Bioreactor

Details Bioreactor Bioreactor

2000-09-05

2003-12-30

Redding, David A. (Department: 1744)

Chemistry: molecular biology and microbiology

Apparatus

Including condition or time responsive control means

C435S286700, C435S289100, C435S293100, C435S295200, C417S360000, C623S003130

Reexamination Certificate

active

06670169

ABSTRACT:

BACKGROUND OF THE INVENTION
The invention relates to a bioreactor which has a reaction container for a substance to be acted upon with a medium and a pump for conveying the medium.
Nowadays one frequently speaks of bioreactors when one speaks about the field of “tissue engineering”. A prominent goal in this field is to produce biological substitutes for damaged tissue or organs. But there is still a large number of other goal fields; for example the effectivity or toxicity of pharmaceutica can be tested using tissue of this kind, which can eliminate the future need for a large number of animal experiments and/or clinical experiments on humans.
Bioreactors are used in the production of tissue of this kind. In this the most diverse of reactor types are used, such as for example the so-called hollow fiber reactors. A hollow fiber reactor of this kind is known for example from U.S. Pat. No. 5,622,857. This reactor comprises a reaction container, through which a centrai strand of porous hollow fibers extends, through which a nutrient solution is pumped. This central strand of hollow fibers is concentrically surrounded by a plurality of strands of hollow fibers, through which a gaseous medium is conveyed. The hollow fibers of these strands are also constituted in such a manner that the gaseous medium—for example oxygen or carbon dioxide—can at least partly emerge from these strands or enter into these strands respectively.
A cavity is in each case formed, both between the central strand and the strands surrounding this central strand as well as between these strands surrounding the central strand and the container wall. There the substance—e.g. parent cells or whatever—which is to be acted upon with the various media can be made available, where appropriate on a so-called “micro-carrier” or a biodegradable matrix material. The nourishing of the substance takes place through the liquid nutrient solution, which can emerge to a certain extent from the pores of the central strand, and its provision with oxygen takes place through the gaseous medium.
Since as a rule the nutrient solution which again emerges from the reaction container is recirculated and used again for the next run, supplemented where appropriate by further nutrient solution, a “contamination” can of course easily occur. This is important insofar as these parts must be very intensively sterilized for the tissue of another patient in order that a contamination cannot arise. In spite of any sterilization of the individual parts, however intensive, a hundred percent sterilization cannot always be ensured. The sterility is however of central importance for the success of the “tissue engineering”.
For the reaction container and for the supply lines a new reaction container and new supply lines respectively are already used in every employment.
But the pump can also be contaminated in employments of this kind. Since considered from the point of view of expenditure, the pumps are devices which still involve great expense, the latter are sterilized with a relatively great expenditure.
SUMMARY OF THE INVENTION
The present invention is dedicated to this disadvantage. An object of the invention is to propose a bioreactor in which the sterility can be ensured with great reliability in order not to endanger from the beginning the success of a “tissue engineering” process which is to be carried out with this reactor for lack of sterility; on the other hand the expenditure for this should be as low as possible.
This object is satisfied in accordance with the invention by providing the bioreactor with an expendable pump.
In particular the pump for the conveying of the medium and/or, respectively, parts of the pump are designed as expendable or disposable parts. Through this the sterilization of the pump involving great expense is omitted.
In an advantageous exemplary embodiment the expendable parts of the expendable pump are manufactured of a plastic, since parts of this kind can be economically manufactured with great reliability, for example through injection molding processes.
In a further advantageous exemplary embodiment the expendable pump comprises a pump housing in which the pump wheel is arranged as well as a separate drive stator into which the pump housing together with the pump wheel which is arranged therein can be inserted. In this the housing together with the pump wheel which is arranged therein is designed as an expendable part. This exemplary embodiment is particularly advantageous insofar as all “contaminatable parts”, namely the pump housing (inner wall) and the pump wheel which is arranged therein, can be replaced after every employment in the simplest manner, and the complicated and expensive parts (electrical supply of the drive, etc.) can be maintained and reused for the next employment without any danger of contamination existing. Furthermore, the electrical drive represents the most complicated and expensive part of the pump not only from the technical, but also from the economical point of view. The latter need however not be replaced, but rather only the less complicated and expensive pump housing with the pump wheel which is arranged therein.
In an advantageous further development of this exemplary embodiment permanent magnets are arranged in the pump wheel which then, together with the electromagnetic field which is produced by the drive stator, drive the pump wheel.
In an advantageous manner the expendable pump can be designed as a gear pump. This is a constructionally particularly simple type of pump which is also very economical to manufacture. Furthermore, gear pumps do not display the fatigue phenomena such as for example squeezed tube pumps, which are otherwise frequently used in such applications.
The bioreactor can for example be designed as a hollow fiber bioreactor, as has already been explained initially with reference to a special exemplary embodiment.
The bioreactor can however also be designed as a so-called airlift reactor (“Blasenreaktor”). In an airlift reactor it is in principle a matter of carrying out the liquid supplying (nutrient solution) and the likewise required supplying with gases such as e.g. oxygen in such a manner that bubbles rise in the liquid or are held there in flotation respectively.
In an exemplary embodiment of an airlift reactor of this kind the latter comprises a reaction container in which a hollow body is arranged, of which the jacket is connected at its lower end to the wall of the reaction container and tapers in the direction towards the upper end of the reaction container so that it subdivides the inner space of the reaction container into an upper chamber and a lower chamber. The upper and lower end side of the hollow body are designed to be liquid and gas permeable (e.g. as membrane) and enclose a cavity in which the substance to be acted upon (e.g. the cells or the micro carrier with the cells or the biodegradable matrix material with the cells) can be arranged. Depending on the kind of the employment however one or both membranes need not necessarily be present. The supply line for the liquid medium opens into the upper chamber and a suction device for the liquid medium is provided in the lower chamber. Through this a liquid flow is produced which comes from above and passes through the cavity in which the substance to be acted upon is arranged and into the lower chamber. A supply device for the gaseous medium is arranged in the lower chamber. This has the effect that the bubbles rise in the liquid. Since the speed of the liquid flow in the upper region of the cavity is however greater (smaller diameter) than in the lower region (greater diameter) the rising bubbles in the upper region are again taken along by the flow downwards where the flow speed of the liquid flow is again lower, for which reason the bubbles again begin to rise. Through a corresponding choice of the flow speed it is thus possible to “concentrate” the bubbles in the cavity in which the substance to be acted upon is arranged.
In a further development of an airlift reactor of this kind the

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