GB2244987A - Small particles - Google Patents
Small particles Download PDFInfo
- Publication number
- GB2244987A GB2244987A GB9111026A GB9111026A GB2244987A GB 2244987 A GB2244987 A GB 2244987A GB 9111026 A GB9111026 A GB 9111026A GB 9111026 A GB9111026 A GB 9111026A GB 2244987 A GB2244987 A GB 2244987A
- Authority
- GB
- United Kingdom
- Prior art keywords
- particles
- molecules
- magnetic
- ferrofluid
- mol
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 239000002245 particle Substances 0.000 title claims description 86
- 239000011554 ferrofluid Substances 0.000 claims description 63
- 238000000034 method Methods 0.000 claims description 34
- 239000002243 precursor Substances 0.000 claims description 32
- 230000008569 process Effects 0.000 claims description 30
- 239000004094 surface-active agent Substances 0.000 claims description 18
- 239000006249 magnetic particle Substances 0.000 claims description 16
- 239000007788 liquid Substances 0.000 claims description 13
- 238000004519 manufacturing process Methods 0.000 claims description 11
- 150000002148 esters Chemical class 0.000 claims description 10
- 239000002253 acid Substances 0.000 claims description 9
- 150000001875 compounds Chemical class 0.000 claims description 6
- 239000002798 polar solvent Substances 0.000 claims description 5
- 229920006295 polythiol Polymers 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 5
- 229920006395 saturated elastomer Polymers 0.000 claims description 5
- 125000001931 aliphatic group Chemical group 0.000 claims description 4
- 229920005862 polyol Polymers 0.000 claims description 4
- 230000009257 reactivity Effects 0.000 claims description 4
- 239000000126 substance Substances 0.000 claims description 4
- 239000013543 active substance Substances 0.000 claims description 3
- 239000003054 catalyst Substances 0.000 claims description 3
- 230000009881 electrostatic interaction Effects 0.000 claims description 3
- 150000003077 polyols Chemical class 0.000 claims description 3
- 229920002545 silicone oil Polymers 0.000 claims description 3
- 125000003158 alcohol group Chemical group 0.000 claims description 2
- 125000003118 aryl group Chemical group 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 230000005415 magnetization Effects 0.000 claims description 2
- 239000012454 non-polar solvent Substances 0.000 claims description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 1
- 229910052799 carbon Inorganic materials 0.000 claims 1
- 230000005285 magnetism related processes and functions Effects 0.000 claims 1
- 239000002244 precipitate Substances 0.000 description 35
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 31
- 239000000243 solution Substances 0.000 description 27
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 24
- WGTYBPLFGIVFAS-UHFFFAOYSA-M tetramethylammonium hydroxide Chemical compound [OH-].C[N+](C)(C)C WGTYBPLFGIVFAS-UHFFFAOYSA-M 0.000 description 22
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 21
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 17
- 229910017604 nitric acid Inorganic materials 0.000 description 17
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 16
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 15
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 15
- 239000012153 distilled water Substances 0.000 description 15
- 238000010438 heat treatment Methods 0.000 description 11
- 239000002609 medium Substances 0.000 description 11
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- ACTRVOBWPAIOHC-UHFFFAOYSA-N succimer Chemical compound OC(=O)C(S)C(S)C(O)=O ACTRVOBWPAIOHC-UHFFFAOYSA-N 0.000 description 9
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 8
- 239000000203 mixture Substances 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- WECIKJKLCDCIMY-UHFFFAOYSA-N 2-chloro-n-(2-cyanoethyl)acetamide Chemical compound ClCC(=O)NCCC#N WECIKJKLCDCIMY-UHFFFAOYSA-N 0.000 description 7
- 210000004534 cecum Anatomy 0.000 description 7
- 239000003921 oil Substances 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 229910019142 PO4 Inorganic materials 0.000 description 6
- ROBFUDYVXSDBQM-UHFFFAOYSA-N hydroxymalonic acid Chemical compound OC(=O)C(O)C(O)=O ROBFUDYVXSDBQM-UHFFFAOYSA-N 0.000 description 6
- JEIPFZHSYJVQDO-UHFFFAOYSA-N iron(III) oxide Inorganic materials O=[Fe]O[Fe]=O JEIPFZHSYJVQDO-UHFFFAOYSA-N 0.000 description 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 6
- 239000010452 phosphate Substances 0.000 description 6
- DOIRQSBPFJWKBE-UHFFFAOYSA-N dibutyl phthalate Chemical compound CCCCOC(=O)C1=CC=CC=C1C(=O)OCCCC DOIRQSBPFJWKBE-UHFFFAOYSA-N 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 229940083575 sodium dodecyl sulfate Drugs 0.000 description 5
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- JWDFQMWEFLOOED-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 3-(pyridin-2-yldisulfanyl)propanoate Chemical compound O=C1CCC(=O)N1OC(=O)CCSSC1=CC=CC=N1 JWDFQMWEFLOOED-UHFFFAOYSA-N 0.000 description 4
- PXXNTAGJWPJAGM-VCOUNFBDSA-N Decaline Chemical compound C=1([C@@H]2C3)C=C(OC)C(OC)=CC=1OC(C=C1)=CC=C1CCC(=O)O[C@H]3C[C@H]1N2CCCC1 PXXNTAGJWPJAGM-VCOUNFBDSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 4
- 239000003849 aromatic solvent Substances 0.000 description 4
- 229960005070 ascorbic acid Drugs 0.000 description 4
- 235000010323 ascorbic acid Nutrition 0.000 description 4
- 239000011668 ascorbic acid Substances 0.000 description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
- 125000002091 cationic group Chemical group 0.000 description 4
- 229910052742 iron Inorganic materials 0.000 description 4
- 125000005498 phthalate group Chemical class 0.000 description 4
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 4
- PXXNTAGJWPJAGM-UHFFFAOYSA-N vertaline Natural products C1C2C=3C=C(OC)C(OC)=CC=3OC(C=C3)=CC=C3CCC(=O)OC1CC1N2CCCC1 PXXNTAGJWPJAGM-UHFFFAOYSA-N 0.000 description 4
- RTBFRGCFXZNCOE-UHFFFAOYSA-N 1-methylsulfonylpiperidin-4-one Chemical compound CS(=O)(=O)N1CCC(=O)CC1 RTBFRGCFXZNCOE-UHFFFAOYSA-N 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 3
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 3
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 3
- JFCQEDHGNNZCLN-UHFFFAOYSA-N anhydrous glutaric acid Natural products OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 3
- 239000012736 aqueous medium Substances 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 230000008878 coupling Effects 0.000 description 3
- 238000010168 coupling process Methods 0.000 description 3
- 238000005859 coupling reaction Methods 0.000 description 3
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 3
- 235000011180 diphosphates Nutrition 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- XEEVLJKYYUVTRC-UHFFFAOYSA-N oxomalonic acid Chemical compound OC(=O)C(=O)C(O)=O XEEVLJKYYUVTRC-UHFFFAOYSA-N 0.000 description 3
- CGFYHILWFSGVJS-UHFFFAOYSA-N silicic acid;trioxotungsten Chemical compound O[Si](O)(O)O.O=[W]1(=O)O[W](=O)(=O)O[W](=O)(=O)O1.O=[W]1(=O)O[W](=O)(=O)O[W](=O)(=O)O1.O=[W]1(=O)O[W](=O)(=O)O[W](=O)(=O)O1.O=[W]1(=O)O[W](=O)(=O)O[W](=O)(=O)O1 CGFYHILWFSGVJS-UHFFFAOYSA-N 0.000 description 3
- 239000001509 sodium citrate Substances 0.000 description 3
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 2
