Bioreactor

Details Bioreactor Bioreactor

1998-02-25

2001-05-08

Redding, David A. (Department: 1744)

Chemistry: molecular biology and microbiology

Micro-organism, tissue cell culture or enzyme using process...

C435S297100, C435S297200, C435S297400, C435S297500, C435S325000, C435S370000, C435S398000, C435S284100

Reexamination Certificate

active

06228607

ABSTRACT:

THE PRIOR ART
Bioreactors for adherent cells are currently built of bundles of hollow fibers, with cells inside or outside the fibers or with a mass culture system inside or outside the fibers. The cells can be encapsulated in a polymer matrix, like collagen, alginate, etc.
All the known bioreactors suffer from the fact that adherent cells, and in particular hepatocytes, require confluence as a single layer to achieve an in-vivo equivalent metabolic function.
Problems of these known bioreactors are: geometry difficult to define accurately; and mass-transfer limitations.
Furthermore in all the known systems or bioreactors, the medium is first oxygenated and thereafter said oxygenated medium is treated by the cells.
The bioreactor of the invention aims to solve these problems. Furthermore, the bioreactor of the invention is suitable for treating media by cells without or with collagen overlay.
BRIEF DESCRIPTION OF THE INVENTION
The present invention relates to a bioreactor for a cell treatment of a medium. Said bioreactor comprises an element defining a chamber in which cells for treating the medium are located, a liquid permeable membrane separating the said chamber from a first channel in which flows the medium to be treated and a gas permeable membrane separating the said chamber from a second channel in which flows a gas containing oxygen.
Advantageously, the liquid permeable membrane has pores or openings with a diameter greater than 3 &mgr;m.
According to an embodiment, the bioreactor comprises two adjacent liquid permeable membranes, a first having pores or openings with a diameter greater than 3 &mgr;m, while the second has pores or openings with a diameter less than to 3 &mgr;m, preferably less than 0.5 &mgr;m.
This embodiment is particularly suitable when the cells used for the treatment are embedded in a collagen matrix or are covered with a collagen layer.
For example, the liquid permeable membrane can have hydrophobic characteristics or a combination of hydrophobic and hydrophylic characteristics.
According to a preferred embodiment, the bioreactor comprises a chamber containing cells, said chamber communicating with the channel in which flows the medium to be treated through a liquid permeable membrane and with the channel in which flows a gas containing oxygen through a gas permeable membrane, the chamber being provided with an outlet so as to remove medium issuing through the liquid permeable membrane from the channel in which flows the liquid medium to be treated. This outlet is very suitable for removing biliary compounds from the chamber, so as to maintain a better working of the cells in the chamber.
Advantageously, the chamber comprises at least two layers of cells, the layers being preferably separated from one another. A co-culture is thus possible in the chamber of the bioreactor. For example, Kupfer cell and hepatocyte cells can be used in the same chamber.
For example a first layer of cells contains a majority of Kupfer cells (for example, the layer adjacent to the channel for the flow of medium to be treated) or cells suitable to fix toxins, while the second layer contains a majority of hepatocyte cells.
According to a further embodiment, the chamber comprises an inlet and an outlet so that a flow of cell medium is possible.
According to another embodiment, the bioreactor comprises a plurality of stacked units consisting each of a frame provided with two layers so as to define therebetween a channel for the flow of a liquid medium or of a gas, one of said layers being a liquid permeable membrane or a gas permeable membrane. Preferably a cavity or passage is defined by or between the edges of the frame, one face of said cavity or passage being one of said layers, preferably a liquid permeable membrane.
According to another embodiment, the bioreactor comprises stacked units consisting each of a frame provided with a bottom layer so as to define a cavity for containing the cells for the treatment. Possibly pipes or fibres extend within the cavity and have liquid or gas permeable characteristics.
The invention relates also:
to units for a bioreactor according to the invention;
to a bioreactor system comprising a bioreactor, said bioreactor having an inlet for introducing medium to be treated to a liquid channel, an outlet for the medium flowing out of said liquid channel, an inlet for gas to flow into the bioreactor, an outlet for the gas flowing out of the bioreactor, and an outlet for collecting liquid flowing out of the chamber, the system being further provided with a means of filtering the liquid flowing out the chamber;
to processes using a bioreactor of the invention, and,
to a liver support (artificial liver or device for facilitating the function of a failing liver.
Major advantages of these embodiments for a bioreactor according to the invention includes:
the geometry of the bioreactor is accurately defined and allows better control of mass transfer;
the cells when used for treating a medium are oxygenated;
easy and simple construction;
possibly to use collagen as well as other matrix support;
possibility to treat biliary products and to evacuate biliary products from the chamber.


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