WO2009115346A2

WO2009115346A2 - Bioreactor and method for operating a bioreactor

Info

Publication number: WO2009115346A2
Application number: PCT/EP2009/002216
Authority: WO
Inventors: Oliver Lange; Dietmar Kunst; Steffen Siegert; Lutz Walter
Original assignee: Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V.
Priority date: 2008-03-19
Filing date: 2009-03-18
Publication date: 2009-09-24
Also published as: WO2009115346A3; DE102008016116A1

Abstract

The invention relates to a bioreactor (1,1'; 10) comprising at least one media container (2; 8, 8') and at least one organism container for cultivating organisms. The at least one media container can be connected or is connected to the at least one organism container by means of a pipe system (4; 40, 40'). In order to temporary immerse an organism that is in the organism container, a lifting device (5; 7, 7') that is designed to lift the at least one media container and/or the at least one organism container is provided.

Description

Bioreactor and method of operating a

bioreactor

The present invention is a bioreactor according to the preamble of claim 1, and a method for growing organisms with a bioreactor.

The ingredients of plants and other plant-like organisms have a not insignificant importance in medicine. The ingredients of plants or the plants themselves are used as starting materials, for example for the pharmaceutical industry or for large-scale plant divers. Various methods are known in the art for growing organisms accordingly.

Here are on the one hand stirred tank reactors or air-lifter reactors to call. With these reactors can Microbes, protozoa, cell groups or roots are grown in the reactors. The aforementioned reactors are already used industrially and serve to produce the aforementioned organisms in a sterile environment. As an example, be in the

Reference EP 1 491 623 A1 discloses the incubator disclosed. The incubator has an organism container for cell cultures, a first media container and a waste container. The three containers are arranged on the outside of a round drum, wherein the organisms container is arranged between the two other containers. The medium contained in the media container, which may contain, inter alia, an antibiotic, is added by means of rotation of the drum via a hose connected to the container of the organisms into the container of organisms which contains cell cultures. After a culture phase, the medium is added by rotation into the waste container connected to a second tube. The finished cell cultures can then be further processed. The cell cultures are isolated cells which are e.g. be solved with trypsin from a cell composite. Therefore, the incubator is not suitable for multicellular organisms: Only by the differentiation of the individual cells in the intact cell composite and the resulting growth of the individual from a variety of differentiated cells existing multicellular organism, the production of ingredients by the multicellular organism itself possible.

However, the multicellular organisms thus grown in the reactors or incubators have abnormal plant growth and content composition, as these are in an often weightless and permanently moist environment of the medium. This is a big disadvantage.

Another method for growing, for example, plants, is the so-called hydroponics, in which the plants grow normally on a nutrient medium and are often housed in an automated greenhouse. Due to the large area, however, it is difficult to perform the rearing of plants in a sterile environment.

For the sterile cultivation of plants there is a method with the temporary immersion method, with which multicellular organisms, in particular plants, can be easily multiplied. It soon develops from a plant leaf or a plant sample one or more whole plants. The cultivation of fungi or sponges, mussels or other lower species is also practicable with the method. The plants are wetted in the temporary immersion process at regular intervals with a nutrient medium, wherein the wetting can be done several times a day for a few minutes. Between wetting the organisms grow undisturbed and without the presence of the nutrient medium. Therefore, they develop the same ingredients and growth forms as in nature. These plants are particularly interesting as starting material for the pharmaceutical industry, as well as for large-scale plant propagators.

Numerous temporary immersion methods are already known in the prior art.

Classically, a temporary immersion system is performed in a twin glass layout. A container has the nutrient medium, an organism container the plants. In order to enable pure "relatively" large-volume productions of organisms, the medium is transported pneumatically from the media container into the organisms container. In this case, the organisms container can have up to 20 1 volume. By means of round filter attachments germ-free connections and decoupling to a time-controlled pneumatics are possible. Due to the used pneumatic overpressure of 0.3 to 0.5 bar, the vessels must not be too thin-walled and the pressure forces of the closures must be correspondingly high. This limits the size of the removal opening during plant harvesting.

