Bioreactor Support System

Abstract

A bioreactor support system, configured to hold a bioreactor bag, the bioreactor support system (1) comprising: a base module (3) comprising an impeller drive unit (5); and at least two container units (11a, 11b, 11c) of different sizes, configured to support and substantially surround the side walls of the bioreactor bag (111a, 111b, 111c) when the bioreactor bag is provided in the bioreactor support system (1), wherein the base module (3) and the at least two container units (11a, 11b, 11c) comprises matching connection means (13a, 13b, 13c, 15a, 15b, 15c) so that at least two container units (11a, 11b, 11c) can be connected to the same base module (3), and so that the impeller drive unit (5) of the base module (3) can be used to drive the impeller (113a, 113b, 113c) in the bioreactor bag (111a, 111b, 111c) when the bioreactor bag is provided in the bioreactor support system (1).

Description

Technical Field

[0001] The present invention relates to a bioreactor support system configured to hold a bioreactor bag, a bioreactor system comprising such a bioreactor support system, a base module of such a bioreactor support system, and to a method for cultivating cells in such a bioreactor system. Background Art

[0002] Bioreactors are typically used for a range of different cell culture volumes. The maximum working volume for a bioreactor is the maximum volume of cell culture that the bioreactor can handle, and the minimum working volume for a bioreactor is the minimum volume of cell culture that the bioreactor can handle. The maximum and minimum working volumes depend on the size of the bioreactor bag and the position of the impeller and sensors within the bag. The ratio between the maximum working volume and the minimum working volume for a bioreactor is called the turn-down ratio. An example of a turn-down ratio for a bioreactor can be 5:1, i.e., for example, a maximum working volume of 10 liters and a minimum working volume of 2 liters. A larger span of working volumes would be desirable and would be advantageous for customers who want to use bioreactors for both laboratory scale and processing and production scale. For large bioreactor bags, there are limits on how small the minimum working volume can be due to the position of the impeller and sensors. Summary of the invention

[0003] It is an object of the present invention to provide a bioreactor system and a method for culturing cells that can handle a wide range of cell cultivation working volumes.

[0004] This is achieved by a bioreactor support system for growing cells, a bioreactor system, a base module of a bioreactor support system and a method according to the independent claims.

[0005] According to one aspect of the present invention, there is provided a bioreactor support system configured to hold a bioreactor bag, the bioreactor support system comprising:

[0006] - a base module comprising an impeller drive unit; and

[0007] - at least two container units of different sizes, which are configured to support and substantially surround the side walls of the bioreactor bag when the bioreactor bag is provided in the bioreactor support system,

[0008] The base module and the at least two container units comprise matching connection means, so that when the bioreactor bag is provided in the bioreactor support system, at least two container units can be connected to the same base module, and so that the impeller drive unit of the base module can be used to drive the impeller in the bioreactor bag.

[0009] According to another aspect of the present invention, a bioreactor system is provided, comprising a bioreactor support system as defined above, and at least two bioreactor bags of different sizes corresponding to the different sizes of at least two container units, each of the at least two bioreactor bags comprising an impeller and an impeller connector.

[0010] According to another aspect of the present invention, there is provided a base module of a bioreactor support system configured to hold a bioreactor bag, the base module comprising:

[0011] - at least a first container unit connection means and a second container unit connection means, wherein the first and second container connection means are configured for connection to container units of different sizes, wherein the container units are comprised in a bioreactor support system and are configured to support and substantially surround a side wall of a bioreactor bag when the bioreactor bag is provided in the bioreactor support system; and

[0012] - An impeller drive unit configured to drive an impeller in the bioreactor bag when the bioreactor bag is provided in the bioreactor support system.

[0013] According to another aspect of the present invention, there is provided a method as defined above for cultivating cells in a bioreactor system.

[0014] A bioreactor system is thus provided, which can handle a wide range of cell cultivation working volumes. Thus the bioreactor system can be used for laboratory scale and for processing and production. Due to the possibility of changing between container units of different sizes, the range of working volumes can be increased. For example, the minimum working volume can be 0.5 liters, and the maximum working volume can be 10 liters. The base module includes an impeller drive unit, and by keeping the same base module connected to at least two container units of different sizes, one at a time, the same impeller drive unit is used for different container units. Thus the same stirring mechanism can be used for container units of different sizes. The ratio between the impeller diameter and the inner diameter of the container can remain the same in different container units. This will improve the predictability of the customer for amplification (scale up). The possibility of amplification and still using the same stirring mechanism and the same ratio between the impeller diameter and the inner diameter of the container will improve predictability. The container unit can be changed simply and quickly, and the customer will obtain the possibility and predictability of amplification.

