Bioreactor assembly
11525113 ยท 2022-12-13
Assignee
Inventors
Cpc classification
B01F2101/44
PERFORMING OPERATIONS; TRANSPORTING
B01F31/23
PERFORMING OPERATIONS; TRANSPORTING
International classification
C12M3/00
CHEMISTRY; METALLURGY
C12M3/06
CHEMISTRY; METALLURGY
B01F31/20
PERFORMING OPERATIONS; TRANSPORTING
B01F31/23
PERFORMING OPERATIONS; TRANSPORTING
C12M1/12
CHEMISTRY; METALLURGY
Abstract
The present invention relates to a bioreactor assembly comprising a plurality of trays (30) for holding a cell culture bag, a holder (2) on which the trays are mounted side by side to form a first series of trays rocking mechanism (4) for rocking the trays, the rocking mechanism (4) being operatively connected to each of the trays (30). The invention also relates to a bioreactor system (100) comprising at least one bioreactor assembly.
Claims
1. A bioreactor assembly comprising: a plurality of trays configured to hold a plurality of cell culture bags, a holder on which the trays are removably mounted side by side to form a first series of trays of the plurality of trays on a first side of the bioreactor assembly and a second series of trays of the plurality of trays on a second side of the bioreactor assembly opposite the first side; a rocking mechanism that is operatively connected to the first series of trays and second series of trays and configured to rock the trays on each side of the bioreactor assembly, wherein the rocking mechanism comprises at least one motor operatively connected to one or more trays and configured to rock the trays; and at least one control unit, said at least one control unit is positioned above a holding area of the holder central to the first series of trays and second series of trays and is arranged to control the rocking mechanism; wherein the plurality of trays are configured to be disconnected from the rocking mechanism such that the rocking of an individual tray of the plurality of trays is stopped while the remining trays are permitted to continue rocking.
2. The bioreactor assembly according to claim 1, wherein at least one of the trays is configured to be removable from the bioreactor assembly.
3. The bioreactor assembly according to claim 2, further comprising a remover for removing the tray from the bioreactor assembly.
4. The bioreactor assembly according to claim 1, wherein the individual tray after stopping may be removed and/or replaced.
Description
DRAWINGS
(1) The invention will now be described in more detail with reference to the appended drawings, wherein
(2)
(3)
DETAILED DESCRIPTION
(4)
(5) The rocking mechanism 4 are operatively connected to each of the trays 30 and arranged to generate a rocking motion for each tray 30 so that contents of a cell culture bag (not shown) placed in the tray 30 are kept moving, in order to improve distribution of nutrients, removal of waste products, to aid in cell expansion. The rocking mechanism 4 can be connected through the holder 2 or directly to each tray 30, depending on what is suitable for a specific embodiment of the invention.
(6) When the rocking mechanism 4 is connected through the holder 2, the trays can be rocked by rotating the holder alternately in a clockwise and an anti-clockwise direction. Alternatively, the holder 2 can be moved or rocked from side to side. The rocking mechanism 4 can comprise a crank on one end of the holder 2, wherein the crank is driven by the motor 41 to rotate the holder 2 back and forth to make the trays 30 rock together on the holder.
(7) When the rocking mechanism 4 are connected to each tray 30 individually, the rocking mechanism 4 may comprise a plurality of rocking units (not shown) that are operatively connected to said at least one motor, each rocking unit being arranged in connection with a tray, and the rocking mechanism can be configured to rock the trays by each rocking unit being driven by the motor to create a rocking motion. Thus, the rocking mechanism 4 is connected to the rocking units such that each rocking unit is driven to rock one or more of said trays directly. The rocking mechanism 4 can comprise multiple cams on a common shaft, the cams and shaft being driven by the motor 41 to rock each of the trays 30 individually.
(8) The rocking motion generated for a tray 30 is preferably an angular motion about a pivot point or a four-bar linkage motion.
(9) In an alternative embodiment, the individual trays 30 can be joined edge on edge to form a string of rocking trays that is able to hold a plurality of cell culture bags. The string of rocking trays is mounted similarly to the individual trays 30 and is rocked in essentially the same way, but will not require a plurality of rocking units.