The object of the present invention is to provide a bioreactor for performing a multi-cell temporary immersion method which reduces the aforementioned disadvantages of a temporary immersion system. The bioreactor should also be suitable for large-scale production of multicellular organisms.

The object is achieved with a bioreactor according to the features of claim 1. Further embodiments are described in the subordinate claims.

The bioreactor according to the invention has at least one media container and at least one organisms container for growing organisms. The organisms referred to below as organisms are all to be understood as multicellular organisms which have a plurality of differentiated cells in a cell composite, ie multicellular refers to an entire organic cell composite of the organism of origin, ie the whole plant, not just individual cells thereof. Such multicellular organisms are thus z. As plants, sponges or multicellular Mushrooms. Unicellular cells or isolated cells are excluded from the term organisms used herein.

The at least one media container can be connected or connected to the at least one organisms container via a tube system. Furthermore, a lifting device is provided, wherein the lifting device is designed to lift the at least one media container and / or the at least one organisms container.

With the aid of the lifting device, either the media container and / or the container for organisms can be moved upwards or downwards, preferably in an exclusively vertical movement. Since the at least one organism container is connected to the at least one media container via a tube system, in the case of a medium in the medium container, the medium can flow into the container through the tube system

Organisms container arrive without a significant overpressure must be applied to the system. The transport of the medium from the media container to the organisms container or back is essentially realized by the principle of the communicating tubes. This means that as soon as the media container is raised above a certain height level of the organism container, a medium in the medium container flows through the tube system for compensation and fills the organism container so that the level of filling between the medium container and the organism container is equalized. The only pressure generated during transport of the medium is essentially the pressure resulting from the difference in height between the media container and the container. Preferably, this serves Tubing system for transporting the medium from the media container to the organisms container and back, whereby a single tube of the tube system can both return and return the medium.

The transport of media from the media container to the container of organisms and vice versa is therefore carried out by vitreometry. One of the consequences of this is that the at least one media container and the at least one organisms container can be configured very simply, since they are no longer under an overpressure. One of the consequences of this is that in the choice of containers for the medium and the organisms hitherto, embodiments which can not be used in the context of the temporary immersion method can be used. Furthermore, can be dispensed pumps for media transport. This facilitates, in particular, the control and monitoring of the bioreactor, since the number of mechanical-working elements is reduced. In the case of the temporary immersion method carried out by means of the bioreactor according to the invention, the medium or nutrient medium is introduced several times into the at least one organisms container to a certain filling level and then returned to the medium container. The medium is therefore used repeatedly before it has to be replaced. In particular, the organisms are not permanently immersed in the medium, but only temporarily.

In addition, since the at least one media container and the at least one organisms container are carried out separately, the modularity of the bioreactor is increased. This means in particular that the organisms container or the media container, both with the appropriate content, during operation of the bioreactor can be replaced. This means, for example, if the media container is in a position in which the entire medium is in the media container, the organisms container, for example because the plants are fully grown, can be exchanged for a new container organisms. In turn, in a spent medium, ie, at a time when the medium has an insufficient concentration of nutrients responsible for the growth of the organisms, can be exchanged for a new container with a medium or filled with a new medium.

To ensure undisturbed growth of the organisms in the at least one organism container, the organism container, after one or more organisms have been introduced, is not more than 25 °, preferably less than 10 °, with respect to the direction of gravity tilted less than 5 °. The tilting leads to a turbulence of the organisms and thus disturbs their natural growth. The tilting of the at least one organism container is to be avoided substantially. A purely horizontal and vertical movement of the at least organisms container is to be preferred according to the natural growth conditions of the organism in nature. Particularly preferred is a stationary or stationary arrangement of the at least one organism container while in this growing organisms are arranged. To remove the organisms they can be removed.

