepared as "sample H" when the V oil/V water was 10, and then mixed at a quantitative stirring speed of five kinds of rotational stirring speeds.
再來，分別採用前述之步驟，製成以下五種纖維素磁性微粒複合物：當轉速為400rpm時所製得的「纖維素磁性微粒複合物H400」；當轉速為600rpm時所製得的「纖維素磁性微粒複合物H600」；當轉速為800rpm時所製得的「纖維素磁性微粒複合物H800」；當轉速為1000rpm時所製得的「纖維素磁性微粒複合物H1000」；以及當轉速為1200rpm時所製得的「纖維素磁性微粒複合物H1200」。並且採用上述五種纖維素磁性微粒複合物進行粒徑分布範圍分析，其結果請參考圖8，明顯呈現出纖維素磁性微粒複合物之粒徑隨轉速而變化的關係。 Then, using the above steps, the following five kinds of cellulose magnetic particle composites were prepared: "cellulose magnetic particle composite H400" prepared at a rotation speed of 400 rpm; when the rotation speed was 600 rpm. Cellulose magnetic particle composite H600"; "cellulose magnetic particle composite H800" prepared at a rotation speed of 800 rpm; "cellulose magnetic particle composite H1000" prepared at a rotation speed of 1000 rpm; The "cellulose magnetic microparticle composite H1200" obtained at 1200 rpm. Further, the above five kinds of cellulose magnetic microparticle composites were used for particle size distribution range analysis. The results are shown in Fig. 8. The relationship between the particle size of the cellulose magnetic microparticle composite and the rotation speed is apparent.
首先，為了取得磁性奈米粒子，先行以下述之化學共沉法製備氧化鐵磁性奈米粒子：先將二價及三價鐵離子以莫耳比1：2之比例混合，以300rpm之轉速進行旋轉攪拌，並以1M NaOH溶液調整反應物之pH值至12，之後於60℃下使其反應1小時後，再以高轉速離心後取其黑色沉澱物，並加入去離子水使其分散，藉此製備具有磁性的氧化鐵磁性奈米粒子(四氧化三鐵)，其平均粒經約為10奈米。 First, in order to obtain magnetic nanoparticles, the iron oxide magnetic nanoparticles are prepared by the following chemical co-precipitation method: first, the divalent and trivalent iron ions are mixed at a molar ratio of 1:2, and the rotation speed is 300 rpm. Rotate and stir, adjust the pH of the reactants to 12 with 1M NaOH solution, then react at 60 ° C for 1 hour, then centrifuge at high speed, then take the black precipitate and add deionized water to disperse it. Thereby, magnetic iron oxide magnetic nanoparticles (ferric oxide) having magnetic properties of about 10 nm were prepared.
在製備氧化鐵磁性奈米粒子同時，提供了海藻酸鈉水溶性高分子，並將其於低溫環境下，溶解在水溶液中，形成一海藻酸鈉水溶性高分子溶液。 In the preparation of the iron oxide magnetic nanoparticles, a sodium alginate water-soluble polymer is provided, and dissolved in an aqueous solution under a low temperature environment to form a sodium alginate water-soluble polymer solution.
接著，將上述製備得之氧化鐵磁性奈米粒子與海藻酸鈉水溶性高分子溶液，分別配製具有不同「氧化鐵磁性奈米粒子與海藻酸鈉水溶性高分子溶液重量比例之比值」(為利於說明，以下稱之為「W氧化鐵磁性奈米粒子/W海藻酸鈉」)且混合均勻的三種第一混合溶液：其一為W氧化鐵磁性奈米粒子/W海藻酸鈉為0.25時所製備的第一種第一混合溶液，稱作「樣品A’」；其二為W氧化鐵磁性奈米粒子/W海藻酸鈉為0.5時所製備的第二種第一混合溶液，稱作「樣品B’」；其三則為W氧化鐵磁性奈米粒子/W海藻酸鈉為1時所製備的第三種第一混合溶液，稱作「樣品C’」。 Next, the iron oxide magnetic nanoparticles prepared above and the sodium alginate water-soluble polymer solution are respectively prepared to have different ratios of the weight ratio of the ferric oxide magnetic nanoparticles to the sodium alginate water-soluble polymer solution (for For the sake of explanation, the following three kinds of first mixed solutions are referred to as "W iron oxide magnetic nanoparticles/W sodium alginate" and uniformly mixed: one is W iron oxide magnetic nanoparticles/W sodium alginate is 0.25. The first first mixed solution prepared is referred to as "Sample A'"; the second is a second first mixed solution prepared when W ferric oxide magnetic nanoparticles/W sodium alginate is 0.5, which is called "Sample B'"; the third is a third first mixed solution prepared when W iron oxide magnetic nanoparticles/W sodium alginate is 1, which is called "sample C".
