WO2000025884A1 - A chromatographic process utilizing a fluidised bed - Google Patents
A chromatographic process utilizing a fluidised bed Download PDFInfo
- Publication number
- WO2000025884A1 WO2000025884A1 PCT/SE1999/001965 SE9901965W WO0025884A1 WO 2000025884 A1 WO2000025884 A1 WO 2000025884A1 SE 9901965 W SE9901965 W SE 9901965W WO 0025884 A1 WO0025884 A1 WO 0025884A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- liquid
- density
- steps
- anyone
- particles
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 51
- 239000007788 liquid Substances 0.000 claims abstract description 139
- 239000002245 particle Substances 0.000 claims abstract description 47
- 150000001875 compounds Chemical class 0.000 claims abstract description 33
- 238000005406 washing Methods 0.000 claims description 15
- 238000004140 cleaning Methods 0.000 claims description 13
- 239000000126 substance Substances 0.000 claims description 11
- 238000011067 equilibration Methods 0.000 claims description 10
- 230000008929 regeneration Effects 0.000 claims description 8
- 238000011069 regeneration method Methods 0.000 claims description 8
- 241001465754 Metazoa Species 0.000 claims description 7
- 150000001720 carbohydrates Chemical class 0.000 claims description 6
- 125000004122 cyclic group Chemical group 0.000 claims description 4
- 230000000694 effects Effects 0.000 claims description 4
- 150000003839 salts Chemical class 0.000 claims description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 18
- 239000003795 chemical substances by application Substances 0.000 description 16
- 239000000243 solution Substances 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 238000002156 mixing Methods 0.000 description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000013060 biological fluid Substances 0.000 description 5
- 238000004587 chromatography analysis Methods 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 235000018102 proteins Nutrition 0.000 description 5
- 102000004169 proteins and genes Human genes 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 230000009261 transgenic effect Effects 0.000 description 5
- 229920001222 biopolymer Polymers 0.000 description 4
- 235000014633 carbohydrates Nutrition 0.000 description 4
- 230000003993 interaction Effects 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 238000001179 sorption measurement Methods 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 3
- 108010046377 Whey Proteins Proteins 0.000 description 3
- 238000013461 design Methods 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 238000010828 elution Methods 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 229920001059 synthetic polymer Polymers 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 108060003951 Immunoglobulin Proteins 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 239000005862 Whey Substances 0.000 description 2
- 102000007544 Whey Proteins Human genes 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 239000000356 contaminant Substances 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 230000002209 hydrophobic effect Effects 0.000 description 2
- 102000018358 immunoglobulin Human genes 0.000 description 2
- 229940072221 immunoglobulins Drugs 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 238000004811 liquid chromatography Methods 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 235000013336 milk Nutrition 0.000 description 2
- 210000004080 milk Anatomy 0.000 description 2
- 239000008267 milk Substances 0.000 description 2
- 150000002894 organic compounds Chemical class 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- MYRTYDVEIRVNKP-UHFFFAOYSA-N 1,2-Divinylbenzene Chemical class C=CC1=CC=CC=C1C=C MYRTYDVEIRVNKP-UHFFFAOYSA-N 0.000 description 1
- BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 1
- 229920000936 Agarose Polymers 0.000 description 1
- 108090000935 Antithrombin III Proteins 0.000 description 1
- 102100022977 Antithrombin-III Human genes 0.000 description 1
- 241000271566 Aves Species 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 108010039209 Blood Coagulation Factors Proteins 0.000 description 1
- 102000015081 Blood Coagulation Factors Human genes 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- FGUUSXIOTUKUDN-IBGZPJMESA-N C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 Chemical compound C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 FGUUSXIOTUKUDN-IBGZPJMESA-N 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 101000911390 Homo sapiens Coagulation factor VIII Proteins 0.000 description 1
- 108090000144 Human Proteins Proteins 0.000 description 1
- 102000003839 Human Proteins Human genes 0.000 description 1
- 102100023915 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 102000010445 Lactoferrin Human genes 0.000 description 1
- 108010063045 Lactoferrin Proteins 0.000 description 1
- 108010023244 Lactoperoxidase Proteins 0.000 description 1
- 102000045576 Lactoperoxidases Human genes 0.000 description 1
- 241000721578 Melopsittacus Species 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 229920001218 Pullulan Polymers 0.000 description 1
- 239000004373 Pullulan Substances 0.000 description 1
- 102000007562 Serum Albumin Human genes 0.000 description 1
- 108010071390 Serum Albumin Proteins 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 150000003926 acrylamides Chemical class 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229910001423 beryllium ion Inorganic materials 0.000 description 1
- 239000003114 blood coagulation factor Substances 0.000 description 1
- 229940019700 blood coagulation factors Drugs 0.000 description 1
- 235000010633 broth Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 230000005465 channeling Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 150000003841 chloride salts Chemical class 0.000 description 1
- 230000003750 conditioning effect Effects 0.000 description 1
- 238000011033 desalting Methods 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 238000007905 drug manufacturing Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 229920000578 graft copolymer Polymers 0.000 description 1
- 239000000122 growth hormone Substances 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- -1 hydroxy alkyl methacrylates Chemical class 0.000 description 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 239000003262 industrial enzyme Substances 0.000 description 1
- 150000002484 inorganic compounds Chemical class 0.000 description 1
