WO2005014149A1 - 複合多孔膜とその製造方法 - Google Patents
複合多孔膜とその製造方法 Download PDFInfo
- Publication number
- WO2005014149A1 WO2005014149A1 PCT/JP2004/011165 JP2004011165W WO2005014149A1 WO 2005014149 A1 WO2005014149 A1 WO 2005014149A1 JP 2004011165 W JP2004011165 W JP 2004011165W WO 2005014149 A1 WO2005014149 A1 WO 2005014149A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- porous membrane
- filter
- membrane
- composite
- film
- Prior art date
Links
- 239000012528 membrane Substances 0.000 title claims abstract description 609
- 239000002131 composite material Substances 0.000 title claims abstract description 180
- 238000000034 method Methods 0.000 title claims abstract description 103
- 230000008569 process Effects 0.000 title description 15
- 210000004027 cell Anatomy 0.000 claims abstract description 153
- 210000000265 leukocyte Anatomy 0.000 claims abstract description 146
- 239000011148 porous material Substances 0.000 claims abstract description 139
- 238000001914 filtration Methods 0.000 claims abstract description 64
- 229920000620 organic polymer Polymers 0.000 claims abstract description 42
- 239000008280 blood Substances 0.000 claims abstract description 41
- 210000004369 blood Anatomy 0.000 claims abstract description 41
- 239000000725 suspension Substances 0.000 claims abstract description 21
- 238000012258 culturing Methods 0.000 claims abstract description 17
- 210000000601 blood cell Anatomy 0.000 claims description 88
- 239000006285 cell suspension Substances 0.000 claims description 64
- 239000003960 organic solvent Substances 0.000 claims description 58
- 230000002209 hydrophobic effect Effects 0.000 claims description 56
- 239000007788 liquid Substances 0.000 claims description 51
- 238000004113 cell culture Methods 0.000 claims description 48
- 150000001875 compounds Chemical class 0.000 claims description 47
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 45
- 238000004519 manufacturing process Methods 0.000 claims description 36
- 238000004891 communication Methods 0.000 claims description 10
- 238000001000 micrograph Methods 0.000 claims description 6
- 238000000638 solvent extraction Methods 0.000 claims description 2
- 239000000463 material Substances 0.000 abstract description 64
- 238000000926 separation method Methods 0.000 abstract description 46
- 230000009467 reduction Effects 0.000 abstract description 7
- 210000003677 hemocyte Anatomy 0.000 abstract description 4
- 229940000351 hemocyte Drugs 0.000 abstract description 4
- 239000013076 target substance Substances 0.000 abstract 1
- 239000010408 film Substances 0.000 description 155
- 239000000243 solution Substances 0.000 description 116
- 239000004745 nonwoven fabric Substances 0.000 description 72
- 125000000524 functional group Chemical group 0.000 description 61
- 238000000576 coating method Methods 0.000 description 56
- 239000002609 medium Substances 0.000 description 51
- 239000011248 coating agent Substances 0.000 description 45
- 229920000642 polymer Polymers 0.000 description 44
- 239000000835 fiber Substances 0.000 description 32
- 238000005530 etching Methods 0.000 description 28
- -1 polyethylene adipate Polymers 0.000 description 27
- 239000002904 solvent Substances 0.000 description 26
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 25
- 239000010409 thin film Substances 0.000 description 25
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 23
- 230000015572 biosynthetic process Effects 0.000 description 20
- 230000000052 comparative effect Effects 0.000 description 20
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 19
- 229920001688 coating polymer Polymers 0.000 description 17
- 239000007789 gas Substances 0.000 description 17
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 16
- 230000000694 effects Effects 0.000 description 16
- 239000000178 monomer Substances 0.000 description 16
- 238000012360 testing method Methods 0.000 description 16
- 239000000758 substrate Substances 0.000 description 15
- 239000003814 drug Substances 0.000 description 14
- 239000000203 mixture Substances 0.000 description 13
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 229920000139 polyethylene terephthalate Polymers 0.000 description 12
- 239000005020 polyethylene terephthalate Substances 0.000 description 12
- 125000001931 aliphatic group Chemical group 0.000 description 11
- 229920001577 copolymer Polymers 0.000 description 11
- 238000005516 engineering process Methods 0.000 description 11
- 229920002492 poly(sulfone) Polymers 0.000 description 11
- 239000000126 substance Substances 0.000 description 11
- 230000007423 decrease Effects 0.000 description 10
- 239000011521 glass Substances 0.000 description 10
- 229910052751 metal Inorganic materials 0.000 description 10
- 239000002184 metal Substances 0.000 description 10
- 230000035699 permeability Effects 0.000 description 10
- 229920005594 polymer fiber Polymers 0.000 description 10
- 238000001179 sorption measurement Methods 0.000 description 10
- 238000011041 water permeability test Methods 0.000 description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- 210000004700 fetal blood Anatomy 0.000 description 9
- 238000012856 packing Methods 0.000 description 9
- 239000004417 polycarbonate Substances 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- 230000001172 regenerating effect Effects 0.000 description 9
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 8
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- 239000004793 Polystyrene Substances 0.000 description 8
- 210000001772 blood platelet Anatomy 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 8
- 239000004744 fabric Substances 0.000 description 8
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 8
- 229920000515 polycarbonate Polymers 0.000 description 8
- 229920002223 polystyrene Polymers 0.000 description 8
- 230000035755 proliferation Effects 0.000 description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 7
- 210000001185 bone marrow Anatomy 0.000 description 7
- 238000003501 co-culture Methods 0.000 description 7
- 210000003743 erythrocyte Anatomy 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 7
- 238000005191 phase separation Methods 0.000 description 7
- 238000011045 prefiltration Methods 0.000 description 7
- 238000001878 scanning electron micrograph Methods 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- 238000005507 spraying Methods 0.000 description 7
- 238000009864 tensile test Methods 0.000 description 7
- 108010035532 Collagen Proteins 0.000 description 6
- 102000008186 Collagen Human genes 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- WOBHKFSMXKNTIM-UHFFFAOYSA-N Hydroxyethyl methacrylate Chemical compound CC(=C)C(=O)OCCO WOBHKFSMXKNTIM-UHFFFAOYSA-N 0.000 description 6
- 230000002411 adverse Effects 0.000 description 6
- 239000010836 blood and blood product Substances 0.000 description 6
- 229940125691 blood product Drugs 0.000 description 6
- 238000005266 casting Methods 0.000 description 6
- 230000010261 cell growth Effects 0.000 description 6
- 229920001436 collagen Polymers 0.000 description 6
- 238000009826 distribution Methods 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- 230000035515 penetration Effects 0.000 description 6
- 229920002401 polyacrylamide Polymers 0.000 description 6
- 238000012545 processing Methods 0.000 description 6
- 210000000130 stem cell Anatomy 0.000 description 6
- 125000001302 tertiary amino group Chemical group 0.000 description 6
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 5
- 229920002678 cellulose Polymers 0.000 description 5
- 239000001913 cellulose Substances 0.000 description 5
- 125000001309 chloro group Chemical group Cl* 0.000 description 5
- 238000001704 evaporation Methods 0.000 description 5
- 238000005259 measurement Methods 0.000 description 5
- 238000012986 modification Methods 0.000 description 5
- 230000004048 modification Effects 0.000 description 5
- 239000002861 polymer material Substances 0.000 description 5
- 238000006116 polymerization reaction Methods 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- 102000004142 Trypsin Human genes 0.000 description 4
- 108090000631 Trypsin Proteins 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
- NNBZCPXTIHJBJL-UHFFFAOYSA-N decalin Chemical compound C1CCCC2CCCCC21 NNBZCPXTIHJBJL-UHFFFAOYSA-N 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 230000018109 developmental process Effects 0.000 description 4
- 238000010586 diagram Methods 0.000 description 4
- 230000004069 differentiation Effects 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 238000011156 evaluation Methods 0.000 description 4
- 238000011049 filling Methods 0.000 description 4
- 238000005227 gel permeation chromatography Methods 0.000 description 4
- 239000003365 glass fiber Substances 0.000 description 4
- 230000005484 gravity Effects 0.000 description 4
- 238000002615 hemofiltration Methods 0.000 description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
- 238000007654 immersion Methods 0.000 description 4
- UAEPNZWRGJTJPN-UHFFFAOYSA-N methylcyclohexane Chemical compound CC1CCCCC1 UAEPNZWRGJTJPN-UHFFFAOYSA-N 0.000 description 4
- 229920000728 polyester Polymers 0.000 description 4
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
- 239000007921 spray Substances 0.000 description 4
- 229920001059 synthetic polymer Polymers 0.000 description 4
- 239000012588 trypsin Substances 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- OZAIFHULBGXAKX-VAWYXSNFSA-N AIBN Substances N#CC(C)(C)\N=N\C(C)(C)C#N OZAIFHULBGXAKX-VAWYXSNFSA-N 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 239000004952 Polyamide Substances 0.000 description 3
- 239000004743 Polypropylene Substances 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 150000003926 acrylamides Chemical class 0.000 description 3
- 230000001476 alcoholic effect Effects 0.000 description 3
- 125000003368 amide group Chemical group 0.000 description 3
- 230000021164 cell adhesion Effects 0.000 description 3
- 201000006662 cervical adenocarcinoma Diseases 0.000 description 3
- 238000007598 dipping method Methods 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 238000010894 electron beam technology Methods 0.000 description 3
- 238000010828 elution Methods 0.000 description 3
- 125000004185 ester group Chemical group 0.000 description 3
- 125000001033 ether group Chemical group 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- 238000011134 hematopoietic stem cell transplantation Methods 0.000 description 3
- 239000012510 hollow fiber Substances 0.000 description 3
- 230000006872 improvement Effects 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- LLYBWQANNKRYST-UHFFFAOYSA-N n-[3-[bis(2-methoxyethyl)amino]-4-methoxyphenyl]acetamide Chemical compound COCCN(CCOC)C1=CC(NC(C)=O)=CC=C1OC LLYBWQANNKRYST-UHFFFAOYSA-N 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 210000005259 peripheral blood Anatomy 0.000 description 3
- 239000011886 peripheral blood Substances 0.000 description 3
- 229920002239 polyacrylonitrile Polymers 0.000 description 3
- 229920002647 polyamide Polymers 0.000 description 3
- 229920001155 polypropylene Polymers 0.000 description 3
- 229920002635 polyurethane Polymers 0.000 description 3
- 239000004814 polyurethane Substances 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 229920005604 random copolymer Polymers 0.000 description 3
- 230000000717 retained effect Effects 0.000 description 3
- 210000002536 stromal cell Anatomy 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 2
- 125000003006 2-dimethylaminoethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 206010001197 Adenocarcinoma of the cervix Diseases 0.000 description 2
- 208000034246 Adenocarcinoma of the cervix uteri Diseases 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- 238000012935 Averaging Methods 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 239000000956 alloy Substances 0.000 description 2
- 229910045601 alloy Inorganic materials 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 238000007664 blowing Methods 0.000 description 2
- ZCDOYSPFYFSLEW-UHFFFAOYSA-N chromate(2-) Chemical group [O-][Cr]([O-])(=O)=O ZCDOYSPFYFSLEW-UHFFFAOYSA-N 0.000 description 2
- 210000004748 cultured cell Anatomy 0.000 description 2
- 238000005034 decoration Methods 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 229920001971 elastomer Polymers 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 238000005187 foaming Methods 0.000 description 2
- 238000004817 gas chromatography Methods 0.000 description 2
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 2
- 230000001771 impaired effect Effects 0.000 description 2
- 239000012784 inorganic fiber Substances 0.000 description 2
- 229910010272 inorganic material Inorganic materials 0.000 description 2
- 239000011147 inorganic material Substances 0.000 description 2
- 238000010884 ion-beam technique Methods 0.000 description 2
- 230000001678 irradiating effect Effects 0.000 description 2
- 239000007769 metal material Substances 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- GYNNXHKOJHMOHS-UHFFFAOYSA-N methyl-cycloheptane Natural products CC1CCCCCC1 GYNNXHKOJHMOHS-UHFFFAOYSA-N 0.000 description 2
- 235000015097 nutrients Nutrition 0.000 description 2
- 239000011368 organic material Substances 0.000 description 2
- 230000000149 penetrating effect Effects 0.000 description 2
- 239000012466 permeate Substances 0.000 description 2
- 239000004014 plasticizer Substances 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 229920006254 polymer film Polymers 0.000 description 2
- 229920005597 polymer membrane Polymers 0.000 description 2
- 230000000379 polymerizing effect Effects 0.000 description 2
- 229920000193 polymethacrylate Polymers 0.000 description 2
- 229920001955 polyphenylene ether Polymers 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 238000010526 radical polymerization reaction Methods 0.000 description 2
- 230000003014 reinforcing effect Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000007789 sealing Methods 0.000 description 2
- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 description 2
- 230000008961 swelling Effects 0.000 description 2
- 238000002145 thermally induced phase separation Methods 0.000 description 2
- 238000002054 transplantation Methods 0.000 description 2
- 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 2
- 239000002759 woven fabric Substances 0.000 description 2
- 239000008096 xylene Substances 0.000 description 2
- OOSZCNKVJAVHJI-UHFFFAOYSA-N 1-[(4-fluorophenyl)methyl]piperazine Chemical compound C1=CC(F)=CC=C1CN1CCNCC1 OOSZCNKVJAVHJI-UHFFFAOYSA-N 0.000 description 1
- VHSHLMUCYSAUQU-UHFFFAOYSA-N 2-hydroxypropyl methacrylate Chemical compound CC(O)COC(=O)C(C)=C VHSHLMUCYSAUQU-UHFFFAOYSA-N 0.000 description 1
- SAQWCPXBLNGTCC-UHFFFAOYSA-N 6-(prop-2-enoylamino)hexanoic acid Chemical compound OC(=O)CCCCCNC(=O)C=C SAQWCPXBLNGTCC-UHFFFAOYSA-N 0.000 description 1
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 1
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 1
- 208000032467 Aplastic anaemia Diseases 0.000 description 1
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- ROFVEXUMMXZLPA-UHFFFAOYSA-N Bipyridyl Chemical group N1=CC=CC=C1C1=CC=CC=N1 ROFVEXUMMXZLPA-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 1
- WWZKQHOCKIZLMA-UHFFFAOYSA-N Caprylic acid Natural products CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- YASYEJJMZJALEJ-UHFFFAOYSA-N Citric acid monohydrate Chemical compound O.OC(=O)CC(O)(C(O)=O)CC(O)=O YASYEJJMZJALEJ-UHFFFAOYSA-N 0.000 description 1
- 102000012422 Collagen Type I Human genes 0.000 description 1
- 108010022452 Collagen Type I Proteins 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- 206010012665 Diabetic gangrene Diseases 0.000 description 1
- 108090000394 Erythropoietin Proteins 0.000 description 1
- 102000003951 Erythropoietin Human genes 0.000 description 1
- 102100037362 Fibronectin Human genes 0.000 description 1
- 108010067306 Fibronectins Proteins 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 description 1
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 description 1
- 101000976075 Homo sapiens Insulin Proteins 0.000 description 1
- 102000002265 Human Growth Hormone Human genes 0.000 description 1
- 108010000521 Human Growth Hormone Proteins 0.000 description 1
- 239000000854 Human Growth Hormone Substances 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 102000004856 Lectins Human genes 0.000 description 1
- 108090001090 Lectins Proteins 0.000 description 1
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical class CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 1
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 1
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 1
- 229920001410 Microfiber Polymers 0.000 description 1
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- AFCARXCZXQIEQB-UHFFFAOYSA-N N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CCNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 AFCARXCZXQIEQB-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 239000002033 PVDF binder Substances 0.000 description 1
- 241000282320 Panthera leo Species 0.000 description 1
- 208000030831 Peripheral arterial occlusive disease Diseases 0.000 description 1
- 229920001283 Polyalkylene terephthalate Polymers 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 108010039918 Polylysine Proteins 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 238000012356 Product development Methods 0.000 description 1
- 229920000297 Rayon Polymers 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 102100035140 Vitronectin Human genes 0.000 description 1
- 108010031318 Vitronectin Proteins 0.000 description 1
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
- 150000001241 acetals Chemical class 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 238000004026 adhesive bonding Methods 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 239000003570 air Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 208000011775 arteriosclerosis disease Diseases 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 238000010923 batch production Methods 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- GONOPSZTUGRENK-UHFFFAOYSA-N benzyl(trichloro)silane Chemical compound Cl[Si](Cl)(Cl)CC1=CC=CC=C1 GONOPSZTUGRENK-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000000560 biocompatible material Substances 0.000 description 1
- 229920001400 block copolymer Polymers 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 238000010322 bone marrow transplantation Methods 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000012292 cell migration Effects 0.000 description 1
- 238000002659 cell therapy Methods 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000013043 chemical agent Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229920001940 conductive polymer Polymers 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 238000010924 continuous production Methods 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 238000010908 decantation Methods 0.000 description 1
- 238000007872 degassing Methods 0.000 description 1
- 238000007033 dehydrochlorination reaction Methods 0.000 description 1
- 238000005137 deposition process Methods 0.000 description 1
- 125000003963 dichloro group Chemical group Cl* 0.000 description 1
- 150000004683 dihydrates Chemical class 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 238000011038 discontinuous diafiltration by volume reduction Methods 0.000 description 1
- 239000002612 dispersion medium Substances 0.000 description 1
- JRBPAEWTRLWTQC-UHFFFAOYSA-N dodecylamine Chemical compound CCCCCCCCCCCCN JRBPAEWTRLWTQC-UHFFFAOYSA-N 0.000 description 1
- 239000008151 electrolyte solution Substances 0.000 description 1
- 229940021013 electrolyte solution Drugs 0.000 description 1
- 239000012776 electronic material Substances 0.000 description 1
- 229920006351 engineering plastic Polymers 0.000 description 1
- 210000003979 eosinophil Anatomy 0.000 description 1
- 229940105423 erythropoietin Drugs 0.000 description 1
- 239000003759 ester based solvent Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- SUPCQIBBMFXVTL-UHFFFAOYSA-N ethyl 2-methylprop-2-enoate Chemical compound CCOC(=O)C(C)=C SUPCQIBBMFXVTL-UHFFFAOYSA-N 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000010304 firing Methods 0.000 description 1
- 238000007667 floating Methods 0.000 description 1
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 230000005251 gamma ray Effects 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 239000003292 glue Substances 0.000 description 1
- 238000010559 graft polymerization reaction Methods 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 229910052734 helium Inorganic materials 0.000 description 1
- 239000001307 helium Substances 0.000 description 1
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 229920001477 hydrophilic polymer Polymers 0.000 description 1
- 238000010191 image analysis Methods 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 238000005470 impregnation Methods 0.000 description 1
- 239000003999 initiator Substances 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- PBGKTOXHQIOBKM-FHFVDXKLSA-N insulin (human) Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 PBGKTOXHQIOBKM-FHFVDXKLSA-N 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 229940079322 interferon Drugs 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000005453 ketone based solvent Substances 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 238000010030 laminating Methods 0.000 description 1