It may be advantageous to form the container of the organism in such a way that the organisms introduced can be localized with respect to the organism container. can firmly arrange or rooted in the organisms container.

As mentioned at the beginning, a large range of possible materials for the containers will be made available due to the fact that the containers need not be under substantial overpressure. This extends from e.g. Bags made of thin plastics up to stable glass containers or stainless steel tanks. The bioreactor according to the invention is particularly suitable for the sterile growing of organisms, preferably, plants, fungi, sponges or algae.

In the following, various embodiments of the bioreactor according to the invention will be explained.

In one embodiment of the bioreactor, the at least one media container and / or the at least one organisms container has a coupling or the tube system has a coupling, wherein the media container can be connected to the tube system or the organisms container can be connected to the tube system via the coupling. With the aid of the couplings and, in particular, in the event that the couplings also have a valve function, the individual containers located in the bioreactor can be removed separately from each other in a particularly simple manner. For example, peristaltic pinch valves, quick couplings, sterile couplings or similar valves or couplings can be used.

In a further embodiment of the bioreactor, the at least one organisms container is closable, preferably resealable, and / or sealed. About the sealing of the minimum At least one organism container can be made so that it is kept sterile and no undesirable microorganisms contaminating the rearing of the organisms can penetrate into the at least one organism container. By closability and reclosability it can be achieved that a container can be used several times for the rearing of organisms. As possibilities for closability or reclosability are here, for example snap closures or

Called screws. As seals, for example, pinch seals made of rubber or plastic can be used.

In a further embodiment, at least one container for organisms is associated with a device for air-conditioning and / or a device for ventilation and / or a device for lighting. With the aid of a device for air conditioning, the suitable conditions for the growth of organisms in the organisms container can be set. This relates, for example, to the humidity within the organisms container or the gas composition with CO ₂ content, ethylene content or trace gas content, which can all be controlled by means of a device for air conditioning. In this case, the device for air-conditioning is preferably connected directly to the at least one container of organisms, whereby the sterility of the interior of the at least one container of organisms, for example via membranes, can be ensured. By means of a ventilation device, in addition to the parameters already mentioned above, a circulation of the atmosphere inside the at least one container of organisms is effected, whereby the growth or the uptake of breeding of organisms is accelerated or improved. Advantageously, the at least one container of organisms associated with a device for lighting, so that the organisms located in the at least one container organisms can develop in a suitable manner. This may involve, for example, the device simulating a daily routine adapted to the natural biotope of the organisms. With regard to the irradiation, preferably a device is used for the illumination which radiates both in the UVB and in the UVA as well as in the visible range. Preferably, the device does not radiate in the far or mid-infrared to cause no heating of the interior of the at least one organism container. In the embodiments of a device for air conditioning and / or a device for ventilation and / or a device for lighting, the aforementioned devices may each be responsible for an organism container or for a plurality, ie at least two, container organisms, ie in these the desired conditions manufactures.

In a further embodiment of the bioreactor there is at least one rack with at least one parking space, preferably several parking spaces, wherein the at least one organisms container is arranged at a parking space. On such a shelf, a plurality of organisms containers can be arranged. Preferably, a plurality of organisms container are supplied by a media container, wherein the ratio of a single container of organisms to the media container is greater than 1: 4, preferably greater than 1:10. Furthermore, it is advantageous if the shelf is stationary, ie, the media container is arranged on a lifting device assigned to it. are net. In particular, by the allocation of a plurality of organisms containers, which are supplied by a media container, an industrial production of the organisms in a simple manner possible. Only the media containers have to be moved up and down, it being necessary to replace precisely this organism container in one of the organisms container only in the case of a ready-made organism. Furthermore, the use of a shelf is advantageous because it can be attached to this various organisms associated with the organisms containers, such as a device for ventilation, air conditioning or lighting.

In a further embodiment, the at least one organism container is transparent in the visible, preferably in the visible and in the ultraviolet, range. In this case, for example, light-permeable plastics, such as polycarbonate or polypropylene or cyclic olefins, are used as materials.