- 229910010272 inorganic material Inorganic materials 0.000 description 1
- 239000011147 inorganic material Substances 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- CSSYQJWUGATIHM-IKGCZBKSSA-N l-phenylalanyl-l-lysyl-l-cysteinyl-l-arginyl-l-arginyl-l-tryptophyl-l-glutaminyl-l-tryptophyl-l-arginyl-l-methionyl-l-lysyl-l-lysyl-l-leucylglycyl-l-alanyl-l-prolyl-l-seryl-l-isoleucyl-l-threonyl-l-cysteinyl-l-valyl-l-arginyl-l-arginyl-l-alanyl-l-phenylal Chemical compound C([C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1 CSSYQJWUGATIHM-IKGCZBKSSA-N 0.000 description 1
- 235000021242 lactoferrin Nutrition 0.000 description 1
- 229940078795 lactoferrin Drugs 0.000 description 1
- 229940057428 lactoperoxidase Drugs 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- FQPSGWSUVKBHSU-UHFFFAOYSA-N methacrylamide Chemical class CC(=C)C(N)=O FQPSGWSUVKBHSU-UHFFFAOYSA-N 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 229920001542 oligosaccharide Polymers 0.000 description 1
- 150000002482 oligosaccharides Chemical class 0.000 description 1
- 239000011368 organic material Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 238000010979 pH adjustment Methods 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000002203 pretreatment Methods 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 230000002250 progressing effect Effects 0.000 description 1
- 235000019423 pullulan Nutrition 0.000 description 1
- 238000007670 refining Methods 0.000 description 1
- 230000001172 regenerating effect Effects 0.000 description 1
- 239000013049 sediment Substances 0.000 description 1
- 239000008279 sol Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 150000003440 styrenes Chemical class 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 238000011282 treatment Methods 0.000 description 1
- 239000002753 trypsin inhibitor Substances 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 235000021119 whey protein Nutrition 0.000 description 1
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
- B01D15/08—Selective adsorption, e.g. chromatography
- B01D15/10—Selective adsorption, e.g. chromatography characterised by constructional or operational features
- B01D15/18—Selective adsorption, e.g. chromatography characterised by constructional or operational features relating to flow patterns
- B01D15/1807—Selective adsorption, e.g. chromatography characterised by constructional or operational features relating to flow patterns using counter-currents, e.g. fluidised beds
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
- B01D15/08—Selective adsorption, e.g. chromatography
- B01D15/10—Selective adsorption, e.g. chromatography characterised by constructional or operational features
- B01D15/20—Selective adsorption, e.g. chromatography characterised by constructional or operational features relating to the conditioning of the sorbent material
- B01D15/203—Equilibration or regeneration
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D2215/00—Separating processes involving the treatment of liquids with adsorbents
- B01D2215/02—Separating processes involving the treatment of liquids with adsorbents with moving adsorbents
- B01D2215/021—Physically moving or fluidising the adsorbent beads or particles or slurry, excluding the movement of the entire columns
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/50—Conditioning of the sorbent material or stationary liquid
- G01N30/56—Packing methods or coating methods
- G01N2030/562—Packing methods or coating methods packing
- G01N2030/565—Packing methods or coating methods packing slurry packing
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/50—Conditioning of the sorbent material or stationary liquid
- G01N30/58—Conditioning of the sorbent material or stationary liquid the sorbent moving as a whole
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/60—Construction of the column
- G01N30/6004—Construction of the column end pieces
- G01N30/6017—Fluid distributors
Definitions
- the present invention concerns a new process for performing liquid chromatography in which there is a sequence of steps of which at least two consecutive steps (step 1 and step 2) are in fluidised bed mode by the use of an upward flow.
- Liquid chromatographic processes are carried out on particle matrices in form of packed or fluidised beds.
- the processes typically contain at least one step according to type (b) below and one or more functional steps selected from the remaining types of steps (a,c,d,e,f): a) equilibrating the particles with a liquid conditioning the particles for capture/binding; b) capturing one or more compounds present in a liquid sample by the particles; c) washing the particles to which said one or more compounds have become bound; d) releasing at least one of said one or more compounds from the particles; e) cleaning the particles; and f) regenerating the particles.
- the capture step (type b) together with the selected steps define an actual sequence in a particular chromatographic process.
- a typical sequence comprise the sequence a,b,c,d,e, f (a) ,b,c,d,e, f (a) , possibly with extra steps inserted in the sequence given, f (a) means that step a and step f may coincide and that chromatographic processes can be cyclic.
- the particles are treated with an appropriate liquid (solution/buffer) that is aqueous or non-aqueous.
- solution/buffer a liquid that is aqueous or non-aqueous.
- capture includes that the compound becomes bound to the particles.
- the binding may occur via the formation of affinity bonds, covalent bonds, entrapment within the particles etc.
- affinity are bioaffinity, ionic interaction, hydrophobic interaction etc.
- the captured compound may be a compound that is to be purified or a contaminant that one wants to separate from another compound or remove from the liquid used in the capture step.
- the liquid used in the releasing step typically contains an agent that will release the captured compound, for instance a buffer giving an appropriate pH, a salt giving an appropriate ionic strength, a substance that competitively will inhibit the binding between the captured compound and an affinity ligand/structure on the particles, etc.
- an agent that will release the captured compound for instance a buffer giving an appropriate pH, a salt giving an appropriate ionic strength, a substance that competitively will inhibit the binding between the captured compound and an affinity ligand/structure on the particles, etc.