接著，提供一油相作為分散相溶液，並分別將上述的樣品A’、樣品B’、樣品C’以旋轉攪拌方式在特定轉速下與分散相均勻混合，配製形成第二混合溶液，再來，加入硬化劑於此第二混合溶液以製得「海藻酸鈉磁性微粒複合物A’」、「海藻酸鈉磁性微粒複合物B’」、「海藻酸鈉磁性微粒複合物C’」。將上述海藻酸鈉磁性微粒複合物A’、海藻酸鈉磁性微粒複合物B’與海藻酸鈉磁性微粒複合物C’分別進行磁性量分析，分析結果請參閱圖9。圖9係本實驗例二中，採用上述三項海藻酸鈉磁性微粒複合物進行磁性量分析後所得之數據圖，以柱狀圖方式呈現。從圖9的柱狀圖可得知，海藻酸鈉磁性微粒複合物A’磁性量約為13.6emu/g；海藻酸鈉磁性微粒複合物B’磁性量24.8emu/g；海藻酸鈉磁性微粒複合物C’磁性量40.9emu/g，三者的磁性量數據明顯呈現出海藻酸鈉磁性微粒複合物磁性量隨著W氧化鐵磁性奈米粒子/W海藻酸鈉的提高而變化的關係，與實驗例一類似。且第一混合溶液之磁性量將影響最終製成之海藻酸鈉磁性微粒複合物之磁性量，顯示樣品磁性量隨此W氧化鐵磁性奈米粒子/W海藻酸鈉而變化。 Next, an oil phase is provided as a dispersed phase solution, and the above sample A', sample B', and sample C' are uniformly mixed with the dispersed phase at a specific rotation speed by a rotary stirring method to prepare a second mixed solution, and then The hardening agent is added to the second mixed solution to prepare "alginate magnetic microparticle composite A'", "alginate magnetic microparticle composite B'", and "sodium alginate magnetic microparticle composite C". The above-mentioned sodium alginate magnetic fine particle composite A', sodium alginate magnetic fine particle composite B' and sodium alginate magnetic fine particle composite C' were each subjected to magnetic quantity analysis, and the analysis results are shown in Fig. 9. Fig. 9 is a graph showing the data obtained by magnetic analysis of the above three sodium alginate magnetic microparticle composites in the second experiment example, which is presented in a histogram manner. As can be seen from the histogram of Fig. 9, the alginate magnetic particle composite A' magnetic amount is about 13.6emu / g; the sodium alginate magnetic particle composite B' magnetic amount is 24.8emu / g; sodium alginate magnetic particles The magnetic quantity of the composite C' is 40.9emu/g, and the magnetic quantity data of the three exhibits a relationship between the magnetic quantity of the sodium alginate magnetic particle composite and the increase of the W iron oxide magnetic nano particle/W sodium alginate. Similar to the experimental example 1. And the magnetic quantity of the first mixed solution will affect the magnetic quantity of the finally prepared sodium alginate magnetic particle composite, indicating that the magnetic quantity of the sample varies with the W iron oxide magnetic magnetic particle / W sodium alginate.