Copolymers, since they have a good UV transmission, are used. In this case, the at least one container organisms may consist of a shaping container, i. a container which does not change its shape or from an informal container, such as a bag, which e.g. is spanned by a frame.

In a further embodiment, the at least one organism container has a ventilation opening, by means of which easily existing pressures due to the penetration of the medium can be compensated by a membrane. Here, the connection of the ventilation access with the device for air conditioning can have a particularly advantageous effect. In a further embodiment, at least one sensor container is assigned to the at least one organism container, wherein the at least one sensor monitors process parameters. Such process parameters include, for example, light, ie the amount of light and intensity impinging on the container, the degree of immersion by the medium, the duration of immersion or wetting of the organisms by the medium, the ventilation, the temperature or the composition of the atmosphere inside the container of the organism. The arrangement of at least one sensor is advantageous in order to carry out a later automation of the monitoring of the processes by means of a data processing system. For this purpose, it is another embodiment of the bioreactor that a data processing system for monitoring and / or control of process parameters is present. In addition to the process parameters mentioned in this section, the nutrient content of the medium or the degree of growth of the individual organisms in the organisms container can also be checked by means of correspondingly arranged sensors in the media container or in the tube system, it being advantageous for a fully grown organism or for irregularities , such as B. one

Light failure, the data processing system outputs a signal or alarm. Furthermore, it is advantageous if the data processing system has a documentation, with regard to the prevailing process parameters and other concomitant circumstances, e.g. tabulated as a time series. In this way, it is possible to industrially utilize the bioreactor on a large scale.

In a further embodiment, the at least one organisms container has a volume of 10 to 200 1, preferably from 20 to 80 1, particularly preferably from 30 to 60 1 on. This size has the advantage that the container organisms are empty or overgrown with organisms can still be implemented by hand. In this way, the bioreactor remains interesting even if automation has not been carried out on an industrial scale. The media container may have a volume of from 10 1 to more than 800 liters in accordance with the number of organisms to be supplied by it.

In a further embodiment, the lifting device is formed by a winch or a crane or a freight train. If necessary, for example, forklift trucks or lifting carts are used in such a way that in the case of small dimensions of the bioreactor, in which an industrially fully automated utilization is not yet worthwhile, the method can also be carried out predominantly manually or there is no permanent lifting device.

In a further embodiment, the tube system has at least one tube and / or a hose and / or a branching element. With the help of hoses, pipes and branching elements, a media container can supply a plurality of organisms containers, or several media containers supply several organisms containers at the same time, or several media containers supply an organism container. As already mentioned above, the tube system may have valves and couplings to consume in a solution of the compound for the exchange of either the media container and / or the Organmenbehälters no medium or not endanger the sterility of the system. It is also possible to form the tube system with fixed tubes, whereby a Vorrich- tion establishes the connection between the media container and the pipe system or between the pipe system and the container organisms. This could be a fifth wheel can be used.

In an alternative embodiment, the bioreactor likewise has at least one media container and at least one organisms container, wherein the at least one media container can be connected or connected to the at least one organisms container via a tube system. However, a conveyor device is used for transporting the medium through the tube system, wherein the delivery pressure of the delivery device does not exceed a gravitometric delivery pressure. This means that the delivery pressure of the delivery device must be less than 0.1 bar. An advantageous conveying device would in this case be a peristaltic pump or a vacuum suction pump, since these are suitable for working with low delivery pressures.

In the following, the invention will be explained in more detail with reference to some embodiments. Show it:

FIGS. Ia and Ib embodiment of the bioreactor and principle of communicating tubes;

2 shows another embodiment of a bioreactor;

Fig. 3 embodiments of a bioreactor system;

Fig. 4 Orientation of a moving organisms container to the direction of gravitational attraction. The principal mode of action of the bioreactor will be described with reference to FIGS. 1a and 1b. In Fig. Ia, a bioreactor 1 is shown with a media container 2 and an organism container 3, wherein the media container 2 and the organisms container 3 are connected to each other by a tube system 4. For this purpose, the tube system 4 to a coupling

20 of the media container 2 and connected to a coupling 30 of the organism container 3. The couplings 20 and 30 simultaneously perform a valve function, i. that the connection between the medium container 2 and the tube system 4 or the organisms container 3 and the tube system 4 can be achieved without the risk that a medium 21 located in the medium container 2 exits.

