Cell Processing System for Housing a Bioreactor - Patent application

Abstract

The present application provides a cell processing system for housing a bioreactor. The cell processing system is adapted to support the bioreactor. The cell processing system includes a load sensing unit operable to detect a weight of the bioreactor. Methods of detecting a weight of a bioreactor in a cell processing system and methods of detecting a leak in the bioreactor are also provided.

Description

[Technical field]

[0001] The present invention relates to a cell processing system for accommodating a bioreactor, and in particular to a cell processing system including a load sensing unit. [Background technology]

[0002] Cell and gene therapy manufacturing processes are often complex and include manual or semi-automated steps across several pieces of equipment. The equipment systems used in the various steps, i.e., unit operations, of cell therapy product (CTP) manufacturing may include equipment for various functions. These various functions may be, for example, cell collection, cell isolation, cell selection, cell growth, cell washing, volume reduction, cell storage or transport. Unit operations may vary widely based on the manufacturing model (i.e., autologous vs. allogeneic), cell type, intended use, among other factors. In addition, cells are “living” entities that are sensitive to even the simplest manipulations, such as, for example, differences in cell transplantation procedures. The role of cell manufacturing equipment in ensuring scalability and reproducibility is a critical element for cell and gene therapy manufacturing.

[0003] In addition, as cell therapy products (CTPs) have gained significant momentum, there is a need for improved cell manufacturing equipment for various cell manufacturing procedures, which may include, for example, enrichment of stem cells, generation of chimeric antigen receptor (CAR) T cells, and various cell manufacturing processes such as collection, purification, genetic modification, culture, harvesting, washing, infusion into patients, or freezing.

[0004] Cultivating or processing cells typically requires the use of a device that holds the cells in a suitable culture medium, for example when culturing the cells. Known devices include shaker flasks, roller bottles, T-flasks, bags, etc. Such devices typically require connection to other devices, such as containers, interfaces, etc., so that various media can be introduced into or removed from the device holding the cells. Typically, cells in culture medium can be added to the device from a flexible bag that is attached using a connecting tube. Alternatively, the cells can be transferred by a pipette or by a syringe. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] International Publication No. 2021 / 123760 Summary of the Invention [Means for solving the problem]

[0006] According to the present disclosure, there is provided a cell processing system for housing a bioreactor, the cell processing system including a load sensing unit adapted to support the bioreactor and operable to detect a weight of the bioreactor.

[0007] Advantageously, by providing a load sensing unit as part of the cell processing system, it is possible to detect the weight of the bioreactor without removing it from the cell processing system. The weight of the bioreactor can be monitored or checked periodically, for example, before, after, and / or during the addition or removal of materials from the bioreactor.

[0008] In an example, the cell processing system may further include a housing and a support that supports the bioreactor within the housing. The housing may provide a controlled environment. The controlled environment may be a sterile environment and may be sealed from the external environment. The housing may have one or more controlled parameters, such as temperature, humidity, pressure, and / or gas concentrations (e.g., oxygen, carbon dioxide). Therefore, it is advantageous to provide a cell processing system with a load sensing unit that can detect the weight of the bioreactor without the need to remove the bioreactor from the housing.

[0009] In an example, the support is pivotally mounted to the housing and the load sensing unit includes a load cell arranged such that a torque of the support is applied to the load cell, such that the load sensing unit can detect the weight of the bioreactor on the support.

[0010] In another example, the load sensing unit is adapted to releasably connect to the bioreactor such that the load sensing unit can connect to the bioreactor to detect the weight of the bioreactor and can be disconnected from the bioreactor to allow other operations to proceed when the load sensing unit does not detect the weight.

[0011] In an example, during use, the load sensing unit can be positioned above the bioreactor and operable to releasably connect to the top of the bioreactor.

[0012] In some examples, the load sensing unit is movable to lift the bioreactor from the support to a raised position where the weight of the bioreactor is supported by the load sensing unit. A sensor (load cell) of the load sensing unit can then detect the weight of the bioreactor.

[0013] Additionally or alternatively, the support can be movable to disengage from the bioreactor so that the weight of the bioreactor is supported by the load sensing unit. That is, the load sensing unit can be connected to the bioreactor and then the support can be disengaged so that the weight of the bioreactor is fully supported by the load sensing unit. A sensor (load cell) of the load sensing unit can then detect the weight of the bioreactor.

[0014] In an example, the load sensing unit can include a coupling operable to releasably connect to the bioreactor.

[0015] In an example, the coupling is attached to a platform that is movable relative to the bioreactor. The platform can be vertically movable toward and away from the top of the bioreactor. The coupling can be attached to the platform via a load cell. In this way, when the bioreactor is coupled to the load sensing unit, the weight of the bioreactor can be detected by lifting the bioreactor using the load sensing unit. Additionally or alternatively, the load cell can measure the compressive force applied to the bioreactor by the load sensing unit.

[0016] In an example, the coupling includes a clamp operable to releasably connect to the bioreactor. The clamp can include an actuator and at least one arm movable by the actuator to clamp onto the bioreactor. The actuator can include an electric motor. The actuator can include a gear train operably disposed between the actuator and the clamp. The clamp can include a pair of opposing arms rotatable in opposite directions by the actuator (e.g., via a gear train) to connect to and disconnect from the bioreactor.

[0017] In examples, the load sensing unit further includes one or more sensors arranged to detect the presence of or proximity of the bioreactor to the clamp. Additionally or alternatively, the load sensing unit further includes one or more sensors arranged to detect gripping of the bioreactor by the clamp.

[0018] In examples, the bioreactor includes a clamping mechanism to which the clamp can connect. The clamping mechanism can include a lip or circular protrusion arranged to match the shape of the clamp arm.

[0019] In examples, the load sensing unit is disposed within the housing above the bioreactor, and the load sensing unit is operable to releasably connect to the top of the bioreactor, which may be part of an expansion vessel on the bioreactor or part of a lid assembly. Preferably, the load sensing unit connects to the top of the bioreactor, and the load sensing unit is generally disposed within the housing above the bioreactor.

[0020] In examples, the load sensing unit can include a pivotally mounted hinge plate. The hinge plate can be releasably connectable to the bioreactor such that the weight of the bioreactor applies a torque to the hinge plate. The clamp can be disposed on the hinge plate. The load sensing unit can include a load cell, the load cell disposed such that a torque applied to the hinge plate is applied to the load cell. That is, the weight of the bioreactor acts on the hinge plate, which in turn applies a force to the load cell. In some examples, the load cell is compressed by the torque of the hinge plate. In other examples, the load cell is in tension by the torque of the hinge plate. In each example, a strain gauge or other sensor on the load cell can detect the force, and a controller of the cell processing system can determine the weight of the bioreactor from the detected force.

[0021] In examples, the coupling can include a bayonet fitting. In examples, the bioreactor can include a first bayonet fitting and the load sensing unit can include a second bayonet fitting coupleable to the first bayonet fitting. In examples, the cell processing system can include an actuator for rotating the bioreactor relative to the load sensing unit to couple the first bayonet fitting and the second bayonet fitting.

[0022] In an example, the coupling of the load sensing unit includes a bayonet fitting having a number of protrusions arranged to engage with a bayonet fitting of the bioreactor. The bayonet fitting of the bioreactor can have a number of recesses through which the protrusions of the coupling can pass, and a number of protrusions. Relative rotation of the bioreactor and the coupling can align the protrusions to couple the load sensing unit to the bioreactor.

[0023] In another example, the load sensing unit includes a bayonet fitting having a number of grooves formed on an exterior surface of a body, e.g., a cylinder. The bioreactor includes an opening having a number of pins extending inwardly into the opening. The pins engage with the grooves to provide a bayonet coupling. The grooves include one or more traps in which the pins are received when the coupling is coupled to the bioreactor. A first trap can engage with the pin when the load sensing unit presses down on the bioreactor and a second trap can engage with the pin when the load sensing unit lifts the bioreactor.