[0015] In one embodiment of the present invention, the base module includes a container unit connecting part, wherein the container unit connecting part includes at least a first container unit connecting device and a second container unit connecting device, wherein the first and second container unit connecting devices are configured to be connected to container units of different sizes, and wherein the at least two container units include at least a first container unit and a second container unit, which have different sizes, wherein the first container unit includes a first base module connecting device, the first base module connecting device is configured so that it can be connected to the first container unit connecting device of the container connecting part of the base module, and wherein the second container unit includes a second base module connecting device, the second base module connecting device is configured so that it can be connected to the second container unit connecting device of the container unit connecting part of the base module.

[0016] In one embodiment of the invention, the at least two container units each comprise a substantially cylindrical side wall, wherein the cylindrical side walls of different container units have different diameters.

[0017] In one embodiment of the invention, when one of the container units is connected to the base module, the container unit and the base module are configured to support the bottom wall and the side walls of the bioreactor bag when the bioreactor bag is provided in the bioreactor support system.

[0018] In one embodiment of the present invention, the impeller drive unit is configured to provide a rotating magnetic field, and wherein the base module includes an impeller connection location, wherein an impeller connector provided in a bioreactor bag can be provided in a position allowing the rotating magnetic field from the impeller drive unit of the base module to drive the impeller of the bioreactor bag, the bioreactor bag being provided in a bioreactor support system.

[0019] In one embodiment of the present invention, the base module includes a container unit connecting part in the form of a bioreactor bottom support plate, wherein the container unit connecting part includes at least a first and a second container unit connecting device and an impeller connection position provided as an opening, wherein at least two container units are configured to be connected to the upper side of the container unit connecting part, and the impeller drive unit is provided on the opposite side of the container unit connecting part, and wherein the opening in the container unit connecting part is configured to receive an impeller connector provided in a bioreactor bag, and the bioreactor bag can be provided in the bioreactor support system so that the impeller connector can be provided in a position relative to the impeller drive unit, which allows the rotating magnetic field from the impeller drive unit to drive the impeller of the bioreactor bag.

[0020] In one embodiment of the invention, at least one of the container units comprises a generally cylindrical side wall including a portion of the side wall that can be pivoted outwardly so that an opening into the interior of the container unit can be provided for loading a bioreactor bag into the bioreactor support system.

[0021] In one embodiment of the present invention, at least one of the container units includes a generally cylindrical side wall, which is divided into a first side wall portion and a second side wall portion, each of which includes a generally semi-cylindrical wall and optionally includes an opening for accessing the interior of the container unit from the outside, wherein the first side wall portion includes a base module connection device and is configured to be connectable to the base module, and the second side wall portion is pivotally connected to the first side wall portion so that the second side wall portion can be pivoted into at least one open position and a closed position, the open position allowing access to the interior of the container unit, and in the closed position the first and second side wall portions together form a generally cylindrical side wall.

[0022] In one embodiment of the invention, at least one of the container units comprises one or more flexible heater pads on the inner surface of the side wall, the flexible heater pads being configured to heat the bioreactor bag when the bioreactor bag is provided in the bioreactor support system.

[0023] In one embodiment of the invention, at least one of the container units comprises at least one opening in a side wall to allow access to the bioreactor bag when the bioreactor bag is provided in a bioreactor support system.

[0024] In one embodiment of the present invention, at least one of the at least one opening comprises graduations for indicating different volumes.

[0025] In one embodiment of the invention, at least one of the container units comprises a sensor holder provided for connection with an opening in a side wall of the container unit, wherein the sensor holder is attached to the side wall of the container unit such that its position can be adjusted along the height of the container unit.

[0026] In one embodiment of the invention, the method is a scale-up process, wherein during scale-up, different sizes of bioreactor bags and container units may be used for cell cultivation.

[0027] In one embodiment of the invention, the method is a perfusion process. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1a-1c A bioreactor support system according to an embodiment of the present invention is schematically shown, and three container units of different sizes are connected.

[0029] FIG. 2a schematically shows a closed position. Figure 1a-1c The container unit of the bioreactor support system shown in FIG.