The media container 2 is attached to a lifting device 5. In this case, the lifting device 5 has a frame 50 and a cable 51, wherein a cable winch is not visible within the frame, so that the media container 2 can be moved upwards and downwards in the Y direction. The length of the tube system 4 is chosen so that for the adjustable height positions of the media container 2 is always a connection between the media container 2 and the organisms container 3 is possible. The medium

21 is intended for immersion of organisms present in the organism container 3. It contains nutrients which contribute to the growth and rearing of the organisms in the organisms container 3.

The media container 2 consists of a hard plastic. This is translucent. Outside the media container 2, arranged on this, there is a sensor which measures the level of the medium 21.

The measurement does not take place from the outside around the sterile path to contaminate. Alternatively, the media container may also be made of an opaque plastic or steel.

The organism container 3 is made of polycarbonate. This is permeable to light, in particular in the visible and UVA / UVB range, so that the organism in the organism container 3 also produces ingredients which are produced only under the influence of ultraviolet rays.

The organism container 3 is elevated relative to the illustrated position of the media container 2 in the Y direction on a shelf 6. The shelf here has the shape of a stool, wherein the height of the stool is selected such that when standing on the bottom B media container 2 located in the media container 2 medium 21 has a level Fl, which measured on a from the ground from height Hl. The organism container 3 is arranged such that the bottom or the coupling

30 of the organism container 3 in the Y direction above the height H sits. This essentially means that in the illustrated position of the media container 2 and the organism container 3, no medium 21 is in the container 3 organisms.

In Fig. Ib the media container 2 is shown in a different position. The media container was pulled upwards in the Y direction by means of the cable 51 and the invisible cable winch. When pulling up, the medium 21 passes through the tube system

4 via the clutch 30 in the organisms container 3 and immersed therein organisms. By lifting the media container 2, the relative filling level in the media container 2 drops to the level F2. Viewed absolutely above the bottom B, the level F2 is at a height H2. The height H2 is located at a height level above the bottom or the coupling 30 of the organisms container 3, so that it has a level F3, wherein the level F3 is essentially formed by the difference between the height H2 and the shelf 6.

The in Figs. Ia and Ib described principle of immersion is described as the principle of communicating tubes. In order to remove the medium 20 again from the organisms container 3, the media container 2 is again lowered to the position shown in FIG. 1a. The pressure which occurs due to the inflow of the medium 21 into the organisms container 3, as occurs in a state between the states shown in FIG. 1 a and in FIG. 1 b, is extremely low. Due to the fact that due to the hydrostatic laws both in the media container 2 and in the organisms container 3, measured absolutely from the bottom B, equal fill levels, the inflow velocity of the medium 21 is determined only by the speed of lifting the media container 2. A pressure difference between the media container 2 and the Organmenbe- container 3 is essentially not.

By an unillustrated connection of the organism container 3 with the media container 2 at the lying in the Y direction upper ceiling, the displaced due to the influx of the medium 21 in the organisms container 3 atmosphere is diverted into the media container 2, as in this due to the sinking level of the level Fl to the level F2 forms a negative pressure, which can be compensated with the atmosphere of the organisms container 3. In one of these Art closed system would be the sterility, which is to prevail in the organisms container 3, at least until replacing one of the media container 2 and the Organmenbehälters 3 given. Alternatively, the containers have an external filter to provide access for the air which must flow out or in due to the medium flowing into or out of the organism container. The pore depth is chosen so that there is no contamination of the sterile path, eg 0.2 μm

Based on the Fign. Ia and Ib can also be discussed on the modul- rity of the bioreactor. In the state shown in FIG. 1 a, there is no medium 21 in the organisms container 3, that is to say that the tube system 4 can be separated from the coupling 30 and the organisms container 3 can be exchanged for an organism container comparable to it. This is the case, for example, when the organism to be raised, such as plants, in particular phytopharmaceuticals, has reached a size which is suitable for further processing or for transfer to a large-scale plant propagator. The new organism container is then connected to the tube system 4 and, like the preceding organism container 3, can be immersed via the medium container 2.