- 239000002523 lectin Substances 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 238000010550 living polymerization reaction Methods 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 238000002715 modification method Methods 0.000 description 1
- 210000005087 mononuclear cell Anatomy 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- OVHHHVAVHBHXAK-UHFFFAOYSA-N n,n-diethylprop-2-enamide Chemical compound CCN(CC)C(=O)C=C OVHHHVAVHBHXAK-UHFFFAOYSA-N 0.000 description 1
- 229940088644 n,n-dimethylacrylamide Drugs 0.000 description 1
- YLGYACDQVQQZSW-UHFFFAOYSA-N n,n-dimethylprop-2-enamide Chemical compound CN(C)C(=O)C=C YLGYACDQVQQZSW-UHFFFAOYSA-N 0.000 description 1
- XQPVIMDDIXCFFS-UHFFFAOYSA-N n-dodecylprop-2-enamide Chemical compound CCCCCCCCCCCCNC(=O)C=C XQPVIMDDIXCFFS-UHFFFAOYSA-N 0.000 description 1
- 210000002445 nipple Anatomy 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 230000000414 obstructive effect Effects 0.000 description 1
- 230000033667 organ regeneration Effects 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- NWVVVBRKAWDGAB-UHFFFAOYSA-N p-methoxyphenol Chemical compound COC1=CC=C(O)C=C1 NWVVVBRKAWDGAB-UHFFFAOYSA-N 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000013618 particulate matter Substances 0.000 description 1
- HJOYQPSKGVZWBC-UHFFFAOYSA-N pentadec-2-enamide Chemical group CCCCCCCCCCCCC=CC(N)=O HJOYQPSKGVZWBC-UHFFFAOYSA-N 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920000921 polyethylene adipate Polymers 0.000 description 1
- 239000004626 polylactic acid Substances 0.000 description 1
- 229920000656 polylysine Polymers 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 229920000915 polyvinyl chloride Polymers 0.000 description 1
- 239000004800 polyvinyl chloride Substances 0.000 description 1
- 229920002620 polyvinyl fluoride Polymers 0.000 description 1
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 1
- 229910052573 porcelain Inorganic materials 0.000 description 1
- OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 description 1
- 238000007639 printing Methods 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000004080 punching Methods 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000002787 reinforcement Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 238000005245 sintering Methods 0.000 description 1
- 230000005476 size effect Effects 0.000 description 1
- 229940074545 sodium dihydrogen phosphate dihydrate Drugs 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000002689 soil Substances 0.000 description 1
- 238000000935 solvent evaporation Methods 0.000 description 1
- 238000004528 spin coating Methods 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 125000001174 sulfone group Chemical group 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- XLNZEKHULJKQBA-UHFFFAOYSA-N terbufos Chemical compound CCOP(=S)(OCC)SCSC(C)(C)C XLNZEKHULJKQBA-UHFFFAOYSA-N 0.000 description 1
- SOBHUZYZLFQYFK-UHFFFAOYSA-K trisodium;hydroxy-[[phosphonatomethyl(phosphonomethyl)amino]methyl]phosphinate Chemical compound [Na+].[Na+].[Na+].OP(O)(=O)CN(CP(O)([O-])=O)CP([O-])([O-])=O SOBHUZYZLFQYFK-UHFFFAOYSA-K 0.000 description 1
- 210000003556 vascular endothelial cell Anatomy 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 239000011800 void material Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 230000037303 wrinkles Effects 0.000 description 1
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D69/00—Semi-permeable membranes for separation processes or apparatus characterised by their form, structure or properties; Manufacturing processes specially adapted therefor
- B01D69/02—Semi-permeable membranes for separation processes or apparatus characterised by their form, structure or properties; Manufacturing processes specially adapted therefor characterised by their properties
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/36—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
- A61M1/3621—Extra-corporeal blood circuits
- A61M1/3627—Degassing devices; Buffer reservoirs; Drip chambers; Blood filters
- A61M1/3633—Blood component filters, e.g. leukocyte filters
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D69/00—Semi-permeable membranes for separation processes or apparatus characterised by their form, structure or properties; Manufacturing processes specially adapted therefor
- B01D69/10—Supported membranes; Membrane supports
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D69/00—Semi-permeable membranes for separation processes or apparatus characterised by their form, structure or properties; Manufacturing processes specially adapted therefor
- B01D69/10—Supported membranes; Membrane supports
- B01D69/107—Organic support material
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D69/00—Semi-permeable membranes for separation processes or apparatus characterised by their form, structure or properties; Manufacturing processes specially adapted therefor
- B01D69/12—Composite membranes; Ultra-thin membranes
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D69/00—Semi-permeable membranes for separation processes or apparatus characterised by their form, structure or properties; Manufacturing processes specially adapted therefor
- B01D69/12—Composite membranes; Ultra-thin membranes
- B01D69/1213—Laminated layers
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D71/00—Semi-permeable membranes for separation processes or apparatus characterised by the material; Manufacturing processes specially adapted therefor
- B01D71/06—Organic material
- B01D71/66—Polymers having sulfur in the main chain, with or without nitrogen, oxygen or carbon only
- B01D71/68—Polysulfones; Polyethersulfones
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/0068—General culture methods using substrates
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D2325/00—Details relating to properties of membranes
- B01D2325/02—Details relating to pores or porosity of the membranes
- B01D2325/021—Pore shapes
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D2325/00—Details relating to properties of membranes
- B01D2325/04—Characteristic thickness
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D2325/00—Details relating to properties of membranes
- B01D2325/18—Membrane materials having mixed charged functional groups
Definitions
- the present invention can effectively and efficiently separate various bacteria, yeasts, cells, and the like, which are micron-sized objects.
- the present invention relates to a composite porous membrane having sufficient membrane strength to facilitate processing into a composite porous membrane.
- the present invention provides a method for producing a leukocyte-removed suspension, which reduces the amount of loss of a leukocyte suspension when removing leukocytes from a blood filtration membrane and a leukocyte suspension represented by whole blood or a blood product for transfusion, and
- the present invention relates to a leukocyte removal filter device.
- the present invention provides a method for co-culturing two or more different cell groups in a culture solution, while maintaining a state in which different cell groups are separated from each other without being mixed with each other and having different forces between cells.
- the present invention relates to a cell culture diaphragm and a cell culture method using a composite porous membrane that enable effective contact.
- the pore size of several microns and the uniformity of the pore size are mainly considered. It is desirable to use a prefilter having a higher porosity.
- the pore size of a polymer fiber mesh filter commonly used as a pre-filter is the smallest at a square hole with a side length of less than 20 ⁇ m. When used, the cells often escape and do not function as an effective filter (or pre-filter).
- a metal mesh filter or a polymer fiber mesh filter manufactured by a special method has a pore size of several / zm.
- the diameter of the metal fiber or the polymer fiber is extremely reduced.
- the result is a significant decrease in porosity.
- the filter since the filter has low water permeability and easily clogs the filter, this cannot be an effective filter for cell separation or removal.
- An "etching film” manufactured through an etching process after irradiating with an ion beam or an ion beam is widely known.
- the etched film has a group of cylindrical holes with a uniform diameter, and the uniformity of the hole size is extremely high. Doing so will result in loss of uniformity of pore size).
- the film thickness must be at least 10 m to maintain strength (usually 15-20 m).
- the pore length becomes larger than the pore diameter, filtration is required. The resistance increases and the filtration efficiency is not sufficient.
- the cylindrical holes formed by such a method are straight holes and are mostly independent, it is extremely unlikely that the holes are connected to each other inside the membrane (the holes communicate with each other inside the membrane). This is a factor of low filtration efficiency.
- Patent Document 1 discloses a porous polymer membrane in which a microporous porous layer (A) and a porous layer (B) having straight pores are present in a laminated structure. It is stated that, as a result, the etching film, which is the porous layer (B), can be made extremely thin (10 ⁇ m or less) as a result of its mechanical strength. However, since the opening ratio, pore structure, and internal structure of the porous layer (B) are the same as those of a conventional etching film, the filtration efficiency is not yet sufficient, and this is also an efficient method for cells and the like. It cannot be a separation filter.
- Patent Document 2 discloses a method for producing a porous film having a controlled pore diameter by irradiating a polymer film with light in the visible or far ultraviolet range through a mask and removing the light-irradiated region of the polymer film. And a method of forming (compositing) such a porous membrane on a substrate (support) such as a nonwoven fabric or a synthetic paper.
- a substrate such as a nonwoven fabric or a synthetic paper.
- this composite method involves spin-coating a polymer solution on a substrate with a rubber roller and drying the polymer solution to form a porous film.
- the polymer solution easily penetrates into the film, making it difficult to make the porous film thinner and uniform, and the structure of the composite film tends to be heterogeneous.
- this phenomenon is caused by low filtration resistance, or on a supporting porous substrate having a large average pore diameter, which allows cells to move easily. It becomes remarkable when the film is formed. Therefore, the membrane material obtained by this technique cannot be an efficient filter for separating cells and the like.
- the filter material is a filter material having a group of pores having a pore diameter of several meters (for example, about 115 m) with high pore diameter uniformity and a high porosity, and the pores are short in the film thickness direction (thin film thickness). ), If the filter material has a structure such that it is connected to each other inside the membrane and the force is also excellent in mechanical strength, an effective and efficient filter for separating cells and the like (or a filter). Filter).
- Non-Patent Documents 1 and 2 small water droplets condensed and formed on the polymer solution due to the removal of latent heat during the solvent volatilization process from the polymer solution become ⁇ -shaped, and finally have pores on the order of several / zm. It has been shown that a porous film having a honeycomb structure having through-holes having a large diameter uniformity and a high opening ratio can be formed using various materials. The thickness of this thin film is almost the same as the diameter of the through hole, and the thin film can have a structure in which adjacent holes are connected to each other even in the inner portion of the film so as to communicate in the plane direction of the film.
- the honeycomb-structured porous thin film having such a structure is expected to be developed as an effective and efficient filter for cell separation (or a pre-filter).
- Such a honeycomb-structured porous thin film is prepared by casting a hydrophobic organic solvent solution of an organic polymer compound on a smooth solid substrate (eg, glass, silicon wafer, metal plate, polymer solid gel, etc.), and having a relative humidity of 40%. — Obtained by blowing a high-humidity air such as 95% on the substrate to form a nodal structure and peeling it off.
- a high-humidity air such as 95%
- Patent Document 3 describes that a hydrophobic organic solvent solution is cast on a water surface to form a honeycomb structure in the same manner, and the honeycomb structure is scooped with a 5 mm ⁇ frame to obtain a honeycomb structure porous thin film. The method is shown.
- the honeycomb structure porous thin film material obtained by the above method has extremely low film strength. Therefore, if it is used alone as a filter for cell separation in the bioprocess and medical fields, it is expected that membrane rupture will occur at a high frequency.In addition, forms other than flat membranes, such as rolls, It is also difficult to process and use pleats, cylinders, and bags. That is, such a thin film material cannot be used as it is as a practical filter material, and practical mechanical strength must be imparted.
- the membrane material is useful as an effective and efficient filter (or prefilter) for separating cells and the like.
- a membrane material is particularly useful for separating blood cells in the field of hemofiltration, specifically for separating plasma from whole blood and removing leukocytes from various blood products.
- blood cells represented by whole blood or blood products for transfusion have been used to reduce the physical burden on patients to whom transfusion therapy has been applied. It is increasingly important to highly remove leukocytes from suspensions.
- a filter method of filtering a blood cell suspension using a fibrous filter medium such as a nonwoven fabric or a porous body having communication holes in a three-dimensional network as a filter medium.
- This filter method has advantages such as high leukocyte removal ability, simple operation, and excellent cost performance, and is currently widely used in medical practice.
- the filter used for this purpose is known as a “leukocyte removal filter”. It is.
- Patent Document 4 A typical leukocyte removal filter is disclosed in Patent Document 4 or Patent Document 5, wherein a non-woven fabric having a very fine fiber force such as polyester is used as a filter medium, and Patent Document 6 discloses a filter medium.
- a porous body having a three-dimensional network-like communicating hole having a strong force such as polyurethane is used as a filter medium. It is disclosed that the leukocyte-removing ability reaches at least 99.99% by using them.
- Patent Document 4 discloses a coating agent containing a nonionic hydrophilic group and a basic nitrogen-containing functional group on the surface of a nonwoven fabric as a filter medium (for example, 2-hydroxyethyl methacrylate and 2- (N, N A leukocyte removal filter is disclosed which is formed by coating a plurality of such coating non-woven fabrics after coating with (cotyledylamino) ethylmetharylate).
- leukocyte removal is performed by an adsorption mechanism
- the basic nitrogen-containing functional group plays a role of selective adsorption of leukocytes
- the nonionic hydrophilic group plays a role of nonselective adsorption of various blood cell components. It is said to play a controlling effect.
- a leukocyte selective affinity functional group is used to increase the leukocyte removal ability per unit volume of the coated nonwoven fabric. It is considered that the content of the basic nitrogen-containing functional group should be increased.
- the increase in the amount of basic nitrogen-containing functional groups increases the adsorption capacity of not only leukocytes but also other blood cell components (red blood cells and platelets) (non-selective adsorption).
- filter clogging may occur due to adsorption of a large amount of blood cell components. Therefore, it cannot be said that increasing the amount of the basic nitrogen-containing functional group is effective.
- Patent Document 7 discloses that leukemia in blood is measured using an etching film having a pore diameter of 3 to 10 m. A method for removing a sphere is disclosed. Further, Patent Document 8 discloses that when human blood was filtered using the porous porous film having a honeycomb structure described in Non-Patent Documents 1 and 2 as a filter material, excellent selective removal of leukocytes was obtained. Has been described.
- the regenerative medicine for transplanting hematopoietic stem cells has attracted attention for its effectiveness in the treatment of acute myeloid leukemia represented by bone marrow transplantation and the treatment of aplastic anemia.
- the efficacy of regenerative medicine has been attracting attention in the treatment of angiogenesis for the most severe peripheral arterial occlusive disease (Burja's disease, obstructive arteriosclerosis, diabetic gangrene, etc.). Emergent therapy is becoming a recognized therapy in the medical community.
- cord blood-derived hematopoietic stem cell transplantation has been rapidly increasing from the viewpoint of non-invasiveness of the donor at the time of hematopoietic stem cell collection and reduction of the restraint time of the donor.
- the monthly number of cord blood transplants (47) exceeded the bone marrow transplant count of 46 for the first time.
- the drawback of collecting hematopoietic stem cells from cord blood is that the amount collected from a single donor is small, and transplantation of cord blood-derived hematopoietic stem cells is mainly applied to small pediatric patients. That is the current situation. Therefore, if hematopoietic stem cells collected from umbilical cord blood of one donor can be expanded effectively in vitro without undifferentiation, transplantation into adult patients will be able to be performed without difficulty. It can be said that it will be a traditional technology.
- Non-Patent Document 3 hematopoietic stem cells and mouse bone marrow-derived stromal cells are co-cultured in a state of being separated by a certain type of polymer diaphragm material. It is stated that by contacting the elongated villi, it grows effectively undivided.
- hematopoietic stem cells are co-cultured with different cells in a state of being separated by a diaphragm material in this way, and a culture technique is developed in which hematopoietic stem cells are expanded by cell-to-cell contact through the pores of the diaphragm, the expanded hematopoietic stem cells will become Can be easily separated and collected. Therefore, such co-culture may be a very practical method for in vitro expansion of hematopoietic stem cells.
- a membrane material having a high pore size uniformity is selected, and the membrane material having such a uniform pore size is as large as possible within a range in which the cells themselves do not move between the diaphragms. It is preferable to use those having an average pore diameter as the diaphragm.
- a membrane material having a high pore size uniformity is, for example, a polymer fiber mesh, a metal mesh, an etching film, and a microdroplet as a ⁇ type.
- a special porous thin film to be formed is exemplified.
- a general polymer fiber-based mesh When a general polymer fiber-based mesh is used as a cell culture membrane having a large pore size, general cells undergo cell migration through pores. In particular, it cannot be used as a diaphragm for culturing hematopoietic stem cells whose diameter is about 7 m.
- Some metal meshes and polymer fiber meshes manufactured by special methods have pore sizes of less than 10 ⁇ m.However, since the porosity is usually significantly reduced, the above condition (2) must be satisfied. Unsatisfactory, even if it can be used as a diaphragm, effective cell-to-cell contact cannot be performed, making it impractical as a diaphragm for cell co-culture.
- Non-Patent Document 3 Although the etched film is used as a diaphragm in Non-Patent Document 3, it has a low porosity and cannot satisfy the above condition (2) like a mesh, so that it can be used as a practical cell co-culture diaphragm. Can not be.
- the membrane composited with the support of Patent Document 2 is still insufficient in force, which satisfies condition (2) somewhat.
- the polymer solution is spin-coated on the support with a rubber roller, it is difficult to form a thin film, and the polymer solution easily penetrates into the base material of the support. 'It is difficult to make the film thickness uniform. Therefore, the structure of the composite film tends to be heterogeneous. Therefore, since it is difficult to obtain a porous membrane as a uniform thin film, the above condition (3) cannot be satisfied, and the membrane material obtained by this technique cannot be an efficient cell culture membrane.