[0030] Figure 2b The same container unit as shown in Fig. 2a is schematically shown, but in an open position.

[0031] Figure 3 Schematically shows the Figure 1a-1c The base module of the bioreactor support system shown in .

[0032] Figure 4 The connection between the impeller drive unit of the base module and the impeller in the bioreactor bag is schematically shown.

[0033] Figure 5 A bioreactor system comprising a bioreactor support system and a bioreactor bag according to one embodiment of the present invention is schematically shown.

[0034] 6a and 6b show a container unit and a base module according to one embodiment of the invention including a header. DETAILED DESCRIPTION

[0035] Figure 1a-1c A bioreactor support system 1 according to one embodiment of the invention is schematically shown. The bioreactor support system 1 is configured to hold a bioreactor bag and comprises according to the invention one base module 3 and at least two container units 11a, 11b, 11c of different sizes, which are configured to support and substantially surround the side walls of the bioreactor bag when the bioreactor bag is provided in the bioreactor support system 1. In this embodiment of the invention, three container units 11a, 11b, 11c of different sizes can be connected to the base module 3, but the number of container units can vary.

[0036] FIG. 2a schematically shows a closed position. Figure 1a-1c The container units 11a, 11b, 11c of the bioreactor support system 1 are shown in FIG. This can be any one of the container units 11a, 11b, 11c of different sizes. They can be suitably designed to be almost identical, but differ in size. Figure 2b The same container units 11a, 11b, 11c as shown in FIG. 2a are schematically shown, but in an open position. Figure 3 Schematically shows the Figure 1a-1c The base module 3 of the bioreactor support system 1 is shown in FIG.

[0037] The base module 3 according to the present invention comprises an impeller drive unit 5. Furthermore, according to the present invention, the base module 3 and the at least two container units 11a, 11b, 11c comprise matching connection means 13a, 13b, 13c, 15a, 15b, 15c, so that at least two container units 11a, 11b, 11c can be connected to the same base module 3, and so that the impeller drive unit 5 of the base module 3 can be used to drive the impellers 113a, 113b, 113c in the bioreactor bags 111a, 111b, 111c when the bioreactor bags are provided in the bioreactor support system 1. An example of a bioreactor system 101 comprises a bioreactor support system 1 according to an embodiment of the present invention, and Figure 5 1 and 12. The bioreactor support system 1 according to the present invention is configured to allow the connection of bioreactor bags 111a, 111b, 111c of different sizes and to allow the control of impellers 113a, 113b, 113c of different sizes as will be further described below.

[0038] The base module 3 further comprises a container unit connection portion 7, wherein the container unit connection portion 7 comprises at least a first container unit connection device 15a and a second container unit connection device 15b, wherein the first and second container unit connection devices 15a, 15b are configured to be connected to container units 11a, 11b of different sizes. The at least two container units 11a, 11b comprise at least a first container unit 11a and a second container unit 11b of different sizes. Figure 1a-1c In the embodiment shown in , a third container unit 11c is also provided. The first container unit 11a includes a first base module connection device 13a, which is configured so that it can be connected to the first container unit connection device 15a of the container unit connection part 7 of the base module 3, and the second container unit 11b includes a second base module connection device 13b, which is configured so that it can be connected to the second container unit connection device 15b of the container unit connection part 7 of the base module 3, and if a third container unit 11c is provided, it includes a third base module connection device 13c, which is configured so that it can be connected to the third container unit connection device 15c of the container unit connection part 7.

[0039] In this embodiment of the invention, at least two container units 11a, 11b, 11c each comprise a substantially cylindrical side wall 21a, 21b, 21c, wherein the cylindrical side walls 21a, 21b, 21c of different container units 11a, 11b, 11c have different diameters. In another embodiment, the shape of the container units may be another shape other than cylindrical, such as square. When one of the container units 11a, 11b, 11c is connected to the base module 3, the container units 11a, 11b, 11c and the base module 3 are configured to support the bottom wall 115 and the side walls 117 of the bioreactor bag 111 when the bioreactor bag is provided in the bioreactor support system 1; 101.