- YCPXWRQRBFJBPZ-UHFFFAOYSA-N 5-sulfosalicylic acid Chemical compound OC(=O)C1=CC(S(O)(=O)=O)=CC=C1O YCPXWRQRBFJBPZ-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 229920002307 Dextran Polymers 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- VTLYFUHAOXGGBS-UHFFFAOYSA-N Fe3+ Chemical compound [Fe+3] VTLYFUHAOXGGBS-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O ammonium group Chemical group [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
- 125000000129 anionic group Chemical group 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000000975 co-precipitation Methods 0.000 description 2
- 230000000536 complexating effect Effects 0.000 description 2
- RNPXCFINMKSQPQ-UHFFFAOYSA-N dicetyl hydrogen phosphate Chemical compound CCCCCCCCCCCCCCCCOP(O)(=O)OCCCCCCCCCCCCCCCC RNPXCFINMKSQPQ-UHFFFAOYSA-N 0.000 description 2
- 229940093541 dicetylphosphate Drugs 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 239000001630 malic acid Substances 0.000 description 2
- 235000011090 malic acid Nutrition 0.000 description 2
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 229920000447 polyanionic polymer Polymers 0.000 description 2
- -1 polyol compounds Chemical class 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 229930195734 saturated hydrocarbon Natural products 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 229960001367 tartaric acid Drugs 0.000 description 2
- 239000011975 tartaric acid Substances 0.000 description 2
- 235000002906 tartaric acid Nutrition 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- 239000008096 xylene Substances 0.000 description 2
- 229910000859 α-Fe Inorganic materials 0.000 description 2
- UUDLQDCYDSATCH-UHFFFAOYSA-N 2,3-dihydroxybutanedioic acid;hydrate Chemical compound O.OC(=O)C(O)C(O)C(O)=O UUDLQDCYDSATCH-UHFFFAOYSA-N 0.000 description 1
- WXHLLJAMBQLULT-UHFFFAOYSA-N 2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-n-(2-methyl-6-sulfanylphenyl)-1,3-thiazole-5-carboxamide;hydrate Chemical compound O.C=1C(N2CCN(CCO)CC2)=NC(C)=NC=1NC(S1)=NC=C1C(=O)NC1=C(C)C=CC=C1S WXHLLJAMBQLULT-UHFFFAOYSA-N 0.000 description 1
- VYQMXBMNWDFBHM-UHFFFAOYSA-K 2-hydroxypropane-1,2,3-tricarboxylate tetramethylazanium Chemical compound C[N+](C)(C)C.C[N+](C)(C)C.C[N+](C)(C)C.OC(CC([O-])=O)(CC([O-])=O)C([O-])=O VYQMXBMNWDFBHM-UHFFFAOYSA-K 0.000 description 1
- DJBRKGZFUXKLKO-UHFFFAOYSA-N 3-(pyridin-2-yldisulfanyl)propanoic acid Chemical compound OC(=O)CCSSC1=CC=CC=N1 DJBRKGZFUXKLKO-UHFFFAOYSA-N 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- LZZYPRNAOMGNLH-UHFFFAOYSA-M Cetrimonium bromide Chemical compound [Br-].CCCCCCCCCCCCCCCC[N+](C)(C)C LZZYPRNAOMGNLH-UHFFFAOYSA-M 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 101710181478 Envelope glycoprotein GP350 Proteins 0.000 description 1
- 229910000708 MFe2O4 Inorganic materials 0.000 description 1
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical group OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 229920005654 Sephadex Polymers 0.000 description 1
- 239000012507 Sephadex™ Substances 0.000 description 1
- 102220497176 Small vasohibin-binding protein_T47D_mutation Human genes 0.000 description 1
- 101150046432 Tril gene Proteins 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 229910001566 austenite Inorganic materials 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical group 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 239000003093 cationic surfactant Substances 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 229910017052 cobalt Inorganic materials 0.000 description 1
- 239000010941 cobalt Substances 0.000 description 1
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 1
- 239000008139 complexing agent Substances 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 238000000151 deposition Methods 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 238000002059 diagnostic imaging Methods 0.000 description 1
- 150000005690 diesters Chemical class 0.000 description 1
- 229940070748 dimercaptosuccinate Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 230000000887 hydrating effect Effects 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- UCNNJGDEJXIUCC-UHFFFAOYSA-L hydroxy(oxo)iron;iron Chemical compound [Fe].O[Fe]=O.O[Fe]=O UCNNJGDEJXIUCC-UHFFFAOYSA-L 0.000 description 1
- 238000010166 immunofluorescence Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000003350 kerosene Substances 0.000 description 1
- 239000011553 magnetic fluid Substances 0.000 description 1
- WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical compound [Mn+2].[S-]C(=S)NCCNC([S-])=S.COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC WPBNNNQJVZRUHP-UHFFFAOYSA-L 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 239000012460 protein solution Substances 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 238000010298 pulverizing process Methods 0.000 description 1
- 238000002791 soaking Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 229910052596 spinel Inorganic materials 0.000 description 1
- 239000011029 spinel Substances 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 239000010414 supernatant solution Substances 0.000 description 1
- QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
- 229930195735 unsaturated hydrocarbon Natural products 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B03—SEPARATION OF SOLID MATERIALS USING LIQUIDS OR USING PNEUMATIC TABLES OR JIGS; MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
- B03C—MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
- B03C1/00—Magnetic separation
- B03C1/005—Pretreatment specially adapted for magnetic separation
- B03C1/01—Pretreatment specially adapted for magnetic separation by addition of magnetic adjuvants
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J35/00—Catalysts, in general, characterised by their form or physical properties
- B01J35/30—Catalysts, in general, characterised by their form or physical properties characterised by their physical properties
- B01J35/33—Electric or magnetic properties
-
- H—ELECTRICITY
- H01—ELECTRIC ELEMENTS
- H01F—MAGNETS; INDUCTANCES; TRANSFORMERS; SELECTION OF MATERIALS FOR THEIR MAGNETIC PROPERTIES
- H01F1/00—Magnets or magnetic bodies characterised by the magnetic materials therefor; Selection of materials for their magnetic properties
- H01F1/44—Magnets or magnetic bodies characterised by the magnetic materials therefor; Selection of materials for their magnetic properties of magnetic liquids, e.g. ferrofluids
Landscapes
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Power Engineering (AREA)
- Materials Engineering (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Soft Magnetic Materials (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Physical Or Chemical Processes And Apparatus (AREA)
- Hard Magnetic Materials (AREA)
Description
1 SMALL PARTICLES
Field of the invention
The present invention relates to a process f or the production of finely divided magnetic supports by controlled modification of the surface of charged magnetic particles, initially dispersed in water in the form of ionic f errof luid, the particles obtainable by this process and their uses. The charged magnetic precursor particles are capable of absorbing various molecules by a chemical reaction at the surface and of being transferred to various solvents with formation of stable ferrofluids.