- a special porous thin film with small water droplets in the shape of a triangle may have the potential to be used as an effective membrane material for cell culture in order to satisfy the above conditions (1)-(3).
- the film thickness is a few microns, the strength is very low, and the film is easily damaged. Therefore, it can be used with a large membrane area for the purpose of culturing a large amount of cells, or processed into various shapes (bags, rolls, etc.) suitable for large-scale cell growth and separation and collection of target cells. Then, since it is difficult at all times, the above conditions (4) and (5) are not satisfied, and a practical cell culture diaphragm cannot be obtained as it is.
- Non-Patent Document 1 Polymer Preprints, Japan Vol. 50, No. 12 (2001), page 2804.
- Non-Patent Document 2 Polymer Preprints, Japan Vol. 51, No. 5 (2002), page 961
- Non-Patent Document 3 Latest Medicine, Vol. 58, No. 1 (2003), page 63.
- Patent Document 1 Japanese Patent Application Laid-Open No. 2-180625
- Patent Document 2 JP-A-56-135525
- Patent Document 3 JP 2001-157574
- Patent Document 4 International Publication No. 87Z05812 pamphlet
- Patent Document 5 U.S. Patent No. 5,298,165
- Patent Document 6 JP-A-5-34337
- Patent Document 7 JP-A-54-46811
- Patent Document 8 Japanese Patent Application Laid-Open No. 2003-149096
- An object of the present invention is to accurately and accurately perform size separation of micron-sized objects (for example, cultured cells and blood cells), and to have sufficient mechanical strength.
- An object of the present invention is to provide a film material which is easy to handle in use and can be processed into various film forms.
- a membrane material as a filter medium, the volume of the filter medium can be significantly reduced while maintaining high leukocyte removal ability, and the amount of loss of the blood cell suspension after the filtration operation can be significantly reduced.
- An object of the present invention is to provide a method for producing a blood cell suspension and a filter device for removing leukocytes.
- Another object of the present invention is to use such a membrane material as a cell culture diaphragm when co-culturing two or more different cell groups in a cell culture solution, so that different cell groups are mixed with each other. It is an object of the present invention to provide a cell culture method capable of effectively making cell-to-cell contact between different cells separated from each other while maintaining a separated state.
- the present inventors have conducted intensive studies to achieve the above object, and as a result, completed the present invention.
- the present inventors have studied the relationship between the number of nonwoven fabrics and the leukocyte removal ability with respect to the leukocyte removal filter using a nonwoven fabric described in the prior art.As a result, within the range where the number of nonwoven fabrics is small, the leukocyte removal ability increases with the number of nonwoven fabrics. The effect was gradually reduced as the number of nonwoven fabrics increased to some extent. Therefore, the composite porous membrane of the present invention, which has holes having a size capable of selectively capturing leukocytes with high size uniformity and has practical mechanical strength, communicates with a nonwoven fabric or a three-dimensional mesh. When used in combination with a porous material having pores under specific conditions, high leukocyte removal ability was maintained. The present inventors have found that a large reduction in the volume of the filter medium can be realized as it is, and have reached the present invention.
- the present invention is as follows.
- a composite porous membrane comprising at least one porous membrane containing an organic polymer compound and at least one supporting porous membrane adjacent thereto.
- the porosity of the porous membrane is 10 to 90%
- the average pore diameter D m) is 0.1 ⁇ D ⁇ 50
- the standard deviation of the pore diameter ⁇ d (m ) Is 0 ⁇ ⁇ d ZD ⁇ 0.6
- the ratio of through-holes in the porous film is 30% or more
- Thickness m) is 0.05 ⁇ T ZD ⁇ 2
- the pores of the porous membrane have a structure in which adjacent pores communicate with each other inside the porous membrane, and the pores of the supporting porous membrane are 0.
- the average pore diameter D (m) of the porous membrane is 0.1 ⁇ D ⁇ 20
- the average thickness T (m) is 0.1 ⁇ T ⁇ 20
- the average pore diameter of the supporting porous membrane is 1-100 / a zm, further the standard deviation of the thickness at ( ⁇ ⁇ ) ⁇ ⁇ a t / T ⁇ 0. 5 a is above (1) or a composite porous membrane according to (2).
- the porosity of the porous membrane is 15-80%, and the average pore diameter D (m) is 0.5 ⁇ D ⁇ 20.
- the blood filtration membrane comprising the composite porous membrane according to any one of (1) to (4) above.
- a leukocyte removal filter device having a first filter on the inlet side of the processed blood cell suspension and a second filter on the outlet side of the blood cell suspension, wherein the leukocyte removal capacity of the first filter is 450 cm for the processed blood cell suspension. per 3 1. 0-3. 5, and the second filter one of the (1) single (4) any one the composite porous above comprising one or two or more membranes according to
- the composite porous membrane according to any one of (1) to (4) above is arranged in a cell culture solution to provide at least two culture regions, and to at least two adjacent culture regions, A cell culture method comprising introducing different cell groups from each other and co-culturing the cells.
- the composite porous membrane of the present invention comprises a porous membrane and a supporting porous membrane.
- Porous membranes that govern size separation have pore sizes on the order of microns, high pore size uniformity, and high porosity.
- the thickness of the porous membrane is thin and uniform, and the inside of the porous membrane has a low filtration resistance. So Furthermore, since the supporting porous membrane imparts sufficient mechanical strength, the composite porous membrane of the present invention is easy to handle in use and can be processed into various membrane forms. As a result, by using the composite porous membrane of the present invention, precise size filtration of various cells and the like can be effectively and efficiently performed.
- the volume of the filter medium can be significantly reduced while maintaining high leukocyte removal ability, so that the blood cell suspension (whole blood, erythrocyte preparation, The amount of loss during filtration of platelet products, plasma products, etc.) can be greatly reduced, and the cost performance of blood products, etc. at medical sites is greatly improved.
- the composite porous membrane of the present invention as a cell culture diaphragm, it is possible to maintain a state in which different cell groups in a cell culture solution are separated from each other without being mixed with each other, and also through a thin uniform porous membrane. And effective cell-to-cell contact between different cells. Therefore, it is possible to effectively grow the target cell by contacting with a different cell (for example, grow in a state where differentiation is suppressed).
- the supporting porous membrane provides sufficient mechanical strength, it can be easily used in a large area suitable for practical cell growth and processed into various membrane forms. It is easy to multiply the cells and to perform the separation operation after the multiplication.
- the composite porous membrane of the present invention comprises at least one porous membrane containing an organic polymer compound and at least one supporting porous membrane adjacent thereto.
- the composite porous membrane only needs to have a structure in which the porous membrane and the supporting porous membrane are adjacent and bonded to each other (a structure in which the porous membrane penetrates the supporting porous membrane).
- a two-layer structure in which one porous membrane and one supporting porous membrane are combined that is, the “porous membrane Z supporting porous membrane” structure
- a three-layer sandwich structure in which both sides of the supporting porous membrane are porous membranes The structure of “porous membrane Z support porous membrane Z porous membrane”
- the three-layer sandwich structure in which both sides of the porous membrane are support porous membranes the structure of “support porous membrane Z porous membrane Z support porous membrane”
- the support porous membrane And a three-layer structure (“porous membrane Z porous membrane Z support porous membrane” structure) in which two porous membranes are present on one side of the membrane.
- a two-layer structure in which one porous membrane and one supporting porous membrane are combined that is, the structure of “porous membrane Z supporting porous membrane
- the shape of the pores is circular unless an external force (for example, pulling the composite porous membrane itself in one axis direction) is applied.
- the shape of the hole may be slightly deformed and become elliptical depending on the composition of the hydrophobic organic solvent solution and the manufacturing conditions (eg, the strength of the gas spray).
- the term “circle” in the present invention includes such an elliptical shape in addition to a perfect perfect circle.
- the porosity of the porous membrane is 10 to 90%
- the average pore diameter D m) is 0.1 ⁇ D ⁇ 50
- the standard deviation of the pore diameter ⁇ d (m ) Is 0 ⁇ d ZD ⁇ 0.6
- the film thickness T m) is 0.05 ⁇ T ZD ⁇ 2.
- the pores of the porous membrane have a structure in which adjacent pores communicate inside the porous membrane.
- porous membrane of the present invention those in which the porosity, D, ⁇ d, the ratio of through-holes, T, and the internal structure of the membrane cannot be experimentally determined are outside the scope of the porous membrane of the present invention.
- nonwoven fabrics that are preferably used as a supporting porous membrane, and porous bodies having communication holes in a three-dimensional network obtained mainly by a phase separation method are difficult to define by the methods described in Examples. Therefore, it is clearly different from the porous membrane according to the present invention.
- the porosity of the porous membrane in the plane of the membrane is 10-90%, preferably 15-80%, more preferably 20-70%, and most preferably 25-60%. If the porosity is less than 10%, the filtration rate will be slow and the efficiency of contact between different separated cells will be low. On the other hand, if it exceeds 90%, the strength of the porous membrane is significantly reduced, which may cause damage to the membrane.
- the value of the average pore diameter D (m) is 0.1 ⁇ D ⁇ 50, preferably 0.1 ⁇ D ⁇ 20, more preferably 0.5 ⁇ D ⁇ 20, most preferably 0.8 ⁇ D ⁇ 20 ⁇ 10. When D exceeds 50 m, it becomes difficult to separate general micron-sized cells and the like, and it may be difficult to effectively separate different cells.
- the standard deviation (adm) of the pore diameter is 0 ⁇ ad / D ⁇ 0.6, preferably 0 ⁇ dZ D ⁇ 0.5, more preferably 0 ⁇ a dZD ⁇ 0.4, and most preferably 0. ⁇ ⁇ dZD ⁇ 0.3. If the adZD exceeds 0.6, the pore diameter size distribution becomes wide, and the efficient separation of the substance to be separated and the precise size separation performance become insufficient.
- the organic polymer compound constituting the porous membrane invades the supporting porous membrane! It is characterized by For example, when the supporting porous membrane constituting the composite porous membrane is a non-woven fabric, when the surface of the porous membrane in the composite porous membrane is observed with an electron microscope, the porous membrane is formed on a part of the non-woven fabric (a fiber portion or a fiber entangled portion).
- the pore shape is disturbed, or the pores are closed on the back surface of the porous membrane (on the side of the supporting porous membrane), so that a curled state (non-penetrating structure) can be observed.
- a curled state non-penetrating structure
- the organic polymer compound constituting the porous membrane invades a part of the supporting porous membrane, a part of the supporting porous membrane (for example, in the case of nonwoven fabric, As a result, the pores are closed due to the decrease of the pore permeability of the porous membrane (this condition is observed in Figs. 1 and 2). It is rare.
- the ratio of the through holes in the porous membrane is 30% or more, preferably 40% or more, more preferably 50% or more, and most preferably 60% or more. If the percentage of through-holes is less than 30%, objects that are originally sized to pass through the through-hole enter the non-through-hole, not only reducing the filtration rate and the contact efficiency between different cells that are separated. Since the state is captured as it is, the size separation effect is reduced.
- the ratio of the through-holes in the porous film is also affected by the film formation conditions (for example, the concentration of the hydrophobic organic solvent solution to be cast, the amount of casting, the type of solvent, etc.).
- the “through hole” of the porous membrane refers to an arbitrary hole P in the porous film, and the electron microscopic force of the film plane of the porous film. If the hole shape is a circle, the hole diameter D force is calculated (DZ2) 2 ⁇ value), and if S ( ⁇ ) is set, the area where the structure of the supporting porous membrane on the opposite side can be observed through the hole (( The area of the so-called penetrating region) is 70% or more of S ( ⁇ ).
- the “ratio of through-holes” refers to the ratio of through-holes among the holes for which the electron microscopic photographic power of the film plane of the porous film is also observed. For example, “a hole has a penetration rate of 50%” means that if there are 10 holes, 5 of them are “through holes”.
- the average thickness of the porous membrane can be measured when the cross section of the composite porous membrane is observed with a microscope (mainly an electron microscope) .
- the value is 0.05 TZD ⁇ 2. is there. It is preferably 0.1 ⁇ T ⁇ 50, more preferably 0.1 ⁇ 20, further preferably 0.5 ⁇ 20, and most preferably 0.8 ⁇ 10.
- ⁇ is less than 0.1, the strength of the porous membrane is reduced, and the membrane tends to be broken during filtration.
- ⁇ exceeds 50 contact between different cells becomes difficult, and the film thickness is correlated with the average pore diameter D.
- the standard deviation ⁇ t (m) of the film thickness at which separation of cells and the like becomes difficult is 0 ⁇ t / T ⁇ 0.5, preferably 0 ⁇ t / T ⁇ 0.4, more preferably Is 0 ⁇ at / T ⁇ 0.3. If tZT exceeds 0.5, the distribution of the film thickness becomes wide, and it becomes difficult to make contact between different cells that are partially separated, and it may be difficult to make effective contact.
- the pores of the porous membrane are characterized in that adjacent pores communicate with each other inside the membrane.
- the cross-sectional structure of the porous membrane is an internal spherical structure (a structure swelling inside) as shown in Fig. 4.
- adjacent holes are connected (spherical through-hole 1), so that etching is performed.
- the filtration resistance of the fluid inside the porous membrane is significantly reduced, and a high filtration efficiency can be obtained.
- the penetration is impeded by the porous support membrane because it is communicated in the membrane plane direction.
- Such a hole can contribute to filtration. It is not necessary that all of the pores of the porous membrane communicate with the adjacent pores inside the membrane, but the more the number of communicating portions, the lower the resistance to filtration of the fluid. Similar to the film thickness, the cross section of the composite porous membrane can be observed with a microscope (mainly an electron microscope).
- the method for producing such a membrane structure is not particularly limited, but adjacent pores communicate with each other inside a porous membrane produced by a film-forming method using water droplets as described below. Department Since many components are found, this membrane forming technique can be preferably used for producing the composite porous membrane of the present invention.
- the organic polymer compound forming the porous film is not limited as long as it is soluble in the hydrophobic organic solvent used.
- polyesters such as polylactic acid, polyhydroxyacetic acid, polyproprolataton, polyethylene adipate, polyurethanes, poly (meth) acrylates, polybutylacetals, polyamides, polystyrenes, polysulfones, cellulose derivatives, Single materials such as polyphenylene ethers and polycarbonates, these powers. Powers of two or more selected polymer alloys and blends, or copolymers of monomers forming the above-mentioned polymers. Powers limited to the above examples. is not. Next, the supporting porous membrane will be described.
- the supporting porous membrane When used as a filtration membrane, the supporting porous membrane has a function of supporting and reinforcing the porous membrane and imparting sufficient mechanical strength to the composite porous membrane without impairing the filtration rate. The larger is preferable.
- the supporting porous membrane When used as a cell culture diaphragm, the supporting porous membrane has a mechanical strength and, in some cases, a function as a scaffold for cultured cells, and furthermore, it allows cell-to-cell contact through the porous membrane.
- the supporting porous membrane Preferably has a pore size capable of moving in the supporting porous membrane. Therefore, the supporting porous membrane has an average pore diameter of 0.5 Dm) or more, preferably 1 ⁇ m or more, more preferably 1 to 100 ⁇ m.
- the average pore diameter is less than 0.5 Dm
- the average pore size exceeds 100 / zm, the adhesiveness may be reduced and the strength of supporting the porous membrane partially may be reduced.
- the “average pore diameter” is a value measured using a palm porometer (manufactured by Porous Materials, Inc.) according to the bubble point method described in ASTM-F316-86.
- the communication hole is a hole that is connected to the other surface of the supporting porous membrane by applying the surface force to the opposite surface.If the liquid or gas can pass through the communication hole, the hole can be used.
- the shape of the film surface and the internal structure of the film may be arbitrary.
- the film thickness is preferably 5 mm or less, more preferably 3 mm or less, and most preferably 1 mm or less. If the supporting porous membrane is too thin, it may not be able to serve as a supporting layer, so that it is preferably at least 1 ⁇ m, more preferably at least 5 ⁇ m, most preferably at least 10 m.
- the supporting porous membrane include nonwoven fabrics obtained from natural fibers, synthetic polymer fibers, regenerated polymer fibers, inorganic fibers typified by glass fibers, and organic Z inorganic composite fibers; Foaming method, phase separation method (thermally induced phase separation method or wet phase separation method), stretching method, firing method, etc., from the state of hot melted material, solution dissolved by solvent, plasticized using plasticizer, etc.
- a porous body (porous membrane) having three-dimensional network communication holes obtained by a knotting method or the like can be given.
- woven and knitted fabrics such as natural fibers, synthetic polymer fibers, recycled polymer fibers, glass fibers, and organic Z inorganic composite fibers, as well as organic and inorganic materials
- organic polymer material used for the supporting porous membrane include polyalkylene terephthalates, polycarbonates, polyurethanes, poly (meth) acrylates, polyacrylonitrile, polyvinyl alcohol, polyvinyl acetal, polyesters, and polyesters.
- Preferred examples of the supporting porous membrane include nonwoven fabric, woven fabric, and meshes.
- Examples of the organic polymer material forming the fiber itself include polyethylene terephthalate, polypropylene, cellulose derivatives, polyamide, polyacrylonitrile, etc., of which polyethylene terephthalate is particularly preferred.
- the support porous membrane having a small filtration resistance, a large communicating hole, and a moderate strength is used in order to increase the filtration efficiency of the liquid to be filtered.
- a nonwoven fabric obtained from organic polymer fibers, woven include main Tsu Pradesh filter One class, nonwoven preferably, n
- the nonwoven fabric diameter is too large, the pore permeability of the porous membrane may be impaired, or the unevenness of the bonding surface with the porous membrane may increase, resulting in the smoothness and thickness of the porous membrane. May hinder uniformity.
- the fiber diameter of the non-woven fabric is preferably 0.1-50 m, more preferably 0.1-30 m, even more preferably 0.5-15 m, and most preferably 0.5-5 m. It is.