Analogously to the preceding section, as shown in FIG. 1a, the media container 2 can also be exchanged with the medium 21 located therein if, for example, the nutrient content of the medium 21 has dropped below a critical state.

2 is another embodiment a bioreactor. The bioreactor I ¹ has a plurality of organisms containers 31 to 38, which are arranged on a shelf 6 ¹ in two planes. The levels are defined by the shelves 60 and 61. The organisms container 31 to 38 have as the organisms container 3 in Figs. Ia and Ib a coupling 30 and 30 ', to which a tube system 40 and 40' is connected. The tube system 40 supplies the organisms containers 35 to 38, the tube system 40 'and the containers 31 to 34.

The organisms containers 35 to 38 are each assigned their own device for illumination 65 to 68. The device illuminators 65 to 68 radiate both in the visible and in the UVA or UVB range, and are designed as light-emitting diodes, since they show only a small heat in the organisms containers with a well-defined radiation spectrum. In addition, the infrared range can be avoided. However, fluorescent tubes and / or filters can also be used, wherein the filter can be arranged both directly on the device for illumination and on the container itself.

The organisms containers 31 to 34 are powered by a single lighting device 62. That is, the irradiation of the organisms container 31 to 34 is substantially the same as long as the material of the organisms container 31 to 34 is the same. Of course, it is also possible to achieve a different radiation characteristic in the interior of the organisms containers 31 to 34 through a different choice of material for the different organisms containers 31 to 34. Arranged on the shelf or to the Organized containers are various developments of the simplest embodiment of the bioreactor, which, however, can be combined. For example, a device for air conditioning 63, 63 'is shown, which the air conditioning container 36. Furthermore, a device for aeration is arranged on the organisms container 36, which circulates and regulates the moisture contained in the interior of the organisms container 36 via the ventilation inlet 360. The organism container 36 has outside a sensor 361 for monitoring the atmospheric composition with respect to the humidity of the CO ₂ content, the proportions of noble gases and ethylene. Arranged on the organism container 37 is a sensor 370 which registers, measures and / or monitors the brightness of the light arriving from the organism container 37 of the illuminating device 67. Thus, for example with the aid of a data processing system, an occurring radiation characteristic in the interior of the organism container 37 can be compared with a desired radiation characteristic for the organisms growing in the organism container 37, and a preferably automatic within a statistically relevant range

Changing the irradiation characteristic of the lighting device 67 are made.

Left and right of the shelf 6 'lifting devices 7, 7 ¹ are arranged, wherein these a carrier 71 and

71 'and a load plane 72 or 72' have. On the load levels 72 and 72 ', a media container 8 and 8' is arranged. By means of a drive of the lifting device 7 or 7 ', the media containers 8 and 8' can be moved up and down in the Y direction. The tube system 40 provides the connection between the Media container 8 and the organisms containers 35 to 38. The tube system 40 in this case has a flexible hose member 401, which is connected via a valve 402 with a rigid tube 403 on. The length or flexibility of the hose element 401 is sufficient to allow the media container 8 to be moved up and down so that a medium located in the media container 8 can pour into the organisms containers 35 to 38 and can also flow completely out of them , On the rigid tube 403 branching elements 404 are arranged, via which the tube system 40 is connected to the couplings of the organisms container 35 to 38. In the present case, the media container 408 supplies four organisms containers 35 to 38, which can be immersed simultaneously through the media container 8. The media container 8 is arranged such that the fill level F2 in the media container 8 leads to a level F3 in each one of the organisms container 35 to 38. In order to stop the immersion of the organisms contained in the organisms containers 35 to 38, the media container 8 is moved down in the Y direction until the filling level F3 has dropped to zero.

