Chemistry: molecular biology and microbiology – Apparatus – Differentiated tissue perfusion or preservation apparatus
Patent
1986-11-07
1987-09-15
Scott, Samuel
Chemistry: molecular biology and microbiology
Apparatus
Differentiated tissue perfusion or preservation apparatus
435286, 435288, 435311, 435316, C12M 300
Patent
active
046939830
DESCRIPTION:
BRIEF SUMMARY
This invention relates to a reactor for cultivating biological material, such asplant and animal cells immobilised in it.
It has long been recognised that complex chemical reactions taking place in biological systems can be manipulated to form the basis of commercial methods for producing chemicals. Recently attention has been focussed on plant cells and on the possibility of extracting chemical products from such cells.
A variety of different reactor systems are used for biochemical reactions, e.g. stirred and aerated tanks fermenters, trickle bed and percolation "filters" and fluid bed systems. In principle, any of these reactor systems might be suitable for biochemical reactions using plant or animal cells.
There are however some special conditions which must be maintained in many plant cell systems if the cells are to produce material at concentrations which could be considered adequate for a production system. It has been shown that, in order for certain species of plant cells to produce products at exploitable concentrations, the local cell concentration in the reactor must be high or, more particularly, the cells must be in contact with one another as for example in aggregates. These conditions cannot be easily attained in stirred tank reactors unless the cells are supported on a suitable mechanical matrix. Even under these conditions, the cells may be subjected to high shear rates. If mechanical agitation by means of an impeller is used, the aggregates can be broken down. On the other hand, if gas agitation (usually air) is used, the gas bubbles may become trapped in the support matrix, which then floats to the top of tank, whereby the nutrient supply rate to the cells is reduced and cell growth is slowed.
No. EP-A-0121981 (Corning Glass Works) shows a cell culture apparatus which is a high surface area monolithic support comprising a bundle of parallel channels. Anchorage-dependent cells are seeded into the channels, anchor themselves to the walls of the channels, and form a film thereon. Nutrient is supplied along the channels for take-up by the anchored cells. However, as the cells multiplied, they could form agglomerates in the channels which would either block the flow of nutrient or would all be flushed out by the pressure of the nutrient.
An artucle by Jensen (Biotechnology and Bioengineering, Vol XXIII, pages 2703 et seq.) discloses a cell cultivation method in which a culture vessel is traversed with hollow, capillary tubes through which nutrient or gaseous media flow (much as smoke-flues traverse a steam-raising boiler). The cells grow on the outsides if the tubes in the culture vessel. The walls of the tubes are however selectively permeable, to allow diffusion of the nutrient to the cells and diffusion of gas to and from the gas tubes.
However, this construction has a number of disadvantages. In particular, it is the interfacial area of the cells which is in contact with the nutrient which is important. This area may be low in the Jensen system due to the distance through the cell mass across which the nutrient must travel to reach the most inaccessible cells. Additionally, if the cells became contaminated, the total culture would have to be replaced.
The invention provides a reactor for cultivating biological material colonized therein, conprising a support matrix having a plurality of first channels for being colonized with biological material and defined by bounding walls across which the biological material cannot pass, each said first channel adjoining a second channel and a third channel, the part of said boundary wall adjoining the second channel and the part of said boundary wall adjoining the third channel being of respectively different permeabilities, one such permeability optionally being zero. By `different permeabilities` is meant being permeable to different materials.
In use of the reactor of the invention, the biological material is localised in the first channels and liquid and/or gas may be transferred between the first channels and the second channels. Thus nutrient
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Lydersen, B. K. et al., "Ceramic Matrix for Large Scale Animal Cell Culture", Biotechnology, Jan. 1985, pp. 63-67.
Jensen, M. D., "Production of Anchorage-Dependent Cell--Problems and Their Possible Solutions", Biotechnology & Bioengineering, vol. XXIII, pp. 2703-2716 (1981).
Davies Graham A.
Mavituna Ferda
Flanigan Allen J.
National Research Development Corporation
Scott Samuel
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