Description of the Prior Art
Processes which enable the production of substituted magnetic particles have already been described in the prior art.
US Patent 4,452,773 describes magnetic particles coated by dextran to which antibodies can be bound. The coating method described in this patent does not allow the charge of the particles to be controlled. Moreover, dextran is a polymer which is poorly defined chemically.
US Patent 4,430,239 describes a process for the production of magnetic particles coated with surfactants from precursor particles which are dispersed in an aqueous medium and not from a stable ionic rerrofluid.
The method for dispersing these particles and the state of their surfaces are not sDecified.
The summary of the Japanese Application 77/125,479 mentions a process for the production of substituted magnetic particles by pulverization of precursor particles in a solution of derivatives of monohydroxytricarboxylic acids.
French Patent 2,461,521 relates to new ferrofluids composed of an aqueous solution of particles of polyoxyanions of Fe (III) and of at least one metal at the oxidation state (II), such as iron, cobalt, manganese, copper and nickel. These magnetic particles are ferrite spinel grains. They are obtained by a coprecipitation reaction in alkaline medium of a mixture of ferric salt and a salt of a divalent metal. Their average diameter, typically in the order of 10 nm, is controlled by the experimental conditions of the coprecipitation.
An essential property of these particles that they are macroanions, i.e. that they carry negative surface charges. The sign of these charges can be progressively and reversibly reversed by acidification. Thus, cationic particles are present in acid 2 1Z medium and anionic particles in basic medium. They are completely without charge at a pH of 7.5 (point of zero charge). When the particles are charged, they can be peptized in water if the counterions are selected accordingly. The anions of low polarizability (such as C104- and NO,-) in acid medium and cations of low polarizing power (such as N(CH3)4') in alkaline medium are used to obtain magnetic sols or ferrofluids. This process thus makes it possible to obtain so-called "ionic" aqueous ferrofluids, in contrast to the earlier processes, which make use of surface10 active agents for dispersing the particles.
These ferrofluids have novel physical properties (especially magnetooptical properties, wetting properties, hydromagnetic properties etc.). one of the features of these ferrofluids is that it is easy to control their properties, especially the physico15 chemical stability by varying the composition of the medium.
The main limitation of these ferrofluids is their field of application. The charge of the particles obtained by this process is indeed due to adsorption of the OH ligand on the iron atoms on the surface. Due to its amphoteric behavior, this ligand gives the 20 grains negative charges in alkaline medium and positive charges
3 in acid medium. It thus produces an interface which is necessary for dispersing particles in water. Since the point of zero charge of the particles is at a pH of 7.4, these ferrofluids can only be obtained in basic medium (pH>10) or acid medium (pH<6). This reduces the actual application range of such ferrofluids.
GENERAL DESCRIPTION OF THE INVENTION
Accordingly, the object of the present invention is to modify the nature of this interface by using properties of surface reactivity of these hydroxylated particles.
The object of the present invention is also to fix on these particles molecules which have a specific activity while controlling the surface reactivity of these particles.
The present invention relates to a process for the production of magnetic particles, which process comprises a step of treating an stabie ionic precursor ferrofluid wftose particles have charges on the surface with at least one agent capable of modifying the nature of the surface of said particles, so as to make them stable, in nonpolar solvents, or polar solvents in a pH range of about 3 to 11, and/or to give them chemical or biological reactivity.
4 1 The treatment of these particles can consist in fixation by electrostatic interaction of charged molecules such that the maximum number of fixed molecules is substantially equal to the number of surface charges, it being possible for said molecules to be separated from the particles by reversing the sign of their charge.
Since the precursor particles carry surface charges in acid and basic media, it is indeed possible to fix at their surface molecules whose charges have the opposite sign. The molecule to be fixed is then considered a counterion for neutralizing the grain surface. These molecules can be polyanions which by virtue of attaching themselves to the surface of the cationic particles in aqueous medium cause them to flocculate. This gives a precipitate composed of magnetic oxide particles on which the polyanions have been deposited. The magnetic particles thus obtained can play the role of catalyst supports, since they have the advantage of being finely divided and having a surface whose state is easily controllable as a result of quantitative control of the fixation.
These molecules can also be surface-active. In this case, the polar head of the surface-active molecule is so chosen that its charge has the opposite sign to that of the grain surface. For 1 - 1 cationic particles, it can be a sulfate, sulfonate, phosphate, pyrophosphate or phosphonate group an for anionic particles an ammonium group.
The nature of the hydrophobic tail of the surface-active agent is chosen depending on the application and can be a long saturated or unsaturated hydrocarbon for transfer into organic solvents or short for other applications. Such surface-active agents can be sodium dodecylsulfate (SDS), industrial surfactants based on phosphoric esters, phospholipids or surfactants based on ammonium.