This scenario is illustrated by the media container 8 ¹ . The media container 8 ¹ is analogous to the media container 8 via a tube system 40 'with a flexible tube member 401' and a rigid tube 403 'via branch elements 404' connected to the couplings of the organisms container 31 to 34. In the position shown, the medium in the media container 8 'occupies a level Fl. This is at a height so that there is no medium in any of the organisms containers 31 to 34. As an alternative to the organisms containers 31 to 38, which consist of forming containers made of polycarbonate, pouches, for example made of polypropylene, can also be attached to the shelf 6 ¹ . The bags have the advantage that they are inexpensive to produce and save space to transport. These would be hung on the ceiling of the shelves, similar to an infusion bag in a hospital, the tube system having a plurality of flexible tubular elements.

The illustrated organisms containers have a volume of 40 to 50 1. In order to achieve an immersion level of at least 75%, the media container must have a volume of between 120 and 150 l. The bioreactor I ¹ shown in Fig. 2 can be scaled up, in the sense that the organisms containers are stacked over more than two levels and between 20 to 60 organisms containers are connected to a media container. In this case, a corresponding size of the media container between, for example, 500 and 1500 1 is possible. This would preferably be made of steel or another stable material. Preferably, however, the stack height of the organisms containers should not exceed the visual height exceeding that for an observer, so that in addition to possibly existing automatic monitoring mechanisms, manual control of the organisms by the operating personnel can also be undertaken.

In the bioreactor I ¹ shown in FIG. 2, the media containers 8 and 8 'are exchanged as soon as the nutrient content of the medium has fallen below a critical value. Once in a the organism container 31 to 38 living beings, such as sponges, has reached the desired level of breeding, the organism container can be replaced individually, independently of the other organisms containers, without any fear that in a renewed immersion the medium from the corresponding branch piece 404 would splash out. In addition, a capacitive sensor can be arranged on the organisms containers, wherein the capacitive sensor monitors the filling level F3 and closes one of the valves of the bioreactor in order to prevent flooding of the organisms container. Pinch valves can preferably be used as valves in order to avoid contamination of the sterile path by valves in the interior of the bioreactor.

FIG. 3 shows a bioreactor system 10, by means of which the possible degrees of automation are to be explained in greater detail. The bioreactor system 10 has a data processing system 11 as well as bioreactors 12, 12 'and 12 ", which respectively correspond to a bioreactor 1' of Fig. 2. The data processing system 11 is connected to the bioreactors 12 to 12" via the connection 100 or 100 'resp ,

100 "The connection records and monitors all values of the values determined by the sensors of the individual container or media container, for example, it can be automatically determined when which media container needs to be replaced, as well as the container Lighting, ventilation and air conditioning are monitored and controlled.

With the system shown in FIG. 3, it is possible to lent to operate the bioreactor on an industrial scale, for example in factory size.

All bioreactors or bioreactor systems disclosed in the description can also clonally reproduce under reproducible conditions. This leads to a high product consistency, which enables a seasonally independent continuous production.

The ingredient profile of the plants may be controlled by the adjustable climatic factors, whereby the ingredient yield may be many times that of other rearing methods. In addition, it is particularly advantageous that the organism grown in the at least one organism container can be produced at the processing location, whereby transport costs and influences are eliminated. In addition, genetically modified plants can be produced without being released, which is of great importance in the context of legislation. The production of pharmaceutical novel ingredients can also be carried out by means of "molecular farming" in a bioreactor according to the invention. The illustrated bioreactors or bioreactor systems produce the products under sterile conditions and with high quality. Consumers of the organisms or ingredients of the organisms are, for example, the pharmaceutical industry, the cosmetics industry or crop producers or ornamental plant producers.