同時，為了製作粒徑不同的海藻酸鈉磁性微粒複合物，取用W氧化鐵磁性奈米粒子/W海藻酸鈉為1時，配製而得之第一混合溶液，並使用了一油相做為分散相溶液，以旋轉攪拌方式，在轉速為800rpm下進行混合，配製具有不同「分散相溶液與第一混合溶液之體積比例之比值」(為利於說明，以下稱之為「V油/V水」)且混合均勻的四種第二混合溶液：其一為V油/V水為2時所製備的第一種第二混合溶液，稱作「樣品D’」；其二為V油/V水為5時所製備的第二種第二混合溶液，稱作「樣品E’」；其三為V油/V水為10時所製備的第三種第二混合溶液，稱作「樣品F’」；最後為，V油/V水為20時所製備的第四種第二混合溶液，稱作「樣品G’」。 At the same time, in order to prepare a sodium alginate magnetic microparticle composite having different particle diameters, when the W iron oxide magnetic nanoparticle/W sodium alginate is used, the first mixed solution is prepared and an oil phase is used. For the dispersed phase solution, the mixture is mixed at a rotation speed of 800 rpm to prepare a ratio of the volume ratio of the dispersed phase solution to the first mixed solution (for the sake of explanation, hereinafter referred to as "V oil / V" Water") and four uniformly mixed solutions: one is the first second mixed solution prepared when V oil/V water is 2, which is called "sample D'"; the second is V oil / The second second mixed solution prepared when V water is 5 is called "sample E'"; the third is the third second mixed solution prepared when V oil / V water is 10, which is called "sample". F'"; Finally, the fourth second mixed solution prepared when V oil/V water is 20 is called "sample G'".
接著，分別以上述四種第二混合溶液進行後續的製作步驟，也就是加入硬化劑甲醇後，最形成四種海藻酸鈉磁性微粒複合物，分別為「海藻酸鈉磁性微粒複合物D’」、「海藻酸鈉磁性微粒複合物E’」、「海藻酸鈉磁性微 粒複合物F’」與「海藻酸鈉磁性微粒複合物G’」。最後，以異丙醇和甲醇溶液來沖洗上述四項海藻酸鈉磁性微粒複合物，並加以烘乾後，即可製得海藻酸鈉磁性微粒複合物。 Then, the subsequent preparation steps are respectively performed by using the above four second mixed solutions, that is, after adding the hardener methanol, the four kinds of sodium alginate magnetic particle composites are formed, respectively, which are respectively "sodium alginate magnetic particle composite D". , "Alginate Magnetic Particle Complex E'", "Sodium Alginate Magnetic Micro Granular composite F'" and "alginate magnetic microparticle composite G'". Finally, the above four sodium alginate magnetic particle composites are rinsed with isopropyl alcohol and methanol solution, and dried to obtain a sodium alginate magnetic particle composite.
請參考圖10，係使用電子顯微鏡分別觀察上述海藻酸鈉磁性微粒複合物E’之照相圖，顯示本實驗例二所製得之海藻酸鈉磁性微粒複合物外觀為球型且大小均勻。由於本實驗例二與實驗例一所得之結果類似，因此在此僅以圖10之海藻酸鈉磁性微粒複合物E’之照相圖為例說明之。 Referring to Fig. 10, a photograph of the above-mentioned sodium alginate magnetic microparticle composite E' was observed by an electron microscope, and it was revealed that the sodium alginate magnetic microparticle composite prepared in the second experiment example was spherical in shape and uniform in size. Since the results obtained in the second experimental example are similar to those in the first experimental example, only the photograph of the sodium alginate magnetic fine particle composite E' of Fig. 10 is taken as an example.
接著，為確認上述海藻酸鈉磁性微粒複合物D’、E’、F’與G’之粒徑大小，以習知的磁性微粒複合物粒徑測量方法，分析測定上述四種海藻酸鈉磁性微粒複合物之粒徑分布範圍。此分析結果類似於實驗例一，因此不再重複以圖式說明。簡而言之，此結果亦顯示了分散相溶液(油相)與第二混合溶液之間的「V油/V水」對於製得的影響了海藻酸鈉磁性微粒複合物之粒徑。 Next, in order to confirm the particle size of the above-mentioned sodium alginate magnetic microparticle composites D', E', F' and G', the above four kinds of sodium alginate magnetic properties are analyzed and determined by a conventional magnetic particle composite particle size measuring method. The particle size distribution range of the microparticle composite. The results of this analysis are similar to the experimental example 1, and therefore will not be repeated for illustration. In short, this result also shows that the "V oil / V water" between the dispersed phase solution (oil phase) and the second mixed solution affects the particle size of the sodium alginate magnetic particle composite.