Preferred surfactants are esters of phosphoric acid with alkylphenols, BEYCOSTAT NA, BEYCOSTAT QA and their neutralized derivatives: BEYCOSTAT NE and NED, which products have been marketed under these names by CECA (FRANCE).
The simultaneous fixation of heteropolyanions and surface- active molecules makes it possible to develop dispersible catalyst supports in nonpolar media, thus enabling homogeneous catalyses to be carried out. For example, a suspension composed of maghemite particles can be added at the point of zero charge by means of silicotungstic acid, so as to block a portion of the accessible 6 surface sites. After protonating the other sites by means of an acid having a non-flocculent counterion (for example nitric acid), the addition of surface-active agents for making these compounds surface- active enables them to be dissolved in organic solvents.
In the case where they are fixed by electrostatic interaction, the number of molecules which can be fixed is controlled by the number of surface charges.
After having reacted, the molecules can be separated from the particles by reversing their surface charges.
The particles can also be treated by fixation of molecules carrying an iron-complexing grouping.
These molecules can be aliphatic saturated or unsaturated polyacid polyol compounds, one or several carbons of which carry at the same time a carboxylic acid function and an alcohol function, especially tartronic acid HOOC-CHOH-COOH, mesoxalic acid HOOC- C(OH)2-COOH, tartaric acid HOOC-(CHOH)2-COOH, malic acid HOOC-CHOH-CH2- COOH, citric acid HOOC-CH2_C(OH)(COOH)-CH2_COOH, and glutaric acid HOOC- (CHOH)4-COOH.
These molecules can also be nonaliphatic, especially aromatic, compounds, in which case the OH grouping can be farther 7 away from the carboxylic grouping, as in the case of 5-sulfosalicylic acid. Certain heterocycle-containing compounds are also fixed, especially ascorbic acid.
These iron-complexing compounds can also comprise an N-SH grouping instead of an N-OH grouping, for example 2,3-dimercaptosuccinic acid, which can form a complex with the particles.
The main condition under which the particles once complexed can still form ferrofluids in polar medium is that the complexing molecule, once it is fixed, still has at least one ionizable function in order to keep the particles charged.
Where the molecule once complexed still has at least one ionizable function in order to keep the particles charged, it is possible to obtain by this process stable aqueous sols in an extended pH range (3-11) and in ionic strengths which are compatible with physiological media, which are the conditions necessary for medical applications. The polyacid alcohols, 2,3-dimercaptosuccinic acid, 5-sulfosalicic acid, and ascorbic acid are non-limiting examples of this type of molecule.
These molecules can likewise give rise to sols in other 8 polar solvents, such as, f or example, ethylene glycol or polyvinyl alcohol for other applications.
It is possible by this process to fix, on the surface of the particles, molecules which have biological activity and in particular antibodies, either directly by means of one or more molecules playing the role of a bridge. In this latter case, it is sufficient to complex the iron atoms of the particles on the surface by a molecule which can fix the active molecule chosen at a different end.
Accordingly, the present invention relates to the particles obtained by the process described above.
Furthermore, the present invention relates to magnetic particles which carry heteropolyanions, or heteropolyanions and saturated or unsaturated surface-active agents, or one or more polyacid polyol or polyacid polythiol compounds which preferably have molecular weights of less than about 5000. These particles can be charged at pH values in a range of about 3 to 11, in order to form ferrofluids, or not be charged for other applications.
These particles can also be present in a magnetic liquid of magnetization between 5 and 1000 G and dispersed without a surf ace- 9 i active agent in a polar solvent at a pH between 3 and 11, said liquid being stable in the presence of a strong magnetic field. This liquid thus forms a stable ionic ferrofluid between a pH of about 3 and 11, even if a magnetic field in the order of 10 T is applied.
The surface-active agents can be especially phosphoric esters, in particular phosphoric esters of alkylphenols.
These particles and the particles obtained by the process described above can be used especially as a support for biologically active molecules, such as, for example, antibodies. The biologically active molecule can then be bound to polythiols by means of a thio bridge.
The present invention furthermore relates to a magnetic liquid comprising particles at the surface of which surface-active molecules are absorbed, such as phosphoric esters of alkylphenols, said particles being dispersed in silicone oil, in particular of the methylphenylpolysiloxane type.
Such particles or magnetic liquids can be used especially in a large number of industrial applications, especially in chemical catalysis, in biological diagnostics and medical imaging.
The invention will now be illustrated without being thereby limited at all by the description which follows:
EXAMPLE 1:
Fixation of heteropolvanions at the surface of particles 5 with total coverinq of the surface.
The precursor is a nitric acid ferrofluid synthesized according to French Patent 2,461,521 and based on ferrite particles of the formula MFe204 or maghemite particles gamma-Fe.03, Its characteristics are typically as follows:
metal atom concentration [Fej + [M] = 1 mol/l ([Fe] = 1 mol/l in the case of maghemite); total acidity [HNO,] = 0.04 mol/l; for an average particle diameter of 9 nm, the surface charge density is equal to 0.2 C/M2. It is ensured by adsorbed protons, such as:
[H+adsj/[Fe) = 1.8 x 10-2.
Silicotungstic acid (0.1 molar) is added to the nitric f errof luid so that the ratio of H4W, 04, added to iron is equal to.2 0.45 x 10-2. In this manner, the suspension obtained is composed of particles, all accessible sites of which are protonated, where the 4counterions are silicotungstate heteropolyanions S'W1204D 11 EXAMPLE 2:
Fixation of heteropolvanions at the surface of the particles I with Dartial covering Of the surface: preparation of cationic particles.
The precursor from Example 1 (100 ml) is brought to its point of zero charge (pH 7.3) by addition of a solution of tetramethylammonium hydroxide (40 ml, 0.1 mol/1). The precipitate is washed several times with distilled water until the conductivity of the supernatant solution is less than 10 pS/cm.
The following two operations are carried out in sequence:
a) Addition of a silicotungstic acid solution H,,.S'W,20,, (50 ml, 2.5 x 10-3 mol/1) in order to obtain a covering of the surface with heteropolyanions equal to one fourth of the maximum covering.
b) After washing the precipitate, excess nitric acid (100 ml, 0.2 mol/1) is added in order to protonate the remaining 3/4 of sites of the surface.
