Automated system for biological treatment

Abstract

An automated system for performing a biological treatment, comprising: an incubation system configured to accommodate at least one incubation chamber for incubating a cell culture chamber having a flexible tube fluidly connected thereto; and a storage system configured to store at least one fluid-containing consumable having a tube fluidly connected thereto; wherein the incubation system and the storage system are collectively arranged to enable the robotic device to manipulate a tube weld between the flexible tube of the incubated cell culture chamber and the tube storing the consumable, thereby forming a sterile fluid connection between the cell culture chamber and the consumable to maintain the closed system.

Description

Technical Field

[0001] The present disclosure relates to automated bioprocessing. More specifically, the present disclosure relates to an automated system that can be configured to perform multiple bioprocessing steps or operations in parallel while maintaining a closed system. Background Art

[0002] Increasingly, therapeutics are using cells rather than small molecules as a starting point. Methods for making these products are evolving rapidly to keep up with the constant stream of new treatments. In recent years, the use of several new types of cell therapies has increased. One of these is autologous cell therapy.

[0003] Autologous cell therapies are a class of treatments with significant clinical and commercial potential, ranging from treating cancer to repairing genetic defects. These therapies involve extracting cells from a patient, manipulating the cells for days to weeks, and then reintroducing the cells into the patient to produce a therapeutic effect. The steps used in autologous cell therapies are often very complex; for example, a typical CAR-T process may involve a series of steps starting with a cryopreserved leukapheresis product (leukopak), thawing, washing to remove DMSO, enriching T cells, activating, transducing, expanding, concentrating, filling the prepared preparation into IV bags, and cryopreserving, which involves multiple other intermediate washing steps.

[0004] Bioprocessing systems have been developed for performing the above steps. In such bioprocessing systems, for example, during the entire cell therapy process, multiple different consumables (e.g., bags containing liquids) may be required to provide culture medium, reagents and / or cell materials to an expansion chamber (e.g., a cell culture chamber). Similarly, one or more consumables (e.g., output or waste bag consumables) can receive fluid samples from the expansion chamber. Therefore, the term "consumable" can refer to a "disposable" element or component of the system.

[0005] Some of the processes discussed above, such as activation, transduction, and expansion, can be performed in a cell culture chamber that can be incubated in a bioreactor (i.e., an "incubation chamber"). During one or more of these processes, various functions need to be performed, such as perfusion, gas and nutrient delivery, reagent mixing, media conditioning, and heat exchange.

[0006] However, due to the need to maintain a closed system when handling cells, reagents and other fluids, conventional consumables (e.g., culture medium bags) include a complex external flexible piping network for connection to the incubation chamber. Such flexible piping networks are difficult to handle, especially by automated means (e.g., robotic devices). In addition, the storage of consumables may be complicated by the need to readily access and use them in a space-efficient manner in a bioprocessing system.

[0007] The ability to store and operate multiple bioreactors simultaneously (including supplying necessary fluids from the consumables to each bioreactor when needed) can be challenging due to the need for specialized equipment to interface with each consumable, making it difficult and expensive to run multiple culture processes in parallel. Furthermore, typical bioprocessing systems have limited bioreactor capacity and a correspondingly limited number of expansion chambers (e.g., cell culture chambers) that can be accommodated simultaneously. Summary of the invention

[0008] The present invention describes an automated system for performing bioprocessing, comprising: an incubation system configured to accommodate at least one incubation chamber for incubating cell culture chambers, the cell culture chambers having a flexible tube connected to the fluid therein; and a storage system configured to store at least one fluid-containing consumable, the fluid-containing consumable having a tube connected to the fluid therein; wherein the incubation system and the storage system are jointly configured to enable a robotic device to manipulate a tube weld between the flexible tube of the incubated cell culture chamber and the tube of the stored consumable, thereby forming a sterile fluid connection between the cell culture chamber and the consumable to maintain a closed system.