- release includes release through breaking of affinity bonds, covalent bonds etc. Covalent bonds can be broken by chemical reactions or enzymatically .
- the liquid used in a step can change continuously or step wise during a step. Releasing by the aid of a gradient, for instance, is typical for elution on packed beds but has been rare on fluidised beds (Shiloach et al., Sep. Sci. Techn. 34(1) (1999) 29-40). Another example is changing a washing solution during a washing step.
- the releasing step typically can consist of one or more substeps.
- the capture step may mean capture of two or more compounds that bind differently to the particles.
- the compounds may require different conditions and different compositions of the liquid.
- Steps can wholly or partly coincide.
- the regeneration step for instance, is primarily related to regeneration of the particles to be used in a second cycle of the process and then coincides with the equilibration step of the second run.
- the capture step can mean that the compound is only retarded suggesting that the releasing step is at the same time ongoing. In case a contaminant is captured by the particles, possibly in combination with passing through the compound to be purified, release can take place in the cleaning step.
- Cip-steps normally comprise high concentration of solutes, such as NaOH, in the liquid used. This means that the liquid for cleaning often has the highest density in an actual sequence.
- Each step can be run in a fluidised or packed bed mode with vertical flow that either may be upward or downward.
- the flow direction may switch between different steps. Plug flow has often been of advantage in chromatography, in particular in capture steps.
- Suitable vessels have an inlet end and an outlet end.
- the vessel is typically placed vertically with the outlet pointing vertically upwards on the top side and the inlet pointing vertically downwards on the bottom side. It can also be the other way round.
- the inlet and outlet function, respectively, may comprise one or more openings into the vessel interior.
- Density differences between liquids used in consecutive steps have been used previously in model experiments of fluidised bed purification. These experiments have included various concentrations of glycerol in the washing solution for small scale fluidised bed treatments. The purpose has been to increase the viscosity, and possibly also the density, of the washing solution compared to the solution applied for the adsorption/capture step. See Draeger & Chase, Bioseparation 2 (1991) 67-80; Chase et al, Sep. Sci. Techn. 27 (1992) 2021- 2039; Chase et al, J. Chromatog.
- the liquid used contains an agent that will release a captured compound from the particles. This means that the density of a liquid will tend to increase during the releasing step. In case the bed is fluidised by an upward flow there will be a tendency that liquid containing the released compound will be transported downwards simultaneously with the front of the release liquid progressing upwards. The result will be a dilution of the released compound and many times an unfavourable increase in the volume of liquid to be handled in the subsequent processing of the released compound.
- Washing liquids may be relatively light. If a washing liquid has a density lower than the density of the liquid of a preceding step it will cause turbulence and lowered efficiency of the washing step. This is particularly pronounced for washing steps that are consecutive to a capture step because the liquid used in a capture step many times is relatively dense.
- the invention is .
- the invention is a method for processing a liquid sample containing one or more compounds to be removed by capturing at least one of them by particles that are brought into contact with the sample.
- the method comprises an actual sequence as defined above comprising a part sequence of at least two consecutive steps (step 1 and step 2) in which the particles are fluidised. Step 1 precedes step 2. It has now been fully appreciated that the above-mentioned drawbacks of this kind of part sequences can be minimised if the density of the liquid used in a fluidised bed step is lower than the density of the liquid used in the consecutive fluidised bed step.
- the characterizing feature of the method is that the density of the liquid (liquid 2) used in step 2 is higher than the density of the liquid (liquid 1) used in step 1.
- the bed is kept in a fluidised state during the two steps.
- the fact that liquids of increasing densities are used for two consecutive steps means that the steps are carried out in the same vessel with liquid 2 replacing liquid 1.
- the bed is kept in a fluidised state during the two steps
- plug flow should essentially be maintained during step 1 and 2.
- the plate number should be > 5, preferably > 10 or > 20 during substantially the whole period of time defined by the two steps.
- the plate number can be measured as described in the experimental part of WO 9717132.
- the density of a liquid used in a step is the density of the liquid as applied to the fluidised bed, i.e. not including the density change that may occur during a step.
- one or more additional steps may be present in the actual sequence used. These extra steps may be selected among equilibration steps, capture steps, washing steps, releasing steps, cleaning steps and regeneration steps and any other step that may be available.
- One or more up to all such extra steps may be in fluidised mode that preferably is carried out in the same vessel as the part sequence comprising steps 1 and 2. Steps that are not carried out in fluidised mode are supposed to be carried out in packed bed mode.
- Typical steps that are carried out in packed bed mode are releasing steps and regeneration steps and equilibration steps and combined regeneration/equilibration steps.
- Packed bed mode steps can be performed either with upward or downward flow as is commonly known for this kind of beds.
- Step 1 may be consecutive to a fluidised bed step or to a sequence of consecutive fluidised bed steps that together with steps 1 and 2 form a sequence that utilizes liquids of increasing densities.
- step 2 may have an immediate subsequent fluidised bed step or an immediate subsequent sequence of fluidised bed steps that together with steps 1 and 2 forms a sequence that utilizes liquids of increasing densities .
- step 1 and step 2 are a functional step, for instance selected among a-f above.
- step 1 and step 2 are functional steps
- step 2 has an increased density compared to step 1.
- Density decreasing step The feature of having fluidised bed steps in which a denser liquid is coming before a lighter liquid may have advantages when dealing with dense and viscous liquids, for instance capture liquids. In these cases it may be difficult to increase the density further. This will be overcome by having a zone of lighter liquid (liquid 1, step 1), for instance a "wash solution”, to pass the bed, and then in the next step (step 2) increase the density of the liquid (liquid 2).