12 EXAMPLE 3:
Fixation of surface-active aqents havinq a pol!'r sulfate head (sodium dodecylsulfate - SDS).
The acidic ferrofluid precursor (40 cc) from Example 1 is acidified to a [H+] of 0.5 mol/l, then stirred at 90C in the presence of SDS (1 g) for 30 minutes. After being washed three times with methanol, the precipitate is dispersed in cyclohexane. The methanol is removed by decanting, and heating to 70C.
Other saturated hydrocarbons of low molecular weight can be used with similar results. EXAMPLE 4:
Fixation of surfactants havinq a polar phosphate head: Beycostat NE (CECA) followed by washing with ethanol.
The acidic ferrofluid precursor (100 cc) from Example I is acidified up to a [H"] of 0.5 mol/l, and then stirred at 90'C in the presence of Beycostat NE (20 g) for 10 minutes. The precipitate obtained is washed with a 0.5 mol/1 nitric acid solution, and then three times with ethanol. The precipitate is then dispersed in aromatic solvents, for example phthalates, decaline, and in certain silicone oils, especially the oil Rhodorsil 763. The ethanol is 13 driven away by decanting, and heating to 90C. EXAMPLE 5:
Preparation of a ferrofluid according to the invention by treatment with Bevcostat NE in volatile solvents.
The procedure described in Example 4 is repeated, except that the washings are carried out in methanol, which is driven away by heating to 700C. The solvents into which the particles are transferred can be volatile, for example: ether, CC1., acetone! cyclohexane, styrene, xylene, toluene.
EXAMPLE 6:
Preparation of a ferrofluid in dibutvl Phthalate by means of Bevcostat NED.
BEYCOSTAT NED (CECA) is a solution of BEYCOSTAT NE in dibutyl phthalate.
BEYCOSTAT NED (CECA) is an anionic detergent in liquid form. It is a neutralized phosphate complex having a pH of 7.5 0.5 in a 5% solution.
The ferrofluid precursor from Example 1 (100 cc) is acidified with nitric acid (2 mol/l, 30 ml), and then stirred at 900C in the presence of BEYCOSTAT NED (20 g) for 10 minutes. The 14 precipitate obtained is washed with a 0.5 mol/1 nitric acid solution, and then 3 times with water. The precipitate is then dispersed in 8 ml of dibutyl phthalate, and the water is driven off by heating to 120'C. The concentrated ferrofluid obtained can be 5 later diluted with DBP.
EXAMPLE 7:
Fixation of surface-active agents having a phosphate grouping as polar head; example of BEYCOSTAT NA.
The surfactants of this type must be made alkaline in order to free the anionic phosphate function; 20 g of BEYCOSTAT NA (CECA) are made alkaline with an aqueous triethanolamine solution (1 mol/l: 30 ml). The ferrofluid precursor from Example 1 (100 ml) acidified with nitric acid (2 mol/l, 30 ml) is added to the neutralized production obtained. The whole is stirred at 900C for 10 minutes. The precipitate obtained is washed with a 0.5 mol/l nitric acid solution, and then 3 times with ethanol. The precipitate is then dispersed in aromatic solvents (8 ml), especially phthalates commercial oils based on phthalate, or in decaline. The ethanol is driven off by decanting, and heating to 90C.
is EXAMPLE 8:
Fixation of surface-active agents havina a phosphate grouping as polar head: example of BEYCOSTAT 0.
g of BEYCOSTAT QA (CECA) are made alkaline with an aqueous triethanolamine solution (1 mol/l: 36 ml). The ferrofluid precursor from Example 1 (100 ml) acidified with nitric acid (2 mol/l, 30 ml) is added to the neutralized production obtained. The whole is stirred at 90"C for 10 minutes. The precipitate obtained is washed with a 0.5 mol/l nitric acid solution, and then 3 times with ethanol. The precipitate is then dispersed in aromatic solvents (8 ml), especially phthalates or commercial oils based on phthalate, or in decaline. The ethanol is driven off by decanting, and heating to 90C.
EXAMPLE 9:
Fixation of surface-active agents having a phosphate grouping as polar head: example of BEYCOSTAT 256 A.
g of BEYCOSTAT 256A (CECA) are made alkaline with an aqueous triethanolamine solution (1 mol/l; 160 ml). The ferrofluid precursor from Example 1 (100 ml) acidified with nitric acid (2 mol/l, 30 ml) is added to the neutralized production obtained.
16 The whole is stirred at 90C for 10 minutes. The precipitate obtained is washed with a 0.5 mol/1 nitric acid solution, and then 3 times with methanol. The precipitate is then dispersed in aliphatic solvents (8 ml), (kerosene, hexane, octane, heptane) and in carbon tetrachloride. The methanol is driven off by decanting, and heating to 70C.
EXAMPLE 10:
Fixation of phos-pholivids.
The ferrofluid precursor from Example 1 (100 ml) is acidified with nitric acid (2 mol/l; 30 ml). It is stirred at 90C in the presence of dicetyl phosphate (5 g) which had previously been neutralized with tetramethylammonium. hydroxide (1 mol/l, 10 ml). The precipitate obtained is washed with water. The dicetyl phosphate can be separated from the particle by making it alkaline.
EXAMPLE 11:
Fixation of the non-wrophosphate fraction of BEYCOSTAT NE.
Like any industrial product, BEYCOSTAT NE is a mixture. It is a mixture of mono- and diesters of phosphoric acid with additional pyrophosphate species.
The pyrophosphate species was isolated and fixed by the 1 following process: the ferrofluid precursor from Example 1 (100 cc) is acidified with nitric acid (2 mol/l; 30 ml), and then stirred at 900C in the presence of 20 g of this fraction for 10 minutes. The precipitate obtained is washed with a 0.5 mol/l nitric acid solution and then 3 times with ethanol. The precipitate is then dispersed in aromatic solvents (8 m!), especially phthalates or commercial oils based on phthalate or in decaline. The ethanol is driven off by decanting, and heating to 90C.
EXAMPLE 12:
Fixation of cationic surfactants havina a polar anmonium head.
The ferrofluid precursor from Example 1 (100 ml) is made alkaline with a solution of tetramethyl ammonium hydroxide (1 mol/1, 10 M1) and then stirred in the presence of hexadecyltrimethyl ammonium bromide (10 g). The precipitate obtained is washed once with distilled water and then 3 times with methanol. It is then dispersed in cyclohexane, and the methanol is removed by heating to 7CC.