[0024] In an example, the coupling can include at least one spring arm. In an example, the load sensing unit can include a plurality of spring arms arranged to engage an edge of an opening in the bioreactor to couple the load sensing unit to the bioreactor. In an example, each of the plurality of spring arms can include a notch arranged to engage an edge of an opening in the bioreactor. The notch can be shaped such that the spring arm flexes inward when the load sensing unit is moved toward the bioreactor and springs outward when the notch aligns with the edge of the opening. The notch can be shaped such that the load sensing unit can be decoupled from the bioreactor by moving the load sensing unit away from the bioreactor to flex the spring arm. Each spring arm can be spring-biased by a torsion spring, helical spring, or similar elastically deformable member.

[0025] In examples, the load sensing unit can further include one or more sensors arranged to detect the presence of or proximity of a bioreactor to the coupling. Additionally or alternatively, the load sensing unit further includes one or more sensors arranged to detect coupling between the load sensing unit and the bioreactor.

[0026] In some examples, the bioreactor includes a compressible element. For example, the bioreactor can include a compressible vessel that defines a main volume of the bioreactor and / or a compressible expansion vessel in fluid communication with the main volume of the bioreactor. In such examples, the load sensing unit can be adapted to detect a compressive force when the compressible element is compressed. An actuator can act to compress the compressible element, and the compressive force can be detected by the load sensing unit.

[0027] In some examples, the load sensing unit includes an actuator operable to compress the compressible element. The actuator can be operable to lift the bioreactor and detect the weight of the bioreactor (as described above) or to compress the compressible element. In examples, the cell processing system can further include a sensor configured to detect a displacement of the compressible element when the compressible element is compressed.

[0028] By detecting the compressive force and / or displacement of the compression element, it is possible to determine whether the bioreactor has a leak. In particular, if a predefined compressive force threshold is reached during compression, it can be assumed that the bioreactor is leak-free. Alternatively, a predefined compressive force can be applied to a compressible element of the bioreactor and the displacement monitored over time to detect an indication of a leak.

[0029] In examples, the cell processing system described above can further include a bioreactor. The bioreactor can include a container and a lid assembly having one or more connector interfaces for accessing the interior volume of the container. As described above, the bioreactor can include a compressible element. The container of the bioreactor can be a compressible element, for example, having a compressible or collapsible sidewall (e.g., a bellows wall). In some examples, the bioreactor, particularly the lid assembly, can include an expandable container, which can be a compressible element. In particular, the expandable container can be compressible, having a compressible or collapsible sidewall (e.g., a bellows wall).

[0030] According to the present disclosure, there is also provided a method of detecting a weight of a bioreactor in a cell processing system adapted to support the bioreactor, the method including supporting a weight of the bioreactor on a load sensing unit of the cell processing system and determining the weight of the bioreactor based on a load detected by the load sensing unit.

[0031] Advantageously, the load sensing unit is arranged within the housing of the cell processing system so that it is not necessary to remove the bioreactor from the cell processing system in order to detect the weight of the bioreactor.

[0032] In examples, the method includes releasably connecting a load sensing unit to the bioreactor. For example, the method can include connecting the load sensing unit to a lid assembly of the bioreactor.

[0033] In an example, the method includes moving the load sensing unit to lift the bioreactor from a support of the cell processing unit. By lifting the bioreactor from the support, the weight of the bioreactor is supported by the load sensing unit. A sensor, for example a load cell, can then detect the weight of the bioreactor.

[0034] Additionally or alternatively, if the bioreactor includes a compressible element, the method can include moving the load sensing unit to compress the compressible element. In such an example, the method can further include detecting a compressive force when the load sensing unit compresses the compressible element of the bioreactor. Additionally or alternatively, the method can include detecting a displacement of the load sensing unit when the load sensing unit compresses the compressible element of the bioreactor. By detecting the compressive force and / or displacement, the bioreactor can be tested for leaks.

[0035] The present disclosure also provides a method of detecting a leak in a bioreactor including a compressible element, the method including compressing a compressible element of the bioreactor, detecting a compressive force applied to the compressible element and / or a displacement of the compressible element, and determining whether the bioreactor has a leak based on the compressive force and / or the displacement.

[0036] In an example, the bioreactor includes a vessel and a lid assembly, and the compressible element is an expansion vessel in fluid communication with the vessel. The method includes compressing the compressible expansion vessel to test the bioreactor for leaks.

[0037] In accordance with the present disclosure, there is also provided a method of detecting a clogged filter in a bioreactor including a compressible element, an outlet, and a filter disposed within the outlet, the method including compressing a compressible element of the bioreactor to expel gas from the outlet, detecting a compressive force applied to the compressible element, and determining whether the compressive force exceeds a predetermined threshold indicating the filter is clogged.

[0038] In examples, the method further includes providing an alert or warning to a user in response to determining that the compressive force exceeds a predetermined threshold. In particular, a signal may be provided to a microprocessor upon determining that the compressive force exceeds a predetermined threshold indicating that the filter is clogged. In such examples, upon receiving the signal at the microprocessor, the microprocessor may provide a (e.g., visual) warning or (e.g., audible) alarm to the user.

[0039] Embodiments of the invention are further described hereinafter with reference to the accompanying drawings. [Brief description of the drawings]

[0040] [Figure 1] FIG. 1 illustrates a cell processing system including a bioreactor. [Figure 2A] FIG. 2 shows a bioreactor of the cell processing system of FIG. 1. [Figure 2B] FIG. 2 shows a bioreactor of the cell processing system of FIG. 1. [Diagram 3] FIG. 2 shows a support for the cell processing system of FIG. 1. [Figure 4A] FIG. 2 is a diagram showing a load sensing unit of the first example of the cell processing system of FIG. 1. [Figure 4B]FIG. 2 is a diagram showing a load sensing unit of the first example of the cell processing system of FIG. 1. [Figure 5A] FIG. 4C shows a clamp of the load-sensing unit of FIGS. 4A and 4B. [Figure 5B] FIG. 13 shows the corresponding clamping mechanism on the bioreactor. [Figure 6] FIG. 4C shows a load cell of the load-sensing unit of FIGS. 4A and 4B. [Figure 7] FIG. 2 is a schematic diagram of an alternative load-sensing unit of the cell processing system of FIG. 1. [Figure 8A] FIG. 1 shows an alternative bioreactor. [Figure 8B] FIG. 1 shows an alternative bioreactor. [Figure 9A] FIG. 8C shows an alternative load-sensing unit for use with the bioreactor of FIGS. 8A and 8B. [Figure 9B] FIG. 8C shows an alternative load-sensing unit for use with the bioreactor of FIGS. 8A and 8B. [Figure 10] FIG. 1 shows an alternative bioreactor. [Figure 11] FIG. 11 shows an alternative load sensing unit for use with the bioreactor of FIG. 10. [Figure 12] FIG. 1 shows an alternative bioreactor. [Figure 13] FIG. 13 shows an alternative load sensing unit for use with the bioreactor of FIG. 12. [Figure 14] FIG. 14 shows the load-sensing unit of FIG. 13 coupled with the bioreactor of FIG. 12. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0041] Figure 1 shows a cell processing system 1 comprising a housing 2 and a bioreactor 3. Figure 1 shows the bioreactor 3 loaded into the housing 2. Figures 2A and 2B show a first example of the bioreactor 3 alone, while Figures 8A, 8B, 10 and 12 show further examples of the bioreactor 3. During use, cells are processed, e.g. cultured, in the bioreactor 3 in the housing 2 of the cell processing system 1.

