BIOREACTOR FOR THE CULTIVATION OF MAMMALIAN CELLS
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.