[0009] In use, the automation system can accommodate or store one or more incubation chambers and / or one or more consumables containing fluid, but it should be understood that these incubation chambers and consumables can be removed from the automation system and are replaceable. The incubation system can have one or more features, such as at least one incubator base with a size corresponding to the incubation chamber, to maintain the incubation chamber in a predetermined position in the incubation system. The storage system can include a plurality of consumable holding positions or grooves, and each holding position or groove can be configured to receive and store consumables. Each groove can be configured to receive a box containing consumables. Each groove can have one or more engagement features, thereby releasably maintaining consumables (such as in a corresponding box) in the groove.

[0010] The system can be configured as a bioreactor system for a biological treatment system. Thus, the system can form part of a larger biological treatment system.

[0011] The incubation system can be further configured to store the cell culture chambers in each incubation chamber with the flexible tubing in a predetermined orientation, optionally with a portion of the flexible tubing held outside the incubation chamber, such as by one or more tubing clamps. In this way, the tubing can be manipulated to connect it to different consumables without opening the incubator and without risk of affecting the incubator temperature.

[0012] The storage system may be further configured to store each consumable with the tube of each consumable held in a predetermined orientation, such as by one or more tube clamps.

[0013] The incubation system may be configured to accommodate a single incubation chamber. Alternatively, the incubation system may be configured to accommodate a plurality of incubation chambers, each of which is arranged to incubate a single cell culture chamber in physical isolation from adjacent incubation chambers.

[0014] The incubation system may comprise a single incubation chamber for a single cell culture chamber, or a single incubation chamber for a plurality of cell culture chambers.Alternatively or additionally, the incubation system may comprise a plurality of incubation chambers, each incubation chamber being configured to receive a single cell culture chamber.

[0015] Each incubation chamber may be temperature controlled. Each incubation chamber may be gas controlled.

[0016] At least a portion of the storage system may be arranged to be elevated relative to the incubation system. Alternatively, at least a portion of the storage system may be located below the incubation system; in this way, backflow of waste from the waste container to the incubation section may be inhibited.

[0017] The storage system may include a support structure (arrangement) having one or more openings for receiving consumable materials.

[0018] The system may further include a cell analysis unit, wherein the at least one robotic device is further configured to manipulate a fluid connection between the cell analysis unit and the incubated cell culture chamber.

[0019] The cell analysis unit may have at least one tube fluidically connected thereto, and the at least one robotic device may be further configured to manipulate the fluid connection between the tube fluidically connected to the cell analysis unit and the tube fluidically connected to the incubated cell culture chamber. The cell analysis unit (or "cell analyzer") may be a cell counter, a cytometer, or any other means of cell analysis or culture medium analysis.

[0020] Alternatively, the system can take samples by welding a vial with a septum on one end and a tube on the other end, then the system pumps the sample into the vial and disconnects the tube. The robot then takes the vial to the cell analysis unit, which then pierces the septum with a needle, since the sample analysis process does not require closure.

[0021] One or more processing parameters of the system can be configured to be adjusted based on the measurements made by the cell analysis unit.

[0022] The system can also include an automated processing station, at which the flow and operation for bioprocessing are automated, such as using one or more robotic devices. The automated processing station is preferably configured as an independent processing station. The automated processing station can include a support surface or a platform configured to form a part for the incubation system. The storage system can be in an elevated position relative to the support surface or the platform.

[0023] The automation system may include a robotic device. At least one robotic device may also be arranged on the processing station. In other words, the robotic device that manipulates the pipe welding is part of the processing station.

[0024] The system (eg, a processing station) may also include a movement system for at least one robotic device, the movement system configured to move the robotic device relative to at least one of the incubation system and the storage system.

[0025] The movement system may include at least one track (eg, on a processing station) on which at least one robotic device is movably mounted, and a drive system for moving the robotic device along the track to one or more predetermined positions.

[0026] Alternatively, at least one robotic device can be separate from the processing station. According to another aspect of the present invention, a bioprocessing system is provided, which includes an automated processing station as described above and herein, and a separate robotic device configured to move independently relative to the automated processing station. In other words, the robotic device that manipulates the tube welding can be a separate robotic device. For example, (at least one) robotic device can perform other functions in the bioprocessing system, as well as manipulate the sterile tube welding between the flexible tubes of the processing station. Optionally, the robotic device can also be provided as part of the processing station (for example, in addition to at least one separate robotic device that can move independently of the processing station).