[0040] In this embodiment of the invention, each container unit 11a, 11b, 11c comprises a substantially cylindrical side wall 21a, 21b, 21c, the substantially cylindrical side wall 21a, 21b, 21c comprising at least a first side wall portion 21a', 21b', 21c' and a second side wall portion 21a'', 21b'', 21c'', wherein the second side wall portion 21a'', 21b'', 21c'' can be pivoted outwardly so that an opening into the interior of the container unit 11a, 11b, 11c can be provided for loading a bioreactor bag into the bioreactor support system. In another embodiment of the invention, all container units need not have the same design. For example, one or more container units may not need to have a second side wall portion that can be pivoted outwardly. The entire container unit may be a single part. This may be the case for more of the features described herein. Some of these features may be necessary only for some of the container units, for example only for container units of large size. However, in a case such as Figure 1a-1c In the embodiment shown in FIG. 3 , the three container units 11 a , 11 b , 11 c are shown to have the same design.

[0041] In the embodiment shown in Figures 1-3, the first and second side wall portions 21a', 21a", 21b', 21b", 21c', 21c" each include a substantially semi-cylindrical wall. Each semi-cylindrical wall may include an opening for accessing the interior of the container unit from the outside. The production of the side wall portions 21a, 21b, 21c is facilitated by dividing the side wall portion into two semi-cylindrical walls. Injection molding of the cylindrical wall is thereby facilitated. Any desired thermoplastic material may be used to mold the container unit. Another alternative is to produce the container unit 11a, 11b, 11c from sheet metal by stamping, or to produce the container unit 11a, 11b, 11c from plastic or metal by 3D printing or 3D printing additives.

[0042] The first and second side wall parts 21a', 21a'', 21b', 21b'', 21c', 21c'' can be connected to each other along one of the side edges by a hinge 22. Suitably, at least one of the opposite side edges of the first and second side wall parts where the hinge 22 is to be provided comprises a locking device 24, so that the container unit side wall 21a, 21b, 21c can be locked in the closed position. The locking device 24 can be, for example, a cooperating magnet provided on the side edges of both the first and second side wall parts 21a', 21a'', 21b', 21b'', 21c', 21c''. Other locking devices 24, such as a snap lock or an external standard latch, can also be used to lock the first and second side wall parts to each other in the closed position of the container unit 11a, 11b, 11c.

[0043] The first side wall portions 21a', 21b', 21c' comprise base module connection means 13a, 31b, 13c and are configured to be connectable to the base module 3, whereas the second side wall portions 21a'', 21b'', 21c'' are pivotally connected to the first side wall portions 21a', 21b', 21c' such that the second side wall portions 21a'', 21b'', 21c'' can be pivoted into at least one open position and a closed position, the open position allowing access to the interior of the container units 11a, 11b, 11c. In this embodiment, the base module connection means 13a, 13b, 13c and the container unit connection means 15a, 15b, 15c are designed to provide a circular lock, i.e. the base module connection means 13a, 13b, 13c of the container unit 11a, 11b, 11c are inserted into the container unit connection means 15a, 15b, 15c of the base module 3 and then the two parts are rotated relative to each other to secure the connection. The container unit connection part 7 can be provided as a bioreactor bottom support plate, i.e. for example a circular plate or a plate of any other geometric shape. The container units 11a, 11b, 11c are connected to the upper side 16a of the container unit connection part 7. Recesses 17a, 17b, 17c may be provided in the upper side 16a of the container unit connecting portion 7, which recesses 17a, 17b, 17c are designed to receive the lower edges 18 of the side walls 21a, 21b, 21c of the container units 11a, 11b, 11c. This may facilitate the mounting of the container units 11a, 11b, 11c to the base module 3 and increase the stability of the connection. If the side walls 21a, 21b, 21c are substantially cylindrical, the recesses 17a, 17b, 17c will be substantially circular.

[0044] The container units 11a, 11b, 11c may include one or more flexible heater pads 41 on the inner surface of the side walls 21a, 21b, 21c. The flexible heater pads 41 are configured to heat the bioreactor bag 111 when the bioreactor bag 111 is provided in the bioreactor support system 1, and they may be provided symmetrically around the bag. Silicone, polyimide or other flexible heat-resistant polymers may be used in the flexible heater pads 41 to cover the electrical heating elements, which are typically conductive fibers or films. In some embodiments, the container unit may additionally or alternatively include a flexible cooling jacket in which a flexible tube having a water inlet and outlet is overmolded.