- step 1 liquid 1
- step 2 the density of the liquid (liquid 2).
- the drawback is that the risk for bed turbulence will increase but the liquid exiting the bed will anyhow be lighter than the dense liquid used prior to liquid 1.
- Liquid 2 can be, for instance a true washing liquid, with an increased density relative the "wash” solution.
- step 1 With respect to the step that precedes step 1, this principle may be applicable to any of steps a-f but in particular to step 1 being a capture step.
- the increase in density when going from step 1 to step 2 includes adding density-increasing agents to the liquid used in step 1 ("wash" solution) . These agents should not decrease the binding of the compound to the particles. Typical agents are uncharged soluble compounds such as uncharged compounds having carbohydrate structure. See below.
- Step 2 may be used to keep the liquid used in the preceding step (step 1) and consecutive step (step 3) physically apart in the vessel used.
- steps 1 and 3 may be selected from steps a-f above.
- the liquid used in step 2 will have a density intermediate to the densities of step 1 and step 3.
- This variant of the invention is particularly useful when step 1 is a releasing step. During a releasing step the density of the liquid used will increase which in turn will cause a dilution of the sample and an increased volume. It may therefore be advantageous to elute with a denser liquid immediately after the releasing step, i.e.
- step 2 of this variant may be the same as the liquid used in step 1 but with a densifying substance added. This substance may be the same as or different from the releasing agent in liquid 1.
- densifying agent are glycerol, other carbohydrates, salts etc.
- a packed bed mode step may be inserted in the actual sequence used if there is a need to bring down the density of the liquid of a subsequent step. For instance after a certain step, it may not be feasible or practical to increase the density further.
- This use of packed mode bed steps provides a simple and practical way of making a process according to the invention cyclic.
- the liquid used in this kind of packed bed mode steps is preferably less dense than the two liquids used in the closest surrounding steps. Once the density of the liquid for a step has been reduced then liquids of increasing densities can be used in consecutive steps. In principle any step a-f above can be carried out in packed bed mode as described in this paragraph. For typical packed bed mode steps see above.
- step 1 is a washing or a releasing step.
- An increase in density can be achieved by increasing the concentration of a substance that is soluble in the liquid used and has a density-increasing effect on the liquid.
- aqueous liquids typical examples of substances are salts such as halides (typically chlorides), phosphates, sulphates etc, for instance soluble metal and ammonium salts thereof, and uncharged substances such as soluble carbohydrates, for instance glycerol and other mono- or oligosaccharides .
- the required relative difference in density between two consecutive fluidised bed steps will depend on various factors, for instance desired number of theoretical plates. This number in turn will depend on the column design including the distributor design. Our results so far achieved suggest that the relative increase in density can be as low as 1/10000 between two consecutive fluidised bed steps in case the system is optimised to a plug flow corresponding to > 35 theoretical plates in the fluidised/expanded bed.
- the relative increment in density for each consecutive fluidised bed step can be > 1/10000, such as > 1/1000 or > 1/100 or > 1/10 of the density of the liquid used in the immediately preceding fluidised bed step (for instance selected from steps a-f as defined above) .
- the number of theoretical plates can be down to 5 provided that the relative density difference for the liquids is sufficiently high between two consecutive fluidised bed step.
- systems providing, for instance, > 5 such as > 15 and > 35 theoretical plates in the fluidised bed may be used.
- An increase in density is often accompanied by an increase in viscosity. Some substances have a more pronounced ability to increase the viscosity than others. This may have unfavourable effects in fluidised bed systems. It may therefore be beneficial to switch from a pronounced to a less pronounced viscosity increasing substance when increasing the density of the fluidising liquid between two fluidised bed steps.
- the density of the liquid used should be above the pure liquid without any density-increasing agent added.
- the upper limit is determined by the density of the particles and/or by practical considerations, such as costs for density-increasing materials. For aqueous liquids this means that the density of the liquids for consecutive fluidised bed steps may change within the interval 0.98 to 1.20 or to 1.50 g/cm 3 , with preference for 1.00 to 1.15 g/cm 3 .
- the lower limit 0.98 g/cm 3 accounts for the fact that density- decreasing agents may be added, such as water-miscible organic solvents, for instance methanol, ethanol etc.
- aqueous liquids used in two consecutive fluidised bed steps according to the invention may have a difference in density in the range starting just above 0 and going up to at least 0.52 g/cm 3 with preference for at least 0.22 g/cm 3 .
- Analogous ranges can be set up in case one selects to use non-aqueous liquids.
- the density of the particles should be > 1.05 g/cm 3 , preferably > 1.14 g/cm 3 , and even > 1.20 g/cm 3 such as > 1.30 g/cm 3 .
- An upper limit of 5-6 g/cm 3 can be envisaged.
- Suitable particles are described in WO 9218237 (Amersham Pharmacia Biotech AB) ; WO 9717132 (Amersham Pharmacia Biotech AB) ; WO 9833572 (Amersham Pharmacia Biotech AB) ; and WO 9200799 (Kem- En-Tek/Upfront Chromatography A/S) .
- Suitable particles often contain inorganic material as a densifying material.
- Suitable particles may also contain synthetic polymers .
- Polymers can be divided into purely synthetic polymers, semisynthetic polymers and biopolymers.