18 EXAMPLE 13:
Ferrofluid in the oil RHODORSYL 763.
The ferrofluid precursor from Example 1 (100 ml) is acidified with nitric acid (2 mol/l, 30 ml) and then stirred at 90C in the presence of BEYCOSTAT NE for 10 minutes. The precipitate obtained is washed with 0.5 mol/l nitric acid solution and then 3 times with ethanol. 8 ml of Rhodorsyl 763 oil are poured over the precipitate, the particles are dispersed in the oil, and the residual ethanol is removed by decanting and heating to 90C 10 with stirring.
EXAMPLE 14:
Fixation of heteropolvanions at the surface of particles with partial coverincr: preparation of -particles made surface-. active.
The product obtained in Example 2 is treated, for example, in a manner identical to Example 6. The particles are transferred into the same solvents as in Example 6.
EXAMPLE 15:
Ferrofluid based on tartronic acid.
70.5 mg of tartronic acid are added to the ferrofluid 19 precursor from Example 1 (5.8 ml). The whole is made up to 100 ml with distilled water with stirring. The precipitate obtained is redissolved with the minimum required amount of 0.1 mol/l tetramethylammonium hydroxide.
EXAMPLE 16:
Ferrofluid based on mesoxalic acid.
69.7 mg of mesoxalic acid are added to the ferrofluid precursor from Example 1 (5.8 ml). The whole is made up to 100 ml with distilled water with stirring. The precipitate obtained is redissolved with the minimum required amount of 0.1 mol/l tetramethylammonium hydroxide.
EXAMPLE 17:
Ferrofluid based on tartaric acid.
88.6 mg of DL-tartaric acid monohydrate are added to the ferrofluid precursor from Example 1 (5.8 ml). The whole is made up to 100 ml with distilled water with stirring. The precipitate obtained is redissolved with the minimum required amount of 0.1 mol/1 tetramethylammonium hydroxide.
1 EXAMPLE 18:
Ferrofluid based on malic acid 79.1 mg of DL-malic acid are added to the ferrofluid precursor from Example 1 (5.8 ml). The whole is made up to 100 ml with distilled water with stirring. The precipitate obtained is redissolved with the minimum required amount of 0.1 mol/l tetramethylammonium hydroxide. EXAMPLE 19:
Ferrofluid based on 10 tetramethvlammonium citrate.
citrated particles: addition of The ferrofluid precursor from Example 1 (400 cc) is stirred at 700C in the presence of tetramethyl ammonium citrate (0.3 mol/1, 160 ml) for 1 hour 30 minutes. 750 ml of acetone are. then added. After dissolution, another.600 ml of acetone are added. This operation (dissolution in water and addition of acetone) is repeated twice. The precipitate is finally taken up into 250 ml of water, and the acetone is driven off under a vacuum, leading to a ferrofluid whose pH is about 8.
21 EXAMPLE 20:
Ferrofluid based on citrated Darticles: addition of sodium citrate.
The ferrofluid precursor from Example 1 (300 cc) is stirred at 900C with 11.5 g of sodium citrate (2H.0) for 30 minutes. The cooled precipitate is washed with acetone and then taken up in water. It is centrifuged at 15,000 rpm for 2 hours. The bottom product is dispersed in 20 ml of water and constitutes a ferrofluid whose particle concentration by volume is in the order of 15% and whose pH is around 7. This ferrofluid can be diluted with distilled water as desired.
EXMPLE 2 1:
Ferrofluid based on citrated particles: addition of citric acid, followed by addition of sodium hydroxide.
A citric acid solution (10 ml, 0.1 mol/1) is added to the precursor from Example 1 (100 ml). The precipitate obtained is washed, suspended in water, (50 ml) and peptized by addition of sodium hydroxide NaOH (4 ml, 1 mol/l). The pH of the solution is near 7.
22 EXAMPLE 22
Ferrofluid based on citrated particles: addition of citric acid, followed bV addition of tetramethvlammonium hydroxide.
A citric acid solution (20 ml, 0.1 mol/1) is added to the 5 precursor from Example 1 (100 ml). The precipitate obtained is -ion of washed, suspended in water (50 ml), and peptized by addit tetramethylammonium hydroxide (4 ml, 1 mol/1). The pH of the solution is near 7. EXAMPLE 23 Ferrofluid based on glutaric acid.
77.9 mg of glutaric acid are added to the ferrofluid precursor from Example 1 (5.8 ml). The whole is made up to 100 ml with distilled water with stirring. The precipitate obtained is redissolved with the minimum amount required of 0.1 mol/l tetramethylammonium hydroxide. EXAMPLE 24:
Ferrofluid based on sulfosalicvlic acid.
mg of sulfosalicylic acid are added to the ferrofluid precursor from Example 1 (5.8 ml). The whole is made up to 100 ml with distilled water with stirring. The precipitate obtained is 23 redissolved with the minimum amount required of 0.1 mol/l tetramethylammonium hydroxide. EXAMPLE 25: Perrofluid based on ascorbic acid. 5 103.9 mg of ascorbic acid are added to the ferrofluid precursor from Example 1 (5.8 ml). The whole is made up to 100 ml with distilled water with stirring. The precipitate obtained is redissolved with the minimum amount required of 0.1 mol/l tetramethylammonium hydroxide.
EXAMPLE 26:
Ferrofluid based on dimercaptosuccinic acid (DMSA)-.
The ferrofluid precursor from Example 1 is stirred in the presence of 2,3dimercaptosuccinic acid (at a [DMSA]/[Fe] + [M] of 0.05). The sol flocculates. The addition of tetramethyl ammonium hydroxide up to a pH of 10 enables the particles to be dispersed and a ferrofluid to be formed which is stable from a pH of 3 to a pH of 11 in high ionic strengths.
EXAMPLE 27:
Ferrofluid based on citrate in ethvlene Qlvcol.
The ferrofluid precursor from Example 1 (300 cc) is stirred 24 1 at 900C with 11.5 g of sodium citrate (2H20) for 30 minutes. The. cooled precipitate is washed with acetone and then taken up in water. It is centrifuged at 15,000 rpm for 2 hours. The bottom product is taken up in ethylene glycol (100 ml). The ferrofluid then obtained is precipitated with acetone and then with ether in order to remove residual water. 20 cc of ethylene glycol are added to the precipitate, which thereby goes into solution; the ether is driven off by heating to 400C, giving a ferrofluid in ethylene glycol although it is obviously possible to obtain by this process a ferrofluid in any water/ethylene glycol mixture. EXAMPLE 28:
Fixation of a monoclonal antibody at the surface of the maqnetic particles.