[0027] The robotic device can be configured to manipulate the fluid connection to create a tube weld between a flexible tube of an incubated cell culture chamber and a flexible tube of a storage consumable to transfer fluid therethrough, wherein the tube weld is a sterile tube weld formed between the free ends of the respective tubes.

[0028] The robotic device can be configured to manipulate the fluid connection to disconnect the flexible tube of the incubating cell culture chamber from the flexible tube of the storage consumable.

[0029] The robotic device may be configured to manipulate the fluid connection to seal one or both of the flexible tubes, preferably prior to disconnecting the fluid connection.

[0030] The robotic device can be configured to manipulate the fluid connection to pump fluid between the consumable and the incubating cell culture chamber through the fluid connection.

[0031] The robotic device may be further configured to pump the fluid by applying a peristaltic pumping action to at least one of the flexible tubes forming the fluid connection.

[0032] The robotic device can be configured to manipulate the fluid connection so that at least one flexible tube of the incubating cell culture chamber and at least one flexible tube of the storage consumable are engaged and / or positioned relative to each other to form the fluid connection.

[0033] The at least one robotic device may be further configured to manipulate a fluid connection between the first incubating cell culture chamber and the second incubating cell culture chamber.

[0034] The robotic device may be configured to use interchangeable end effectors (eg, for use with a robotic arm of the robotic device), the system further comprising an end effector storage system for storing one or more interchangeable end effectors for use with the robotic device.

[0035] The robotic device may include an end effector on a robotic arm, and the robotic device may further include at least one of a probe or sensor located on the end effector. The probe or sensor may be a Raman probe, an optical probe, a microscope, and / or any other suitable type of probe or sensor. It should be understood that such probes do not need to directly contact the cells in order to collect data, thereby allowing the cells to be monitored while maintaining a closed system.

[0036] The system may also include a movement system for at least one robotic device, the movement system configured to move the robotic device relative to at least one of the incubation system and the storage system.

[0037] The movement system may include at least one track on which at least one robotic device is movably mounted, and a drive system for moving the robotic device to one or more predetermined locations along the track.

[0038] The at least one robotic device may include a first robotic device and a second robotic device.

[0039] The first robotic device can be configured to create a sterile tube weld, and the second robotic device can be configured to perform at least one of the following: manipulate the fluid connection to pump fluid therethrough or seal the tube, preferably prior to disconnecting the fluid connection. In this way, the second robotic device can be used to seal the weld or pump fluid away from the weld; if the weld fails, the first robotic device can be used to re-weld the tube.

[0040] The system may further comprise a controller for controlling the automated sequence of operations of the system. The controller may be configured to control the automated sequence of operations according to one or more predetermined workflows. Preferably, the one or more predetermined workflows are reconfigurable workflows.

[0041] The controller may be configured to automatically schedule a sequence of actions to be followed by the system. The system may also include a user interface configured to enable a user to program a predetermined workflow to be followed by the system. The controller may be configured to simulate an automated sequence of operations before the system executes the sequence. The system may be connected to a computer network so that one or more systems may be remotely monitored and controlled. One or more systems may be controlled as a group of processing stations or as a subsystem in a more complex system.

[0042] The system may further comprise a fluid agitation system for agitating the fluid contained in the incubated cell culture chamber. The fluid agitation system may be configured to agitate the fluid in the or each incubated cell culture chamber prior to transferring the fluid from the cell culture chamber to the output container and / or sample container.

[0043] The at least one robotic device can be configured to manipulate the fluid connection to facilitate transfer of fluid from at least one incubating cell culture chamber to a waste container prior to agitation of the incubating cell culture chamber by the fluid agitation system.

[0044] The storage system may include a refrigeration or heating unit for regulating the temperature of one or more consumables.

[0045] The system may include at least one probe or sensor located on an end effector of the robotic arm.

[0046] The system may further comprise a tube supply device arranged to provide replenishment of tubes to at least one of the cell culture chambers or consumables, preferably the device comprises a tube supply reel.