[0042] The housing 2 provides a closed environment for the bioreactor 3. The housing 2 is provided with power, connectivity and other utilities required for cell processing in the bioreactor 3. The cell processing system 1 includes a temperature control system that controls the temperature within the housing 2. The cell processing system 1 includes a humidity control system that controls the humidity within the housing 2. The cell processing system 1 includes a gas control system that controls the flow of gases into and out of the housing 2, e.g., controls the pressure within the housing 2, and / or controls the gas concentrations, e.g., oxygen and carbon dioxide concentrations, within the housing 2. The housing 2 may be an incubator in which the bioreactor 3 is housed during cell processing.

[0043] As shown in Figures 2A and 2B, the bioreactor 3 includes a vessel 6 and an interface plate 7. The interface plate 7 is a lid for the vessel 6. The interface plate 7 includes at least one connector interface 8 for connecting to an external component, for example, a consumable, which can be temporarily attached to the bioreactor 3. In an example, each connector interface 8 includes a septum seal that maintains a sealed environment within the vessel 6. Access to the vessel 6 can be provided by a needle that passes through the septum seal of the connector interface 8 to create a fluid connection into the vessel 6. Thus, a consumable can be connected to the connector interface 8 to add or remove material to the bioreactor 3, particularly the vessel 6.

[0044] The container 6 is a compressible container. In particular, the container 6 has a bottom wall 9 located opposite the interface plate 7, and a compressible wall 10 that defines a sidewall of the container 6. The compressible wall 10 extends between the interface plate 7 and the bottom wall 9 and is attached to the interface plate 7 and the bottom wall 9. The compressible wall 10 and the bottom wall 9 may be formed integrally. The compressible wall 10 is compressible such that the bottom wall 9 can move towards and away from the interface plate 7 to change the internal volume of the container 6. The compressible wall 10 also allows the angle of the bottom wall 9 relative to the interface plate 7 to be changed, for example to mix or stir the contents of the container 6.

[0045] The compressible wall 10 is a bellows wall and has a concertina structure that allows the compressible wall 10 to fold so that it collapses. In particular, the compressible wall 10 includes a series of alternating inward folds 11a and outward folds 11b that allow the compressible wall 10 to collapse like a bellows or concertina. The inward folds 11a and outward folds 11b are formed by thinned portions in the compressible wall 10. The inward folds 11a include thinned portions disposed on an outer surface of the compressible wall 10, and the outward folds 11b include thinned portions disposed on an inner surface of the compressible wall 10.

[0046] The vessel 6 of the bioreactor 3 can thus expand and contract or be expanded and contracted. In particular, as the cell culture in the vessel 6 grows and / or as additional material is added, the compressible vessel 6 can expand or the vessel 6 can be moved (e.g., compressed or expanded) to change the volume of the vessel 6. The cell processing system (1, see FIG. 1) can include an actuator (not shown) adapted to move the bottom wall 9 and / or the interface plate 7 of the vessel 6, e.g., pushing or pulling, to change the volume of the vessel 6. The actuator can be operable to agitate the contents of the vessel 6, e.g., by moving the bottom wall 9 in a reciprocating motion. The actuator can be an agitator assembly.

[0047] As shown in Figures 2A and 2B, the interface plate 7 also includes an expandable container 12, also referred to as a breathing bellows. The expandable container 12 is collapsible and is formed of a bellows, for example, like the container 6. The expandable container 12 is in fluid communication with the container 6 through an opening in the interface plate 7. The expandable container 12 can include a filter 13 that filters air and other gases entering and leaving the expandable container 12. The filter 13 can be closable to seal the expandable container 12. In other examples, the expandable container 12 is closed and sealed from the outside environment.

[0048] A cage 14 is provided around the expandable container 12 to keep the expandable container 12 aligned as the expandable container 12 expands and contracts. As shown in FIG. 2A and FIG. 2B, the cage 14 includes a first cage portion 14a attached to the interface plate 7 and a second cage portion 14b slidably attached to the first cage portion 14a. The second cage portion 14b can slide in the direction of expansion / contraction of the expandable container 12. A block prevents the second cage portion 14b from disengaging from the first cage portion 14a.

[0049] Thus, the expandable vessel 12 can expand or contract depending on the operational and environmental characteristics of the bioreactor 3. As the expandable vessel 12 expands and contracts, the cage 14 restricts the movement of the expandable vessel 12, and the first cage section 14a and the second cage section 14b slide relative to each other.

[0050] A coupling is provided for connecting the bioreactor 3, in particular the second cage part 14b, to the load-sensing unit, as will be explained below with reference to figures 4A to 6. In this example, the coupling comprises a clamp.

[0051] 2A and 2B, the cage 14 also includes a clamping mechanism 15, in this example a lip. The clamping mechanism 15 is grippable by an actuator of a load-sensing unit, as described further below. In other examples where the bioreactor 3 does not include an expansion vessel 12, the lip 15 can be provided on the interface plate 7 or other part of the bioreactor 3.

[0052] The cell processing system 1 includes a support 16 mounted within the housing 2 to receive and support the bioreactor 3, as shown in Figures 1 and 3. The support 16 can slide in and out of the housing 2 like a drawer for convenient loading and unloading of the bioreactor 3. The support 16 includes a support portion 18 adapted to engage with the interface plate 7 to support the bioreactor 3. The support 16 also includes an opening 17 adapted to receive the vessel 6 of the bioreactor 3, such that the interface plate 7 rests on the support portion 18 and the vessel 6 hangs downwardly in the opening 17. The support 16 holds the interface plate 7 of the bioreactor 3 in a substantially horizontal position.

[0053] 1-3, when the bioreactor 3 is supported on the support 16, the expandable vessel 12 is disposed on top of the interface plate 7 and is expandable and contractible in a substantially vertical direction. The vessel 6 hangs below the interface plate 7 and can hang freely, be supported on another plate, and / or be moved by an actuator or agitator assembly as described above.

[0054] In some instances, the bioreactor 3 is rotatable within the housing 2. In such instances, the support 16, and in particular the support portion 18, can include a rotation mechanism. For example, the support portion 18 can have a pancake motor adapted to rotate the interface plate 7 and thus the bioreactor 3.

[0055] 2A, the bioreactor 3 includes a plurality of connector interfaces 8, and the rotation mechanism can be operable to rotate the interface plate 7 to align successive connector interfaces 8 with another component or assembly, such as a consumable for sampling or material addition. The rotation mechanism can be adapted to index the interface plate 7 to align successive connector interfaces 8 with a connector, such as a connector for a consumable for sampling or material addition.

[0056] The cell processing system 1 may further include one or more consumables. The consumables may be attachable to the bioreactor 3 and / or to another assembly provided within the housing 2. In particular, the one or more consumables may be attached to an actuator that connects the consumables to the bioreactor 3. Alternatively, the one or more consumables may be connected to the bioreactor 3, for example, at a connector interface 8, and the cell processing system 1 may include an actuator that operates the consumables. For example, the cell processing system 1 may include an actuator adapted to depress or compress the consumable to move material from the consumable into the container 6, and / or the actuator may be operable to retract or expand the consumable to withdraw material from the container 6. The cell processing system 1 may include a consumable loading mechanism by which a user loads the consumable into the housing 2. The consumable loading mechanism may then be operable to attach the consumable to the bioreactor 3, for example, at a connector interface 8 as shown in Figures 2A and 2B.

[0057] In an example, the consumables may be connected to the bioreactor 3 by a common connector, in particular to the connector interface 8 of the interface plate 7. The connector may maintain sterility between the consumables and the bioreactor 3 by having one or more seals, such as, for example, a septum seal. The connector may be one of those described in Applicant's co-pending US Patent Application Publication No. 2007 / 0139996.