[0045] The container unit 11a, 11b, 11c may suitably comprise at least one opening 43a, 43b, 43c in the side wall 21a, 21b, 21c for allowing access to the bioreactor bag 111 when the bioreactor bag is provided in the bioreactor support system 1. Figure 1a-1c In the embodiment shown in the figure, the first and second openings 43a, 43b are provided in the second side wall portion 21a'', 21b'', 21c'', while the third opening 43b is provided in the first side wall portion 21a', 21b', 21c'. Access to the bioreactor bag from different sides of the bioreactor system is thereby provided. One or more of the openings 43a, 43b, 43c may be provided with a scale 44 for indicating different volumes in some embodiments of the invention.

[0046] The container unit 11a, 11b, 11c may also include a sensor bracket 45. The sensor bracket 45 is provided to be connected to one of the openings 43b in the sidewalls 21a, 21b, 21c of the container unit 11a, 11b, 11c. In the embodiment shown in Figures 1-3, the sensor bracket 45 is provided outside the second opening 43b. The sensor bracket 45 is attached to the sidewalls 21a, 21b, 21c of the container unit 11a, 11b, 11c so that its position can be adjusted along the height of the container unit. In the embodiment shown in Figures 1-3, a rod 46 is provided along a portion of the height of the container unit 11a, 11b, 11c, and the sensor bracket 45 is attached to the rod 46 so that it can slide along the rod 46 to adjust the height position of the sensor bracket 45. The sensor bracket 45 can be an elongated, horizontally provided track on which the sensor can lean. Sensors, such as pH and DO sensors are often provided protruding into the bioreactor bag, and the sensor holder 45 in the container unit 11a, 11b, 11c may be adapted to provide support and stability. In some embodiments of the invention the sensor holder 45 may also be swung out of the container unit 11a, 11b, 11c. If the sensor holder 45 is attached to a rod 46 as shown in FIGS. 1-3 , the sensor holder 45 may be rotated around the attachment point to the rod 46. The possibility of swinging out the sensor holder 45 from the container unit 11a, 11b, 11c may be advantageous when loading the bioreactor bag and / or when the required access to the bioreactor is provided within the bioreactor support system 1.

[0047] The impeller drive unit 5 is configured in this embodiment of the invention to provide a rotating magnetic field. Figure 4 The details of the impeller drive unit 5 according to one embodiment of the present invention are shown in FIG. Figure 4 Also shown is an impeller connector 119 connected to the impeller drive unit 5. The impeller connector 119 can be welded to a disposable bioreactor bag that can be provided in the bioreactor support system 1. However, Figure 4 The bioreactor bag is not shown in the figure. The base module 3 comprises an impeller connection location 35, wherein an impeller connector 119 can be provided in a position that allows a rotating magnetic field from an impeller drive unit 5 of the base module 3 to drive the impellers 113a, 113b, 113c of the bioreactor bag. The impellers 113a, 113b, 113c of the bioreactor bag thus comprise a magnet 131. The impeller drive unit 5 in some embodiments comprises a magnet 31 and a motor 33 for rotating the magnet 31. In another embodiment the impeller drive unit 5 may comprise a stationary coil that can be powered in such a way that a rotating magnetic field is provided.

[0048] In the embodiment shown in Figures 1-3, the base module 3 comprises a container unit connection part 7 in the form of a bioreactor bottom support plate. The container unit connection part 7 comprises container unit connection means 15a, 15b, 15c and an impeller connection location 35. The impeller connection location 35 is provided here as an opening 35, where an impeller connector 119 of the bioreactor can be provided. At least two container units 11a, 11b, 11c are configured to be connected to an upper side 16a of a container unit connection portion 7, and an impeller drive unit 5 is provided on an opposite side 16b of the container unit connection portion 7, and an opening 35 in the container unit connection portion 7 is configured to receive an impeller connector 119 provided in a bioreactor bag 111a, 111b, 111c, and the bioreactor bag 111a, 111b, 111c can be provided in the bioreactor support system 1 so that the impeller connector 119 can be provided at a position relative to the impeller drive unit 5 that allows a rotating magnetic field from the impeller drive unit 5 to drive the impellers 113a, 113b, 113c of the bioreactor bags 111a, 111b, 111c. The impeller connector 119 does not have to be in contact with the impeller drive unit 5, but needs to be close enough to allow a magnetic force to affect the magnets 131 in the impellers 113a, 113b, 113c. The impeller connection position 35 provided as the opening 35 may be provided as a circular opening 35 in the center of the container unit connection portion 7. The grooves 17a, 17b, 17c may be provided centered around the opening 35.