The antibody used (7B10), which is marketed by the company Biologie et Industrie, is an IgG directed against human tumor cells, in particular mammary tumor cells.
- In a f irst step, the antibody coupled with SPDP (Nsuccinimidyl) 3-(2pyridyldithio)propionate; 100 'U1 of the 1.6 mg/ml protein solution (10-9 mol) are added to 2 ml of a mixture of 0.1 mol/1 NaCl and 0.1 mol/l phosphate buffer (pH 7.5). After addition of 200 M1 of an alcoholic solution of 10 mol/1 SPDP, the mixture"is incubated at ambient temperature for 30 minutes. Excess free SPDP is removed by filtration through a Sephadex G25 column, after which 2 ml of a solution containing a mixture of the free 5 antibody and antibodies coupled with SPDP are recovered, in a second step, this solution is added to 50 M1 of a ferrofluid based on maghemite y-Fe203 coupled with DMSA, as described in Example 26 ([Fe] = 1 mol/1 DMSA/Fe = 0.05).
The coupling is carried out after incubation at ambient temperature for 30 minutes. The "magnetic particle/DMSA-SPDPantibody,, complex is separated magnetically from the free antibody.
Tests carried out after the antiaen/antibody coupling with T47D cells, marketed by the company Biologie et Industrie, and carrying the membrane antigen specific to the 7B 10 antibody, turned out to be Dositive.
- presence of iron around the cells detected by staining according to Perls; - antigenlantibody coupling by immunofluorescence.
Staining of the particles by the method of Perls consists in hydrating the slides in water for 10 minutes, depositing on 26 these slides the particle /protein complex at 370C over a period of 1 hour, and then soaking them three times in distilled water for 5 minutes.
The slides are then placed in equal parts of 2% potassium ferrocyanidesolution and 2% hydrochloric acid for 30 minutes, then washed three times with distilled water for 10 minutes and left in a solution of Nuclear Red for 5 minutes.
The slides thus treated are washed with distilled water, then mounted in aqueous medium containing 70 strength alcohol, 60' strength alcohol or xylene. When viewed through a microscope, the particles with ferric iron appear stained blue to blue-green, while the nuclei of the cells are stained red.
EKAYIPLE 29:
Fixation of two complexing agents at the surface of the, particles.
The ferrofluid precursor from Example 1 (5.9 ml) is stirred in the presence of citric acid (11.4 mg in 48 ml of distilled water). The citric acid/iron ratio is 10-2, which is less than that necessary for complexing all the accessible sites of the surface.
The solution obtained is placed under nitrogen, and 32.3 mg of 27 28 dimercaptosuccinic acid dissolved in 50 Tril of distilled water are added. A tetrainethylarrIonium hydroxide solution (0.1 ml/1) is added to the precipitate obtained. At a pH of about 10.5, the precipitate redissolved. The sol then 5 obtained is composed particles carrying the citrate. and dimercaptosuccinate ligands. It remains stable up to a pH of about 3.5.
The embodiments of the invention described above are intended by way of example only. Many other processes, lo magnetic particles, and magnetic fluids falling within the scope of the present invention will be apparent to the skilled reader.
Claims (24)
1. A process for the production of magnetic process comprises a step of treating a stable ferrofluid whose particles have charges with at least one agent capable of modifying the surface of said particles, so as to make nonpolar or polar solvents in a pH range of about to give them chemical or biological reactivity.
2. The process as claimed in claim 1, wherein the treatment 10 consists in fixing charged molecuies by electrostatic interaction such that the maximum number of f ix-ed molecules is substantially equal to the number of surface charges, it being possible for said molecules to be separated from the particles by reversing the sign of their charge.
3. The process as claimed in claim 2, wherein the charged molecules are heteropolyanions.
4. The process as claimed in claim 2, wherein the charged molecules are surface-active agents.
5. The process as claimed in claim 4, wherein the surface20 active agents are phosphoric esters, and in particular phosphoric particles, which ionic precursor on the surface nature of the them stable in 3 to 11, and/or 29 i esters of alkylphenols.
6. The process as claimed in claim 1, wherein the treatment consists in fixing molecules carrying an iron-complexing grouping.
7. The process as claimed in claim 6, wherein the molecules are 5 aliphatic saturated or unsaturated or aromatic polyacid polyols.
8. The process as claimed in claim 7, wherein the molecules are aliphatic, in which case the acid and alcohol functions are carried by the same carbon.
9. The process as claimed in claim 6, wherein the molecules are 10 polyacid polythiols.
10. Particles obtained by the process as claimed in any one of claims 1 to 9.
11. Magnetic particles forming ferrofluids, which particles carry heteropolyanions, or heteropolyanions and saturated or unsaturated surface-active agents.
12. The particles as claimed in claim 11,wherein the surface-active agents are phosphoric esters, and in particular phosphoric esters of alkylphenols.
13. magnetic particles forming f errof luids, which particles 20 carry one or more polyacid polyol or polyacid polythiol compounds 1 having a molecular weight of less than about 5000 and are charged between pH 3 and pH 11 in order to form ferrofluids at these pH values.
14. The particles as claimed in claim, 13, which particles furthermore carry a biologically active molecule, in particular an antibody.
15. The particles as claimed in claim 14, wherein the biologically active molecule is bound to polythiols by means of a thio bridge.
16. A magnetic liquid comprising particles at the surface of which surface-active molecules are adsorbed, such as phosphoric esters of alkylphenols, said particles being dispersed in silicone oil, of the methylphenylpolysiloxane type.
17. Magnetic liquid of magnetization between about 5 and 1000 G and comprising charged particles as claimed in claim 11 and being dispersed without a surface-active agent in a polar solvent at a pH between 3 and 11, said liquid being stable in the presence of a strong magnetic field.
18. Use of particles or liquids as claimed in any one of 31 X 32
19.
claims 10 to 16 as catalyst support or as a support for a biologically active molecule.
A process f or the production of magnetic particles according to claim 1 substantially as hereinbef ore described.
20. Magnetic particles according to claim 11 or 13 substantially as hereinbefore described.
A magnetic liquid according to claim 16 or 17 substantially as hereinbefore described.
22.
23.
Use of particle or liquids according to claim 18 substantially as hereinbefore described.