- Synthetic polymers may have monomeric units selected amongst acryl amides, methacrylamides, hydroxy alkyl acrylates, hydroxy alkyl methacrylates, styrenes, divinyl benzenes etc.
- Semisynthetic polymers comprise for instance cross-linked biopolymers and copolymerisates thereof and grafted polymers exhibiting structures originating from biopolymers.
- Biopolymers comprise polysaccharides, such as dextran, agarose, cellulose, starch and pullulan.
- Well known particles that have been used for fluidised bed applications are sold under the trade mark Streamline (Amersham Pharmacia Biotech AB, Uppsala, Sweden) and belong to a group of particles comprising both density increasing material, often inorganic, and hydrophilic organic material, typically polymeric.
- the process temperature for various steps involved depends on the liquid used and the compound to be captured, among others.
- the process temperature may be from 0°C up to e.g. 70-90°C although for practical considerations the temperature is often in the interval 0- 50°C. For other liquids other ranges apply.
- the inventive method has its largest use in processes of relatively large productivity.
- the flow velocities used should be at least 70-3000 cm/h, preferably from 80-90 cm/h and upwards.
- the vessels should have a cross sectional area that typically corresponds to the area of a square having a side of at least 10 cm, such as at least 15 cm.
- the cross-sectional area referred to is perpendicular to the liquid flow fluidising the particles.
- the actual sequence may comprise one or more steps that are best performed in packed bed mode, possibly by reversing the flow relative the particles.
- this may be accomplished by allowing the particles to sediment to a "packed bed” and then apply an upward or downward flow through the vessel.
- An alternative utilizes a tiltable vessel that is tilted 180° when changing bed mode. See figures 7a-b of our copending International Patent Application deriving from SE 9803813-6 and SE. This type of change in flow direction may be particularly valuable in case the particles are to be regenerated, for instance to be used in a second run of the same process.
- the advantages derives from the fact that the cleaning step often makes use of the liquid with the highest density while a combined regeneration/equilibration step utilizes a liquid of low density.
- An alternative to a packed bed mode step for instance via tilting, may be to accept a lowered plate number during the releasing step and perform the step under fluidising conditions with a liquid having a lowered density compared to the preceding step. See above. Packed bed steps may be combined with fluidised bed steps in devices designed therefore. See copending International Patent Application with priority from SE 9803813-6 and SE 9803737-7. Hence, the full actual sequence of the inventive process may be carried out in one common vessel device in which the collector arrangement is maintained at a fixed distance from the distributor arrangement during consecutive fluidised bed steps.
- the preferred type of vessels thus may have fixedly mounted collector and distributor arrangements. This does not exclude that the full sequence also can be performed in a vessel having a movable outlet adapter, for instance as described in WO 9520427 (Amersham Pharmacia Biotech AB) and WO 9218237 (Amersham Pharmacia Biotech AB) . Neither does it exclude a system of vessels in which different vessels are dedicated to fluidised bed steps and packed bed steps, respectively (see figures 8-10 in copending International
- the invention is primarily used in liquid chromatography techniques. Examples are size exclusion (gel permeation) chromatography and adsorption techniques and techniques involving formation of covalent bonds between the particles and the compound to be removed from the liquid. Adsorption techniques are also called affinity chromatography. The important variants are ion exchange chromatography and techniques based on other affinity principles, such as bioaffinity, hydrophobic interaction (HIC) , chelating interaction etc. The structure on the particles causing adsorption is often called affinity ligand or affinity structure.
- the compound to be captured on the particles may be ions, for instance metal ions, and inorganic and organic compounds, for instance biomolecules, such as proteins, carbohydrates, lipids, amino acids, hormones etc.
- proteins may have been produced recombinantly in host cells (bacteria, yeast, mammalian, plant and insect cells, for instance) , by in vitro translation or in transgenic animals, such as transgenic mammals and transgenic avians, for instance budgerigars.
- host cells bacteria, yeast, mammalian, plant and insect cells, for instance
- transgenic animals such as transgenic mammals and transgenic avians, for instance budgerigars.
- transgenic mammals and transgenic avians for instance budgerigars.
- production of human proteins in cows, sheeps, goats, horses etc may be mentioned.
- Important proteins are native and recombinant forms of plasma proteins, such as blood coagulation factors, immunoglobulins, ATIII, ⁇ l-antitrypsin, serum albumin etc; whey proteins such as lactoferrin and lactoperoxidase; enzymes; peptide or protein hormones such as growth hormones, insulin etc; erythropoetin; protein antigens and their fragments to be used, for instance, as vaccines or agents in hyposensitization therapy; and other proteins that are of therapeutic interest.
- blood coagulation factors FVIII, FVII, FIX etc may be mentioned.
- immunoglobulins various forms of monoclonal antibodies (IgA, IgD, IgE, IgG, IgM) including fragments and fused forms thereof may be mentioned.
- Industrial enzymes such as those used in washing powders and in other compositions intended for cleaning are of potential importance.
- the samples to be applied to the fluidised bed are liquids containing the compound to be bound to the particles in the capture step.
- This includes fermentation broths, and other biological fluids derived from animals, such as mammals and other vertebrates, and evertebrates . In particular it includes transgenic animals as discussed above.
- Particular biological fluids from animals are blood, serum, urine, milk (including whey) etc and other samples containing the biomolecules discussed above together with sticky and/or particulate components .
- the original sample may have undergone a number of pretreatment steps before being applied in a capture step.
