CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a 35 U.S.C. 371 National Phase of PCT Application No. PCT/EP2017/077389, filed on Oct. 26, 2017, which claims priority to IN Application No. 201611037205 filed Oct. 31, 2016, the disclosures of each of which are hereby incorporated by reference in their entirety.

TECHNICAL FIELD

The present invention relates to a bioreactor assembly for cell manufacturing. The invention also relates to a bioreactor system comprising at least one such bioreactor assembly.

BACKGROUND

The use of bioreactors for cultivation of cell samples is well known within the art, for instance through US2007/0269888 (Houtzager et al.) and U.S. Pat. No. 6,190,913 (Singh). In some embodiments, large batches are grown in fermentation vessels with capability for many liters of fluid, but in many cases it is more desirable to have a number of smaller samples in individual bags of only a few liters or less. Each bag generally needs access to nutrients, removal of waste products, and to be subjected to movements through stirring or rocking in order to allow the nutrients and air to mix with the cell sample.

The document US2007/0269888 (Houtzager et al.) mentioned above discloses one such bioreactor, comprising a plurality of cell samples in individual bags that are mounted in a reactor frame. The bags are kept in individual trays that are connected through a system of cooperating links in order to rock the bags.

One problem associated with the known bioreactors is that they are generally not able to handle large quantities of bags with sufficient monitoring and treatment to achieve the desired cell cultivation, and that they also take up large space. There is therefore a need for an improved bioreactor.

SUMMARY OF THE INVENTION

An object of the present invention is to eliminate or at least to minimize the problems mentioned above. The inventors have addressed these problems by devising a bioreactor, wherein a series of trays are arranged in connection with a holder. Thereby, a large number of cell culture bags can be cultivated simultaneously and in a space efficient way.

According to an aspect of the invention, the rocking mechanism comprises at least one motor, the motor being arranged to rock the trays by rotating or moving the holder. Thereby, the trays can be rocked in a simple and efficient way, generating the rocking required to facilitate cultivation of cells.

According to another aspect of the invention, the rocking mechanism comprise at least one motor and a plurality of rocking units operatively connected to said at least one motor, each rocking unit being arranged in connection with a tray, and wherein the rocking mechanism are configured to rock the trays by each rocking unit being driven by the motor to create a rocking motion such that each rocking unit is driven to rock one or more of said trays directly. Thereby, the holder can remain stationary and each tray can be rocked individually, allowing for the rocking of each tray to be determined based on the requirements of the specific cell culture bag placed in the tray.

According to yet another aspect of the invention, the assembly further comprises a control unit that is arranged to control the rocking mechanism, and that is preferably arranged to receive input signals from a plurality of interaction units and to transmit output signals to said interaction units. The interaction units can comprise a supply unit for supplying nutrients to cell culture bags placed in the trays and a waste unit for removing waste products from the cell culture bags, wherein the supply unit and the waste unit are driven by at least one pump for pumping nutrients and waste products to and from the cell culture bags via tubes. Thereby, the cell culture bags in the trays can be supplied with nutrients and have waste products removed, and this supply and removal can be controlled by the control unit, as well as the rocking of the trays. This allows for improving the cultivation of cells in the bioreactor assembly.

According to a further aspect of the invention, the bioreactor assembly further comprises a holding area for holding the interaction units and/or the control unit, said holding area being arranged at the holder. Thereby, the interaction units can be held in close vicinity to the cell culture bags, further reducing the space needed for the bioreactor assembly. Preferably, the control unit can monitor the contents of the cell culture bags and also store and/or transmit data regarding said contents to a user, either locally at the bioreactor assembly or at a distance.

According to yet another aspect of the invention, at least one of the trays is removably arranged. Thereby, that tray can be disconnected from the bioreactor assembly and accessed by an operator or an automated processing system for further handling the cell culture bag. Preferably, remover are provided for performing the disconnection and delivering the tray to a predetermined place, to facilitate handling of the tray in large bioreactor assemblies where it would be difficult for a human operator to access every tray manually. Of course, the removable arrangement also serves to allow for an addition of a new cell culture bag and the connection of that cell culture bag to the bioreactor assembly, so that a replacement of the contents of a tray is facilitated.

According to a further aspect of the invention, at least one of the trays is configured to be disconnected from the rocking mechanism. Thereby, the rocking of an individual tray can be stopped, to allow for removal/replacement or other handling, monitoring or testing, while the remaining trays can be allowed to continue rocking. This is especially advantageous in allowing the cultivation to continue even during removal, replacement, loading or emptying of the bioreactor assembly, and serves to shorten the cultivation time for the cell samples in the cell culture bags.

According to yet another aspect of the invention, the bioreactor assembly further comprises a second series of trays that are mounted on the holder opposite to the first series of trays and that are also operatively connected to the rocking mechanism. Preferably, the holder and the trays form a layer in the bioreactor assembly, and wherein the bioreactor assembly comprises at least one further such layer. Thereby, the number of trays and thereby the number of cell culture bags that can be cultivated simultaneously is further increased.

According to a further aspect of the invention, the plurality of trays are joined edge on edge to form a string of rocking trays. Thereby, the bioreactor assembly can be made with increased space efficiency and still reliably hold a large number of cell culture bags for cultivation.

The invention also comprises a bioreactor system according to the appended independent claim, having at least one bioreactor assembly as described above and also comprising a control unit for controlling the operation of the bioreactor assembly, interaction units, comprising a supply unit for providing a supply of nutrients to the cell culture bags and a waste unit for removing waste products from the cell culture bags, said supply unit and waste unit being arranged to be connected to each cell culture bag via tubes and each of the interaction units being driven by at least one pump, input for providing input to the system, and output for providing output from the system, wherein the control unit is operatively connected to the input, the rocking mechanism and each of the interaction units and to the output, and wherein the control unit is configured to control the operation of the rocking mechanism and the interaction units and to provide output signals for the output.

According to one aspect of the invention, the control unit is configured receive data regarding at least one property of the cell culture bags, and optionally to store said data and transmit it to said output. Thereby, the cultivation of cells in the cell culture bags can be monitored and data regarding them can be stored, displayed and/or transmitted to external units or presented to a user of the system.

Many additional benefits and advantages of the invention will become readily apparent to the person skilled in the art in view of the detailed description below.