- basis weight of the nonwoven fabric for example, if the thickness of 200 m nonwoven, preferably rather the 10- 200gZm 2, more preferably 15- 150gZm 2, more preferably 20- lOOgZ m (? Mel.
- the supporting porous membrane When the supporting porous membrane is to exhibit a positive separation performance, for example, when applied to a filtration system in which the liquid to be filtered first flows through the supporting porous membrane and is subsequently separated by the porous membrane, the supporting porous membrane may be used.
- the pre-filter effect of separating or adsorbing particles larger than the size separated by the porous membrane on the supporting porous membrane it is possible to prevent clogging of the porous membrane and increase the separation efficiency .
- the composite porous membrane of the present invention is a composite of a porous membrane and a supporting porous membrane, and an organic polymer compound constituting the porous membrane is formed on at least a part of the supporting porous membrane adjacent to the porous membrane. Penetrates into the supporting porous membrane, so that a structure in which both adhere to each other exists. The existence of this structure can be confirmed by electron microscopic observation of the porous film, and the presence of this structure develops high adhesion between the porous film and the supporting porous film.
- the composite porous membrane may have a structure in which both side surfaces of the supporting porous membrane are sandwiched by porous membranes.
- the average pore diameter and porosity of each porous membrane, or the substance constituting the porous membrane Etc. may be the same or different.
- the film thickness of the composite porous film of the present invention is preferably 5 mm or less, more preferably 3 mm or less. It is most preferably 1 mm or less.
- the film thickness is preferably 1 ⁇ m or more, more preferably 5 ⁇ m or more, and most preferably 10 or more.
- the composite porous membrane of the present invention has sufficient strength for processing, it is possible to convert the flat membrane into hollow fiber, bag, pleated, and other various forms. I can do it. For example, if two composite porous membranes cut into a square shape of the same size are overlapped with a support porous membrane (for example, nonwoven fabric) on the inside and sealed by heat sealing on three sides, the nonwoven fabric will be present inside. Thus, a bag-like sheet whose entire periphery is covered with a porous membrane can be obtained. If one composite porous membrane cut into a fan shape is rolled and two strings are heat-sealed, a funnel structure (conical structure) can be obtained. If a rectangular composite porous membrane is rolled and heat-sealed on two opposing sides, a tubular (hollow fiber) shape is obtained, which can be used for various purposes.
- a support porous membrane for example, nonwoven fabric
- the composite porous membrane can be processed so as to be integrated with other members.
- the composite porous membrane and the tube can be integrated with the end surface of a glass or plastic tube by bonding using an adhesive or fusion bonding. Gluing the composite porous membrane to one end of the tube can be used to make a cup-shaped container, or it is easier to glue to both ends to make a closed container.
- the composite porous membrane may be used alone (one sheet) or may be used by constructing various layer structures by superposing a plurality of layers. Furthermore, by superimposing (combining) one or more composite porous membranes with one or more support porous membranes constituting the composite porous membrane, it is possible to provide membrane materials with various performances.
- the method for producing a composite porous membrane of the present invention comprises the steps of: (a) holding a liquid incompatible with a solution of an organic polymer compound in a hydrophobic organic solvent on a supporting porous membrane; Conversion The hydrophobic organic solvent solution of the compound is cast, and then (c) the hydrophobic organic solvent is evaporated in an environment where the relative humidity near the liquid surface is 20 to 100% to make the organic polymer compound the main component.
- the three process powers of forming a porous membrane on the supporting porous membrane are also included.
- the "organic polymer compound in a hydrophobic organic solvent solution” used in the present invention is obtained by dissolving an organic polymer compound as a main component of a porous film formed on a supporting porous film in a hydrophobic organic solvent. Solution.
- the solution concentration is preferably from 0.01 to 30 wt%, more preferably from 0.03 to 15 wt%, most preferably from 0.04 to 5 wt%. If the concentration is less than 0.01 wt%, the pore regularity of the porous membrane may decrease, and the membrane strength may decrease.
- the concentration exceeds 30 wt%, a regular honeycomb structure may be formed.
- the formation of through holes requires the use of a solution of an organic polymer compound in a hydrophobic organic solvent. Since the film thickness must be reduced by remarkably reducing the amount of casting on the supporting porous membrane, it is not preferable because the degree of difficulty in the film forming technique becomes extremely high.
- a “hydrophobic organic solvent” is an organic solvent that is incompatible with water at an arbitrary ratio, and that does not homogenize! /, And that dissolves an organic polymer compound that forms a porous membrane. It is not limited. However, since the solvent is evaporated at a relative humidity of 20 to 100%, a highly volatile hydrophobic solvent that can be relatively easily removed by evaporation is preferable. Examples of such a solvent include halogen-based organic solvents such as chloride or fluoride such as chloroform, dichloromethane and dichloroethane, benzene, toluene, xylene, n-hexane, cyclohexane, methylcyclohexane, and decalin.
- halogen-based organic solvents such as chloride or fluoride such as chloroform, dichloromethane and dichloroethane, benzene, toluene, xylene, n-hexane, cyclohexan
- the organic polymer compound is not compatible with the hydrophobic organic solvent solution!
- the liquid is held on the supporting porous membrane.
- the hydrophobic organic solvent solution is cast on the supporting porous membrane, it is necessary to prevent the hydrophobic organic solvent solution from entering the pores of the supporting porous membrane and closing the pores.
- a liquid that is not compatible with the hydrophobic organic solvent solution is previously held on the supporting porous membrane, and the internal pores of the supporting porous membrane are filled with the liquid.
- the hydrophobic organic solvent solution to be cast on the support porous membrane easily permeates.
- the method is effective. Since the hydrophobic organic solvent solution is prevented from entering the inside of the supporting porous membrane, the solution can be thinly and smoothly cast on the supporting porous membrane. As a result, the porous membrane can be formed thinly, uniformly and smoothly on the supporting porous membrane, and finally, the organic polymer compound does not block the supporting porous membrane.
- a liquid that is not compatible with a hydrophobic organic solvent solution! (Hereinafter, also referred to as a liquid that is not compatible!) Is a solution that is homogeneous even when mixed with the solution in any amount.
- the liquid that is not compatible is not limited because it is selected according to the type of the hydrophobic organic solvent to be used, but after forming the porous membrane, the liquid is easily removed from the inside of the supporting porous membrane by drying or washing. Those that can be removed are preferred.
- the porous membrane easily forms a through-hole, and therefore, for example, water, an aqueous solution containing various salts such as sodium salt, a water-soluble liquid polymer such as polyethylene glycol, Or their aqueous solutions are preferred as the above-mentioned incompatible liquids.
- Water of which a simple composition is preferred for industrial handling, is particularly preferred. It is required that the incompatible liquid does not dissolve the organic polymer compound. However, when the hydrophobic organic solvent solution and the liquid come into contact with each other during film formation, the organic high molecular compound in the hydrophobic organic solvent solution is not dissolved.
- the liquid may be one that slightly dissolves the organic polymer compound, if it does not substantially migrate into the liquid.
- the supporting porous membrane may be sufficiently immersed in the liquid in advance, and then taken out and used. If applied, the liquid can be more effectively retained inside the supporting porous membrane. Before casting the hydrophobic organic solvent solution, the liquid may be dripped directly into the supporting porous membrane and impregnated, or the liquid may be sufficiently sprayed and held.
- a hydrophobic organic solvent solution of the organic polymer compound is cast on the supporting porous membrane.
- the method of casting is not particularly limited as long as the solution is uniformly and completely cast on the supporting porous membrane. If the viscosity of the solution is low, it is poured directly onto the supporting porous membrane. When the viscosity is high, it is cast uniformly using a blade coater or the like. In the present invention! If it is a substance that dissolves in the hydrophobic organic solvent solution used, other additives are used for the purpose of improving film formation stability, strength, surface modification (for example, imparting hydrophilicity), and imparting toughness of the porous film.
- amphipathic conjugates such as bishexadecylammonium bromide described in Mater. Sci. Eng., Vol. C8-9, page 495 (1999).
- the polyacrylamide-based amphiphilic conjugate of the following structural formula (I) is preferable because the film formation stability and pore size of the porous film and the uniformity of the pore shape are increased. Items.
- the composition ratio of the organic polymer compound to the amphiphilic compound is limited. Although not specified, it is preferably in the range of 99Z1-50Z50 (wtZwt). If the amphiphilic compound is less than 99Z1, a uniform porous film is formed. If the amphiphilic compound is more than 50Z50, the mechanical strength of the porous film is reduced and the film is easily broken. Become.
- the relative humidity in the vicinity of the liquid surface is set to 20-100%
- Any method may be used.
- Examples include a method of raising the temperature of the environment surrounding the film formation, a method of appropriately reducing the pressure of the film formation environment, and a method of gently spraying an appropriate gas onto the liquid surface.
- the method of spraying a gas onto the liquid surface is a preferable method because it is easy to form minute water droplets that form a ⁇ shape of the porous film, the humidity can be easily adjusted, and the apparatus is simple.
- the hydrophobic organic solvent can be effectively evaporated by spraying on the hydrophobic organic solvent solution.
- Any suitable gas may be used. However, in the process of film formation, those which are chemically inert to the porous membrane, the supporting porous membrane and the hydrophobic organic solvent solution are preferred. Specific gases include air, nitrogen, oxygen, helium, argon, and the like, and mixtures thereof. Air is preferred in consideration of cost performance.
- a method of spraying gas to the hydrophobic organic solvent solution a method of installing a pump on the supply gas side and supplying an appropriate nozzle force gas and spraying it, and conversely, when using a closed type constant temperature constant room box etc. Then, a method is used in which the pressure inside the box is reduced and the external gas also inhales the gas, and sprays the gas onto the hydrophobic organic solvent solution via an appropriate nozzle.
- the evaporation is performed in an environment where the relative humidity near the film is 20 to 100%, preferably 30 to 90%, more preferably 35 to 90%. — 80%.
- the relative humidity is less than 20%, the growth of water droplets, which form a ⁇ shape for forming holes, becomes insufficient, so that it is difficult to form a uniform honeycomb-shaped hole structure, and the hole penetrability also increases. become worse.
- “In an environment where the relative humidity near the film is 20-100%” may be set by adjusting the relative humidity of the entire film formation environment, such as in a thermo-hygrostat box! / ⁇ .
- the setting can be made by adjusting the relative humidity of the blown gas.
- the hydrophobic organic solvent evaporates, and in the process, minute water droplets formed on the solution surface become ⁇ -shaped, and a porous membrane having a uniform pore structure is formed on the supporting porous membrane. After the holes are formed, the liquid held by the supporting porous membrane is dried and removed as it is. The liquid is once immersed in alcohol or the like to replace the liquid, and then dried and removed.
- the support porous membrane and the composite porous membrane obtained in the production method of the present invention include production such as improvement of water permeability, improvement of separation performance by introducing a selective functional group, and suppression of adhesion of biological substances and the like.
- Various surface modifications can be made in response to various process or use requirements.
- the method for producing a composite porous membrane preferably used in the present invention that is, a method for forming a porous membrane by retaining water in the supporting porous membrane, if the hydrophobicity of the supporting porous membrane is strong, the inside of the supporting porous membrane is not sufficient. Water cannot be uniformly retained, and the hydrophobic organic solvent solution for forming the porous membrane permeates the inside of the supporting porous membrane, so that the hydrophobic organic solvent solution is held smoothly on the supporting porous membrane In some cases, it may be difficult to produce a composite porous membrane having a desired form. In this case, it is preferable that the surface of the supporting porous membrane is subjected to a hydrophilic treatment to increase water retention.
- the support porous membrane is preliminarily subjected to a hydrophilic treatment based on the above manufacturing reasons, or if the resulting composite porous membrane is used in practical use (improved water permeability, improved blood compatibility, improved non-protein adsorption)
- a hydrophilic treatment is performed for the purpose of improving the properties, it is preferable to introduce an appropriate hydrophilic functional group to the film surface as necessary.
- a hydrophilic functional group for the purpose of suppressing non-selective adsorption of blood cell components and a leukocyte are added to the leukocyte. It is effective to introduce a basic nitrogen-containing functional group for the purpose of expressing the selective affinity of the compound in a well-balanced manner.
- Hydrophilic functional group means a functional group having an affinity for water molecules, and various known hydrophilic functional groups are applicable thereto. Specifically, alcoholic hydroxyl groups, phenolic water Functionality known for its relatively high hydrophilicity, such as acid groups, carboxyl groups, sulfone groups, carboxyl groups, ester groups, ether groups, amide groups, N-monosubstituted amide groups, and N, N-disubstituted amide groups Groups. It is preferable to introduce one or a combination of two or more of these.
- nonionic hydrophilic functional groups such as an alcoholic hydroxyl group, a carboxy group, an ester group, an ether group, an amide group, and an N, N-disubstituted amide group. Preferred,.
- the “basic nitrogen-containing functional group” introduced for the purpose of expressing selective affinity for leukocytes is, for example, an aliphatic primary amino group, an aliphatic secondary amino group, an aliphatic tertiary amino group, a pyridyl group. And a nitrogen-containing aromatic group such as a bipyridyl group and an imidazole group. It is preferable to introduce one or a combination of two or more thereof. Aliphatic primary amino group (one NH), fat
- Aliphatic secondary amino groups and aliphatic tertiary amino groups are particularly preferable for achieving selective affinity of leukocytes, since they have lower hydrophobicity than aromatic amino groups.
- the specific secondary aliphatic Amino group has the structure of NHR 1, R 1 may be any structure is not particularly limited, for example, methyl, Echiru group, straight-chain such as propyl And a branched alkyl group such as an isopropyl group.
- the number of carbon atoms and the structure of these alkyl groups are not particularly limited, and one or more of the hydrogens contained therein may be substituted by any functional group having a hydroxyl group, an ester group, a carbonyl group or an ether group. May be.
- the aliphatic tertiary Amino group has the structure -NR 3, to R 2 and R 3 may also have various structures similar to R 1, R 2 and R 3 are the same structure to each other Even if it is different, it may be.
- an aliphatic tertiary amino group is a preferable structure, and a functional group having an aliphatic tertiary amino group is effective as a leukocyte-selective affinity functional group.
- Specific methods for introducing a functional group, such as a hydrophilic functional group or a basic nitrogen-containing functional group, onto the membrane surface include: (a) a functional group originally present on the membrane substrate surface by a polymer reaction to a desired functional group; (B) Irradiation of electron beam or ⁇ -ray to the surface of the membrane substrate to generate radicals, which are then reacted with a monomer having a desired functional group to perform graft polymerization And (c) various living polymerization methods (for example, a living radical polymerization method or a living-one polymerization method) in which a necessary initiator group is introduced onto the surface of the membrane base material and then a catalyst or the like is added as necessary.
- a functional group such as a hydrophilic functional group or a basic nitrogen-containing functional group
- Examples include a method of graft-polymerizing a monomer having a desired functional group, and a method (d) of coating a polymer having a desired functional group on the surface of a membrane substrate by using an impregnation method or a spray method.
- the type and amount of the functional group to be introduced during the synthesis reaction of the coating polymer and the distribution of the polymerization chain can be easily designed, and the coating process itself is simple and the productivity is high. I like it.
- the type of the hydrophilic functional group-containing monomer used in the synthesis of the polymer for coating is not particularly limited, but is particularly limited. Those having a nonionic hydrophilic functional group are preferred.
- Examples of such a compound include (meth) acrylic esters having an alcoholic hydroxyl group, such as 2-hydroxyethyl methacrylate and 2-hydroxypropyl methacrylate, (meth) acrylamide, N-substituted ( (Meth) acrylamides such as N, N-dimethylacrylamide, N, N-diethylacrylamide, N, N-disubstituted (meth) acrylamides and other (meth) acrylamides, and -CH CH O— repeating units 1 to 100 Polyoxyje
- the hydrophilicity of the coating polymer is too high, the elution of the coating agent into the filtrate or cell culture in actual use often becomes a problem (especially low elution is important for medical applications). It is preferable to synthesize a polymer for coating by copolymerizing other hydrophobic monomers in an appropriate amount for the purpose of suppressing the property.
- the types of basic nitrogen-containing functional group-containing monomers used in the synthesis of the coating polymer are particularly limited. Although not particularly preferred, those having an aliphatic tertiary amino group are particularly preferred.
- Such compounds include, for example, 2- (N, N-dimethylamino) ethyl (meth) acrylate, 2- (getylamino) ethyl (meth) acrylate, 2- (ethylmethylamino) ethyl (meth) acrylate, 2 -(Diethanolamino) ethilethyl (meta) Tallylate, 2- (Dimethylamino) propylethyl (meth) acrylate, 3- (Dimethylamino) propyl (meth) acrylate, 3- (Jethylamino) propyl (meth) acrylate, 2- (Jetanolamino) propyl (meth) acrylate , 3- (diethanolamino) propyl (meth) acrylate, and the like.
- a polymer for coating is synthesized in advance, and the polymer is dissolved in an appropriate solvent. To prepare a coating solution.
- the support porous membrane or the composite porous membrane As a method for coating the support porous membrane or the composite porous membrane, the support porous membrane or the composite porous membrane (coating target membrane) to be coated is immersed in a coating solution, and the coating target membrane is set in an appropriate filter holder.
- a method of passing a coating solution through the coating solution a method of spraying the solution onto a film to be coated by a spray method, and the like can be mentioned.
- a dipping method is preferable.
- the coating polymer After dissolving in a suitable solvent, if the coating polymer can introduce the required amount of hydrophilic functional group or basic nitrogen-containing functional group into at least the surface portion of the supporting porous membrane or composite porous membrane after dissolving in a suitable solvent, the coating polymer can be used.
- the type and composition are not limited.
- the coating polymer a polymer obtained by polymerizing one or more of the above-described hydrophilic functional group-containing monomers and one or more of the basic nitrogen-containing functional group-containing monomers is polymerized. Or a copolymer obtained by copolymerizing one or more hydrophilic functional group-containing monomers with one or more basic nitrogen-containing functional group-containing monomers. , Or a copolymer.
- the coating polymer When the coating polymer is a copolymer, it may be a random copolymer or a block copolymer.