In the embodiments shown here, the organisms container during the rearing of an organism in the same are arranged stationary. Consequently, the orientation of the organisms containers in relation to the direction of gravitational attraction during breeding essentially unchanged. If a variant of the bioreactor according to the invention is to be intended with an organism container to be moved by the lifting device, care should be taken that the organism container 39 shown by way of example in FIG. 4 is less than α = 25 °, with respect to the direction of gravity G less than α = 10 °, more preferably inclined less than α = 3 °.

The lifting movement of the lifting device described in the exemplary embodiments can also be achieved by a particularly low delivery pressure, e.g. a peristaltic pump.

Claims

claims

1. Bioreactor (1; 1 '; 10) for a temporary immersion method with at least one media container (2; 8, 8') and at least one organisms container (3; 31, 32, 33, 34, 35, 36, 37, 38) for the cultivation of multicellular organisms, wherein the at least one media container is connectable or connected to the at least one organisms container via a tube system (4; 40, 40 '), characterized in that a lifting device (5; 7, 7 ¹ ) is present, wherein the lifting device is designed to lift the at least one media container and / or the at least one organisms container and the at least one organisms container during the breeding of the multicellular organisms in

With respect to the direction of gravitational pull is tilted by less than 10 °.

2. bioreactor according to claim 1, characterized in that the at least one organism container during the breeding of the multicellular organisms in its orientation with respect to the direction of gravitational attraction is substantially unchanged or is stationary.

3. Bioreactor according to one of claims 1 or 2, characterized in that the at least one

Medium container (2; 8, 8 ¹ ) and / or the at least one container organisms a coupling (10; 30, 30 ') and / or have a valve and via the coupling and / or the valve with the tube System (4; 40, 40 ') are connectable or connected.

4. bioreactor according to any one of the preceding claims, characterized in that the at least one organisms container (3; 31, 32, 33, 34, 35,

36, 37, 38) at least one sensor is assigned, wherein the at least one sensor monitors process parameters.

5. Bioreactor according to one of the preceding claims, characterized in that the at least one organisms container (3; 31, 32, 33, 34, 35, 36, 37, 38) is closable, preferably recloseable, and / or sealed.

6. Bioreactor according to one of the preceding claims, characterized in that the at least one container organisms (3; 31, 32, 33, 34, 35, 36, 37, 38), a device for air conditioning and / or a ventilation device and / or a device for lighting is associated.

7. Bioreactor according to one of the preceding claims, characterized in that at least one shelf (6; 60) with at least one parking space, preferably a plurality of parking spaces, is present, and the at least one container organisms is arranged at a parking space.

8. bioreactor according to any one of the preceding claims, characterized in that the at least one organism container (3; 31, 32, 33, 34, 35, 36, 37, 38) in the visible, preferably in the visible and in the ultraviolet region, is translucent.

9. Bioreactor according to one of the preceding claims, characterized in that the at least one organisms container (3; 31, 32, 33, 34, 35, 36, 37, 38) has at least one ventilation access.

10. Bioreactor according to one of the preceding claims, characterized in that the at least one organism container has a volume of 10 to 2001, preferably 20 to 801.

11. Bioreactor according to one of the preceding claims, characterized in that the at least one media container (2, 8, 8 ') has at least one sensor.

12. Bioreactor according to one of the preceding claims, characterized in that the tube system (4; 40, 40 ') at least one tube (403, 403') and / or a hose (401, 401 ') and / or at least one Branching element (404).

13. Bioreactor according to one of the preceding claims, characterized in that a data processing system (11) for monitoring and / or control of process parameters is present.

14. Use of a bioreactor according to one of the preceding claims for the cultivation of plants or sponges or mussels or fungi or algae.

15. A method for operating a bioreactor according to any one of the preceding claims, character- ized in that a delivery pressure within the

Tube system does not exceed 0.1 bar.