(10) In the preferred embodiment, a second series of trays 32 are also arranged along the holder 2 in essentially the same distribution as the first series of trays 31 mentioned above. Together, the first and second series of trays 31, 32 and the holder 2 form a layer of trays 33 where each individual tray 30 is on substantially the same height above a floor on which the bioreactor assembly 1 stands. The rocking mechanism 4 is preferably connected in the same way to each tray 30, regardless of to which series the tray 30 belongs.
(11) Thus, the rocking mechanism 4 preferably include at least one motor and either individual rocking units placed in connection with each tray 30 or a rocking device for the holder 2, where the rocking device is arranged to create the rotational movement or the rocking movement of the holder 2. The rocking mechanism 4 also comprise a connection between the motor or motors and the rocking units or rocking device, to allow the motor to drive the rocking motion of the trays 30.
(12) In order to further increase the number of trays available, at least one but preferably two or more further layers of trays 34 are preferably provided in the bioreactor assembly 1. This way, a multilayered bioreactor assembly 1 is created. Thereby, a large number of trays 30 can be provided in a very space efficient way, allowing for the cultivation of a very large number of cell culture bags simultaneously.
(13) Preferably, at least one storage area 5 is provided in connection with the holder 2 and configured to hold at least one but preferably a plurality of interaction units that serve and monitor the cell culture bags in the trays 30. The storage area 5 is preferably in the form of a static shelf 5. These interaction units include a supply unit that is arranged to hold a supply of nutrients, generally in the form of Meida, air mixout (oxygen, CO.sub.2, N.sub.2), and a waste unit that is arranged to receive a waste product from the cell culture bags. The supply unit and waste unit are preferably connected to each cell culture bag in the trays 30 via tubes that run along the holder 2 and extend to each tray, ending in connectors for easy connection to the cell culture bags, and at least one pump 54 that pumps the nutrients to the cell culture bags and at least one pump 54 that pumps the waste products from the cell culture bags.
(14) The interaction units can comprise one large unit for each type of interaction unit placed in the bioreactor assembly 1, but may optionally comprise a plurality of interaction units of each type, mounted on each layer 33, 34 in connection with each holder 21, 22, to have easy access to the cell culture bags in the trays 30 on each layer 33, 34. The number of pumps 54 may vary depending on this.
(15) Also included among the interaction units is at least one control unit 53 that is arranged to monitor at least one property of the cell culture bags in the trays 30. That property may be the concentration or amount of a substance in the cell culture bag, the supply rate of nutrient or removal rate of waste, the temperature in the cell culture bag, or any other property connected with the cultivation of cells in the cell culture bags. The control unit 53 is operatively connected to each cell culture bag and may also store and/or process collected data that corresponds to said property or properties. Data may also be displayed at the bioreactor assembly 1 or remotely on a separate unit, and may also be configured to receive input from a control unit or from a human operator and to alter its operation depending on that input. The control unit 53 may also be configured to control the operation of the other interaction units, such as the supply unit 51, waste unit 52, and pumps 54 to and from these units.
(16) The trays 30 are preferably arranged to be removable from the bioreactor assembly 1, so that the individual tray 30 can be disconnected from the holder 2 and taken out of the bioreactor assembly 1. This removal can be made by a human operator but is preferably automated and performed by a remover 6 in the form of a robot or similar that serves to disconnect the interaction units from the cell culture bag and the tray 30 from the holder 2. The tray 30 can then be taken to a desired location, either to a human operator or to an automated system for removal of the cell culture bag and/or placement of a new cell culture bag in the tray 30 before reinsertion into the bioreactor assembly 1. Preferably, the rocking mechanism can be disconnected from each tray 30 individually, so that the remaining trays 30 in the bioreactor assembly can continue rocking while one tray 30 is removed and reinserted.
(17) The trays 30 can be mounted on the holder 2 by any suitable connection, such as a slide and lock mechanism or other mechanism that can hold the tray 30 robustly with the holder 2, either directly or via a rocking unit as described above.
(18) The bioreactor assembly 1 forms a bioreactor system 100 together with the interaction units mentioned above, namely the supply unit 51, the waste unit 52 and the control unit 53, as shown schematically by
(19) It is to be noted that any features described above with reference to one embodiment or suitable mode of operation for the bioreactor assembly 1 and bioreactor system 100 may freely be combined with other features of the present invention, unless such a combination is clearly stated as unsuitable herein.