[0047] The system may also include a method for identifying an identification mark on at least one of the following: a consumable, a tube, a cell culture chamber. The identification mark may be optical or non-optical. The identification mark may be a barcode, a QR code, an RFID or an NFC code.

[0048] The system may include a self-contained processing station configured to facilitate transfer of fluid from a storage consumable to an incubated cell culture chamber at the processing station.

[0049] Also described herein is a bioprocessing system comprising a plurality of the automated processing systems described above and herein.

[0050] Also described herein is a method comprising performing (automating) a bioprocess using the system described above and herein.

[0051] As used herein, the term "processing station" preferably refers to a device, workstation, unit, module or "stand-alone" system, which can form part of a larger system, such as an automated bioprocessing system. As used herein, the term "stand-alone" preferably means that the processing station is capable of operating independently as part of a larger system, because it is capable of providing the consumables, incubation chambers, cell culture chambers and conduits required to perform the necessary processes and operations.

[0052] As used herein, the term "automated" preferably refers to a process or operation that, once initiated, can be completely performed without human intervention. Preferably, the process or operation can also be initiated and completed without human intervention, except for programming the equipment that performs the operation or process.

[0053] As used herein, the term "closed system" preferably means that during the operation or process performed at the processing station, no contamination is caused to or from the surrounding environment (e.g., transfer of materials from the cell culture chamber to the surrounding environment or vice versa). As used herein, the term "closed system" may also mean a "functionally" closed system, or more preferably a completely closed system in which a physical barrier is maintained between the surrounding environment and the contents and consumables of the cell culture chamber. In a functionally closed system, air can be supplied to the system through a sterile air filter, for example, which, while not completely closed, is considered a sufficiently "closed system" to prevent contamination.

[0054] As used herein, the term "tube welder" refers to a device configured to connect (i.e., weld) a first tube to a second tube (preferably at their free ends), thereby providing a sterile (preferably closed) fluid connection between the tubes. In short, the tube welder may include a first clamping unit and a second clamping unit. Each clamping unit may include a pair of jaws that can be moved between an open position for receiving a flexible tube therebetween and a closed position for clamping the received tube. The clamping unit may be located on a robotic arm. When the tube is clamped, the flexible tube is clamped closed, preferably inhibiting any fluid from passing through.

[0055] The clamping unit can be operated to clamp the tube without clamping it closed; this can enable the tube to be joined and positioned without inhibiting the flow of fluid. When the first tube is clamped by the first clamping unit and the second tube is clamped by the second clamping unit, the cutting blade can be heated and moved to intersect with the clamping portion of the two tubes. This cuts each tube into an upstream portion leading to the respective consumables and a downstream portion previously leading to the closed end of the tube. The heat from the cutting blade is transferred to the tube, thereby at least partially melting each flexible tube at the newly formed cut end. Subsequently, the clamping unit moves to position the upstream portion of the tube adjacent to each other. The downstream portion can be discarded. Once the blade is removed, the upstream portion can be pressed together, thereby welding the tubes together to form a single tube. The joint can be called a butt weld. At this stage, the joint between the tubes can still remain clamped closed; the clamp release mechanism can be operated to remove the clamping portion, thereby establishing a fluid path through the connecting tube. Visual or mechanical quality control (QC) means can also be provided to confirm the success of the welding.

[0056] As used herein, the term "peristaltic pump" may refer to a rotary peristaltic pump or a linear peristaltic pump. A peristaltic pump is configured to compress a portion of a flexible tube and then move the compressed portion along the length of the tube in a pumping direction, thereby forcing a fluid through the tube. Advantageously, a peristaltic pump may allow fluid to be pumped quickly through the tube with minimal wear on the tube and minimal potential for contamination.

[0057] As used herein, the term "consumable" preferably refers to a container, such as a bag containing a fluid, containing, for example, a cell sample (or cell material), a reagent or a fluid, which can be used to be processed at a processing station as, for example, a part of a cell therapy process. Therefore, a cell suspension bag is an example of a consumable in the context of the present disclosure. Other types of consumables include culture medium bags, sample bags, intermediate process bags, waste bags and output bags. In the context of the present disclosure, each consumable has an "upstream" end portion of a tube connected to its fluid, which provides a fluid passage to a "downstream" (opposite) end portion of the tube, and when not connected to another such (second) tube, the "downstream" end portion is fluid-sealed by the clamped closed portion of the tube.