[0058] The cell processing system 1 may additionally include various components and systems that interact with the housing 2, the bioreactor 3, and / or the consumables. For example, as described above, the housing 2 may include an agitator that acts to agitate the bioreactor 3 to agitate the cell suspension provided therein. In other examples, the cell processing system 1 may include a consumable loading mechanism adapted to hold one or more consumables. In examples, the cell processing system 1 may include an actuator operable to actuate the one or more consumables. The cell processing system 1 may be configured for automated or semi-automated operation and / or may allow for manual operation.

[0059] As described above, the bioreactor 3 includes a vessel 6 and an interface plate 7. During use for cell processing, the vessel 6 holds a fluid in which cell processing takes place. In particular, the fluid includes a population of cells present in a liquid medium. Consumables can be attached to the bioreactor 3 to add materials to the vessel 6. For example, the consumables can add cells (e.g., a cell suspension), cell growth medium, or other materials. Alternatively, consumables can be attached to the bioreactor 3 to remove materials from the vessel 6. For example, the consumables can remove waste materials, samples, and / or processed cells. Consumables thus connect to the bioreactor 3 to facilitate the process steps of cell processing.

[0060] In use, the population of cells processed in bioreactor 3 may comprise any cell type. Preferably, the population of cells may comprise a homogenous population of cells. Alternatively, the population of cells may comprise a mixed population of cells.

[0061] The population of cells can include any human or animal cell type, for example, any type of adult stem cell or primary cell, T cells, CAR-T cells, monocytes, white blood cells, red blood cells, NK cells, gamma delta t cells, tumor infiltrating t cells, mesenchymal stem cells, embryonic stem cells, induced pluripotent stem cells, adipose-derived stem cells, Chinese hamster ovary cells, NS0 mouse myeloma cells, HELA cells, fibroblasts, HEK cells, insect cells, organoids, etc. Suitably, the population of cells can include T cells.

[0062] Alternatively, the population of cells can include any microbial cell type, for example, bacterial, fungal, archaean, protozoan, and algal cells.

[0063] In an example, liquid medium can be added to container 6 during cell processing. The liquid medium can be any sterile liquid capable of sustaining the cells. The liquid medium can be selected from saline or can be a cell culture medium. The liquid medium can be any suitable medium, for example, a cell culture medium selected from DMEM, XVIVO 15, TexMACS. The liquid medium can be appropriate for the type of cells present in the population. For example, the population of cells includes T cells and the liquid medium includes XVIVO 10.

[0064] In examples, the liquid medium can further include additives, such as growth factors, nutrients, buffers, minerals, stimulants, stabilizers, and the like.

[0065] In an example, the liquid medium comprises growth factors such as cytokines and / or chemokines. The growth factors may be appropriate for the type of cells present in the population and the desired process to be performed. The liquid medium may comprise a stimulating agent such as an antigen or an antibody, which may be immobilized on a carrier. A suitable stimulating agent may be appropriate for the type of cells present in the population and the desired process to be performed. For example, when culturing T cells, an antibody is provided as a stimulating agent in the liquid medium. The antibody may be immobilized on an inert carrier such as beads, e.g., Dynabeads.

[0066] Additives may be present in the liquid medium at effective concentrations that can be determined by one of skill in the art based on the population of cells and the desired process to be carried out using known teachings and techniques in the art.

[0067] In an example, a population of cells is inoculated into a liquid medium at a concentration between 1×10 4 cfu / ml and 1×10 8 cfu / ml.

[0068] 4A to 6 show the load sensing unit 20 of a first example of the cell processing system 1. The load sensing unit 20 is disposed in the housing 2 of the cell processing system 1. In particular, the load sensing unit 20 is mounted above the bioreactor 3 in the housing 2.

[0069] As will be further described below, in some examples the load sensing unit 20 is adapted to connect to the bioreactor 3 and detect the weight of the bioreactor 3. In examples, the load sensing unit 20 is adapted to connect to the bioreactor 3 and lift the bioreactor 3 off the support portion 18 such that the entire weight of the bioreactor is supported by the load sensing unit 20. In other examples, the load sensing unit 20 can be connected to the bioreactor 3 and the support portion 18 can be moved to disengage from the bioreactor 3 such that the entire weight of the bioreactor is supported by the load sensing unit 20. The load sensing unit 20 can include a load cell for detecting the weight of the bioreactor 3.

[0070] In another example, the load sensing unit 20 is adapted to compress a part of the bioreactor, in particular the expansion vessel (12, see Figs. 2A and 2B), to measure the compressive force. The load sensing unit 20 may include a load cell arranged to detect the compressive force. The detected compressive force may be used to test the bioreactor 3 for leaks and / or to determine whether the filter (13, see Figs. 2A and 2B) is clogged.

[0071] As shown in Figures 4A and 4B, the load sensing unit 20 includes a clamp 21 operable to clamp onto the bioreactor (3, see Figures 2A and 2B), as further described below. As mentioned above, the load sensing unit 20 is positioned within the housing above the bioreactor 3, with the clamp 21 facing downwards to clamp onto the top of the bioreactor, as shown in Figure 4A. In particular, the clamp 21 is operable to clamp onto the clamping mechanism 15 of the bioreactor 3, as shown in Figures 2A and 2B.

[0072] The clamp 21 is mounted on a hinge plate 22 which is pivotally connected to a base plate 23 via pivots provided by shafts 24a, 24b.

[0073] The base plate 23 is mountable to the housing 2 of the cell processing system 1 shown in Figure 1. The base plate 23 includes one or more linear actuators 25 that linearly move the base plate 23 and the load sensing unit 20 relative to the housing 2. In particular, the linear actuators 25 allow for vertical movement of the base plate 23 within the housing 2 of the cell processing system 1. The base plate 23 can thereby be moved within the housing 2 towards and away from the bioreactor 3.

[0074] In use, the clamp 21 can be clamped onto the top of the bioreactor (specifically the clamping mechanism 15 shown in Figures 2A and 2B) and the base plate 23 can be lifted by the linear actuator 25 so that the weight of the bioreactor is supported by the load sensing unit 20. The weight of the bioreactor causes the hinge plate 22 to rotate about the shaft 24.

[0075] As shown in FIG. 4B, a load cell 27 is disposed between the base plate 23 and the hinge plate 22 such that the torque of the hinge plate 22 acts on the load cell 27. In this example, the torque of the hinge plate 22 acts to compress the load cell 27, but in other examples, the torque of the hinge plate 22 can act to apply a tensile stress to the load cell 27. The load cell 27 includes one or more sensors disposed to detect a load acting on the load cell 27. For example, the load cell 27 can include one or more strain gauges, such as a piezoresistive strain gauge, an inductive or magnetoresistive strain gauge, or a magnetostrictive strain gauge. The sensor signal output from the load cell sensor can be received by a controller of the cell processing system 1. The controller can be configured to determine the weight of the bioreactor.

[0076] 5A and 5B show the clamp 21 and the clamping mechanism 15 on the bioreactor 3 in more detail. As shown in FIG. 5A, the clamp 21 has two clamping arms 28a, 28b that are pivotally mounted to the hinge plate 22 at pivots 29a, 29b, respectively. A motor 30 is provided to actuate the clamping arms 28a, 28b via a gear train 31 that is arranged to translate a rotation output by the motor into an opposing rotation of the clamping arms 28a, 28b about the pivots 29a, 29b. In this manner, the clamping arms 28a, 28b can be driven to engage or disengage the clamping mechanism 15 on the top of the bioreactor 3, shown in FIG. 5B. As shown, the clamping mechanism 15 includes a lip formed by a recess 32 that receives the clamping arms 28a, 28b, allowing the clamp 21 to be secured to the bioreactor 3. The gear train 31 may include a self-locking mechanism such that in the clamped position the clamp arms 28 a , 28 b are held in place and cannot be moved from the clamped position unless actuated by the motor 30 .

