Chemistry: molecular biology and microbiology – Apparatus – Bioreactor
Patent
1997-02-12
2000-05-23
Beisner, William H.
Chemistry: molecular biology and microbiology
Apparatus
Bioreactor
4353033, 435809, 4353041, 4352865, C12M 124
Patent
active
060664975
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
This invention relates to apparatus for the large scale processing of cell cultures.
BACKGROUND TO THE INVENTION
The rapid growth of biotechnology has led to the need for large scale tissue culture techniques for anchorage dependent cells. Roller bottles are used extensively in the industry for this purpose. Cells are cultured whilst attached to the interior of the roller bottle. Existing roller bottle machines provide for rotation of the bottles to keep the cells bathed in culture medium during culture stages. The processing operations such as innoculation, culture medium supply, or harvesting for example which require the flow of fluids into or out of the roller bottle are carried out manually or by expensive mechanical handling systems such as robots.
For large scale production, this process can be awkward, time consuming, and carries the risk of infection of the bottle contents by foreign organisms during handling.
In some systems, the need to physically handle the roller bottles is eliminated by providing each bottle with a special cap that is equipped with a rotary seal and feed tubes that allows the bottle to rotate and yet facilitates the injection or extraction of process fluids. This system is prone to external infection via the rotary seals however, and is in any case mechanically complex and thus expensive.
A system that would provide aseptic access to the interior of a large number of roller bottles via a single connection whilst still allowing the bottles to rotate, but which did not require the use of a large number of rotating seals, would be of greater practical and economic advantage to large scale roller bottle processes using anchorage dependent cells.
DISCLOSURE OF INVENTION
According to one aspect of the present invention, there is provided, cell culture apparatus comprising a chassis or supporting frame, a rotor releasably housing a plurality of cell culture vessels/roller bottles, said rotor being mounted about a substantially horizontal axis or shaft supported by said frame, with means provided to facilitate rotation of the rotor at a controlled speed, a reversible multi-channel pump or pumps, mounted on and rotating with the rotor, a manifold with one or more sealable external connections and a plurality of connections communicating with the individual channels of the muti-channel pump or pumps, each of the cell culture vessels being equipped with a microporous air vent to atmosphere and a dip tube, the dip tube of each vessel being individually connected to one channel of said multi-channel pump or pumps, the arangement of the parts being such that the assembly comprising the rotor, cell culture vessels, pump, manifold and the connections to the cell culture vessels may be rotated about said horizontal axis, and the arrangement also allowing fluid to be injected into or extracted from the roller bottles simultaneously via a single external connection, under the influence of said multi-channel pump or pumps.
It is preferred to employ a multi-channel pump having a common pumping element, but as an alternative several pumps may be employed. It is convenient to use a pump of the peristaltic type.
Preferably means is provided for selectively opening and closing each of the connections individually whereby fluid is injected into or extracted from selected culture vessels.
The cell culture vessel may comprise a conventional roller bottle whose cap is replaced by a cap equipped with said microporous air vent and with said dip tube.
Alternatively, the cell culture vessel may be purpose made for the apparatus in which case it is proposed to dispense with the filling cap and to provide the vessel with an integral air vent and dip tube. These may be moulded or bonded in place. The use of an integral dip tube further reduces the cost and complexity, whilst the risk of external infections whilst connecting the bottle is likewise reduced.
Accordingly another aspect of the invention provides a cell culture vessel/roller bottle, comprising a substantially cylindrical cultur
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Beisner William H.
Powell Biological Machines Limited
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