Bioreactor for the cultivation of mammalian cells

Abstract

Large-scale bioreactors having at least two impellers, large-scale bioreactor systems and methods for the large-scale cultivation and propagation of mammalian cells using these bioreactors.

1 . A bioreactor for the cultivation of mammalian cells wherein said bioreactor has a volume of at least 4000 l and at least one top impeller and at least one bottom impeller, wherein the top impeller is a hydrofoil impeller. 
     
     
         2 . The bioreactor according to  claim 1 , wherein the top impeller is a three bladed hydrofoil design impeller, and the bottom impeller is a four pitched-bladed high solidity impeller. 
     
     
         3 . The bioreactor according to  claim 1 , wherein the impeller to tank diameter ratio is at least 0.35 and at most 0.55. 
     
     
         4 . The bioreactor according to  claim 1 , wherein a top impeller power number (N p ) is at least 0.1 and at most 0.9. 
     
     
         5 . The bioreactor according  claim 1 , wherein a top impeller flow number (N q ) is at least 0.4 and at most 0.9. 
     
     
         6 . The bioreactor according to  claim 1 , wherein a bottom impeller power number (N p ) is at least 0.5 and at most 0.9. 
     
     
         7 . The bioreactor according to  claim 1 , wherein a bottom impeller flow number (N q ) is at least 0.50 and at most 0.85. 
     
     
         8 . The bioreactor according to  claim 1 , wherein the bioreactor has at least one sparger. 
     
     
         9 . The bioreactor according to  claim 1 , wherein the bioreactor has at least one baffle. 
     
     
         10 . The bioreactor according to  claim 1 , wherein the bioreactor has at least two ports for alkali addition. 
     
     
         11 . The bioreactor according to  claim 1 , wherein the bioreactor has a volume of at least 10000 l. 
     
     
         12 . A method for cultivating and propagating mammalian cells, wherein at least one mammalian cell is cultivated under suitable conditions and in a suitable culture medium in a bioreactor according to  claim 1 . 
     
     
         13 . The method according to  claim 12 , wherein an agitation rate of the at least two impellers is at least 55 W/m 3  and at most 85 W/m 3 . 
     
     
         14 . A bioreactor system for the cultivation of mammalian cells wherein
 a) a first bioreactor with a volume of at least 500 l is connected with   b) a second bioreactor with a volume of at least 2000 l, wherein the second bioreactor has a volume greater than the first bioreactor and wherein the second bioreactor is connected with   c) a third bioreactor according to  claim 1  having a volume of at least 10 000 l, wherein the third bioreactor has a volume greater than the second bioreactor.   
     
     
         15 . The bioreactor system according to  claim 14 , wherein at least one of the first or second bioreactors is a bioreactor for the cultivation of mammalian cells, said bioreactor having a volume of at least 4000 l and at least one top impeller and at least one bottom impeller, wherein the top impeller is a hydrofoil impeller. 
     
     
         16 . A method for cultivating and propagating mammalian cells, wherein
 a) at least one mammalian cell is cultivated under suitable conditions and in a suitable culture medium in a first bioreactor with a volume of at least 500 l,   b) the medium containing the cells obtained by propagation from the at least one mammalian cell is transferred into a second bioreactor with a volume of at least 2000 l,   c) the transferred cells are cultivated in the second bioreactor,   d) the medium containing the cells obtained in step c) is transferred into a third bioreactor with a volume of at least 10000 l, and   e) the transferred cells are cultivated in the third bioreactor.   
     
     
         17 . The method according to  claim 16 , wherein at least one of the first, second and third bioreactors is a bioreactor for the cultivation of mammalian cells, said bioreactor having a volume of at least 4000 l and at least one top impeller and at least one bottom impeller, wherein the top impeller is a hydrofoil impeller. 
     
     
         18 . The method according to  claim 16 , wherein the cultivation-conditions are the same in the bioreactors of steps a), c) and e). 
     
     
         19 . The bioreactor according to  claim 3 , wherein the impeller to tank diameter ratio is at least 0.40 and at most 0.48. 
     
     
         20 . The bioreactor according to  claim 3 , wherein the impeller to tank diameter ratio is at least 0.44 and at most 0.46. 
     
     
         21 . The bioreactor according to  claim 10 , wherein said at least two ports are spatially separated from one another. 
     
     
         22 . The bioreactor according to  claim 11  has a volume of at least 20000 l. 
     
     
         23 . The bioreactor system according to  claim 14 , wherein the first bioreactor has a volume of at least 1000 l. 
     
     
         24 . The bioreactor system according to  claim 14 , wherein the second bioreactor has a volume of at least 4000 l. 
     
     
         25 . The bioreactor system according to  claim 14 , wherein the third bioreactor has a volume of at least 20000 l. 
     
     
         26 . The method according to  claim 16 , wherein the first bioreactor has a volume of at least 1000 l. 
     
     
         27 . The method according to  claim 16 , wherein the second bioreactor has a volume of at least 4000 l. 
     
     
         28 . The method according to  claim 16 , wherein the third bioreactor has a volume of at least 20000 l.