[0077] Thus, the motor 30 can be driven in one direction so that the clamp arms 28 a , 28 b clamp onto the clamp mechanism 15 , and in the other direction so that the clamp arms 28 a , 28 b release the clamp mechanism 15 .

[0078] The load sensing unit 20 may include one or more sensors positioned to detect the gripping of the bioreactor (in particular the clamping mechanism 15) by the clamp 21 and / or the position of the clamp arms 28a, 28b to confirm that the clamp 21 is connected to the bioreactor 3.

[0079] As described above, the load sensing unit 20 is substantially vertically movable to and from a position where it can clamp the bioreactor 3. In an example, the clamp 21 can include one or more sensors that detect the presence or position of the bioreactor 3 relative to the clamp arms 28a, 28b. For example, a capacitive proximity sensor can be provided to detect the cage 14, the clamping mechanism 15 and / or the filter 13 of the bioreactor 3. The one or more sensors can include a switch or a proximity sensor, for example a capacitive proximity sensor. The one or more sensors are actuated when the clamp 21 is in the correct position relative to the bioreactor 3 for clamping onto the clamping mechanism 15. The one or more sensors can communicate a sensor signal to a controller configured to control the motor 30 to close the clamp 21 when the clamp 21 is in the correct position.

[0080] 6 shows the load cell 27 in more detail. As shown, the load cell 27 is disposed between the hinge plate 22 and the base plate 23, in this example between the hinge plate 22 and a mounting arm 26 that is attached to the base plate 23. A load pin 32 connects the hinge plate 22 to the load cell 27. In use, when the weight of the bioreactor is supported by the load sensing unit 20, the torque of the hinge plate 22 acts to compress the load cell 27 against the base plate 23. The strain exerted on the load cell 27 can be detected by a sensor to determine the weight of the bioreactor.

[0081] In some examples, the load pin 32 is threaded and is threadedly attached to both the hinge plate 22 and the base plate 23 (or mounting arm 26). In this example, the hinge plate 22 is spaced from the load cell 27. Thus, when the bioreactor is lifted, the weight of the bioreactor rotates the hinge plate 22, exerting a torque on the load cell 27 via the load pin 32.

[0082] Thus, a first method for determining the weight of a bioreactor 3 is provided. In this method, the load sensing unit 20 is placed and clamped onto the bioreactor 3 to connect the load sensing unit 20 to the bioreactor 3. The load sensing unit 20 is then lifted such that the bioreactor 3 is also lifted and the entire weight of the bioreactor 3 is supported by the load sensing unit 20. The force applied to the load cell 27 can be determined and used to determine the weight of the bioreactor 3.

[0083] In some examples, the load sensing unit 20 is operable to apply a compressive force to the bioreactor 3. In particular, the linear actuator 25 can be operated to move the base plate 23 and the hinge plate 22 towards the bioreactor 3 to compress the bioreactor 3, in particular the expansion vessel 12 and / or the vessel 6 of the bioreactor as described with reference to Figures 2A and 2B. When the bioreactor 3 is compressed, the load cell 27 will be subjected to a strain and the strain force can be detected by the load cell 27. In this example, the load pin 32 is threaded to both the hinge plate 22 and the load cell 27 to ensure full torque transmission.

[0084] In this example, the cell processing system 1 can additionally detect the displacement of the load-sensing unit 20 when the bioreactor 3 is compressed. For example, the linear actuator 25 can include an encoder (e.g., a digital encoder) that detects the displacement of the base plate 23. Alternatively, a separate sensor can detect the displacement of the base plate 23. The controller can be configured to determine whether the bioreactor 3 has a leak from the detected displacement and / or the force detected by the load cell 27. That is, the load-sensing unit 20 can be operated to compress the bioreactor 3 to test the bioreactor 3 for leaks.

[0085] Thus, a second method for testing a bioreactor 3 for leaks is provided. In this method, the load sensing unit 20 is moved to compress the bioreactor 3. In particular, the load sensing unit 20 is moved to compress the expansion vessel 12 of the bioreactor 3. The compressive force applied to the bioreactor is detected as a strain on the load cell 27. The displacement of the load sensing unit 20 is also detected. Based on the compressive force and the displacement, the controller can determine whether the bioreactor 3 has a leak.

[0086] In some examples, the load sensing unit 20 can be used to test whether the filter 13 (embedded in the expandable vessel 12 as shown in Figures 2A and 2B) is clogged. In this example, the method first includes coupling the load sensing unit 20 to the bioreactor 3 as described above. The load sensing unit 20 is then moved to compress the bioreactor 3, and in particular the expandable vessel 12. At the same time, the compressible vessel 6 is also compressed by another actuator of the cell processing system 1, which forces gas from the vessel 6 into the expandable vessel 12. Normally, this gas would exit through the filter 13, but if the filter 13 is clogged, pressure will build up in the bioreactor 3 and the load cell 27 will detect the pressure increase. The load cell 27 can be calibrated to determine the pressure detected when the gas flow rate through the filter 13 is normal (i.e., the filter 13 is not clogged), such that a control unit receiving a signal from the load cell 27 can determine when the filter 13 is clogged (or partially clogged). The control unit includes a microprocessor which receives such signals and can provide a visual or audible alarm to an operator of the load sensing unit 20 upon receiving a signal from the load cell 27 indicating that the filter 13 is partially or completely clogged.

[0087] FIG. 7 shows a schematic diagram of an alternative example of a cell processing system 1. As shown, the cell processing system 1 includes a housing 2 in which a bioreactor 3 is received. The housing 2 is the same as that described with reference to FIG. 1. A support 16, in particular a support portion 18, supports the bioreactor 3. In particular, as shown in FIG. 3, the support 16 includes a support portion 18 on which an interface plate 7 of the bioreactor 3 is supported. As shown in FIG. 7, in this example the support portion 18 is pivotally attached to the housing 2 at a pivot 33. Thus, the weight of the bioreactor 3 generates a torque about the pivot 33. The load sensing unit 20 in this example includes a load cell 34 disposed between the support portion 18 and a portion 2a of the housing 2, such that the load cell 34 is compressed by the torque of the support portion 18. Thus, similar to the above example, the weight of the bioreactor 3 can be determined based on the torque detected by the load cell 34. In another example, the load cell 34 can be disposed such that it is subjected to a tensile stress by the weight of the bioreactor 3 on the support portion 18.

[0088] The method of detecting the weight of the bioreactor 3 in the example of FIG. 7 includes disengaging any other parts of the cell processing system 1 from the bioreactor 3. For example, any actuators, stirring mechanisms, etc. are disconnected from the bioreactor 3 so that only the weight of the bioreactor 3 acts on the support portion 18. The load detected by the load cell 34 in this state can be used to determine the weight of the bioreactor 3. In some examples, a consumable can be attached to the bioreactor 3 during the method of detecting the weight of the bioreactor 3. The consumable can have a known weight that can be accounted for. An advantage of the example of FIG. 7 is that the load sensing unit 20 does not need to be clamped or released onto the bioreactor 3 during use, and the weight of the bioreactor 3 can be constantly monitored.

[0089] An actuator (not shown) in the housing 2 in the example of Fig. 7 may be operable to compress the expandable vessel 12 of the bioreactor 3. The actuator may act on the expandable vessel 12 to compress it against the support 16. When the actuator compresses the expandable vessel 12, the compressive force may be detected with the load cell 34. Additionally, the displacement of the expandable vessel 12 may be detected, for example, by detecting the displacement of the actuator. Thus, the bioreactor 3 may be tested for leaks and / or a clogged filter 13 may be detected in the same manner as described for the previous example.