[0058] As used herein, the term "amplification chamber" is a specific type of cell culture chamber. Therefore, the term "cell culture chamber" can be used interchangeably with "amplification chamber" within the scope of the present disclosure, and it is noted that the processing station can be used to perform the processes and operations described herein on different types of cell culture chambers (e.g., fluid connection consumables), and the amplification chamber is just one example.

[0059] Those skilled in the art will appreciate that any device feature described herein can be provided as a method feature, and vice versa. It will also be appreciated that the specific combination of each feature described and defined in any aspect described herein can be implemented and / or provided and / or used independently.

[0060] Furthermore, it will be understood that the embodiments described herein are purely exemplary and that modifications of detail may be made within the scope of the present disclosure. Furthermore, as used herein, "means plus function" features may be expressed alternatively with their corresponding structures. BRIEF DESCRIPTION OF THE DRAWINGS

[0061] One or more embodiments will now be described, by way of example only, with reference to the accompanying drawings, in which:

[0062] Figure 1 A first embodiment of an automated processing system is shown;

[0063] Figure 2a Shown for Figure 1 An example of an incubation chamber of a processing system, wherein Figure 2b and 2b The components of the incubation chamber are shown in greater detail;

[0064] Figure 3 Shown for Figure 1 An example of a consumables holder for a processing system;

[0065] Figure 4A and 4B A second embodiment of the automated processing system is shown;

[0066] Figure 5A and 5B A third embodiment of an automated processing system is shown; and

[0067] FIG. 6 illustrates an example of a consumables rack for use with the processing system of FIGS. 4 and 5 . DETAILED DESCRIPTION

[0068] In the following description and drawings, corresponding features are preferably identified using corresponding reference numerals to avoid the need to describe in detail the common features of each embodiment.

[0069] In general, an automated processing system is described herein that can be configured to perform multiple processes or operations in parallel while maintaining a closed system. The processing system can form part of a larger automated bioprocessing system. Such an automated system can be configured, for example, to perform a cell therapy process. Operations and steps traditionally performed by manual operators are automated to improve the accuracy and precision of operations and processes, thereby improving repeatability. More specifically, the automated processing system can facilitate certain operations and processes in parallel; in particular, the incubation of cell culture chambers and the supply of fluids containing reagents (or other materials, such as cell materials) from consumables to cell culture chambers while maintaining a closed system. In a preferred embodiment that will be described in more detail, the automated processing system may include a processing station (e.g., a "device") at which such processes and operations are automatically performed using one or more robotic devices.

[0070] In a preferred embodiment, a closed system can be maintained by manipulating (e.g., creating) a fluid connection between a fluid-containing consumable and an incubated cell culture chamber at a processing station using an automated robotic device. The robotic device can form a sterile fluid connection between other consumables; for example, the robotic device can manipulate a fluid connection between two incubated cell culture chambers, and / or can manipulate a fluid connection between a cell culture chamber and an analysis chamber (or any other suitable container or consumable). The fluid connection created by the automated robotic device is by tube welding formed between (free end) portions of (usually) flexible tubing, which are fluidically connected to the consumable and the incubation (usually) chamber / cell culture chamber, respectively.

[0071] More specifically, the tube welds formed by the robotic device are sterile tube welds, which can be created by a tube welding device or a "tube welder". This can be achieved by a robotic device including an end effector mounted thereon, the end effector configured as a "tube welder". For example, the end effector can be configured to engage an end portion of a tube connected to a consumable fluid, clamp a portion of the tube at a position spaced apart from the tube end along the tube to form a clamping portion of a fluid-tight tube (and thereby seal the consumable), remove the existing (free) end of the tube to form a new tube (free) end that has not previously contacted another such tube, and then connect the new tube end together with the correspondingly formed new end of another such tube connected to the cell culture chamber fluid, and connect the ends of the two tubes together by performing tube welding, thereby forming a connected fluid between the consumable and the cell culture chamber.