A process f or the production of magnetic particles substantially as hereinbefore described in Examples 1 to 12, 28 and 29.
24. A process for the preparation of a magnetic liquid substantially as hereinbefore described in Examples 13 to 27.
Published 1991 at The Patent Office. Concept House. Cardiff Road, Newport. Gwent NP9 ' I RH. Further copies may be obtained from Sales Branch. Unit 6. Nine Mile Point, CwnifeWach. Cross Keys. Newport. NPI 7HZ. Printed ky Multiplex techniques ltd, St Mary Cray, Kent.
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FR909006484A FR2662539B1 (en) | 1990-05-23 | 1990-05-23 | PROCESS FOR OBTAINING FINELY DIVIDED MAGNETIC MEDIA BY CONTROLLED MODIFICATION OF THE SURFACE OF LOADED MAGNETIC PRECURSOR PARTICLES AND PRODUCTS OBTAINED. |
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JP (1) | JPH04261002A (en) |
DE (1) | DE4116093A1 (en) |
FR (1) | FR2662539B1 (en) |
GB (1) | GB2244987A (en) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6150181A (en) * | 1995-06-29 | 2000-11-21 | Universite Pierre Et Marie Curie | Magnetic nanoparticles coupled to annexine, and utilization thereof |
US20090220431A1 (en) * | 2005-12-02 | 2009-09-03 | Jin-Woo Cheon | Magnetic resonance imaging contrast agents containing water-soluble nanoparticles of manganese oxide or manganese metal oxide |
CN106111323A (en) * | 2016-08-29 | 2016-11-16 | 上海交通大学 | For reclaiming the half of Magnaglo reverse-flow concentration equipment in ultra-fine mixed-powder |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE19516323C2 (en) * | 1995-04-27 | 1997-02-27 | Dirk Dipl Chem Guenther | Process for the preparation of magnetizable dispersions and their use |
DE10025964A1 (en) * | 2000-05-25 | 2001-12-06 | Henkel Kgaa | Heterogeneous catalyst based on magnetic carrier, useful in oxidation of organic compounds, e.g. epoxidation, allows easy catalyst separation |
JP2005060221A (en) * | 2003-07-31 | 2005-03-10 | Rikogaku Shinkokai | Composite material of organic substance and ferrite, and its production method |
DE102005016873A1 (en) * | 2005-04-12 | 2006-10-19 | Magforce Nanotechnologies Ag | New nano-particle useful for production of composition to treatment and/or prophylaxis of proliferative illnesses, cancer and bacterial infections, where nano-particle is bonded therapeutic substance |
EP2150963A4 (en) | 2007-04-25 | 2012-01-18 | Univ Laval | Magnetically deformable ferrofluids and mirrors |
WO2009074692A2 (en) * | 2007-12-13 | 2009-06-18 | Sven Oscarsson | Partial derivatization of particles |
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GB917030A (en) * | 1959-01-12 | 1963-01-30 | Du Pont | Improvements in or relating to pigments |
GB1361004A (en) * | 1970-06-15 | 1974-07-24 | Avco Corp | Ferrofluid compositions and method of controlling a petroleum oil slick or spill |
GB1526865A (en) * | 1975-06-30 | 1978-10-04 | Ibm | Emulsion containing magnetic particles |
GB2083452A (en) * | 1980-09-15 | 1982-03-24 | Ferrofluidics Corp | Stable Colloidal Dispersions |
US4329241A (en) * | 1979-07-20 | 1982-05-11 | Agence Nationale De Valorisation De La Recherche (Anvar) | Magnetic fluids and process for obtaining them |
US4430239A (en) * | 1981-10-21 | 1984-02-07 | Ferrofluidics Corporation | Ferrofluid composition and method of making and using same |
US4452773A (en) * | 1982-04-05 | 1984-06-05 | Canadian Patents And Development Limited | Magnetic iron-dextran microspheres |
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US4834898A (en) * | 1988-03-14 | 1989-05-30 | Board Of Control Of Michigan Technological University | Reagents for magnetizing nonmagnetic materials |
-
1990
- 1990-05-23 FR FR909006484A patent/FR2662539B1/en not_active Expired - Lifetime
-
1991
- 1991-05-17 DE DE4116093A patent/DE4116093A1/en not_active Withdrawn
- 1991-05-22 GB GB9111026A patent/GB2244987A/en not_active Withdrawn
- 1991-05-23 JP JP3147859A patent/JPH04261002A/en not_active Withdrawn
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
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GB917030A (en) * | 1959-01-12 | 1963-01-30 | Du Pont | Improvements in or relating to pigments |
GB1361004A (en) * | 1970-06-15 | 1974-07-24 | Avco Corp | Ferrofluid compositions and method of controlling a petroleum oil slick or spill |
GB1526865A (en) * | 1975-06-30 | 1978-10-04 | Ibm | Emulsion containing magnetic particles |
US4329241A (en) * | 1979-07-20 | 1982-05-11 | Agence Nationale De Valorisation De La Recherche (Anvar) | Magnetic fluids and process for obtaining them |
GB2083452A (en) * | 1980-09-15 | 1982-03-24 | Ferrofluidics Corp | Stable Colloidal Dispersions |
US4430239A (en) * | 1981-10-21 | 1984-02-07 | Ferrofluidics Corporation | Ferrofluid composition and method of making and using same |
US4452773A (en) * | 1982-04-05 | 1984-06-05 | Canadian Patents And Development Limited | Magnetic iron-dextran microspheres |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6150181A (en) * | 1995-06-29 | 2000-11-21 | Universite Pierre Et Marie Curie | Magnetic nanoparticles coupled to annexine, and utilization thereof |
US20090220431A1 (en) * | 2005-12-02 | 2009-09-03 | Jin-Woo Cheon | Magnetic resonance imaging contrast agents containing water-soluble nanoparticles of manganese oxide or manganese metal oxide |
CN106111323A (en) * | 2016-08-29 | 2016-11-16 | 上海交通大学 | For reclaiming the half of Magnaglo reverse-flow concentration equipment in ultra-fine mixed-powder |
Also Published As
Publication number | Publication date |
---|---|
DE4116093A1 (en) | 1991-11-28 |
JPH04261002A (en) | 1992-09-17 |
FR2662539B1 (en) | 1994-09-30 |
FR2662539A1 (en) | 1991-11-29 |
GB9111026D0 (en) | 1991-07-17 |
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