且根據上述之電子顯微鏡照相圖與粒徑分布範圍分析結果，呈現出海藻酸鈉磁性微粒複合物之粒徑隨V油/V水的提高而增加的關係。 According to the above-mentioned electron micrograph and particle size distribution range analysis results, the relationship between the particle size of the sodium alginate magnetic particle composite and the increase of V oil/V water increased.
以上所述僅為本發明較佳實施例及實驗例而已，並非用以限定本發明申請專利權利；同時以上的描述對於熟知本技術領域之專門人士應可明瞭與實施，因此其他未脫離本發明所揭示之精神下所完成的等效改變或修飾，均應包含於下述之申請專利範圍。 The above description is only for the preferred embodiments and experimental examples of the present invention, and is not intended to limit the claims of the present invention. The above description should be understood and implemented by those skilled in the art, so that the other embodiments are not deviated from the present invention. Equivalent changes or modifications made in the spirit of the disclosure are intended to be included in the scope of the claims below.
S11、S12、S13、S14、S15‧‧‧步驟 S11, S12, S13, S14, S15‧‧ steps
圖1、為根據本發明所提出之第一較佳實施例，係一種磁性微粒複合物製作方法步驟流程圖。 1 is a flow chart showing the steps of a magnetic particle composite manufacturing method according to a first preferred embodiment of the present invention.
圖2、為根據本發明所提出實驗例一中，係以不同「氧化鐵磁性奈米粒子與纖維素水溶性高分子溶液重量比例之比值」製備之纖維素磁性微粒複合物A(W氧化鐵磁性奈米粒子/W纖維素為0.25)、纖維素磁性微粒複合 物B(W氧化鐵磁性奈米粒子/W纖維素為0.5)與纖維素磁性微粒複合物C(W氧化鐵磁性奈米粒子/W纖維素為1)的磁性量分析結果，以柱狀圖表示；圖3、為根據本發明所提出實驗例一，當「分散相溶液與第一混合溶液之體積比例之比值」為2時，製備而得之纖維素磁性微粒複合物D之電子顯微鏡照相圖，放大倍率為400倍，粒徑分布範圍介於10微米至20微米；圖4、為根據本發明所提出實驗例一，當「分散相溶液與第一混合溶液之體積比例之比值」為5時，製備而得之纖維素磁性微粒複合物E之電子顯微鏡照相圖，放大倍率為400倍，粒徑分布範圍介於20微米至40微米；圖5、為根據本發明所提出實驗例一，當「分散相溶液與第一混合溶液之體積比例之比值」為10時，製備而得之纖維素磁性微粒複合物F之電子顯微鏡照相圖，放大倍率為400倍，粒徑分布範圍介於30微米至50微米；圖6、為根據本發明所提出實驗例一，當「分散相溶液與第一混合溶液之體積比例之比值」為20時，製備而得之纖維素磁性微粒複合物G之電子顯微鏡照相圖，放大倍率為400倍，粒徑分布範圍介於50微米至70微米；圖7、為根據本發明所提出實驗例一，係以不同「分散相溶液與第一混合溶液之體積比例之比值」製備而得的纖維素磁性微粒複合物D(V油/V水為2)、纖維素磁性微粒複合物E(V油/V水為5)、纖維素磁性微粒複合物F(V油/V水為10)與纖維素磁性微粒複合物G(V油/V水為20)的磁性量分析結果，以柱狀圖表示；圖8、為根據本發明所提出實驗例一，係以不同旋轉攪拌之「轉速」製備而得的纖維素磁性微粒複合物H400(轉速為400rpm)、纖維素磁性微粒複合物H600(轉速為600rpm)、纖維素磁性微粒複合物H800(轉速為800rpm)、纖維素磁性微粒複合物H1000(轉速為1000rpm)與纖維素磁性微粒複合物H1200(轉速為1200rpm)之粒徑分布範圍分析結果，以柱狀圖表示； 圖9、為根據本發明所提出實驗例二，係以不同「氧化鐵磁性奈米粒子與海藻酸鈉水溶性高分子溶液重量比例之比值」製備之海藻酸鈉磁性微粒複合物A’(W氧化鐵磁性奈米粒子/W海藻酸鈉為0.25)、海藻酸鈉磁性微粒複合物B’(W氧化鐵磁性奈米粒子/W海藻酸鈉為0.5)與海藻酸鈉磁性微粒複合物C’(W氧化鐵磁性奈米粒子/W海藻酸鈉為1)的磁性量分析結果，以柱狀圖表示；圖10、為根據本發明所提出實驗例二，當「分散相溶液與第一混合溶液之體積比例之比值」為5時，製備而得之海藻酸鈉磁性微粒複合物E’之電子顯微鏡照相圖，放大倍率為400倍，粒徑分布範圍介於15微米至38微米。 2 is a cellulose magnetic particle composite A (W iron oxide prepared by the ratio of the ratio of the weight ratio of the iron oxide magnetic nanoparticles to the cellulose water-soluble polymer solution in the experimental example 1 according to the present invention. Magnetic nanoparticle / W cellulose is 0.25), cellulose magnetic particle composite The magnetic quantity analysis result of the material B (W iron oxide magnetic nanoparticle / W cellulose is 0.5) and the cellulose magnetic microparticle composite C (W iron oxide magnetic nanoparticle / W cellulose is 1), a histogram Figure 3 is an experimental example 1 of the present invention. When the ratio of the volume ratio of the dispersed phase solution to the first mixed solution is 2, the prepared electron micrograph of the cellulose magnetic microparticle composite D is obtained. The magnification is 400 times and the particle size distribution ranges from 10 micrometers to 20 micrometers. FIG. 