[0090] 8A-9B show a further example cell processing system, in particular a bioreactor 3 and a load-sensing unit 20. The bioreactor 3 is substantially the same as described above with reference to FIGS. 2A and 2B, except for the coupling as further described below. In particular, the bioreactor 3 has a vessel 6 and an interface plate 7. The interface plate 7 includes at least one connector interface 8 for connecting to an external component. The vessel 6 is a compressible vessel, having a bottom wall 9 and a compressible wall 10 extending between the interface plate 7 and the bottom wall 9. The bioreactor 3 also includes an expansion vessel (not visible in FIGS. 8A-10) and a cage 14a, 14b surrounding the expansion vessel. The expansion vessel 12 can include a filter 13.

[0091] The load sensing unit 20 is disposed within the housing 2 of the cell processing system 1 shown in Figure 1. In particular, the load sensing unit 20 is mounted above the bioreactor 3 within the housing 2.

[0092] As in the previous example, the load sensing unit 20 is adapted to connect to the bioreactor 3 and detect the weight of the bioreactor 3. In an example, the load sensing unit 20 is adapted to connect to the bioreactor 3 and lift the bioreactor 3 from the support portion 18 such that the entire weight of the bioreactor is supported by the load sensing unit 20. In another example, the load sensing unit 20 can be connected to the bioreactor 3 and the support portion 18 can be moved to disengage from the bioreactor 3 such that the entire weight of the bioreactor is supported by the load sensing unit 20. The load sensing unit 20 can include a load cell for detecting the weight of the bioreactor 3.

[0093] In another example, the load sensing unit 20 is adapted to compress a part of the bioreactor, in particular the expansion vessel (12, see Figs. 2A and 2B), to measure the compressive force. The load sensing unit 20 may include a load cell arranged to detect the compressive force. The detected compressive force may be used to test the bioreactor 3 for leaks and / or to determine whether the filter 13 is clogged.

[0094] Figures 8A to 9B show the connection between the load sensing unit 20 and the bioreactor 3, in particular the second cage part 14b. In this example, the connection is a bayonet connection, as will be explained below.

[0095] As shown in Figures 8A and 8B, in this example, the cage 14 of the bioreactor 3 includes a first bayonet fitting 35. One end of the cage 14, and in particular the second cage section 14b, includes an opening 39. The first bayonet fitting 35 is formed in the opening 39. The first bayonet fitting 35 includes three recesses 38a-38c separated by protrusions 37a-37c. The protrusions 37a-37c extend into the opening 39. In other examples, the first bayonet fitting 35 can include a different number of recesses 38 and protrusions 37, for example, two, four, or five.

[0096] In other examples where the bioreactor 3 does not include an expansion vessel 12 , the first bayonet fitting 35 can be provided on the interface plate 7 or other part of the bioreactor 3 .

[0097] The first bayonet fitting 35 can be engaged by a corresponding second bayonet fitting 36 on the load sensing unit 20, shown in Figures 9A and 9B.

[0098] As shown in Figure 9A, the load sensing unit 20 includes a platform 40 that is mounted above the bioreactor 3 (see Figure 1) within the housing 2 of the cell processing system 1. The platform 40 is mounted on linear bearings 41a, 41b and can be moved towards and away from the bioreactor 3 (i.e., up and down) by actuators.

[0099] The second bayonet fitting 36 is attached to the platform 40 via a load cell 42. A threaded portion 44 (e.g., a bolt) extends from the second bayonet fitting, through an opening in the platform 40, to the load cell 42 where the threaded portion 44 is secured by a nut 43. A bracket 45 attaches the load cell 42 to the platform 40.

[0100] The load cell 42 may include one or more strain gauges, such as piezoresistive, inductive or magnetoresistive, or magnetostrictive strain gauges. The sensor signal output from the load cell sensor may be received by a controller (control unit) of the cell processing system 1. The controller (control unit), particularly its microprocessor, may be configured to determine the weight of the bioreactor and provide a visual and / or audible alarm to the user.

[0101] In this manner, when the second bayonet fitting 36 engages the first bayonet fitting 35 and the platform 40 rises to lift the bioreactor, the load cell 42 will detect the weight of the bioreactor.

[0102] As shown in FIG. 9B, the second bayonet fitting 36 includes three protrusions 46a-46c (only two are visible in FIG. 9B) extending radially from a hub 47. The protrusions 46a-46c are sized to fit into the recesses 38a-38c (see FIGS. 8A and 8B) of the first bayonet fitting 35. After relative rotation between the first bayonet fitting 35 and the second bayonet fitting 36, the protrusions 37a-37c of the first bayonet fitting 35 and the protrusions 46a-46c of the second bayonet fitting 36 align, thereby coupling the load sensing unit 20 to the bioreactor 3.

[0103] As explained above, the bioreactor 3 is rotatable within the housing 2, for example within the support 16 shown in FIG. 3. To couple and separate the first bayonet fitting 35 and the second bayonet fitting 36, the vertical movement can be provided by the platform 40, and the rotation can be provided by rotating the bioreactor 3 (and thus the first bayonet fitting 35). In this way, the first bayonet fitting 35 and the second bayonet fitting 36 can be used to couple and separate the load-sensing unit 20 to and from the bioreactor 3. In another example, at least a portion of the second bayonet fitting 36 can be rotatable to couple and separate with the first bayonet fitting 35.

[0104] Once coupled, the platform 40 can be lifted to also lift the bioreactor 3, and the load cells 42 can detect the weight of the bioreactor 3. In another example, the platform 40 can be driven down towards the bioreactor 3, and the load cells 42 can detect the force applied to the bioreactor to perform leak testing as described above and / or detect clogged filters.

[0105] The load sensing unit 20 may include one or more sensors positioned to detect coupling with the bioreactor (particularly engagement of the first bayonet fitting 35 and the second bayonet fitting 36).

[0106] As described above, the load sensing unit 20 is substantially vertically movable to and from a position where the bioreactor 3 and the load sensing unit 20 can be coupled. In an example, the second bayonet fitting 36 can include one or more sensors to detect the presence or position of the bioreactor 3 relative to the projections 46a-46c. For example, a capacitive proximity sensor can be provided to detect the cage 14, or projections 37a-37c, and / or the filter 13 of the bioreactor 3. The one or more sensors can include a switch or a proximity sensor, for example a capacitive proximity sensor. The one or more sensors are activated when the second bayonet fitting 36 is in the correct position to couple with the bioreactor 3. The one or more sensors can communicate a sensor signal to a controller configured to control the rotation of the bioreactor 3 and / or the second bayonet fitting 36 and / or the movement of the platform 40.

[0107] Figures 10 and 11 show an alternative coupling between the load sensing unit 20 and the bioreactor 3. In this example, the coupling is an alternative bayonet coupling, similar to that of Figures 8A to 9B, as further described below. In particular, Figure 10 shows an alternative bioreactor 3, which is as described with reference to Figures 2A and 2B and 8A and 8B, except for the coupling, which is a first bayonet fitting 52. Figure 11 shows an alternative load sensing unit 20 with a second bayonet fitting 53 attached to a platform 40, which is otherwise as described with reference to Figure 9A.

[0108] As shown in FIG. 10, the cage, and in particular the second cage portion 14b, includes an opening 39 within which a first bayonet fitting 52 is formed. The first bayonet fitting 52 includes three inwardly projecting pins 46a-46c (only two are visible in FIG. 10). In this example, there are three pins 46a-46c, but there could be a different number, for example, two, four, or five pins 46a-46c. In this example, the pins 46a-46c have a square cross section, but they could also be circular or triangular or other shapes. The pins 46a-46c are arranged such that a corner of each pin 46a-46c faces vertically upward and the opposite corner of the pin 46a-46c faces vertically downward.