[0049] The impeller connection position 35 is provided as an opening 35 large enough to allow bioreactor bags of different sizes to be positioned there. The impeller connector 119 can be provided as a support plate, which supports the impellers 113a, 113b, 113c in its center. The impeller connector 119 further suitably includes a spray head inlet. The location of the spray head inlet and the size of the impeller can be suitably different for bioreactor bags of different sizes. However, the size and design of the impeller connector 119 can be adapted to all different bioreactor sizes to be suitable for positioning in the impeller connection position 35 so that the impellers 113a, 113b, 113c can be driven by the impeller drive unit 5. The connection between the impeller connector 119 and the impellers 113a, 113b, 113c that allows rotation is particularly designed to allow small impellers to be provided to small bioreactor bags. The impellers 113a, 113b, 113c are connected to the central shaft 119a of the impeller connector 119 via the bearing 114. In order to maintain the same shaft diameter of the central shaft 119a for all different sizes of impellers 113a, 113b, 113c, at least for the smaller impellers, the bearing 114 is provided, for example, as a sleeve bearing rather than a larger ceramic bearing. For the smaller impellers, ceramic bearings are not needed due to the small forces for the smaller bioreactors. Sleeve bearings or alternatively small ceramic bearings may be provided to save space.

[0050] Clamps, plug connectors and other types of sockets 141a, 141b may be provided for the container units 11a, 11b, 11c as shown in FIG. 6a and for example Figure 6b The bottom side 16b of the container unit connection part 7 of the base module 3 is shown in FIG. Thereby the tubes can be fastened and neatly guided instead of being freely wound from the bioreactor.

[0051] The container units 11a, 11b, 11c can be provided in different sizes as explained above. If, for example, the diameter Dt of the three containers is 127mm, 178mm and 203mm, a range of volumes that can be processed by the bioreactor support system 1 can be 0.5-10 liters. A wide range of volumes can thus be processed by a single product. Laboratory scale and process scale can thus be processed by the same product. The container units 11a, 11b, 11c can be designed to have the same adjustment, i.e., the relationship between the maximum volume and the minimum volume that they can process. This adjustment can be in the range of 4-6 or 4.5-5.5 in some embodiments of the invention.

[0052] With the present invention it is possible to process working volumes as low as 0.5 liters in a stirred bioreactor and at the same time have the same DO, pH and RTD sensors as for larger reactors. Due to the present invention, sensors and impellers can be positioned and used in the same way for container units of different sizes. Thus cell cultures of different working volumes can be processed in the same way, which will facilitate scalability and predictability of results.

[0053] Furthermore, in some embodiments of the present invention, the relationship Di / Dt between the impeller diameter Di and the container unit diameter Dt can remain the same for all different container unit sizes. This is advantageous for predictability in the bioreactor process.

[0054] In some embodiments of the present invention, the relationship between the maximum available height LMax of the container unit and the diameter Dt of the container unit may also remain the same for all different container unit sizes.

[0055] Since the packaging of the bioreactor support system of the present invention can be modularized, the container units 11a, 11b, 11c and the base module 3 can be packaged in different boxes for easy transportation, which will reduce the risk of damage during transportation.

[0056] Furthermore, according to the present invention, a bioreactor system 101 is provided. Figure 5 Such a bioreactor system is shown in . The bioreactor system comprises a bioreactor support system 1 as described above and at least two bioreactor bags 111a, 111b, 111c of different sizes, which correspond to the different sizes of at least two container units 11a, 11b, 11c. Each of the at least two bioreactor bags 111a, 111b, 111c comprises an impeller 113a, 113b, 113c and an impeller connector 119 as described above. The impeller 113a, 113b, 113c comprises a magnet 131 so that it can be rotated by magnetic force, and the size of the impeller 113a, 113b, 113c in the bioreactor bag 111a, 111b, 111c is adapted to the size of the bioreactor bag. Thereby, impellers 113a, 113b, 113c of different sizes are provided for bioreactor bags 111a, 111b, 111c of different sizes, and the bioreactor support system 1 according to the present invention is configured so that impellers 113a, 113b, 113c of different sizes can be used.

[0057] The impeller connector 119 of the bioreactor bag 111a, 111b, 111c is configured to be provided in a closed position to the impeller drive unit 5 of the base module 3 via the impeller connection location 35 provided in the base module 3 as discussed above.