4 is the experimental example 1 according to the present invention, when the ratio of the volume ratio of the dispersed phase solution to the first mixed solution is At 5 o'clock, an electron micrograph of the prepared cellulose magnetic microparticle composite E has a magnification of 400 times and a particle size distribution ranging from 20 micrometers to 40 micrometers; FIG. 5 is an experimental example 1 according to the present invention. When the ratio of the volume ratio of the dispersed phase solution to the first mixed solution is 10, an electron micrograph of the prepared cellulose magnetic microparticle composite F has a magnification of 400 times and a particle size distribution range of 30 microns to 50 microns Figure 6 is an electron micrograph of the prepared cellulose magnetic particle composite G when the ratio of the ratio of the volume ratio of the dispersed phase solution to the first mixed solution is 20, according to the experimental example 1 of the present invention. The magnification is 400 times, and the particle size distribution ranges from 50 micrometers to 70 micrometers; FIG. 7 is the experimental example 1 according to the present invention, which is prepared by using different ratios of the volume ratio of the dispersed phase solution to the first mixed solution. The obtained cellulose magnetic particle composite D (V oil / V water is 2), cellulose magnetic particle composite E (V oil / V water is 5), cellulose magnetic particle composite F (V oil / V water The results of the magnetic quantity analysis of 10) and the cellulose magnetic particle composite G (V oil / V water is 20) are represented by a histogram; FIG. 8 is an experimental example 1 according to the present invention, which is stirred with different rotations. Cellulose magnetic particle composite H400 (rotation speed 400 rpm) prepared by "rotation speed", cellulose magnetic particle composite H600 (rotation speed 600 rpm), cellulose magnetic particle composite H800 (rotation speed 800 rpm), cellulose magnetic Microparticle composite H1000 (rotation speed 1000rpm) and cellulose magnetic micro The particle size distribution range analysis result of the particle composite H1200 (rotation speed: 1200 rpm) is represented by a histogram; Figure 9 is a second embodiment of the present invention, the sodium alginate magnetic particle composite A' (W) prepared by different "the ratio of the weight ratio of the ferric oxide magnetic nanoparticles to the sodium alginate water-soluble polymer solution". Iron oxide magnetic nanoparticles/W sodium alginate is 0.25), sodium alginate magnetic particle composite B' (W iron oxide magnetic nanoparticles/W sodium alginate is 0.5) and sodium alginate magnetic particle composite C' The results of magnetic quantity analysis of (W iron oxide magnetic nanoparticles/W sodium alginate is 1) are shown in a histogram; FIG. 10 is an experimental example 2 according to the present invention, when "the dispersed phase solution is mixed with the first When the ratio of the volume ratio of the solution is "5", an electron micrograph of the prepared sodium alginate magnetic microparticle composite E' has a magnification of 400 times and a particle size distribution ranging from 15 micrometers to 38 micrometers.