[0109] As shown in Figure 11, a second bayonet fitting 53 is provided on the platform 40, which is the same as that described with reference to Figure 9A, except for the second bayonet fitting 53. The second bayonet fitting 53 includes a body, in this example a cylinder 48. In other examples the body can have a different shape, such as having a square or hexagonal cross section. The cylinder 48 is attached to the platform 40 via a load cell 42 and a bracket 45.

[0110] The cylindrical body 48 includes grooves 49a, 49b formed in its circumferential surface. The grooves 49a, 49b are spaced to align with the pins 46a-46c of the first bayonet fitting 52 when the cylindrical body 48 is lowered into the opening 39 of the first bayonet fitting 52. There can be a corresponding number of grooves 49a, 49b and pins 46a-46c or there can be more grooves 49a, 49b than pins 46a-46c, provided there is circumferential spacing that allows each pin 46a-46c to engage with the grooves 49a, 49b.

[0111] Each groove 49a, 49b includes a first trap 50a, 50b that faces downward (towards the bioreactor). The first trap 50a, 50b is formed by the angled sides of the grooves 49a, 49b that define a convergence point into which the pins 46 will rest as the platform 40 moves towards the bioreactor 3. When the platform 40 is lowered towards the bioreactor 3, the pins 46a-46c will be located in the first trap 50a, 50b, allowing the transfer of force from the platform 40 to the second cage section 14b to compress the bioreactor 3.

[0112] Each groove 49a, 49b also includes a second trap 51a, 51b that faces upward (away from the bioreactor). The second trap 51a, 51b is formed by the angled sides of the grooves 49a, 49b that define a convergence point into which the pin 46 will rest as the platform 40 moves away from the bioreactor 3. As the bioreactor 3 rotates relative to the load-sensing unit 20 and the platform 40 rises away from the bioreactor 3, the pins 46a-46c will rest in the second traps 51a, 51b, allowing the transfer of force from the platform 40 to the second cage section 14b, lifting the second cage section 14b and the bioreactor 3.

[0113] During binding and separation, the bioreactor 3 (and also the pins 46a-46c) can be rotated to align with the grooves 49a, 49b, the first traps 50a, 50b, and the second traps 51a, 51b as required. Alternatively, the cylinder 48 can be rotatably mounted on the platform 40, and the angled sides of the grooves 49a, 49b can cooperate with the pins 46a-46c to rotate the cylinder 48 to align the pins 46a-46c with the first traps 50a, 50b, and the second traps 51a, 51b. An actuator can rotate the cylinder 48, or the cylinder 48 can be freely rotatable.

[0114] In this manner, the first bayonet fitting 52 and the second bayonet fitting 53 can be used to couple and separate the load sensing unit 20 and the bioreactor 3. Once coupled, the platform 40 can be raised to also lift the bioreactor 3, and the load cell 42 can detect the weight of the bioreactor 3. In another example, the platform 40 can be driven down towards the bioreactor 3, and the load cell 42 can detect the force applied to the bioreactor to perform a leak test and / or detect a clogged filter as described above.

[0115] The load sensing unit 20 may include one or more sensors positioned to detect coupling with the bioreactor (particularly engagement of the first bayonet fitting 52 and the second bayonet fitting 53).

[0116] As described above, the load sensing unit 20 is substantially vertically movable to and from a position where the bioreactor 3 and the load sensing unit 20 can be coupled. In an example, the second bayonet fitting 53 can include one or more sensors to detect the presence or position of the bioreactor 3 relative to the grooves 49a, 49b. For example, a capacitive proximity sensor can be provided to detect the cage 14, or the pins 46a-46c, and / or the filter 13 of the bioreactor 3. The one or more sensors can include a switch or a proximity sensor, for example a capacitive proximity sensor. The one or more sensors are activated when the second bayonet fitting 53 is in the correct position to couple with the bioreactor 3. The one or more sensors can communicate a sensor signal to a controller configured to control the rotation of the bioreactor 3 and / or the second bayonet fitting 53 and / or the movement of the platform 40.

[0117] 12 to 14 show further example connections between the bioreactor 3, in particular the second cage part 14b, and the load-sensing unit 20. In the embodiment shown in FIG.

[0118] Figures 12 to 14 show an alternative coupling between the load sensing unit 20 and the bioreactor 3. In this example, the coupling is a coupling unit 55 having spring arms 57a-57c, as further described below. In particular, Figure 12 shows an alternative bioreactor 3. The bioreactor 3 is as described with reference to Figures 2A and 2B and Figures 8A, 8B and 10, except for the coupling unit 55. Figure 13 shows an alternative load sensing unit 20 with a coupling unit 55. The coupling unit 55 is attached to a platform 40 as described with reference to Figure 9A.

[0119] 12, in this example, second cage section 14b includes an opening with an inwardly facing edge 54. Edge 54 is circular.

[0120] 13, the load sensing unit 20 includes a coupling unit 55 including a hub 56 and three spring arms 57a to 57c. The hub 56 is attached to the platform 40 (see FIG. 9A) via the load cell 42 and a bracket 45.

[0121] The spring arms 57a-57c are pivotally connected to the hub 56 at pivots 58a-58c and extend upwardly (away from the bioreactor 3 towards the platform (not shown)). The spring arms 57a-57c have ends 59a-59c, respectively. Torsion springs may be provided at the pivots 58a-58c to urge the spring arms 57a-57c away from the hub 56. Alternatively, a helical spring may be provided between the end 59a-59c of each spring arm 57a-57c and the hub 56 to urge the spring arms 57a-57c away from the hub 56.

[0122] Each spring arm 57a-57c includes a notch 60 on its outer surface. The notch 60 is formed by two angled sides forming an obtuse angle. As shown in FIG. 14, when the coupling unit 55 is pushed into the opening 39 in the second cage part 14b, the spring arms 57a-57c flex inward until the notch 60 engages the edge 54 of the opening 39. The spring arms 57a-57c are directed outward, pressing the notch 60 against the edge 54 of the opening. In this position, the load sensing unit 20 is coupled to the bioreactor 3 and can raise the platform (40, see FIG. 9A) to lift the bioreactor 3. Additionally, the notch 60 is configured such that the coupling unit 55 cannot move further into the opening 39 relative to the second cage part 14b, such that the load sensing unit 20 can also press the bioreactor 3 down.

[0123] To detach the coupling unit 55 from the second cage section 14b, the coupling unit 55 can be raised by raising the platform (40, see FIG. 9A) while holding down the bioreactor 3 (e.g., in the support 16 shown in FIG. 3). The angle of each notch 60 causes the spring arms 57a-57c to flex inwardly, allowing the coupling unit 55 to detach from the opening 39.

[0124] In this manner, the coupling unit 55 can be used to couple and separate the load sensing unit 20 and the bioreactor 3. When coupled, the platform 40 can be raised to also lift the bioreactor 3, and the load cell 42 can detect the weight of the bioreactor 3. In another example, the load sensing unit 20 can push the second cage part 14b down towards the bioreactor 3, and the load cell 42 can detect the force applied to the bioreactor 3 to perform a leak test as described above and / or detect a clogged filter 13.

[0125] The load sensing unit 20 may include one or more sensors positioned to detect coupling with the bioreactor (particularly engagement of the coupling unit 55 with the opening 39).

