Chemistry: molecular biology and microbiology – Miscellaneous
Patent
1987-05-18
1991-07-16
Flanigan, Allen J.
Chemistry: molecular biology and microbiology
Miscellaneous
435313, 435316, C12M 106, C12M 112
Patent
active
050325248
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
1. Field of the Invention
The invention relates to a further development of apparatus and methods of gassing a liquid and is an improvement over the apparatus and method of German apparatus for bubble-free gassing of culture media.
BRIEF DESCRIPTION OF THE PRIOR ART
To this end, according to the invention an apparatus comprising a membrane sheet provided by means of a membrane cage is provided which is characterised in that the membrane cage is formed from one or more hydrophobic porous hollow membrane filaments.
BRIEF DESCRIPTION OF THE DRAWINGS
FIGS. 1-3 are graphical representations of fermentations according to the Examples 1-3, respectively.
FIG. 4 is a schematic representation of embodiment apparatus used in the Examples 1-3.
FIGS. 5-6 show fermentation apparatus with membrane cages according to the invention.
DETAILED DESCRIPTION OF THE INVENTION
With the hydrophobic porous or microporous hollow membrane filaments provided in accordance with the invention, gassing is effected by way of the membrane pores. The membrane pores are filled with gas so that the gas/liquid phase boundary lies approximately in the pores approximately in the plane of the external face of the hollow membrane filaments, and liquid medium does not enter the hollow membrane filaments. The position of the phase boundary can be adjusted by suitable choice of the pressure in the hollow membrane filaments against the prevailing external pressure.
Apparatus for the bubble-free gassing of liquids, especially of culture media for propagating tissue cultures, are used in reactors that, in addition to the gas supply and removal system, as a rule comprise a system for the cell-free exchange of media. For example, when culturing animal cells in bioreactors the cell-free exchange of media is a problem if cell densities of more than 1.times.10.sup.7 cells/ml are to be achieved.
For the continuous cell-free exchange of media, for example spinning filters mounted on a stirrer shaft have been proposed; Develop. biol. Standard, 60 (1985) 229 to 236. As regards the disadvantages that result when tissue cultures are stirred, reference can be made to Patent P 34 30 924.1. External circulation systems with filter units and/or sedimentation paths for microcarrier cultures have also been proposed; Ann. Rep. Ferment. Proc., 6 (1983) 35 to 74. With external circulation systems however, high shearing forces occur as a result of the cell suspensions continuously being pumped around, with the result that the cells are severely damaged. Flat membranes are susceptible to blockage and are also not very satisfactory as regards the throughput of liquid.
To overcome the problems of the State of the Art, the apparatus according to the invention may be provided, in addition, with one or more hydrophilic porous hollow membrane filaments. These hydrophilic porous hollow membrane filaments, together with the hydrophobic porous hollow membrane filame ts, form the membrane cage.
The use of hollow membrane filaments made of polypropylene, for example of polypropylene according to DE-A-31 07 874, has proved advantageous. Porous and microporous hollow membrane filaments made of polypropylene are hydrophobic per se. These hollow membrane filaments can, however, be hydrophilised by being wetted with an organic solvent and then with water. This hydrophilisation can be reversed by drying. The membrane cage can thus be formed from polypropylene hollow membrane filaments, some of which are untreated and some of which have been hyrophilised in a convenient manner.
If liquid medium is alternately introduced into and removed from the reactor by way of the hydrophilic hollow membrane filters, then the hollow membrane filaments are rinsed in an advantageous manner.
In the following the invention is explained in detail by six Figures and four Examples.
FIGS. 1 to 3 show three fermentations according to Examples 1 to 3,
FIG. 4 shows schematically the apparatus used Examples 1 to 3;
FIGS 5 and 6 show reactors with membrane cages according to the in
REFERENCES:
patent: 3674440 (1972-07-01), Kitrilakis
patent: 4649114 (1987-03-01), Miltenburger et al.
patent: 4649118 (1987-03-01), Anderson
patent: 4738782 (1988-04-01), Yamauchi et al.
Buntemeyer Heino
Lehmann Jurgen
Flanigan Allen J.
Gesellschaft fur Biotechnologische Forschung mbH (GBF)
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