- the molecular weight of the coating polymer has a weight average molecular weight (Mw) of preferably 1. 0 X 10 3 -. 2. OX 10 6, more preferably 5. 0 X 10 3 -1 5 X 10 6, and most preferably 1 . 0 X 10 4 -1. a OX 10 6.
- Mw weight average molecular weight
- OX 10 6 may solubility in a solvent decreases the uniformity of the solvent liquid decreases, also the too high solution viscosity to the surface of the membrane material Hitoshi In some cases, a uniform coating cannot be obtained.
- Mw is a value obtained by gel permeation chromatography (GPC, standard polystyrene conversion).
- Solvents for dissolving the polymer for coating include those which do not significantly swell or dissolve the supporting porous membrane or the composite porous membrane, particularly the porous membrane constituting the composite porous membrane, and which sufficiently dissolve the coating polymer.
- the solvent is not limited as long as the solvent can be finally removed from the porous membrane, and various solvents can be used according to the type of the coating polymer.
- alcohols such as methanol, ethanol, propanol and butanol, ketones such as acetone and methyl ethyl ketone, esters such as ethyl acetate, aromatic hydrocarbons such as benzene, toluene and xylene, hexane and cyclohexane Aliphatic hydrocarbons such as hexane, methylcyclohexane and decalin; halogenated hydrocarbons such as chloroform, dichloromethane and dichloroethane; sulfur-containing solvents such as dimethylsulfoxide; N, N-dimethylformamide; Examples thereof include one or a mixture of two or more amides such as N-dimethylacetamide.
- alcohols have an appropriate drying rate, ease of handling, and high affinity with polymers having hydrophilic functional groups. Very preferred above. If necessary, an appropriate amount of water may be mixed for the purpose of finely adjusting the hydrophilicity / hydrophobicity of the solvent.
- a coating method is used as a method for modifying the surface of the support porous membrane used in the production method of the present invention or the obtained composite porous membrane, a polymer for coating is synthesized in advance, and the polymer is coated with an appropriate solvent. To prepare a coating solution.
- the polymer concentration of the coating solution is preferably 0.01 to 50 wt%, and 0.1 to 30 wt% is more preferable. 0.5-20% by weight is most preferred. If the coating solution concentration is less than 0.01 wt%, the coating is insufficient and the membrane surface of the supporting porous membrane tends to be partially exposed. On the other hand, if the content exceeds 50 wt%, the solution viscosity becomes high, so that it is difficult to uniformly coat the porous support membrane, or the pores of the porous support membrane are easily closed.
- the polymer concentration of the coating solution is preferably 0.01 to 10 wt%. 0.05-5 wt% is more preferred 0.1 lwt% is most preferred. If the concentration of the coating solution is less than 0.01 wt%, the coating becomes insufficient and the surface of the porous membrane is likely to be partially exposed. If the coating solution concentration exceeds 10 wt%, the solution viscosity will increase, making it difficult to coat the porous membrane uniformly, and the pores of the porous membrane will also be easily blocked.As a coating process, prepare an appropriate concentration in advance.
- the immersion time of the supporting porous membrane or the composite porous membrane in the polymer solution for coating is preferably 0.5 to 60 seconds, more preferably 1 to 30 seconds, and most preferably 2 to 10 seconds. If the immersion time is less than 0.5 seconds, the coating may be uneven and insufficient, and even if it exceeds 60 seconds, the coating amount hardly increases. Also, depending on the type of the porous membrane, there may be cases where swelling of the porous membrane itself occurs.
- the porous membrane in the process in which the porous membrane is formed on the surface of the supporting porous membrane, the porous membrane is formed with minute surface irregularities of the supporting porous membrane (when the supporting porous membrane is made of a nonwoven fabric or a mesh). In the case of a fibrous medium, it penetrates into the fiber entangled portion), so that it is possible to realize a strong adhesion state between the supporting porous membrane and the porous membrane.
- a porous film is once formed on a solid substrate such as glass, peeled off, and then simply superimposed on the supporting porous film as in the past, the porous film and the supporting porous film are bonded. For example, the two are displaced by pulling, and the porous membrane is easily damaged.
- the composite porous membrane obtained by the production method of the present invention has extremely high strength of the composite porous membrane including the porous membrane, and thus is very easy to handle when used. Further, it can be easily processed into various forms such as a roll shape, a cylindrical shape, a pleated shape and the like.
- the leukocyte removal filter device of the present invention is a filter device having a first filter on the inlet side of the processed blood suspension and a second filter on the outlet side.
- Processed blood suspension “Liquid” refers to a blood cell suspension before filtration through a filter.
- the “leukocyte removal ability” of the first filter is determined by the following equation (1) from the leukocyte concentration in the blood cell suspension before and after filtration obtained when 450 cm 3 of the treated blood cell suspension is passed through the first filter.
- Leukocyte removal ability log (white blood cell concentration of blood cell suspension after filtration Z white blood cell concentration of blood cell suspension before filtration) ⁇ ' ⁇ (1)
- the second filter composed of the composite porous membrane may be blocked by a large amount of leukocytes. Or, in order to avoid clogging with the second filter, an extremely large area second filter is required, so that the product size of the leukocyte removal filter becomes significantly larger than the conventional level, resulting in a medical current. It becomes difficult to handle in the field.
- the leukocyte removal ability exceeds 3.5, the volume of the filter medium of the first filter is inevitably increased, and the effect of the present invention, that is, the “effect of reducing the loss of blood cell suspension due to the reduction of the volume of the filter medium” is achieved. It gets smaller.
- the ratio of the amount of blood cell suspension remaining in the filter after filtration i.e., the amount of blood cell suspension loss
- the second filter composed of the composite porous membrane may be clogged with a large amount of leukocytes. 2000 cm 3 or less is preferable because the filtration speed of the filter may be significantly reduced or blockage may occur.
- Treatment hemocyte suspension amount is more preferably 50- 1500 cm 3, further preferably 100- 1 000cm 3, most preferably ⁇ is 200- 600 cm 3.
- the first filter 1 may have any structure as long as the leukocyte removal ability is 1.0 to 3.5.
- Specific examples include natural fibers, synthetic polymer fibers, regenerated polymer fibers, inorganic fibers typified by glass fibers, and organic Z as described above as specific examples of the supporting porous membrane of the composite porous membrane.
- non-woven fabric or organic polymer material obtained from inorganic composite fiber, etc. is in a state of being melted by heat, in a solution state of being dissolved by a solvent, or in a state of being plasticized by using a plasticizer, etc.
- a porous body (porous membrane) having three-dimensional network communication holes obtained by foaming, phase separation (thermally induced phase separation or wet phase separation), stretching, sintering, etc.
- nonwoven fabrics made of organic polymer fibers and relatively uniform three-dimensional communication holes are easily formed! / A porous body obtained by a phase separation method is preferred.
- organic polymer material that forms the fibers of the nonwoven fabric examples include polyethylene terephthalate, polypropylene, cellulose derivatives, polyamide, and polyacrylonitrile. Of these, polyethylene terephthalate is particularly preferred.
- the fibers constituting the nonwoven fabric preferably have a fiber diameter of 0.3 to 3 ⁇ m, more preferably 0.5 to 2 ⁇ m, and most preferably, in terms of strength and leukocyte trapping property, which are preferred by ultrafine fibers. 0.5-1.1.5 ⁇ " ⁇ 3 ⁇ 4) ⁇ .
- the average pore diameter of the nonwoven fabric is preferably 2 ⁇ m or more from the viewpoint of clogging of leukocytes and increase in pressure loss, and is preferably 30 m or less from the viewpoint of leukocyte trapping. More preferably it is 2-20 ⁇ m, most preferably 2-10 ⁇ m.
- nonwoven fabric When a nonwoven fabric is used as a filter medium, two or more nonwoven fabrics with different average fiber diameters / average pore diameters, basis weights, etc. may be combined to improve leukocyte removal performance and prevent clogging! /, One or more non-woven fabrics may be combined with one or more non-woven fabrics, each having a three-dimensional network-like porous body and a non-woven fabric.
- Packing density when filling the filter medium in the filter holder for leukocyte removal filter apparatus in terms of increase or the like of the eye clog and pressure loss of the point force 0. lgZcm 3 or preferably fixture blood leukocyte removal capacity 0.5 g / cm 3 or less is preferable. More preferably 0.
- the form of the filter medium, or the form of the first filter formed by combining one (one) or a plurality thereof (plural), may be a flat membrane (flat plate) if blood can be filtered. ), A cylindrical shape (hollow fiber shape), a bag shape, etc., but a flat membrane shape is preferred because it is easy to handle. In that case, superimpose one or more sheets and apply the first filter. It is preferable to configure. When multiple sheets are stacked, each filter medium may have the same material, microstructure, average pore size, pore size distribution, film thickness, etc., or some or all of these elements may be different. May be. In addition, one filter medium (one sheet) may have a uniform microstructure, average pore size, pore size distribution, or the like, or may have a heterogeneous structure such as an inclined structure.
- the size of the first filter processing if hemocyte suspension 450cm per 3 1. 0-3. 5 may be sized to soil, but the workability in the medical field when too large As the filter size decreases and the size of the filter holder increases, this leads to a significant increase in costs on the part of the producer. Therefore, as a practical value, an effective area force of 300 cm 2 is preferred. 10—250 cm 2 More preferably, it is 10-200 cm 2 .
- the effective area of the first filter refers to the planar area of a part of the filter through which the blood cell suspension actually passes, excluding the filter gripping part (the part fixed to the filter holder). It does not mean anything that includes the surface.
- the surface of the filter media is made of acid, alkali, etc. for the purpose of introducing new functional groups by a coating method or the like and making the immobilization (to minimize elution of the coating material during use) sufficient.
- a treatment with an appropriate chemical, a treatment with plasma, an electron beam, or the like may be performed.
- the first filter 1 When a non-woven fabric obtained from an organic polymer fiber or a porous material having a three-dimensional network-like communicating hole obtained by a phase separation method is used as the first filter 1, as it is, 1 filter per 450 cm 3 of the processed blood suspension is used.
- the leukocyte-removing ability of 0-3.5 cannot be achieved, it is preferable to modify the surface of the filter medium that can come in contact with the suspension of blood cells by modifying the filter.
- a known method for imparting a hydrophilic functional group and a basic nitrogen-containing functional group in a well-balanced manner is particularly effective.
- the "surface portion of the filter medium that can come into contact with the blood cell suspension” includes, for example, in the case of a flat membrane, not only the front and back surfaces thereof but also the surface of the inside of micropores present inside the flat membrane. It is a thing.
- the filter media is a non-woven fabric, the entire surface of the fibers constituting the non-woven fabric (excluding the fiber entangled portion) is the surface portion of the filter media.
- a hydrophilic functional group or a basic nitrogen-containing functional group on at least the surface of the filter medium is not particularly limited.
- the method does not significantly block the pores of the filter media, and if the surface of the original filter media exhibits non-selective adsorption of blood cell components, the necessary functional groups can be obtained without exposing the surface.
- the method is not particularly limited as long as it is a method capable of uniformly introducing the compound. Examples thereof include the methods described in the method for modifying the surface of the composite porous membrane of the present invention and the supporting porous membrane constituting the composite porous membrane, and a coating method is particularly preferable.
- the surface strength of the filter that can come into contact with the blood cell suspension has a material strength that does not adversely affect blood cells.
- Materials that do not adversely affect blood cells '' refer to the performance inherent in blood cell components (mainly red blood cells, platelets, and a small amount of white blood cells) collected after filtration due to contact between the blood cells and the material during filtration.
- a polymer material having a hydrophilic functional group is suitable, and as the hydrophilic functional group, there may be mentioned one or two or more selected from the group of hydrophilic functional groups described above. it can.
- the material constituting the filter medium used for the first filter should have such a hydrophilic functional group originally! /, But if the filter medium does not contain any hydrophilic functional group, it may or may not be contained. However, if the amount is very small and may have an adverse effect on blood cells, at least the surface part that can come into contact with the blood cell suspension must be treated using the surface modification methods described above. It is preferable to select an appropriate one and introduce a hydrophilic functional group as necessary. Also in this case, a hydrophilic functional unit can be introduced by a similar method, which is preferred by the coating method.
- the second filter 1 is composed of one or more of the above-described composite porous membranes of the present invention.
- the form of the second filter may be any form such as a flat membrane shape or a cylindrical shape as long as blood can be filtered, but a flat membrane shape is preferred because it is easy to handle.
- a flat membrane shape is preferred because it is easy to handle.
- the materials, the porosity, the average pore diameter, the standard deviation of the pore diameter, the thickness, the internal structure of the membranes, and the like of each composite porous membrane are exactly the same. It may be Some or all of them may be different from each other. Further, also in the supporting porous membrane constituting the composite porous membrane, the material, the average pore diameter and the like may be completely the same, or some or all of them may be different from each other.
- the surface of the second filter that can come into contact with the blood cell suspension may be made of a material that does not adversely affect the blood cell components, or a non-selective blood cell component that has a low affinity for the blood cell components. It is also preferable that the material has a material strength that is unlikely to cause adhesion (the composite porous membrane may be blocked by blood cell adhesion).
- the composite porous membrane may be blocked by blood cell adhesion.
- high hydrophilicity and a high molecular weight material are suitable as described above. It is preferable that one or two or more selected from at least the surface portion of the composite porous membrane are provided.
- the material forming the composite porous membrane originally has a hydrophilic functional group.However, the composite porous membrane does not contain any hydrophilic functional group at least on its surface, or contains it. However, if the amount is very small even though it may have an adverse effect on blood cells, it can be used as a second filter after surface modification by coating as described above. Preferred,.
- the coating polymer to be introduced into at least the surface portion of the composite porous membrane by the coating method is preferably one obtained by polymerizing (copolymerizing) one or more selected monomers having a hydrophilic functional group.
- the basic nitrogen-containing functional group may be contained in the polymer for coating the composite porous membrane as long as it does not cause non-selective adsorption of blood cell components or does not adversely affect blood cell components.
- the coating polymer used for the first filter as it is as the coating polymer for the second filter, because it is advantageous in improving the productivity and reducing the cost on the filter device producer side.
- the effective area of the second filter is 4 cm 2 or more in view of the number of pores in the second filter, clogging with white blood cells, and the amount of processing of the blood cell suspension.
- Filter device size is 300 cm 2 or less from the viewpoint of operability in ⁇ beauty medical field.
- a 10- 200 cm 2 preferably Ri 10- 150 cm 2 force, 10- 100 cm 2 is most preferred.
- the effective area of the second filter refers to the planar area of a part of the filter, through which the blood cell suspension actually passes, excluding the filter holding part (the part fixed to the filter holder). It does not mean that it includes the surface of the internal hole.
- the leukocyte removal filter device of the present invention is a filter device having a first filter on the inlet side of the blood cell suspension and a second filter on the outlet side. Basically, any configuration is possible as long as the whole blood cell suspension flowing out through the first filter is configured to be filtered by the second filter following the bow I. If the second filter is installed on the blood cell suspension inlet side, the composite porous membrane may be blocked by a large amount of leukocytes.
- both filters of the present invention can be set to independent arbitrary forms and sizes. For example, if the effective area of the second filter is set to be twice as large as that of the first filter, clogging of the second filter will occur. Therefore, it is possible to further reduce the capacity of the filter medium of the first filter.
- first filter and the second filter are filled into one filter holder for use (integrated type).
- integrated type only one filter holder is required, which is preferable in terms of production cost.
- shape of the filter holder in various ways, it is possible to have the same effect as the above-mentioned split type.
- the first filter of the flat membrane type for example, a stack of multiple nonwoven fabrics
- the second filter composed of one or more composite porous membranes of the same size are stacked.
- an integrated configuration in which the filter holder is filled into a simple-shaped filter holder is preferable in terms of operability at a medical site and production cost.
- FIG. 5 is a conceptual diagram showing the basic configuration of an integrated leukocyte removal filter device.
- This leukocyte removal filter device basically includes a first filter (2), a second filter (3), a filter holder (4), a blood cell suspension inlet (5), and a filtered blood cell suspension outlet (6).
- Power is also.
- the first filter and the second filter are arranged at a certain distance for the sake of simplicity in the drawing. It can be considered that it is filled in the holder.
- the filter holder of Fig. 5 for the sake of illustration, for the sake of convenience, there is a large amount of space where no filter media exists. Such a space leads to loss of blood cell suspension, so it does not actually exist.
- the second filter (composite porous membrane) is formed so that the porous membrane surface is located on the blood cell suspension liquid inlet side. ) Is preferably placed in the filter holder. If the supporting porous membrane surface is arranged on the blood cell suspension liquid inlet side, the filtration resistance increases, and the filtration efficiency may be significantly reduced.
- the leukocyte removal ability of the leukocyte removal filter device of the present invention is preferably at least 4.0, more preferably at least 4.5, and most preferably at least 5.0 per 450 cm 3 of the treated blood cell suspension. If the leukocyte removal capacity is less than 4.0, the probability of side effects due to residual leukocytes during transfusion increases. In order to make the filter medium volume reduction effect of the leukocyte removal filter device remarkable, the leukocyte removal ability is preferably 8.0 or less.
- Medium volume of the leukocyte-removing filter device V (medium volume of the combined first filter and the second filter) is a 2-18cm 3, more preferably 2-15cm 3 is preferable instrument 3- 12cm 3, 3- 10 cm 3 is most preferred. If the volume of the filter medium is less than 2 cm 3 , the ability of the first filter to remove leukocytes will be insufficient. When the filter medium volume exceeds 18 cm 3 , the effect of reducing the filter medium is reduced, and as a result, the effect of reducing the loss amount of the blood cell suspension is also reduced.
- the filter medium volume V (cm 3 ) refers to the void volume of the filter medium.
- V can be obtained by filling a filter holder filled with a filter medium with a blood cell suspension or a liquid alternative thereto, for example, physiological saline, and measuring the volume of liquid (cm 3 ) filling the filter holder.
- the supporting porous membrane of the composite porous membrane used as the second filter is the same material as the first filter, and the amount of the porous membrane of the composite porous membrane used is the first filter. When it can be substantially ignored as compared with, the value calculated by the following equation (2) can be used for V.