[0126] As described above, the load sensing unit 20 is substantially vertically movable to and from a position where the bioreactor 3 and the load sensing unit 20 can be coupled. In an example, the coupling unit 55 can include one or more sensors to detect the presence or position of the bioreactor 3 relative to the spring arms 57a-57c. For example, a capacitive proximity sensor can be provided to detect the cage 14, or the edge 54, and / or the filter 13 of the bioreactor 3. The one or more sensors can include a switch or a proximity sensor, for example a capacitive proximity sensor. The one or more sensors are activated when the coupling unit 55 is in the correct position to couple with the bioreactor 3. The one or more sensors can communicate a sensor signal to a controller configured to control the rotation of the bioreactor 3 and / or the movement of the platform 40.

[0127] Throughout the description and claims of this specification, the words "comprise" and "contain" and variations thereof mean "including but not limited to" and are not intended to (and do not) exclude other elements, wholes or steps. Throughout the description and claims of this specification, the singular encompasses the plural unless the context requires otherwise. In particular, when the indefinite article is used, the specification should be understood as contemplating the plural as well as the singular, unless the context requires otherwise.

[0128] It should be understood that features, wholes, properties or groups described in conjunction with a particular aspect, embodiment or example of the invention are applicable to any other aspect, embodiment or example described herein, unless incompatible therewith. All of the features disclosed in this specification (including any accompanying claims, abstract and drawings), and / or all of the steps of any method or process so disclosed, may be combined in any combination, except combinations in which at least some of such features and / or steps are mutually exclusive. The invention is not limited to the details of any of the foregoing embodiments. The invention extends to any novel, or any novel combination of features disclosed in this specification (including any accompanying claims, abstract and drawings), or to any novel, or any novel combination of steps of any method or process so disclosed. [Explanation of symbols]

[0129] 1. Cell Processing System 2. Housing 2a Part of the housing 3. Bioreactor 6 Containers, compressible containers 7 Interface Plate 8 Connector Interface 9 Bottom Wall 10 Compressible Walls 11a Inward fold 11b Outward fold 12 Expansion Container 13 Filters 14 Cage 14a First cage section 14b Second cage section 15 Clamping mechanism 16 Support 17 Aperture 18 Support part 20 Load sensing unit 21 Clamp 22 Hinge plate 23 Base plate 24 Shaft 24a, 24b shaft 25 Linear Actuator 26 Mounting arm 27 Load Cell 28a, 28b Clamp arm 29a, 29b pivot 30 Motor 31 Gear Train 32 Load pin 33 Pivot 34 Load Cell 35 First Bayonet Fitting 36 Second bayonet fitting 37a~37c protrusion 38a~38c Recess 39 Aperture 40 Platform 41a, 41b Linear bearings 42 Load Cell 43 Nut 44 Threaded Part 45 Bracket 46a~46c Protrusions, pins 47 Hub 48 Cylinder 49a, 49b groove 50a, 50b First trap 51a, 51b Second trap 52 First Bayonet Fitting 53 Second bayonet fitting 54 Edge 55 Combined Unit 56 Hub 57a~57c Spring arm 58a~58c Pivot 59a~59c End 60 notches

Claims

1. A cell processing system for accommodating a bioreactor, the cell processing system comprising a load sensing unit adapted to support the bioreactor and operable to detect a weight of the bioreactor.

2. The cell processing system of claim 1 , further comprising a housing and a support for supporting the bioreactor within the housing.

3. The cell processing system of claim 2 , wherein the support is pivotally mounted to the housing, and the load sensing unit includes a load cell, the load cell being positioned such that a torque of the support is applied to the load cell.

4. The cell processing system of claim 2 , wherein the load sensing unit is adapted to releasably connect to the bioreactor.

5. 5. The cell processing system of claim 4, wherein, in use, the load sensing unit is positioned above the bioreactor and is operable to releasably connect to the top of the bioreactor.

6. 6. The cell processing system of claim 4, wherein the load sensing unit is movable to lift the bioreactor from the support to a raised position where the weight of the bioreactor is supported by the load sensing unit.

7. 7. The cell processing system of claim 4, wherein the support is movable to disengage from the bioreactor such that the weight of the bioreactor is borne by the load sensing unit.

8. The cell processing system of claim 4 , wherein the load sensing unit comprises a coupling operable to releasably connect to the bioreactor.

9. The cell processing system of claim 8 , wherein the coupling comprises a clamp operable to releasably connect to the bioreactor.

10. 10. The cell processing system of claim 9, wherein the clamp comprises an actuator and at least one arm movable by the actuator to clamp onto the bioreactor.

11. 11. The cell processing system of claim 4, wherein the load sensing unit comprises a pivotally mounted hinge plate releasably connectable to the bioreactor such that the weight of the bioreactor applies a torque to the hinge plate, and the load sensing unit comprises a load cell positioned such that the torque applied to the hinge plate is applied to the load cell.

12. 9. The cell processing system of claim 8, wherein the coupling comprises a bayonet fitting, the bioreactor comprises a first bayonet fitting, the load sensing unit comprises a second bayonet fitting coupleable to the first bayonet fitting, and further comprising an actuator for rotating the bioreactor relative to the load sensing unit to couple the first bayonet fitting and the second bayonet fitting.

13. 9. The cell processing system of claim 8, wherein the coupling includes at least one spring arm, and the load sensing unit includes a plurality of spring arms arranged to engage with an edge of an opening in the bioreactor to couple the load sensing unit to the bioreactor, each of the plurality of spring arms including a notch arranged to engage with the edge of the opening in the bioreactor.

14. 14. The cell processing system of claim 1, wherein the bioreactor includes a compressible element, and the load sensing unit is adapted to detect a compressive force when the compressible element is compressed.

15. The cell processing system of claim 14 , wherein the load sensing unit comprises an actuator operable to compress the compressible element.

16. 16. The cell processing system of claim 14 or 15, further comprising a sensor configured to detect displacement of the compressible element when the compressible element is compressed.

17. 17. The cell processing system of any one of claims 1 to 16, further comprising a bioreactor comprising a vessel and a lid assembly having one or more connector interfaces for accessing an interior volume of the vessel.

18. 1. A method for detecting a weight of a bioreactor in a cell processing system adapted to support the bioreactor, the method comprising: supporting the weight of the bioreactor on a load sensing unit of the cell processing system; and determining the weight of the bioreactor based on the load detected by the load sensing unit.

19. 20. The method of claim 18, comprising releasably connecting the load sensing unit to the bioreactor.

20. 20. The method of claim 19, comprising connecting the load sensing unit to a lid assembly of the bioreactor.

21. 21. The method according to claim 19 or 20, comprising the step of moving the load-sensing unit so as to lift the bioreactor from a support of the cell processing unit.

22. 21. The method of claim 19 or 20, wherein the bioreactor includes a compressible element, the method comprising the step of moving the load sensing unit to compress the compressible element, and further comprising the step of detecting a compressive force when the load sensing unit compresses the compressible element of the bioreactor, and / or detecting a displacement of the load sensing unit when the load sensing unit compresses the compressible element of the bioreactor.

23. 1. A method for detecting a leak in a bioreactor including a compressible element, the method comprising: compressing the compressible element of the bioreactor; detecting a compressive force applied to the compressible element and / or a displacement of the compressible element; and determining whether the bioreactor has a leak based on the compressive force and / or displacement.

24. 24. The method of claim 23, wherein the bioreactor includes a vessel and a lid assembly, and the compressible element is an expandable vessel in fluid communication with the vessel.

25. 1. A method for detecting a clogged filter in a bioreactor including a compressible element, an outlet, and a filter disposed within the outlet, the method comprising: compressing the compressible element of the bioreactor to expel gas through the outlet; detecting a compressive force applied to the compressible element; and determining whether the compressive force exceeds a predetermined threshold indicating the filter is clogged.

26. 26. The method of claim 25, further comprising providing an alert or warning to a user in response to determining that the compressive force exceeds the predetermined threshold.

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