- Pretreatment steps may be dilution, concentration, desalting, removal of specific components, centrifugation, filtration, dialysis, ultrafiltration, pH-adjustments etc.
- a typical procedure is to dilute the sample in a buffer providing the same conditions as the buffer used in the equilibration step.
- An alternative is to equilibrate the particles to the conditions provided by the sample.
- the invention will find uses within a large variety of technical fields, such as food industry, water purification and water deionisation, drug manufacturing, metal refining etc,
- a particular important aspect of using density differences as described herein is for working up a compound from a sample deriving from a biological fluid of an animal, in particular a transgenic animal.
- the process as such comprises an actual sequence of steps with characteristic features as defined above.
- the biological fluids concerned and their origin have been discussed above.
- the biological fluid concerned are primarily those that contains particulate and/or sticky components and/or are more or less highly viscous, for instance blood, serum, plasma, milk, whey etc.
- the compounds are the same as discussed above.
- the preferred modes of the invention utilize vessels and systems as described in copending International Patent Application derived from SE 9803813-6 and SE 9803737-7.
- the background of this test is to be able to run the column in expanded mode throughout all the operating steps without loosing performance due to instability of the bed (mixing, channeling etc.).
- the theory was that the density of the liquids is the key factor whether two different liquids will mix or not in a fluidised bed and not the viscosity of the liquids. This means that a heavy liquid that is pumped into an expanded bed column (even distribution of liquid) which contains a lighter liquid, will create a sharp boundary between the two liquids and no mixing will occur. Whilst on the other hand, a light liquid pumped into a heavy liquid will cause severe mixing. By using increasing densities from liquid to liquid no mixing will occur and thereby a minimum of buffer consumption will be gained.
- yeast 1.017 More viscous than 50 mM susp. NaCl
Landscapes
- Chemical & Material Sciences (AREA)
- Analytical Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Treatment Of Liquids With Adsorbents In General (AREA)
- Feeding, Discharge, Calcimining, Fusing, And Gas-Generation Devices (AREA)
- Devices And Processes Conducted In The Presence Of Fluids And Solid Particles (AREA)
Abstract
Description
Claims
Priority Applications (7)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AT99958558T ATE245048T1 (en) | 1998-10-31 | 1999-10-31 | CHROMATOGRAPHIC PROCESS USING A FLUIDIZED BED |
EP99958558A EP1131146B1 (en) | 1998-10-31 | 1999-10-31 | A chromatographic process utilizing a fluidised bed |
JP2000579317A JP4458679B2 (en) | 1998-10-31 | 1999-10-31 | Chromatographic method using fluidized bed. |
US09/830,863 US6706191B1 (en) | 1998-10-31 | 1999-10-31 | Chromatographic process utilizing a fluidized bed |
AU15898/00A AU768241B2 (en) | 1998-10-31 | 1999-10-31 | A chromatographic process utilizing a fluidised bed |
CA002350690A CA2350690C (en) | 1998-10-31 | 1999-10-31 | A chromatographic process utilizing a fluidised bed |
DE69909644T DE69909644T2 (en) | 1998-10-31 | 1999-10-31 | CHROMATOGRAPHIC METHOD USING A FLUID BED |
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
SE9803737A SE9803737D0 (en) | 1998-10-31 | 1998-10-31 | a new system and its units and the use thereof |
SE9803813-6 | 1998-11-08 | ||
SE9803737-7 | 1998-11-08 | ||
SE9803813A SE9803813D0 (en) | 1998-11-08 | 1998-11-08 | A new system, its units and their use in separations |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2000025884A1 true WO2000025884A1 (en) | 2000-05-11 |
Family
ID=26663422
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/SE1999/001965 WO2000025884A1 (en) | 1998-10-31 | 1999-10-31 | A chromatographic process utilizing a fluidised bed |
PCT/SE1999/001957 WO2000025883A1 (en) | 1998-10-31 | 1999-10-31 | A new system and its units |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/SE1999/001957 WO2000025883A1 (en) | 1998-10-31 | 1999-10-31 | A new system and its units |
Country Status (8)
Country | Link |
---|---|
US (2) | US6610200B1 (en) |
EP (2) | EP1131147A1 (en) |
JP (2) | JP2002528256A (en) |
AT (1) | ATE245048T1 (en) |
AU (2) | AU767183B2 (en) |
CA (2) | CA2350690C (en) |
DE (1) | DE69909644T2 (en) |
WO (2) | WO2000025884A1 (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2005121163A2 (en) | 2004-06-07 | 2005-12-22 | Upfront Chromatography A/S | Isolation of plasma or serum proteins |
Families Citing this family (19)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5902485A (en) | 1994-10-03 | 1999-05-11 | Amersham Pharmacia Biotech Ab | Access valve devices, their use in separation apparatus and corresponding methods |