- V Wf [(l / d)-(l / p)]---(2)
- d (g / cm 3 ) is the packing density of all the filter media in the first and second filters to be filled in the filter holder
- Wf (g) is the weight of the first and second filters to be filled.
- the amount and p (g / cm 3 ) mean the density of the material forming the supporting porous membrane of the first filter and the second filter (composite porous membrane). For example, if the first filter and the supporting porous membrane are a non-woven fabric made of polyethylene terephthalate, p is about 1.3.
- the cell culture diaphragm of the present invention will be described.
- the cell culture diaphragm of the present invention is used for co-culturing cells by partitioning different cell groups in a cell culture solution so as to be in contact with each other, and is a composite of the present invention. It is a cell culture diaphragm using a porous membrane.
- co-culture of cells means that at least one kind of cell group is brought into contact with each other by simply growing two or more kinds of cell groups simultaneously in a culture medium, and thereby, at least one kind of cell group is brought into contact with each other.
- a case where cell growth and Z or cell growth are promoted includes a case where at least one kind of cell is grown while suppressing cell growth.
- the cell culture membrane of the present invention is placed in a cell culture solution.
- a cell culture solution Depending on the number and morphology of the septum, at least two culture zones separated by the septum of the present invention are obtained. Different groups of cells are co-cultured in the at least two adjacent culture areas.
- a bag-shaped diaphragm sheet obtained by laminating two cell culture diaphragms cut into squares of the same size with a support porous membrane (for example, nonwoven fabric) on the inside and heat sealing three sides If one sheet is placed in the culture solution (open the bag above the liquid surface or seal it), the porous membrane is separated between the inside and outside of the bag-like diaphragm sheet (the inside and outside of the bag).
- different cell groups are co-cultured in at least two adjacent culture areas separated by a porous membrane, and the average pore diameter of the supporting porous membrane and the average pore diameter of the porous membrane are adjusted according to the cell size to be cultured. Cells that enable effective cell-to-cell contact Vesicle co-culture can be performed.
- the cell culture membrane of the present invention can be processed into a desired form, it is very easy to separate and collect the target cells after proliferation.
- the target cells can be easily separated and collected simply by removing the bag-shaped diaphragm sheet from the culture solution. it can.
- the target cells can be easily separated and collected in the co-culture using the above-described cup-type incubator, even when the target cells proliferate in the cup, they can be easily separated and collected.
- the cell culture method of the present invention at least two types of cell groups are partitioned in a cell culture solution so that they can come into contact with each other. And co-cultured.
- the combination of the cell groups to be co-cultured is not limited, but a combination of the cell groups that affects the proliferation of at least one type of cell when different cells come into contact with each other is preferable.
- a combination of cell groups that promotes proliferation and / or differentiation of at least one type of cell by contact with each other, or promotes only proliferation while suppressing differentiation is preferred.
- a combination for example, a combination of a "hematopoietic stem cell group and a mouse bone marrow-derived stromal cell group", which is said to promote hematopoietic stem cells preferentially in an undifferentiated state by cell-cell contact, and a "hematopoietic stem cell group” And human vascular endothelial cell group.
- Hematopoietic stem cell groups are preferred as the target cell group to be proliferated by cell-cell contact, because various applications to regenerative medicine are being studied, and there is also the potential for expansion into the cultured blood business.
- the membrane for cell culture of the present invention may be subjected to a surface modification such as a hydrophilic treatment as described in the method for producing the composite porous membrane and the supporting porous membrane thereof.
- the method for modifying the surface of the cell culture membrane is not limited, but a coating method is preferable as in the case of the composite porous membrane and the supporting porous membrane.
- the surface modification of the cell culture membrane is also carried out for the purpose of suppressing cell adhesion or conversely imparting cell adhesion.
- conventionally known biocompatible materials such as the aforementioned hydrophilic polymers, collagen, fibronectin, vitronectin, proteodalican, glycosaminodalican, gelatin, lectin, polylysine, etc. are used as the coating polymer.
- One or two or more types of conductive polymers The above can be used.
- the measuring method used in the present invention is as follows.
- the obtained composite porous membrane was punched out from the vicinity of the center into a square sample of 6.7 cm on a side, and the center (point A) and the four corners were B ', C', D ', E ', And the four midpoints of these four points and point A are B, C, D, and E, respectively.
- the nine photographs obtained in this way were imported into image analysis software, and in each photograph, the image area containing about 200 holes was randomly selected and adjusted sufficiently to analyze the image contrast, and the dark area ( (Hole area) is automatically extracted. Furthermore, from the extracted dark areas, those that are clearly different from the holes are manually deleted, and the average hole diameter of the holes included in the selected nine image ranges is calculated. Next, the “average pore diameter D” is calculated by averaging the values of the nine photographs.
- the standard deviation ⁇ d of the hole diameter is a value obtained by further averaging the standard deviations of the respective hole diameters in the nine image ranges defining the “average hole diameter D”.
- “Aperture ratio” is the average of nine aperture ratios obtained in the same image area.
- the number of through holes was Nl
- the total number of holes included in each photograph was Nl
- the number of through holes was N2.
- both are counted and the value of N2ZN1 X 100 (%) is calculated, and calculated as the average value of these nine.
- the average hole diameter D, the standard deviation ⁇ d of the hole diameter, and the opening ratio of the porous film having the honeycomb structure and the etching film are measured and calculated in the same manner.
- the disk-shaped sample for the scanning microscope is passed through the hole.
- the composite porous film is gently adhered and fixed on a disk-shaped sample stage for a scanning electron microscope using a double-sided tape and platinum is deposited (the thickness of the deposited film is set to be about 12 nm). This was observed with a scanning electron microscope (S-3000N, manufactured by Hitachi, Ltd.), and a photograph of the film cross-section was taken from the side of the film (in the direction of the film plane). Based on the scale, the average thickness T of the composite porous film and the porous film constituting the composite porous film is measured.
- Samples for cross-sectional observation are prepared by immersing in ethanol, freezing in liquid nitrogen, and then cleaving, as is generally done as a pretreatment for scanning electron microscope observation.
- the average pore diameter is evaluated according to the bubble point method described in ASTM-F316-86 using Automated Perm Porometer (registered trademark) (manufactured by Porous Materias, Inc.). For the measurement, a liquid that sufficiently wets the inside of the pores of the nonwoven fabric is used. (4) Adhesion test
- the composite porous membrane is cut into a square of 10 mm x 10 mm to make a test piece. Put this into a 50ml beaker containing 50ml water and soak for 30 minutes. After that, a stirrer with a length of 25 mm (maximum diameter 8 mm) was put in, stirred at a speed of 200 rpm for 30 minutes, and it was observed whether or not the porous membrane was separated from the supporting porous membrane. ⁇ , X when peeled.
- a composite porous film, a honeycomb structure porous thin film (Comparative Example 1), or an etched film (Comparative Example 4) is cut into 15 ⁇ 25 mm and used as a test piece. 5 mm from both ends (short side) of each test piece is sandwiched with BINDER CLIPS (registered trademark) (LION No. 107), and one of them is fixed and the membrane is suspended vertically. Attach a 30g or 50g weight to the other clip and observe if the composite porous membrane, honeycomb structured porous thin film, or etched film breaks. If the force is still strong even at 50 g (tensile strength is 50 g or more), it is evaluated as ⁇ , and if it is broken at 30 g (tensile strength is less than 30 g), it is evaluated as X.
- a composite porous membrane punched into a 25 mm diameter (Example 14), a porous porous film with a honeycomb structure and a supporting porous membrane (a coated nonwoven fabric in this example) of a composite porous membrane whose water permeability is to be compared.
- a 25 mm diameter circular punched sample (Comparative Examples 1-2) and an etching film (Comparative Example 4) 25 mm circular shape are set in a commercially available filter holder (Swin-Lok TM Filter Holder manufactured by CORNING). And conduct a water permeability test.
- the porous membrane or the porous porous membrane having a honeycomb structure is set on the water inlet side of the filter holder.
- a 50 ml disposable syringe manufactured by Terumo Corporation
- the filter sample is moistened with about 1 ml of ethanol, and then distilled into the disposable syringe.
- Fill with water measure the time for distilled water to fall naturally from a syringe scale of 60 ml to about 30 m, and calculate the amount of water permeated per unit area per unit time of the filter.
- a composite porous film or an etched film punched out into a 25 mm Set in a commercially available filter holder (Swin-Lok TM Filter Holder, manufactured by CORNING) and test the permeability of the blood cell suspension.
- a composite porous membrane set it so that the porous membrane is located on the blood cell suspension liquid inlet side of the filter holder.
- the blood cell suspension used here was previously obtained by removing leukocytes from fresh human whole blood using a coated nonwoven fabric or the like to reduce the leukocyte concentration to 1Z630.
- a 10 ml disposable syringe (made of Thermonet earth) is directly connected to the inlet side of the blood cell suspension of the above filter holder, and it stands upright. Measure the time to fall. It was evaluated as the permeation time of a 2 ml blood cell suspension.
- “Human fresh whole blood” is a filtered CPD solution as anticoagulant (26.3 g of trisodium taenoate dihydrate, 3.27 g of citrate monohydrate, and 23.30 g of glucose) per 100 cm 3 of collected blood. Dissolve 2 g and 2.51 g of sodium dihydrogen phosphate dihydrate in 1 liter of distilled water for injection, filter with a filter having a pore size of 0.2 m), mix in 14 cm 3 pieces, and mix at 20 ° C. Prepare by storing at room temperature for 3 hours.
- the evaluation was performed using an integrated filter configuration as shown in FIG.
- Leukocyte-removing capability the fresh human whole blood 450 cm 3 to the filter device, use a syringe pump V, flushed Te at a constant flow rate 25 cm 3 Z min, from all whole blood recovered after filtration before and filtration certain amount of blood
- the collected leukocyte concentration is measured using a residual leukocyte measurement reagent system, LeucoCO UNT TM kit, flow cytometer FACS Calibur, and analysis software CELL Quest (BD Bioscience, USA).
- the value of the leukocyte removal ability was the average of the respective values calculated from the following equation (1) as a result of performing the blood filtration experiment twice.
- Leukocyte removal ability log (white blood cell concentration of blood cell suspension after filtration Z white blood cell concentration of blood cell suspension before filtration) ⁇ ' ⁇ (1)
- the supporting porous membrane of the composite porous membrane used as the second filter uses the same material as the first filter. Since the amount of the porous membrane used was substantially negligible compared to the first filter, V was calculated by the following equation (2).
- V Wf [(l / d)-(l / p)]---(2)
- d (g / cm 3 ) is the packing density of all the filter media to be filled in the filter holder
- Wf (g) is the weight of the first and second filters to be filled
- p (g / cm 3 ) Means the density of the material forming the supporting porous membrane of the first filter and the second filter (composite porous membrane). For example, if the first filter and the supporting porous membrane are non-woven fabrics made of polyethylene terephthalate, P is about 1.3.
- the polymer yield after purification was 72% by weight.
- GPC measurement standard The number average molecular weight of the polymer obtained by quasi-polystyrene conversion
- Mn 1.2 ⁇ 10 5
- Mw 4.1 ⁇ 10 5
- Mw / Mn 3.4.
- the measurement power of the residual amount of the monomer by the gas chromatography (GC) of the reaction solution after the polymerization was also calculated.
- a 1. Owt% ethanol solution of the HEMAZDMAMA (97Z3 molar ratio) copolymer obtained in 1 above was prepared and used as a coating solution.
- PCL Polyclonal ⁇ - caprolactatone
- PCA polyacrylamide-based amphiphilic polymer
- a solution of lgZL in a hydrophobic organic solvent using (1) as a solute was prepared.
- the weight ratio of the PCLZ polyacrylamide-based amphiphilic polymer was 9Z1.
- 6-Acrylamidohexanoic acid is synthesized by dehydrochlorination of Shii-Dani Atariloyl (manufactured by Aldrich) and 6-aminoaminoacid (manufactured by Aldrich) in an aqueous solvent at 0 ° C. did.
- Dodecyl acryloylamide was synthesized by subjecting a salted atariloyl and dodecylamine (manufactured by Aldrich Co., Ltd.) to a desalted salted hydrogen reaction at 0 ° C in a chloroform solvent.
- the coated nonwoven fabric prepared in 1-2 was cut into a square having a side of 16 cm, immersed in pure water in a beaker, and sufficiently dewatered with an ultrasonic cleaner for 5 minutes to retain water.
- the non-woven fabric water-containing non-woven fabric
- the non-woven fabric that sufficiently holds water is taken out of the beaker, placed on a glass plate, and a lmm-thick metal frame obtained by punching a 15 cm square is cut from the entire punched portion of the metal frame.
- a lmm-thick metal frame obtained by punching a 15 cm square is cut from the entire punched portion of the metal frame.
- the structure of the nonwoven cloth, which is the supporting porous membrane could be observed. It was also observed that fibers constituting the nonwoven fabric penetrated the porous membrane on the surface of the porous membrane, and as a result, the pores were partially closed.
- FIG. 1 A scanning electron micrograph of a cross section of the composite porous membrane is shown in FIG.
- the holes had a spherical through-hole structure swelled in the porous membrane, and it was observed that adjacent holes were communicating with each other.
- HEMAZDMAMA (97Z3 (molar ratio)) based on the composite porous membrane obtained in 1-1
- the coating was applied by dipping for 10 seconds in a 0.1wt% solution of the copolymer (the solvent was ethanol). After immersion, it was sufficiently dried to obtain a coated composite porous membrane.
- a simple blood cell suspension liquid permeability test (permeation time of 2 ml of the blood cell suspension) of the coated composite porous membrane was 30 seconds, which was a better permeation rate than Comparative Example 4 described later.
- a composite porous membrane was produced in the same manner as in 2. of Example 1, except that dichloromethane was used instead of chloroform in the solvent of the hydrophobic organic solvent solution used.
- the porosity, D, ⁇ dZD, the ratio of through-holes, T, and o / T of the porous membrane of the obtained composite porous membrane were as shown in Table 1.
- a composite porous membrane was prepared in the same manner as in Example 1, except that polysulfone (PSU: UDEL P-3500 made by Teijin Acomo Engineering Plastics) was used instead of PCL as the solute of the hydrophobic organic solvent solution to be used. Manufactured.
- PSU polysulfone
- PCL solute of the hydrophobic organic solvent solution to be used.
- the porosity, D, ⁇ dZD, the ratio of through-holes, T, and o / T of the porous membrane of the obtained composite porous membrane were as shown in Table 1.
- Black port as a solute of the hydrophobic organic solvent solution, a PSU instead of PCL, 4GZL polymer concentration, casting the liquid volume 21cm 3, at room temperature 28 ° C, relative humidity of 43% constant temperature and humidity chamber in used Except for removing the form, a composite porous membrane was produced in the same manner as in 2. of Example 1.
- the porosity, D, ⁇ dZD, the ratio of through holes, T, ot / T of the porous membrane of the obtained composite porous membrane were as shown in Table 1.
- a pure water permeability test was 19.6 ml Zcm 2 'min.
- a honeycomb structure porous thin film was formed in the same manner as in 2. of Example 1, except that 11 cm 3 of a hydrophobic organic solvent solution was directly poured into a circular glass dish having a diameter of 15 cm without using the coated nonwoven fabric.
- the porous thin film on the petri dish was peeled off by adding ethanol, attached to a ring-shaped support frame, fixed and taken out.
- the opening ratio, D, ⁇ dZD, the ratio of through-holes,, ⁇ t / T of the obtained porous film having a two-cam structure were as shown in Table 1.
- a pure water permeability test was 18.9 mlZcm 2 'min.
- a honeycomb structure porous thin film was produced in the same manner as in Example 4 except that 11 cm 3 of a hydrophobic organic solvent solution was directly poured into a circular glass dish having a diameter of 15 cm without using the coated nonwoven fabric.
- T was as shown in Table 1.
- a composite porous membrane was produced in the same manner as in Example 4, except that the coated nonwoven fabric was used in a dry state without being hydrated, and 17 ml of a hydrophobic organic solvent solution was cast. From the scanning electron micrograph of the obtained composite porous membrane, it was found that PSU derived from the cast solution had penetrated into the inside of the support membrane, and the pores of the support membrane were partially closed. Also, in the PSU portion of the composite porous membrane on the side where air was blown, a group of holes in the shape of a cam was seen, but most of the nonwoven fabric was exposed or the holes were torn.
- PC polycarbonate
- a HEMAZDMAMA (97Z3 (molar ratio)) copolymer was coated in the same manner as in Example 1, and a simple blood cell suspension permeability test was conducted. As a result, the result was 57 seconds.
- the porosity, D, ⁇ d / D, ⁇ , and ⁇ tZT of the etching film made of PC were as shown in Table 1.
- the ratio of the through-holes was estimated to be almost 100% due to the force manufacturing method, which cannot be confirmed by observing the film plane force due to the large thickness.
- the hole shape of the membrane cross section was cylindrical.
- Example 1-2 one square sample of the same size as the first filter was cut out near the center of the coating composite porous membrane obtained in Example 1-2, and this was used as the second filter one.
- the effective area of the second filter is 45cm 2 ).
- the first filter and the second filter were stacked, and all the filter media were filled in the filter holder so that the packing density became 0.23 gZcm 3 , thereby forming an integrated leukocyte removal filter device.
- the first filter was arranged on the inlet side of the treated blood cell suspension, and the supporting porous membrane of the second filter was arranged on the outlet side of the treated blood cell.
- Wf is calculated as the weight of 17 square nonwoven fabric samples using the above formula (2).
- the filter medium volume V was 12 cm 3 .
- Table 2 shows the above results. Compared with Comparative Example 5 described below, the volume of the filter medium has been significantly reduced despite maintaining the same leukocyte-removing ability, and the leukocyte-removing filter device that can greatly reduce the amount of blood cell suspension loss It can be seen that was obtained.
