Chemistry: molecular biology and microbiology – Miscellaneous
Patent
1987-04-06
1990-07-24
Schwadron, Martin P.
Chemistry: molecular biology and microbiology
Miscellaneous
435286, 435314, C12M 112
Patent
active
049435353
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to a continuous fermenter vessel for receiving an agitated suspension culture of cells.
2. Description of the Prior Art
Recent advances in the commercialization of products produced by the in vitro fermentation of cells have led to a growing interest in the design of improved fermenter vessels and fermentation processes.
Fermentation is usually carried out either in a batch process or in a continuous process. Continuous processes are advantageous since they enhance the productivity of a given fermenter and reduce the downtime necessary for cleaning and sterilization which is normally required in a batch fermenter.
In known continuous fermenter vessels, a suspension of cells in an appropriate culture medium is agitated and maintained at a suitable temperature for fermentation. Suspension culture is continuously withdrawn from the fermenter, balanced by a continuous supply of fresh culture medium. A significant disadvantage of such fermenters is the continual loss of cells caused by the removal of culture. Fermenters are known in which the removed suspension culture is passed through a continuous centrifugal separation device which separates cells from the culture supernatant. The cells are then fed back into the suspension culture.
In another known fermenter, a rotating basket of a filter material is provided, partially submerged in the culture, such that the inside of the basket is separated from the suspension culture by the filter. Culture supernatant passes through the filter and may be withdrawn continuously, whilst cells remain in the suspension culture. The rotation of the basket in the suspension culture reduces clogging of the filter material.
These known devices for providing cell feedback in continuous suspension cultures are complicated mechanically, require energy for their operation and may cause detrimental effects, such as cell rupture, upon the suspension culture. These features combine to reduce the economic viability of fermentation processes based on such fermenters.
SUMMARY OF THE INVENTION
The object of the present invention is to provide a continuous fermenter vessel which substantially overcomes these disadvantages.
According to the present invention there is provided a continuous fermenter vessel for receiving a suspension culture of cells, the vessel comprising; means, in use, for agitating a suspension culture received in the vessel and causing a gross flow movement of the suspension culture, an inlet for continuously supplying culture medium to the vessel, an outlet for removing culture supernatant, and a filter material between the outlet and the vessel to prevent removal of cells from the suspension culture wherein the filter material is located such that, in use, the gross flow movement of the suspension culture substantially prevents clogging of the filter material by cells and/or cell debris.
The fermenter vessel of the invention requires no moving parts in order to achieve separation of the culture supernatant from the suspension and therefore provides an advantageous saving in costs. The filter material has a pore size which depends upon the diameter of the cells to be cultured. For animal cells the filter material may have a pore size of from 1 to 10 .mu.m, 1 to 5 .mu.m, and most preferably 3 to 5 .mu.m. The filter material may be a ceramics material, sintered stainless steel or a stainless steel mesh.
Gross flow movement of the culture supernatant may be produced using a pump or impeller. However such devices add to the cost and complexity of the fermenter. In a preferred form of the invention the fermenter is a so called "air-lift" fermenter in which a gas such as air is injected into an upwardly extending part of the fermenter known in the art as a "riser". The riser communicates at top and bottom with the top and bottom respectively of a further upwardly extending part of the fermenter known in the art as a "downcomer". A known configuration of an air-lift fermenter comprises a central di
REFERENCES:
patent: 4178209 (1979-12-01), Tolbert et al.
patent: 4183787 (1980-01-01), Roesler et al.
patent: 4276384 (1981-06-01), Mueller
Thompson Philip W.
Wood Lesley A.
Celltech Limited
Flanigan Allen J.
Schwadron Martin P.
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