[0058] The bioreactor system according to the invention can be used for scale-up processes, such as seed culture. The connections for transferring the harvest from vials, through bioreactors of different sizes provided in the bioreactor support system according to the invention, and further to larger bioreactors can be provided as sterile connections. A closed loop seed culture can thereby be provided.

[0059] The bioreactor system of the present invention can also be used in high-density cell cultivation, ie in a perfusion process.

[0060] According to the present invention there is also provided a method for cultivating cells in a bioreactor system as described above. The method may be a scale-up process, wherein during scale-up different sizes of bioreactor bags and container units may be used for cell cultivation. The method may also be a perfusion process.

Claims

1. A bioreactor support system configured to hold a bioreactor bag, the bioreactor support system (1) comprising: A base module (3) comprising an impeller drive unit (5); as well as at least two container units of different sizes, configured to support and substantially surround the side wall of a bioreactor bag when the bioreactor bag is provided in the bioreactor support system (1), the at least two container units each comprising a substantially cylindrical side wall, the cylindrical side walls of different container units having different diameters, The base module (3) and the at least two container units comprise matching connection means, so that the at least two container units can be connected to the same base module (3), and the impeller drive unit (5) of the base module (3) can be used to drive the impeller in the bioreactor bag when the bioreactor bag is provided in the bioreactor support system (1), wherein the upper side of the container unit connection part (7) of the base module (3) is provided with a plurality of substantially circular grooves for receiving the lower edge of the side wall of the container unit.

2. The bioreactor support system according to claim 1, wherein: The container unit connecting portion (7) comprises at least a first container unit connecting device (15a) and a second container unit connecting device (15b), wherein the first container unit connecting device and the second container unit connecting device are configured to be connected to container units of different sizes, and wherein the at least two container units comprise at least a first container unit (11a) and a second container unit (11b) of different sizes, wherein the first container unit (11a) comprises a first base module connecting device (13a), the first base module connecting device (13a) being configured so that it can be connected to the first container unit connecting device (15a) of the container unit connecting portion (7) of the base module (3), and wherein the second container unit (11b) comprises a second base module connecting device (13b), the second base module connecting device (13b) being configured so that it can be connected to the second container unit connecting device (15b) of the container unit connecting portion (7) of the base module (3).

3. The bioreactor support system according to claim 1 or 2, wherein: When one of the container units is connected to the base module (3), the container unit and the base module (3) are configured to support a bottom wall (115) and side walls (117) of a bioreactor bag when the bioreactor bag is provided in the bioreactor support system (1).

4. The bioreactor support system according to claim 1 or 2, wherein: The impeller drive unit (5) is configured to provide a rotating magnetic field, and wherein the base module (3) comprises an impeller connection position (35), wherein an impeller connector (119) provided in a bioreactor bag can be provided in a position allowing the rotating magnetic field of the impeller drive unit (5) from the base module (3) to drive the impeller of the bioreactor bag to be provided in the bioreactor support system (1).

5. The bioreactor support system according to claim 4, wherein: The base module (3) comprises a container unit connection part (7) in the form of a bioreactor bottom support plate, wherein the container unit connection part (7) comprises at least a first and a second container unit connection device and the impeller connection position (35) provided as an opening, wherein the at least two container units are configured to be connected to an upper side (16a) of the container unit connection part (7), and the impeller drive unit (5) is provided on an opposite side (16b) of the container unit connection part (7), and wherein the opening in the container unit connection part (7) is configured to receive an impeller connector (119) provided in a bioreactor bag, the bioreactor bag being capable of being provided in the bioreactor support system (1) so that the impeller connector can be provided in a position relative to the impeller drive unit (5) which allows the rotating magnetic field from the impeller drive unit (5) to drive the impeller of the bioreactor bag.

6. The bioreactor support system according to claim 1 or 2, wherein: The generally cylindrical side wall includes a portion of the side wall that can be pivoted outwardly so as to provide an opening into the interior of the containment unit for loading a bioreactor bag into the bioreactor support system.

7. The bioreactor support system according to claim 1 or 2, wherein: The substantially cylindrical side wall is divided into a first side wall portion and a second side wall portion, each of which includes a substantially semi-cylindrical wall including an opening for external access to the interior of the container unit, wherein the first side wall portion includes the base module connection device and is configured to be connectable to the base module (3), and the second side wall portion is pivotally connected to the first side wall portion so that the second side wall portion can be pivoted into at least one open position and a closed position, wherein the open position allows access to the interior of the container unit and in the closed position the first side wall portion and the second side wall portion together form the substantially cylindrical side wall.