- Example 6 Except that the two coated composite porous membranes obtained in 2. of Example 1 were used as a second filter, and the first filter was obtained using 15 coated nonwoven fabrics manufactured in 1-2 of Example 1. In the same manner as in Example 6, a leukocyte removal filter device was manufactured.
- the packing density of all the filter media was 0.23 g / cm 3
- the volume of the filter media was 12 cm 3 (first filter + two support membranes).
- the composite porous membrane obtained in Example 2 was coated with a HEMA / DMAMA (97/3 (molar ratio)) Coating was carried out by dipping in a 0.1% wt solution of Rimmer (solvent: ethanol) for 10 seconds, then taking out and drying to obtain a coated composite porous membrane.
- a leukocyte removal filter device was manufactured in the same manner as in Example 6, except that one coated composite porous membrane was used as the second filter.
- the packing density of all the filter media was 0.23 g / cm 3
- the volume of the filter media was 12 cm 3 (first filter + two support membranes).
- Example 1 2 obtained in HEMAZDMAMA (97Z3 (molar ratio)) copolymer was coated nonwoven of Example 1, a square nonwoven sample (effective filter size as a filter effective area 45cm 2 6. 7cm X 6. 7cm )
- a filter holder was filled in a filter holder to form a leukocyte removal filter device (filling density 0.23 g / cm 3 ) 0
- the composite porous membrane that is, the second filter
- the volume of the filter medium was 24 cm 3
- the effective area of the filter was 45 cm 2 .
- Table 2 shows the results. Although the leukocyte removal ability is high, the volume of the filter medium is twice as large as that of Example 5.
- Example 5 In the same manner as in Example 5, except that the number of coated nonwoven fabrics constituting the first filter was set to three and the number of coated composite porous membranes constituting the second filter was set to two, A leukocyte removal device was manufactured.
- the leukocyte-removing ability of the first filter was 0.5, and the volume of the filter medium (the first filter + the support membrane of the composite porous membrane) of the finally constituted integrated leukocyte-removing filter device was 2 cm 3 .
- the composite porous membrane produced in Example 3 was cut out into a 13 mm ⁇ circular shape, and a glass ring (made by Asahi Technoglass Co., Ltd. -Ring ring, inner diameter 10mm, outer diameter 12mm, height 10mm) was adhered to the porous membrane surface of the punched circular composite porous membrane, and processed into a cup shape.
- the cup-shaped culture vessel was air-dried and vacuum-dried, and then sterilized by autoclaving at 121 ° C for 10 minutes.
- the autoclaved cup-shaped culture vessel was immersed in a 0.3% type I collagen aqueous solution (CELLGENI-PC manufactured by Koken Co., Ltd.) and air-dried to obtain a collagen-coated cup-type culture vessel.
- the cup-type incubator was taken out, and 5 ml of a 0.05% trypsin solution was passed therethrough. Then, 10 ml of the culture solution was further passed to collect the cells in the supporting porous membrane. The number of cells in the recovered solution was counted under a phase-contrast optical microscope using a hemocytometer. As a result, the number of cells grew three-fold, and it became clear that the number of cells increased.
- the cup-type incubator in which culturing was performed was removed, and the cells were fixed with a 2% aqueous solution of dartartaldehyde, and then the composite porous membrane was cut off using the cup-type culture vessel.
- the cross section of the cut composite porous membrane was observed with a scanning electron microscope to examine the distribution of cells in the supporting porous membrane. As a result, it was observed that cells were packed in the vicinity of the porous membrane, and that cells were present in other parts of the supporting porous membrane.
- a cup-type incubator was prepared, sterilized, and collagen-coated in the same manner as 1. in Example 8 using an etching film made of polycarbonate (PC) and a membrane filter made by Millipore.
- PC polycarbonate
- the cells were cultured for 2 days in the same manner as in 2 to 2 of Example 8, the cells were collected using a trypsin solution, and the number of cells was counted. As a result, the cells had doubled.
- a collagen-coated cup-type incubator manufactured in the same manner as 1 in Example 8 was introduced with 1 ⁇ 10 4 human childhood cervix adenocarcinoma cells Z100 1 in the same manner as in 2-1 in Example 8. . 30 minutes after the introduction, place the cup-type incubator in the well of a 24-well polystyrene culture plate with the supporting porous membrane facing down, add 1 ml of the culture solution, and incubate for 2 days in the incubator. .
- the supporting porous membrane serves as a scaffold for the cells, so that the cells are retained in the composite porous membrane that does not easily fall off, and thus are collected.
- the number of cells was large. From these results, it was strongly suggested that the subsequent seeding of the second cells on the porous membrane could be performed very easily.
- a collagen-coated cup-type incubator was prepared using an etching film made of polycarbonate (PC) (Millipore, Isopore Membrane Filter). Cancer cell 1 ⁇ 10 4 cells Cell suspension 100 1 of ZlOO / z 1 is dropped on the etching film with the etching film side of the cup-type incubator facing upward, and the etching film is kept up for 30 minutes Then, the membrane surface was placed in a sterile state while being careful not to dry.
- PC polycarbonate
- the solution was placed in a well of a 24-well polystyrene culture plate with the etching film part facing down, and 1 ml of the culture solution was removed and cultured in an incubator for 2 days. Two days later, as in Example 8, the cells adhered to the etching film were collected using a trypsin solution, and the number of cells was counted. As a result, the cell number was increased to 0.5 times. When the etching membrane was placed in the well, it is likely that many cells were shed.
- Sickle example 4 Chloro 4 21 PSU 35 6.80.1 5 72 6.50.27 ⁇ ⁇ ⁇ 19.6
- Lum cloth (hydrated)
- Lum cloth (dislike
- the composite porous membrane of the present invention has a pore size on the order of m, high uniformity, a high porosity, has a structure with high filtration efficiency inside the membrane, and has sufficient mechanical strength due to the support membrane. I have. Therefore, in applications that require filtration (separation and recovery) of objects on the m-order, such as various cells, bacteria, and yeast, as well as applications that require precise size separation on the m-order, main filters, prefilters, Or it can be widely used as a final filter.
- a composite porous membrane alone or in combination with a conventional filter medium can be used as a leukocyte removal filter for whole blood, red blood cell preparations, platelet preparations, plasma preparations, and the like.
- It can be used as a filter for separating blood cells such as erythrocyte separation, leukocyte separation, platelet separation, etc., and also for whole blood as a plasma separation filter.
- the volume of the filter medium when removing leukocytes, can be significantly reduced while maintaining high leukocyte removal ability.
- Platinum products, plasma products, etc. can greatly reduce the amount of loss during filtration, greatly improving the cost performance of blood products, etc. in medical practice.
- various effects are exhibited, such as cost reduction on the side of the medical device, and a thin product, which can improve the efficiency of the storage space at the medical site and improve the workability of the user.
- an IV filter to remove contaminants (bacteria and particulate matter) from peripheral blood, cord blood, bone marrow and other hematopoietic stem cell sources
- Leukocyte cell collection filter, mononuclear cell collection filter, hematopoietic stem cell collection filter, cell separation filter in the field of regenerative medicine for various organs It is also possible to use as.
- the diaphragm for cell culture of the present invention is used when the growth of useful useful cells is controlled by cell-to-cell contact with different cells (for example, when proliferation is suppressed while suppressing differentiation) Later, it is effectively used as a cell culture diaphragm when it is desired to selectively recover only useful cells.
- it is highly effective in the field of regenerative medicine and blood transfusion (clean blood transfusion using cultured blood cells) because hematopoietic stem cells can be proliferated in large quantities without separation using this cell culture diaphragm. It is expected to be used for In addition, it is expected to be similarly effective in the field of regenerative medicine and cell therapy by the proliferation of organ-specific stem cells.
- the composite porous membrane of the present invention can be used as a uniform dispersion medium such as ink in the field of electronic materials such as a master in stencil printing.
- FIG. 1 is a scanning electron micrograph ( ⁇ 1000) of the surface of the composite porous membrane obtained in Example 1 on the porous membrane side.
- FIG. 2 is a scanning electron micrograph ( ⁇ 3000) of the surface of the composite porous membrane obtained in Example 1 on the porous membrane side.
- FIG. 3 is a scanning electron micrograph ( ⁇ 3000) of a cross section of the composite porous membrane obtained in Example 1.
- FIG. 4 is a conceptual diagram of a cross section of a porous membrane having a spherical through-hole bulging inside.
- FIG. 5 is a conceptual diagram of a body type leukocyte removal filter device.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Vascular Medicine (AREA)
- Heart & Thoracic Surgery (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biotechnology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Hematology (AREA)
- Cardiology (AREA)
- Anesthesiology (AREA)
- Cell Biology (AREA)
- General Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Microbiology (AREA)
- Separation Using Semi-Permeable Membranes (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- External Artificial Organs (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
Abstract
Description
Claims
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP04771202.1A EP1666129B1 (en) | 2003-08-07 | 2004-08-04 | Composite porous membrane |
JP2005512939A JP4863714B2 (ja) | 2003-08-07 | 2004-08-04 | 複合多孔膜とその製造方法 |
US10/567,022 US8999167B2 (en) | 2003-08-07 | 2004-08-04 | Composite porous membrane and process for producing the same |
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2003288882 | 2003-08-07 | ||
JP2003-288882 | 2003-08-07 | ||
JP2003-358980 | 2003-10-20 | ||
JP2003358980 | 2003-10-20 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2005014149A1 true WO2005014149A1 (ja) | 2005-02-17 |
Family
ID=34137925
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/JP2004/011165 WO2005014149A1 (ja) | 2003-08-07 | 2004-08-04 | 複合多孔膜とその製造方法 |
Country Status (4)
Country | Link |
---|---|
US (1) | US8999167B2 (ja) |
EP (1) | EP1666129B1 (ja) |
JP (2) | JP4863714B2 (ja) |
WO (1) | WO2005014149A1 (ja) |
Cited By (22)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2008132861A1 (ja) * | 2007-04-23 | 2008-11-06 | Olympus Corporation | 培養用容器、細胞又は組織の培養方法、及び細胞又は組織の解析方法 |
JP2009207430A (ja) * | 2008-03-05 | 2009-09-17 | Asahi Kasei Corp | 複合膜とその製造方法 |
WO2009128435A1 (ja) * | 2008-04-14 | 2009-10-22 | 旭化成メディカル株式会社 | 凝集物除去フィルター材及び血液製剤のろ過方法 |
JP2009242495A (ja) * | 2008-03-28 | 2009-10-22 | Fujifilm Corp | 多孔フィルム |
WO2009139177A1 (ja) | 2008-05-15 | 2009-11-19 | 国立大学法人大阪大学 | 血小板の誘導方法 |
US20090301957A1 (en) * | 2006-09-06 | 2009-12-10 | Massimo Bertolucci | Filter for the removal of substances from blood products |
WO2014192803A1 (ja) * | 2013-05-31 | 2014-12-04 | 学校法人同志社 | 組織再生基材 |
JP2015065942A (ja) * | 2013-09-30 | 2015-04-13 | 富士フイルム株式会社 | 細胞培養担体および細胞培養容器 |
JP2015065946A (ja) * | 2013-09-30 | 2015-04-13 | 富士フイルム株式会社 | 細胞培養担体および細胞培養容器 |
JP2015528300A (ja) * | 2012-09-12 | 2015-09-28 | ザトーリウス ステディム ビオテーク ゲーエムベーハー | 組み合わせたフィルター |
KR101648487B1 (ko) * | 2015-06-23 | 2016-08-17 | 주식회사 아모그린텍 | 주사기용 안전필터 |
JP2016182553A (ja) * | 2015-03-26 | 2016-10-20 | 東京応化工業株式会社 | 積層膜 |
KR101675865B1 (ko) * | 2015-06-23 | 2016-11-15 | 주식회사 아모라이프사이언스 | 안전필터, 그 제조방법 및 이를 구비한 주사기 |
WO2017199993A1 (ja) * | 2016-05-17 | 2017-11-23 | 日東電工株式会社 | 分離デバイス |
WO2018037841A1 (ja) * | 2016-08-24 | 2018-03-01 | 富士フイルム株式会社 | 細胞処理装置および細胞処理方法 |
JP2018083914A (ja) * | 2016-11-25 | 2018-05-31 | 三菱ケミカル株式会社 | 多孔質膜 |
US10137665B2 (en) | 2016-01-14 | 2018-11-27 | Tokyo Ohka Kogyo Co., Ltd. | Method for manufacturing laminate, and laminate |
JPWO2018135252A1 (ja) * | 2017-01-18 | 2019-11-07 | 国立研究開発法人農業・食品産業技術総合研究機構 | 半透膜及びその使用 |
WO2021215205A1 (ja) * | 2020-04-22 | 2021-10-28 | 住友化学株式会社 | 多孔質セラミックス積層体及びその製造方法 |
JP2021533736A (ja) * | 2018-08-16 | 2021-12-09 | テルモ株式会社 | 細胞培養基材 |
JP2021533735A (ja) * | 2018-08-16 | 2021-12-09 | テルモ株式会社 | 細胞培養基材 |
WO2022168578A1 (ja) * | 2021-02-05 | 2022-08-11 | 東レ株式会社 | 積層体の製造方法、高分子薄膜の製造方法、および積層体 |
Families Citing this family (51)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR100709640B1 (ko) | 2003-12-04 | 2007-04-24 | 아사히 가세이 일렉트로닉스 가부시끼가이샤 | 이방 도전성 접착 시트 및 접속 구조체 |
WO2006119251A2 (en) | 2005-04-29 | 2006-11-09 | University Of Rochester | Ultrathin porous nanoscale membranes, methods of making, and uses thereof |
WO2006119252A2 (en) * | 2005-04-29 | 2006-11-09 | University Of Rochester | Ultrathin nanoscale membranes, methods of making, and uses thereof |
US8119394B2 (en) * | 2006-03-14 | 2012-02-21 | University Of Rochester | Cell culture devices having ultrathin porous membrane and uses thereof |
US7923054B2 (en) | 2006-04-19 | 2011-04-12 | Gore Enterprise Holdings, Inc. | Functional porous substrates for attaching biomolecules |
FR2912740B1 (fr) * | 2007-02-21 | 2012-02-17 | Cougoulic Catherine Cadorel | Materiau composite poreux a usage biomedical |
NL2002870C2 (en) * | 2009-05-11 | 2010-11-15 | Fluxxion B V | Method and device for desorbing a component from a liquid into a gas. |
US20100291534A1 (en) * | 2009-05-12 | 2010-11-18 | National Central University | Methods and Systems for Isolating, Ex Vivo Expanding and Harvesting Hematopoietic Stem Cells |
JP5461948B2 (ja) * | 2009-10-13 | 2014-04-02 | 旭化成メディカル株式会社 | 体外循環用白血球除去器 |
KR20130024950A (ko) * | 2010-06-16 | 2013-03-08 | 닛토덴코 가부시키가이샤 | 방수 통기 필터 및 그의 용도 |
KR101967934B1 (ko) | 2010-06-16 | 2019-04-10 | 닛토덴코 가부시키가이샤 | 방수 통기 필터 및 그의 용도 |
IT1401316B1 (it) * | 2010-08-06 | 2013-07-18 | Gvs Spa | Filtro perfezionato per la rimozione di sostanze dal sangue o da emoderivati e metodo per il suo ottenimento |
RU2446863C1 (ru) * | 2010-09-10 | 2012-04-10 | Сергей Михайлович Кузьмин | Способ изготовления мембранного фильтра |
SG194779A1 (en) | 2011-05-04 | 2013-12-30 | Univ Cornell | Multiblock copolymer films, methods of making same, and uses thereof |