AU2001258238B2 (en) * | 2000-05-12 | 2005-06-23 | Upfront Chromatography A/S | A bed adsorption system |
SE0001859D0 (en) * | 2000-05-17 | 2000-05-17 | Amersham Pharm Biotech Ab | Inlet device and its use |
DE10029142B4 (en) * | 2000-06-14 | 2004-08-05 | InfraServ GmbH & Co. Höchst KG | Method for unpacking chromatography columns and device suitable therefor |
SE0100714D0 (en) * | 2000-07-13 | 2001-02-28 | Ap Biotech Ab | Reaction vessel and method for distributing fluid in such a vessel |
EP1199099A1 (en) * | 2000-10-19 | 2002-04-24 | Amersham Biosciences AB | Reactor |
US7943393B2 (en) * | 2003-07-14 | 2011-05-17 | Phynexus, Inc. | Method and device for extracting an analyte |
US7507337B2 (en) * | 2004-09-03 | 2009-03-24 | Symyx Technologies, Inc. | System and method for rapid chromatography with fluid temperature and mobile phase composition control |
JP5888481B2 (en) * | 2007-03-28 | 2016-03-22 | ディーピーエックス ホールディングス ビー.ブイ. | Expanded bed column and disposable chromatography |
WO2010138061A1 (en) * | 2009-05-29 | 2010-12-02 | Ge Healthcare Bio-Sciences Ab | Fluid distributor unit |
JP5737671B2 (en) * | 2010-11-16 | 2015-06-17 | 国立大学法人九州工業大学 | Waste water treatment equipment containing metal ions |
CN102078706B (en) * | 2010-12-02 | 2012-12-12 | 温州市东瓯微孔过滤有限公司 | Ion exchange chromatography filtration method and chromatographic separation column thereof |
US10773863B2 (en) | 2011-06-22 | 2020-09-15 | Sartorius Stedim North America Inc. | Vessel closures and methods for using and manufacturing same |
JP6348507B2 (en) * | 2012-12-14 | 2018-06-27 | ジーイー・ヘルスケア・バイオプロセス・アールアンドディ・アクチボラグ | Washing method for packed bed chromatography column |
JP6334569B2 (en) | 2013-01-31 | 2018-05-30 | イー・エム・デイー・ミリポア・コーポレイシヨン | Disposable direct capture device |
US11319201B2 (en) | 2019-07-23 | 2022-05-03 | Sartorius Stedim North America Inc. | System for simultaneous filling of multiple containers |
US11691866B2 (en) | 2017-11-14 | 2023-07-04 | Sartorius Stedim North America Inc. | System for simultaneous distribution of fluid to multiple vessels and method of using the same |
JP2021503304A (en) | 2017-11-14 | 2021-02-12 | ザルトリウス ステディム ノース アメリカ インコーポレイテッド | Fluid transfer assembly with junctions with multiple fluid paths |
US11577953B2 (en) | 2017-11-14 | 2023-02-14 | Sartorius Stedim North America, Inc. | System for simultaneous distribution of fluid to multiple vessels and method of using the same |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4976865A (en) * | 1985-01-04 | 1990-12-11 | Centre National De La Recherche Scientifique | Method for the separation of biological macromolecules by chromatography |
WO1995020427A1 (en) * | 1994-01-28 | 1995-08-03 | Pharmacia Biotech Ab | Column arrangement |
WO1998033572A1 (en) * | 1997-02-04 | 1998-08-06 | Amersham Pharmacia Biotech Ab | An adsorption/separation method and a medium for adsorption/separation |
Family Cites Families (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE278687C (en) * | ||||
US4450082A (en) * | 1981-06-11 | 1984-05-22 | Asahi Kasei Kogyo Kabushiki Kaisha | Method for obtaining uniform stream in adsorption column |
CA1247329A (en) | 1985-05-06 | 1988-12-28 | Craig J. Brown | Fluid treatment process and apparatus |
DD278687A3 (en) * | 1986-10-27 | 1990-05-16 | Adw Ddr | DEVICE FOR PRAEPARATIVE FLUID COUNTER CHROMATOGRAPHY |
JPS63231262A (en) * | 1987-03-19 | 1988-09-27 | Sekisui Chem Co Ltd | Method for changing liquid composition in column and column supporting device |
US4871463A (en) | 1988-08-23 | 1989-10-03 | Sepratech | Vertical reaction vessel |
US5409813A (en) * | 1993-09-30 | 1995-04-25 | Systemix, Inc. | Method for mammalian cell separation from a mixture of cell populations |
US5466377A (en) * | 1994-01-19 | 1995-11-14 | Grandics; Peter | Chromatography media and their uses |
SE9402091D0 (en) | 1994-06-14 | 1994-06-14 | Pharmacia Biotech Ab | chromatography column |
DE19718652C2 (en) | 1996-05-03 | 2000-07-20 | Pfeiffer Wolfdietrich | Liquid chromatography device |
IL137649A (en) * | 1998-02-18 | 2004-08-31 | Genentech Inc | Method of adsorption chromatography |
-
1999
- 1999-10-31 EP EP99971344A patent/EP1131147A1/en not_active Withdrawn
- 1999-10-31 AU AU14324/00A patent/AU767183B2/en not_active Ceased
- 1999-10-31 CA CA002350690A patent/CA2350690C/en not_active Expired - Fee Related
- 1999-10-31 AT AT99958558T patent/ATE245048T1/en not_active IP Right Cessation
- 1999-10-31 JP JP2000579316A patent/JP2002528256A/en not_active Withdrawn
- 1999-10-31 DE DE69909644T patent/DE69909644T2/en not_active Expired - Lifetime
- 1999-10-31 US US09/830,843 patent/US6610200B1/en not_active Expired - Fee Related
- 1999-10-31 WO PCT/SE1999/001965 patent/WO2000025884A1/en active IP Right Grant
- 1999-10-31 CA CA002348298A patent/CA2348298A1/en not_active Abandoned
- 1999-10-31 EP EP99958558A patent/EP1131146B1/en not_active Expired - Lifetime