S11、S12、S13、S14、S15‧‧‧步驟 S11, S12, S13, S14, S15‧‧ steps
Claims (9)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| TW101101902A TWI446924B (en) | 2012-01-18 | 2012-01-18 | Manufacturing method of magnetic composite particles |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| TW101101902A TWI446924B (en) | 2012-01-18 | 2012-01-18 | Manufacturing method of magnetic composite particles |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| TW201330862A TW201330862A (en) | 2013-08-01 |
| TWI446924B true TWI446924B (en) | 2014-08-01 |
Family
ID=49478743
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW101101902A TWI446924B (en) | 2012-01-18 | 2012-01-18 | Manufacturing method of magnetic composite particles |
Country Status (1)
| Country | Link |
|---|---|
| TW (1) | TWI446924B (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1688001A (en) * | 2005-03-30 | 2005-10-26 | 深圳市人民医院 | Nano-magnetic microsphere and nona-magnetic immuno-microsphere, and preparing process and application thereof |
| CN1872028A (en) * | 2006-04-28 | 2006-12-06 | 深圳市人民医院 | Immune magnetic Nano microsphere, preparation method, and application |
| CN1994469A (en) * | 2006-09-13 | 2007-07-11 | 上海师范大学 | Biodegradable magnetic nanoparticle, preparation method and application thereof |
-
2012
- 2012-01-18 TW TW101101902A patent/TWI446924B/en not_active IP Right Cessation
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1688001A (en) * | 2005-03-30 | 2005-10-26 | 深圳市人民医院 | Nano-magnetic microsphere and nona-magnetic immuno-microsphere, and preparing process and application thereof |
| CN1872028A (en) * | 2006-04-28 | 2006-12-06 | 深圳市人民医院 | Immune magnetic Nano microsphere, preparation method, and application |
| CN1994469A (en) * | 2006-09-13 | 2007-07-11 | 上海师范大学 | Biodegradable magnetic nanoparticle, preparation method and application thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| TW201330862A (en) | 2013-08-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US7754278B2 (en) | Magnetic polymer microbeads and method for preparing the same | |
| EP1883818B1 (en) | Magnetically-responsive microparticles with improved response times | |
| EP1287359B1 (en) | Silica coated nanoparticles | |
| US6773812B2 (en) | Magnetically-responsive microspheres | |
| US6682660B2 (en) | Ultrasonically generated paramagnetic polymer particles | |
| CN104031201B (en) | A kind of preparation method and applications of the magnetic microsphere separated for bioprotein | |
| CN111393574B (en) | Magnetic microsphere with functional groups on surface and preparation method and application thereof | |
| US20150183655A1 (en) | Microparticles and a sytem and method for the synthesis of microparticles | |
| AU2001261841A1 (en) | Coated nanoparticles | |
| JP2003513093A (en) | Composite nanospheres and their complexes with biomolecules | |
| JP6913908B2 (en) | Magnetic composite particles, their manufacturing methods, and immunoassay particles | |
| WO2013106948A1 (en) | Method for manufacturing magnetic particle composite | |
| JP4548598B2 (en) | Magnetic particle, method for producing the same, and carrier for biochemistry | |
| JP2018132505A (en) | Magnetic composite particles, manufacturing method therefor, and immunoassay particles | |
| Liu et al. | Preparation and characterization of superparamagnetic functional polymeric microparticles | |
| TWI446924B (en) | Manufacturing method of magnetic composite particles | |
| CN105536725B (en) | The preparation method of the amido modified magnetic microsphere of higher suspension | |
| CN116836704B (en) | Fluorescent microsphere and preparation method thereof | |
| Shestakova et al. | Microsized uniform magnetic polymer microspheres with carboxyl groups | |
| CN115127972A (en) | Magnetic bead and manufacturing method thereof | |
| CN115127973A (en) | Fluorescent magnetic bead and manufacturing method thereof | |
| CN115127976A (en) | Fluorescent magnetic bead and manufacturing method thereof | |
| Penamon | Gold-coated magnetic polymer microsphere synthesis and characterization: applications in biological contexts | |
| Yao | ‘One-pot’manufacturing process yielding low-cost magnetic supports for bioprocessing |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | Annulment or lapse of patent due to non-payment of fees |