CZ303453B6 (cs) * | 2011-07-14 | 2012-09-19 | Elmarco S.R.O. | Substrát pro kultivaci bunek a zpusob jeho výroby |
EP2545984A1 (en) * | 2011-07-15 | 2013-01-16 | Gambro Lundia AB | Composite membrane |
KR101360393B1 (ko) * | 2012-03-14 | 2014-02-11 | (주)동양화학 | 기공크기가 제어된 금속메쉬필터 제조방법 및 그 방법으로 제조된 금속메쉬필터 |
KR101295826B1 (ko) | 2012-04-19 | 2013-08-12 | 중앙대학교 산학협력단 | 나노기공을 가지는 고분자 또는 고분자복합재료 멤브레인 및 그 제조방법 |
EP2859904A4 (en) * | 2012-06-11 | 2015-07-22 | Asahi Kasei Medical Co Ltd | SEPARATION MEMBRANE FOR BLOOD TREATMENT AND BLOOD TREATMENT DEVICE INCORPORATING THE SAME MEMBRANE |
KR101727632B1 (ko) * | 2013-04-05 | 2017-04-17 | 인하대학교 산학협력단 | 광합성 미생물 대량배양을 위한 광생물 반응기 |
US9782707B2 (en) | 2014-03-24 | 2017-10-10 | Fenwal, Inc. | Biological fluid filters having flexible walls and methods for making such filters |
US10376627B2 (en) | 2014-03-24 | 2019-08-13 | Fenwal, Inc. | Flexible biological fluid filters |
US9968738B2 (en) | 2014-03-24 | 2018-05-15 | Fenwal, Inc. | Biological fluid filters with molded frame and methods for making such filters |
US9796166B2 (en) | 2014-03-24 | 2017-10-24 | Fenwal, Inc. | Flexible biological fluid filters |
US10159778B2 (en) | 2014-03-24 | 2018-12-25 | Fenwal, Inc. | Biological fluid filters having flexible walls and methods for making such filters |
EP3185995B1 (en) * | 2014-07-22 | 2021-09-29 | Diomics Corporation | Air flow system and method for collecting an airborne agent |
US20170266362A1 (en) | 2014-08-26 | 2017-09-21 | 3M Innovative Properties Company | System for removal of pro-inflammatory mediators as well as granulocytes and monocytes from blood |
JP2016195986A (ja) * | 2015-04-06 | 2016-11-24 | 富士フイルム株式会社 | ろ材、フィルタユニット、及び細胞シート |
HUE056208T2 (hu) * | 2015-05-27 | 2022-02-28 | Mitsubishi Chem Corp | Hidrofilizált pórusos fluorpolimer film |
WO2016208922A1 (ko) * | 2015-06-23 | 2016-12-29 | 주식회사 아모라이프사이언스 | 안전필터, 그 제조방법 및 이를 구비한 주사기 |
CN105039257A (zh) * | 2015-07-24 | 2015-11-11 | 深圳爱生再生医学科技有限公司 | 造血干细胞的体外扩增培养方法 |
WO2017078043A1 (ja) * | 2015-11-05 | 2017-05-11 | 栄研化学株式会社 | フィルタ付き注出部材 |
US9737859B2 (en) * | 2016-01-11 | 2017-08-22 | Lg Nanoh2O, Inc. | Process for improved water flux through a TFC membrane |
TWI708684B (zh) * | 2016-01-14 | 2020-11-01 | 日商東京應化工業股份有限公司 | 積層體之製造方法、及積層體 |
JP6763374B2 (ja) * | 2016-01-29 | 2020-09-30 | 東レ株式会社 | 分離膜 |
KR102558002B1 (ko) | 2016-02-17 | 2023-07-20 | 삼성전자주식회사 | 필터 및 이를 포함하는 장치 |
EP3448551A1 (en) | 2016-04-28 | 2019-03-06 | Terapore Technologies, Inc. | Charged isoporous materials for electrostatic separations |
US20190264156A1 (en) * | 2016-07-25 | 2019-08-29 | Ube Industries, Ltd. | Siphon type cultivation method |
EP3489348A4 (en) * | 2016-07-25 | 2020-04-15 | UBE Industries, Ltd. | CELL CULTURE MODULE |
US9768104B1 (en) | 2016-08-19 | 2017-09-19 | International Business Machines Corporation | Method and structure to fabricate a nanoporous membrane |
EP3521417A4 (en) | 2016-09-27 | 2019-10-16 | FUJIFILM Corporation | METHOD FOR THE PRODUCTION OF CELL TISSUE AND POROUS FILM |
KR102596197B1 (ko) | 2016-11-17 | 2023-11-02 | 테라포어 테크놀로지스, 인코포레이티드 | 고 분자량 친수성 첨가제를 포함하는 이소포러스 자기-조립 블록 공중합체 필름 및 이의 제조방법 |
JP7053678B2 (ja) | 2017-02-22 | 2022-04-12 | テラポア テクノロジーズ,インコーポレイテッド | リガンド結合mbp膜、使用及び製造方法 |
CA3057439A1 (en) * | 2017-03-23 | 2018-09-27 | Ube Industries, Ltd. | Inhibiting and inducing differentiation of neural stem cells |
CN110621394A (zh) | 2017-05-12 | 2019-12-27 | 特拉波雷技术有限公司 | 耐化学性氟化多嵌段聚合物结构、制造方法和用途 |
WO2019013519A1 (ko) * | 2017-07-10 | 2019-01-17 | 주식회사 아모라이프사이언스 | 세포배양 지지체용 멀티레이어 원단 |
EP3691775A1 (en) | 2017-10-05 | 2020-08-12 | Fresenius Medical Care Holdings, Inc. | Polysulfone-urethane copolymer, membranes and products incorporating same, and methods for making and using same |
WO2019113596A1 (en) * | 2017-12-08 | 2019-06-13 | The Trustees Of Columbia University In The City Of New York | Scalable method of fabricating structured polymers for passive daytime radiative cooling and other applications |
EP3765179A4 (en) | 2018-03-12 | 2021-12-29 | Terapore Technologies, Inc. | Isoporous mesoporous asymmetric block copolymer materials with macrovoids and method of making the same |
JP7291599B2 (ja) * | 2019-10-17 | 2023-06-15 | 日産自動車株式会社 | ガス分離膜用塗工液及びこれを用いたガス分離膜の製造方法 |
US20230139619A1 (en) * | 2021-10-28 | 2023-05-04 | Southwest Research Institute | Devices for cell separation |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH07204477A (ja) * | 1994-01-19 | 1995-08-08 | Nkk Corp | 気体分離膜の製造方法 |
JP2001252540A (ja) * | 2000-03-10 | 2001-09-18 | Toray Ind Inc | 逆浸透複合膜 |
Family Cites Families (33)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3912834A (en) | 1972-06-05 | 1975-10-14 | Kanegafuchi Chemical Ind | Process for producing a selectively permeable composite |
JPS5446811A (en) | 1977-09-20 | 1979-04-13 | Asahi Chem Ind Co Ltd | Method for removing leukocytes from blood |
JPS56135525A (en) | 1980-03-27 | 1981-10-23 | Mitsubishi Rayon Co Ltd | Production of porous membrane |
US4673504A (en) * | 1980-10-27 | 1987-06-16 | Cuno Inc. | Charge modified microporous membrane |
US4936998A (en) * | 1986-03-28 | 1990-06-26 | Asahi Medical Co., Ltd. | Filter medium for selectively removing leucocytes |
JPH0712416B2 (ja) * | 1986-07-17 | 1995-02-15 | 東洋紡績株式会社 | 中空糸型物質分離膜 |
JPH02180625A (ja) | 1989-01-06 | 1990-07-13 | Sumitomo Electric Ind Ltd | 多孔性高分子膜 |
JPH0825886B2 (ja) * | 1989-07-14 | 1996-03-13 | テルモ株式会社 | 白血球捕捉用フィルター材およびその製造方法 |
IT1248934B (it) * | 1990-06-01 | 1995-02-11 | Fidia Spa | Membrane forate biocompatibili,processi per la loro preparazione,loro impiego come supporto per la crescita in vitro di cellule epiteliali, pelli artificiali cosi' ottenute e loro impiego nei trapianti di pelle |
JP3172542B2 (ja) * | 1990-06-25 | 2001-06-04 | テルモ株式会社 | 白血球捕捉用フィルター材及びその製造方法 |
ES2189787T3 (es) * | 1990-09-25 | 2003-07-16 | Asahi Medical Co | Metodo y sistema de filtracion para eliminacion de leucocitos. |
US5171445A (en) | 1991-03-26 | 1992-12-15 | Memtec America Corporation | Ultraporous and microporous membranes and method of making membranes |
JPH04317732A (ja) | 1991-04-17 | 1992-11-09 | Tokuyama Soda Co Ltd | アニオン荷電型半透性複合膜 |
JPH0534337A (ja) | 1991-07-26 | 1993-02-09 | Terumo Corp | 白血球分離用フイルター |
US5240615A (en) * | 1991-08-20 | 1993-08-31 | Fishman Jerry H | Composite membrane composed of microporous polyvinylidene difluoride membrane laminated to porous support and process for its preparation |
US5522991A (en) * | 1994-07-20 | 1996-06-04 | Millipore Investment Holdings Limited | Cellulosic ultrafiltration membrane |
JPH08311231A (ja) * | 1995-05-17 | 1996-11-26 | Toyota Central Res & Dev Lab Inc | ハニカム状多孔質体及びその製造方法 |
US5665596A (en) * | 1995-07-31 | 1997-09-09 | Becton, Dickinson And Company | Device for cell co-culture and method for its use in culturing cells |
JPH10295369A (ja) | 1997-02-26 | 1998-11-10 | Japan Tobacco Inc | 造血幹細胞の製造方法 |
US6280791B1 (en) * | 1997-04-11 | 2001-08-28 | Cuno, Inc. | Process of making a three-region reinforced microporous filtration membrane |
JP4431233B2 (ja) * | 1999-11-30 | 2010-03-10 | テルモ株式会社 | ハニカム構造体およびその調製方法、ならびにその構造体を用いたフィルムおよび細胞培養基材 |
US6645388B2 (en) * | 1999-12-22 | 2003-11-11 | Kimberly-Clark Corporation | Leukocyte depletion filter media, filter produced therefrom, method of making same and method of using same |
JP2001238681A (ja) * | 2000-03-03 | 2001-09-04 | Japan Science & Technology Corp | 共培養による血液脳関門再構築モデル |
DE10058258B4 (de) * | 2000-11-23 | 2005-01-27 | Goedel, Werner Andreas | Poröse Membranen, deren Herstellung und Verwendung |
US20030150808A1 (en) * | 2001-02-16 | 2003-08-14 | Hirofumi Morikawa | Separating film, separating film element, separating film module, sewage and waste water treatment device, and separating film manufacturing method |
JP4752993B2 (ja) | 2001-09-10 | 2011-08-17 | 日産化学工業株式会社 | ポリイミド多孔質膜およびその製造法 |
JP4148897B2 (ja) * | 2001-10-31 | 2008-09-10 | 旭化成株式会社 | 胚性幹細胞培養用基材および培養方法 |
JP2003149096A (ja) | 2001-11-07 | 2003-05-21 | Fuji Photo Film Co Ltd | 血液濾過膜および方法 |
US7410066B2 (en) * | 2001-12-03 | 2008-08-12 | Ashai Kasei Medical Co., Ltd | Filter for selectively eliminating leukocytes |
US6943021B2 (en) * | 2002-06-07 | 2005-09-13 | Mattek Corporation | Three dimensional vaginal tissue model containing immune cells |
EP1582329A4 (en) * | 2002-11-27 | 2006-12-20 | Japan Science & Tech Agency | MICROVOLUTION STRUCTURE AND ITS MANUFACTURING METHOD |
JP2004236788A (ja) | 2003-02-05 | 2004-08-26 | Asahi Kasei Corp | 白血球除去血球浮遊液の製造方法、及び白血球除去フィルター装置 |
EP1479760A1 (de) * | 2003-05-19 | 2004-11-24 | ProBioGen AG | Künstliches Immunorgan |
-
2004
- 2004-08-04 WO PCT/JP2004/011165 patent/WO2005014149A1/ja active Application Filing
- 2004-08-04 US US10/567,022 patent/US8999167B2/en not_active Expired - Fee Related
- 2004-08-04 EP EP04771202.1A patent/EP1666129B1/en not_active Not-in-force
- 2004-08-04 JP JP2005512939A patent/JP4863714B2/ja not_active Expired - Fee Related
-
2011
- 2011-08-10 JP JP2011174859A patent/JP5566348B2/ja not_active Expired - Fee Related
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH07204477A (ja) * | 1994-01-19 | 1995-08-08 | Nkk Corp | 気体分離膜の製造方法 |
JP2001252540A (ja) * | 2000-03-10 | 2001-09-18 | Toray Ind Inc | 逆浸透複合膜 |
Cited By (31)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20090301957A1 (en) * | 2006-09-06 | 2009-12-10 | Massimo Bertolucci | Filter for the removal of substances from blood products |
WO2008132861A1 (ja) * | 2007-04-23 | 2008-11-06 | Olympus Corporation | 培養用容器、細胞又は組織の培養方法、及び細胞又は組織の解析方法 |
JP2009207430A (ja) * | 2008-03-05 | 2009-09-17 | Asahi Kasei Corp | 複合膜とその製造方法 |
JP2009242495A (ja) * | 2008-03-28 | 2009-10-22 | Fujifilm Corp | 多孔フィルム |
US8932470B2 (en) | 2008-04-14 | 2015-01-13 | Asahi Kasei Medical Co., Ltd. | Filter material for removing aggregates and method of filtering blood product |
WO2009128435A1 (ja) * | 2008-04-14 | 2009-10-22 | 旭化成メディカル株式会社 | 凝集物除去フィルター材及び血液製剤のろ過方法 |
WO2009139177A1 (ja) | 2008-05-15 | 2009-11-19 | 国立大学法人大阪大学 | 血小板の誘導方法 |
JP2009297023A (ja) * | 2008-05-15 | 2009-12-24 | Asahi Kasei Corp | 血小板の誘導方法 |
EP2298865A1 (en) * | 2008-05-15 | 2011-03-23 | Osaka University | Blood platelet induction method |
EP2298865A4 (en) * | 2008-05-15 | 2012-06-27 | Univ Osaka | METHOD OF INDUCING BLOOD PLAQUETTES |
US8535943B2 (en) | 2008-05-15 | 2013-09-17 | Osaka University | Blood platelet induction method |
JP2015528300A (ja) * | 2012-09-12 | 2015-09-28 | ザトーリウス ステディム ビオテーク ゲーエムベーハー | 組み合わせたフィルター |
US9963668B2 (en) | 2012-09-12 | 2018-05-08 | Sartorius Stedim Biotech Gmbh | Combined filter |
WO2014192803A1 (ja) * | 2013-05-31 | 2014-12-04 | 学校法人同志社 | 組織再生基材 |
JP2015065946A (ja) * | 2013-09-30 | 2015-04-13 | 富士フイルム株式会社 | 細胞培養担体および細胞培養容器 |
US9677037B2 (en) | 2013-09-30 | 2017-06-13 | Fujifilm Corporation | Cell culture carrier and cell culture vessel |
JP2015065942A (ja) * | 2013-09-30 | 2015-04-13 | 富士フイルム株式会社 | 細胞培養担体および細胞培養容器 |
JP2016182553A (ja) * | 2015-03-26 | 2016-10-20 | 東京応化工業株式会社 | 積層膜 |
KR101648487B1 (ko) * | 2015-06-23 | 2016-08-17 | 주식회사 아모그린텍 | 주사기용 안전필터 |
KR101675865B1 (ko) * | 2015-06-23 | 2016-11-15 | 주식회사 아모라이프사이언스 | 안전필터, 그 제조방법 및 이를 구비한 주사기 |
US10137665B2 (en) | 2016-01-14 | 2018-11-27 | Tokyo Ohka Kogyo Co., Ltd. | Method for manufacturing laminate, and laminate |
WO2017199993A1 (ja) * | 2016-05-17 | 2017-11-23 | 日東電工株式会社 | 分離デバイス |
WO2018037841A1 (ja) * | 2016-08-24 | 2018-03-01 | 富士フイルム株式会社 | 細胞処理装置および細胞処理方法 |
JP2018083914A (ja) * | 2016-11-25 | 2018-05-31 | 三菱ケミカル株式会社 | 多孔質膜 |
JPWO2018135252A1 (ja) * | 2017-01-18 | 2019-11-07 | 国立研究開発法人農業・食品産業技術総合研究機構 | 半透膜及びその使用 |
JP7112736B2 (ja) | 2017-01-18 | 2022-08-04 | 国立研究開発法人農業・食品産業技術総合研究機構 | 半透膜及びその使用 |
JP2021533736A (ja) * | 2018-08-16 | 2021-12-09 | テルモ株式会社 | 細胞培養基材 |
JP2021533735A (ja) * | 2018-08-16 | 2021-12-09 | テルモ株式会社 | 細胞培養基材 |
JP7315653B2 (ja) | 2018-08-16 | 2023-07-26 | テルモ株式会社 | 細胞培養基材 |
WO2021215205A1 (ja) * | 2020-04-22 | 2021-10-28 | 住友化学株式会社 | 多孔質セラミックス積層体及びその製造方法 |
WO2022168578A1 (ja) * | 2021-02-05 | 2022-08-11 | 東レ株式会社 | 積層体の製造方法、高分子薄膜の製造方法、および積層体 |
Also Published As
Publication number | Publication date |
---|---|
EP1666129A1 (en) | 2006-06-07 |
JP5566348B2 (ja) | 2014-08-06 |
US20070029256A1 (en) | 2007-02-08 |
JPWO2005014149A1 (ja) | 2007-09-27 |
JP2012006010A (ja) | 2012-01-12 |
EP1666129A4 (en) | 2009-07-15 |
JP4863714B2 (ja) | 2012-01-25 |
US8999167B2 (en) | 2015-04-07 |
EP1666129B1 (en) | 2017-06-21 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5566348B2 (ja) | 複合多孔膜とその製造方法 | |
CA2724043C (en) | Blood platelet induction method | |
JP4252449B2 (ja) | 白血球除去フィルター素材コート用ポリマー及びフィルター材 | |
Kikuchi et al. | Nanostructured designs of biomedical materials: applications of cell sheet engineering to functional regenerative tissues and organs | |
US8491561B2 (en) | Micromachined bilayer unit of engineered tissues | |
Teotia et al. | Bifunctional polysulfone-chitosan composite hollow fiber membrane for bioartificial liver | |
KR19980702494A (ko) | 백혈구 제거 필터재 | |
WO2005034624A2 (en) | Microfabricated compositions and processes for engineering tissues containing multiple cell types | |
JP6628416B2 (ja) | 細胞培養方法 | |
US20100216240A1 (en) | Non-invasive automated cell proliferation apparatus | |
JP4992115B2 (ja) | 複合膜とその製造方法 | |
JP7023717B2 (ja) | 半透膜及びその製造方法 | |
Ray et al. | Surface engineering of a bioartificial membrane for its application in bioengineering devices | |
JP2009254271A (ja) | 心筋細胞の誘導方法 | |
JP2004236788A (ja) | 白血球除去血球浮遊液の製造方法、及び白血球除去フィルター装置 | |
JP7454596B2 (ja) | 分離基材、細胞分離フィルターおよび血小板の製造方法 | |
JP2003284767A (ja) | 組織工学用スキャホールド材及び人工血管 | |
Groth et al. | Biomedical Application of Membranes in Bioartificial Organs and Tissue Engineering | |
JP2001078757A (ja) | 細胞分離方法及び細胞分離用流体 | |
JP2006025635A (ja) | 多孔質の支持体に細胞を内在化させる方法、器具または装置 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AK | Designated states |
Kind code of ref document: A1 Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BW BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE EG ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NA NI NO NZ OM PG PH PL PT RO RU SC SD SE SG SK SL SY TJ TM TN TR TT TZ UA UG US UZ VC VN YU ZA ZM ZW |
|
AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): BW GH GM KE LS MW MZ NA SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IT LU MC NL PL PT RO SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG |
|
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
REEP | Request for entry into the european phase |
Ref document number: 2004771202 Country of ref document: EP |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2004771202 Country of ref document: EP |
|
WWP | Wipo information: published in national office |
Ref document number: 2004771202 Country of ref document: EP |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2005512939 Country of ref document: JP |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2007029256 Country of ref document: US Ref document number: 10567022 Country of ref document: US |
|
WWP | Wipo information: published in national office |
Ref document number: 10567022 Country of ref document: US |