- 1999-10-31 US US09/830,863 patent/US6706191B1/en not_active Expired - Fee Related
- 1999-10-31 AU AU15898/00A patent/AU768241B2/en not_active Ceased
- 1999-10-31 JP JP2000579317A patent/JP4458679B2/en not_active Expired - Fee Related
- 1999-10-31 WO PCT/SE1999/001957 patent/WO2000025883A1/en active IP Right Grant
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4976865A (en) * | 1985-01-04 | 1990-12-11 | Centre National De La Recherche Scientifique | Method for the separation of biological macromolecules by chromatography |
WO1995020427A1 (en) * | 1994-01-28 | 1995-08-03 | Pharmacia Biotech Ab | Column arrangement |
WO1998033572A1 (en) * | 1997-02-04 | 1998-08-06 | Amersham Pharmacia Biotech Ab | An adsorption/separation method and a medium for adsorption/separation |
Non-Patent Citations (1)
Title |
---|
CHANG Y.K. ET AL: "Ion Exchange Purification of G6PDH from Unclarified Yeast Cell Homogenates USing Expanded Bed Adsorption", BIOTECHNOLOGY AND BIOENGINEERING, vol. 49, no. 2, 20 January 1996 (1996-01-20), pages 204 - 216, XP002922378 * |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2005121163A2 (en) | 2004-06-07 | 2005-12-22 | Upfront Chromatography A/S | Isolation of plasma or serum proteins |
EP2277912A2 (en) | 2004-06-07 | 2011-01-26 | Upfront Chromatography A/S | Isolation of plasma or serum proteins |
US9428545B2 (en) | 2004-06-07 | 2016-08-30 | Therapure Biopharma Inc. | Process for isolation of plasma or serum proteins |
EP3127916A1 (en) | 2004-06-07 | 2017-02-08 | Therapure Biopharma Inc. | Isolation of plasma or serum proteins |
US9624260B2 (en) | 2004-06-07 | 2017-04-18 | Therapure Biopharma Inc. | Process for isolation of plasma or serum proteins |
Also Published As
Publication number | Publication date |
---|---|
EP1131146A1 (en) | 2001-09-12 |
DE69909644T2 (en) | 2004-06-09 |
AU1589800A (en) | 2000-05-22 |
AU768241B2 (en) | 2003-12-04 |
DE69909644D1 (en) | 2003-08-21 |
US6610200B1 (en) | 2003-08-26 |
AU1432400A (en) | 2000-05-22 |
EP1131146B1 (en) | 2003-07-16 |
CA2350690A1 (en) | 2000-05-11 |
CA2348298A1 (en) | 2000-05-11 |
ATE245048T1 (en) | 2003-08-15 |
WO2000025883A1 (en) | 2000-05-11 |
AU767183B2 (en) | 2003-11-06 |
EP1131147A1 (en) | 2001-09-12 |
JP2002528737A (en) | 2002-09-03 |
JP4458679B2 (en) | 2010-04-28 |
CA2350690C (en) | 2008-07-22 |
US6706191B1 (en) | 2004-03-16 |
JP2002528256A (en) | 2002-09-03 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US6706191B1 (en) | Chromatographic process utilizing a fluidized bed | |
US6139746A (en) | Method and apparatus for purification of biological substances | |
CA2361545C (en) | Purification of biological substances | |
KR101601812B1 (en) | Removal of protein aggregaates from biopharmaceutical preparations in a flow-through mode | |
JP2000500063A (en) | Adsorption and separation media | |
JP4139333B2 (en) | Method and composition for chromatography | |
WO2012015908A2 (en) | Chromatography media and method | |
EP1506809A1 (en) | Regeneration of hydrolysis sensitive adsorbent matrices | |
US5466377A (en) | Chromatography media and their uses | |
KR20070065896A (en) | Method and apparatus for separating a target molecule from a liquid mixture | |
Sii et al. | Bioseparation using affinity techniques | |
Coffinier et al. | Separation of IgG from human plasma using thiophilic hollow fiber membranes | |
Lihme et al. | Expanded bed adsorption in the purification of biomolecules | |
Avramescu et al. | Membrane chromatography |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
ENP | Entry into the national phase |
Ref country code: AU Ref document number: 2000 15898 Kind code of ref document: A Format of ref document f/p: F |
|
AK | Designated states |
Kind code of ref document: A1 Designated state(s): AU CA JP US |
|
AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE |
|
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
WWE | Wipo information: entry into national phase |
Ref document number: 15898/00 Country of ref document: AU |
|
WWE | Wipo information: entry into national phase |
Ref document number: 1999958558 Country of ref document: EP |
|
ENP | Entry into the national phase |
Ref document number: 2350690 Country of ref document: CA Ref country code: CA Ref document number: 2350690 Kind code of ref document: A Format of ref document f/p: F |
|
ENP | Entry into the national phase |
Ref country code: JP Ref document number: 2000 579317 Kind code of ref document: A Format of ref document f/p: F |
|
WWE | Wipo information: entry into national phase |
Ref document number: 09830863 Country of ref document: US |
|
WWP | Wipo information: published in national office |
Ref document number: 1999958558 Country of ref document: EP |
|
DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
WWG | Wipo information: grant in national office |
Ref document number: 1999958558 Country of ref document: EP |
|
WWG | Wipo information: grant in national office |
Ref document number: 15898/00 Country of ref document: AU |