Continuous fermentation system

Details Continuous fermentation system Continuous fermentation system

2000-10-06

2003-07-29

Beisner, William H. (Department: 1744)

Chemistry: molecular biology and microbiology

Apparatus

Including condition or time responsive control means

C435S289100, C435S299200, C435S810000

Reexamination Certificate

active

06599735

ABSTRACT:

FIELD OF THE INVENTION
The present invention relates to a continuous process for the manufacture of proteins. In particular, the invention relates to fermentation assemblies and processes for manufacturing proteins.
SUMMARY OF THE INVENTION
In accordance with the present invention it has been found that splitting of cultivation media used in a continuous fermentation process allows one to study the influence on growth and metabolite-production of microorganisms, and thus to determine optimal conditions for the fermentation process. A continuously delivered fermentation medium can generally be split into as many fractions as it contains ingredients. Examples of such ingredients are carbon, nitrogen, phosphorus, and sulfur sources as well as vitamins and complex substrates such as corn steep, yeast extract, and other natural products. Furthermore, every required mineral, micro- or trace element can be provided separately as a solution of a water-soluble salt, such as a chloride, sulfate or nitrate. In this manner, a fermentation medium of any desired composition can be obtained, provided that the desired amounts of the ingredients are (water)-soluble and no disturbing interactions (e.g., precipitation, reaction) occur in the individual feed solutions or in the fermentation medium.
One embodiment of the invention is a fermentation assembly containing a vessel for culturing living cells, at least two storage flasks in fluid communication with the vessel for supply of liquids and a first transport means for transferring the liquids from the storage flasks to the vessel, individual appliances operably connected to the transport means for monitoring the supply of the contents of the storage flasks to the vessel, a harvest flask in fluid communication with the vessel and a second transport means for transferring the fermentation broth from the vessel to the harvest flask, and a device operably connected to the first transport means for controlling and maintaining a constant dilution rate in the vessel with varying rates of individual supply of liquid from the storage flasks to the vessel.
Another embodiment of the invention is a process for the manufacture of a protein. This process includes providing a continuous culture of living cells in a fermentation reactor; and individually feeding nutrients and other agents required for the growth of the cells into the reactor at a constant dilution rate to achieve optimal production of the protein.
A further embodiment of the invention is a fermentation assembly. This fermentation assembly includes a fermentor
1
equipped with inlet tubes
2
a
in fluid communication with a storage flask
2
for supply of liquids to the fermentor, a pump
3
operably connected to the inlet tubes for transporting liquids from the storage flask
2
to the fermentor
1
, a scale
4
in contact with each storage flask for monitoring the amount of liquid supplied to and discharged from the fermentor, a gas inlet
9
and outlet tubes
10
in communication with the fermentor for introducing and removing gas therefrom, a pump
6
operably connected to an outlet tube
5
a
which is in fluid connection with the fermentor, wherein the pump discharges fermentation broth from the fermentor to a harvest flask
5
, a main controlling unit
7
operably connected to the fermentation assembly for overall process monitoring and steering, a controlling unit
11
operably connected to individual control systems
17
for monitoring and steering temperature, pH, gas pressure, fermentor content, and antifoam agents, a circuit
12
for monitoring gas supply and taking samples including an outlet tube from the fermentor, which circuit is operably connected to the outlet to be pump
13
, and gas inlet and outlet flow control devices
14
and
15
operably connected to the gas inlet and outlet tubes
9
,
10
.


REFERENCES:
patent: 3338792 (1967-08-01), Patton et al.
patent: 4840902 (1989-06-01), Lawford
patent: 5081035 (1992-01-01), Halberstadt et al.
patent: 0 684 313 (1995-11-01), None
patent: 0 897 010 (1999-02-01), None
patent: 0 897 985 (1999-02-01), None

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