8. The bioreactor support system according to claim 1 or 2, wherein: At least one of the container units includes one or more flexible heater pads (41) on the inner surface of the side wall, the flexible heater pads (41) being configured to heat the bioreactor bag when the bioreactor bag is provided in the bioreactor support system (1).

9. The bioreactor support system according to claim 1 or 2, wherein: At least one of the container units comprises at least one opening in a side wall for allowing access to a bioreactor bag when the bioreactor bag is provided in the bioreactor support system (1).

10. The bioreactor support system according to claim 9, wherein: At least one of the at least one openings includes graduations (44) for indicating different volumes.

11. The bioreactor support system according to claim 9, wherein: At least one of the container units comprises a sensor holder (45) provided for connection with an opening (43b) in a side wall of the container unit, wherein the sensor holder (45) is attached to the side wall of the container unit such that its position can be adjusted along the height of the container unit.

12. A bioreactor system comprising a bioreactor support system according to any one of claims 1 to 11, and at least two bioreactor bags of different sizes corresponding to the different sizes of at least two container units, each of the at least two bioreactor bags comprising an impeller and an impeller connector (119).

13. The bioreactor system according to claim 12, wherein: The impeller comprises a magnet (131) so that it can be rotated by magnetic force, and wherein the size of the impeller in the bioreactor bag is adapted to the size of the bioreactor bag.

14. The bioreactor system according to claim 12 or 13, wherein: The impeller connector (119) of the bioreactor bag is configured to be provided in a closed position to the impeller drive unit (5) of the base module (3) via an impeller connection location (35) provided in the base module (3).

15. The bioreactor system according to claim 12 or 13, wherein: The bioreactor system is used for scale-up processes.

16. A base module (3) of a bioreactor support system (1) configured to hold a bioreactor bag, the base module comprising: at least a first container unit connection device and a second container unit connection device, wherein the first container unit connection device and the second container unit connection device are configured to be connected to container units of different sizes, wherein the container units are included in the bioreactor support system (1) and are configured to support and substantially surround the side walls of the bioreactor bag when the bioreactor bag is provided in the bioreactor support system (1), each of the container units includes a substantially cylindrical side wall, and the cylindrical side walls of different container units have different diameters, wherein the upper side of the container unit connection portion of the base module is provided with a plurality of substantially circular grooves to receive the lower edges of the side walls of the container units; as well as An impeller drive unit (5) is configured to drive an impeller in a bioreactor bag when the bioreactor bag is provided in the bioreactor support system (1).

17. The base module according to claim 16, wherein: The container unit connecting portion (7) comprises at least the first container unit connecting means and the second container unit connecting means.

18. A base module according to claim 16 or 17, wherein: The impeller drive unit (5) is configured to provide a rotating magnetic field, and wherein the base module (3) comprises an impeller connection position (35), wherein an impeller connector (119) provided in a bioreactor bag can be provided in a position allowing the rotating magnetic field of the impeller drive unit (5) from the base module (3) to drive the impeller of the bioreactor bag to be provided in the bioreactor support system (1).

19. The base module according to claim 18, wherein: The base module (3) comprises a container unit connection part (7) in the form of a bioreactor bottom support plate, wherein the container unit connection part (7) comprises at least a first and a second container unit connection device and the impeller connection position (35) provided as an opening, wherein the base module (3) is configured so that a container unit can be connected to an upper side (16a) of the container unit connection part (7), and the impeller drive unit (5) is provided on an opposite side (16b) of the container unit connection part (7), and wherein the opening in the container unit connection part (7) is configured to receive an impeller connector (119) provided in a bioreactor bag, the bioreactor bag being capable of being provided in the bioreactor support system (1) so that the impeller connector can be provided in a position relative to the impeller drive unit (5) that allows the rotating magnetic field from the impeller drive unit (5) to drive the impeller of the bioreactor bag.

20. A method for cultivating cells in a bioreactor system according to any one of claims 12 to 15.

21. The method according to claim 20, wherein: The method is a scale-up process, wherein bioreactor bags and container units of different sizes can be used for cell cultivation during scale-up.

22. The method according to claim 20 or 21, wherein: The method described is a perfusion process.

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