Chemistry: molecular biology and microbiology – Micro-organism – per se ; compositions thereof; proces of... – Separation of micro-organism from culture media
Patent
1987-02-19
1988-05-31
Scott, Samuel
Chemistry: molecular biology and microbiology
Micro-organism, per se ; compositions thereof; proces of...
Separation of micro-organism from culture media
435286, 435311, 435314, 210629, C12N 102
Patent
active
047481234
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 Related Art
Recent advances in the commercialisation 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 nonproductive downtime necessary for cleaning and sterilisation 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 Suspension culture is continuously withdrawn from the fermenter, balanced by a continuous supply of fresh culture medium.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 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 Culture supernatant passes through the filter and may be withdrawn continuously, whilst cells remain in the suspension culture.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 for agitating a suspension culture received in a first portion of the vessel; a second portion of the vessel defining, in use, a static settling zone, at least part of the bottom of the second portion communicating with the first portion; an inlet means for the continuous supply of culture medium to the vessel; and an outlet for the continuous withdrawal of culture supernatant from the second portion of the vessel from a point spaced above the bottom of the second portion wherein, in use, cells settling in the second portion are returned to the agitated suspension culture, and culture supernatant having a lower concentration of cells than the suspension culture is withdrawn from the second portion.
According to the present invention there is thus provided a continuous fermentation device for receiving a suspension culture of cells, the device comprising: a fermentation vessel having inlet means to deliver suspension culture medium; baffle means defining, in combination with interior walls of said vessel, a downcomer and a riser; pump means for forcing a suspension culture to circulate in the riser and downcomer; a portion of said baffle means further defining a static settling zone disposed within said vessel, wherein said zone is surrounded by at least one of said riser and said downcomer, said zone having a bottom opening communicating with at least one of said riser and downcomer, and a top opening connected to outlet means to draw off culture supernatant, and wherein said zone provides for cells to settle out in its bottom so as to result in a cell concentration lower in the supernatant than in the suspension.
In the ferme
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Birch John R.
Boraston Robert C.
Celltech Limited
Kamen Noah P.
Scott Samuel
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