[0072] In other words, the robotic device may be configured to manipulate a fluid connection. To this end, it may engage and / or position (end portions of) a flexible tube of an incubated cell culture chamber and (end portions of) a flexible tube of a storage consumable relative to each other to form a fluid connection, which is preferably created by the robotic device, further performing tube welding to connect the respective end portions of the two tubes together.

[0073] Once the fluid is connected, the fluid in the consumable can be transferred to the cell culture chamber. This can be achieved by, for example, a pumping mechanism (or method), which is configured to apply a peristaltic pumping action to the tube connected to the fluid to push the fluid from the consumable to the cell culture chamber, and the mechanism includes a plurality of movable pressing elements, which are arranged to contact a portion of the tube in turn, and the action can be repeated. In other words, the pumping mechanism may include a peristaltic pump. The pumping mechanism can be provided by a robotic device, which includes a robotic arm having an end effector mounted thereon, and the end effector is configured as such a pumping mechanism. Alternatively, the pumping mechanism can be provided at a processing station, which is arranged to receive a portion of the fluid-connected tube and apply a pumping action thereto to push the fluid through the tube from the consumable to the cell culture chamber.

[0074] Once fluid transfer has occurred between the consumables and the cell culture chamber, the fluid connection formed between their respective flexible tubes can be disconnected. When the tubes are disconnected, they are sealed to maintain a closed system. Preferably, the tubes are sealed before the fluid connection is disconnected. Disconnection and sealing can be achieved by a tube welder (e.g., it is further configured to seal and disconnect the tube), or a separate tube sealer can be used for this purpose. The tube sealer can be arranged on the same robotic device as the tube welder and / or peristaltic pump. The tube sealer can use heat and / or RF radiation to seal the flexible tube.

[0075] As will be discussed further, one or more robotic devices may be mounted to a processing station, or they may be provided as part of an autonomous mobile ("manipulator") unit / robotic device configured to autonomously move around a bioprocessing system (e.g., a system arranged in an enclosed space) provided with one or more such processing stations and to access the or each processing station when it is necessary to manipulate a fluid connection. A plurality of robotic devices / robotic arms may be provided, each having an end effector mounted thereon that is configured to perform a specific function, or a single robotic device / robotic arm may be configured with interchangeable end effectors that may be stored at the processing station and / or the autonomous mobile unit.

[0076] Figure 1A first embodiment of a closed processing system 10 is shown and will now be described. The processing system 10 includes an automated processing station 100, which in turn includes an incubation system 102 (which is configured to facilitate incubation of one or more cell culture chambers 104) and a storage system 106 (which is configured to facilitate storage of one or more fluid-containing consumables 108). The storage system 106 is in an elevated position relative to the incubation system 102.

[0077] Each cell culture chamber 104 has a portion of one or more tubes 104a attached through which fluids can be introduced into the cell culture chamber 104. Such tubes 104a can be more clearly seen in Figure 2. Similarly, each consumable 108 has a portion of a tube 108a attached through which the contents of the consumable 108 can be extracted. At least one, and preferably both, of the tubes 104a, 108a are flexible (i.e., non-rigid) tubes.

[0078] The incubation system 102 and the (consumable) storage system 106 are arranged together at the processing station 100 so that the robotic device can manipulate the sterile tube welding between the tube connected to the storage consumable 108 and the tube 104a connected to the incubated cell culture chamber 104, as described above. In this way, a sterile fluid connection can be created between the cell culture chamber 104 and the consumable 108, thereby maintaining a closed system at the processing station 100.

[0079] In this embodiment, the processing station 100 includes a first robotic device 112 and a second robotic device 114, which together help automate the processing system 10. The robotic devices 112, 114 are mounted to the processing station 100. The first robotic device 112 includes a robotic arm having a first end effector 112a, the first end effector 112a being configured to perform aseptic tube welding, as previously described. The second robotic device 114 includes a robotic arm having a second end effector 114a, the second end effector 114a being configured as a pumping mechanism, as previously described. Either or both of the robotic devices 112, 114 may include a tube sealer. Alternatively, the tube sealer may be provided on a separate robotic device.

[0080] The processing station 100 includes a base unit 116, and the upper side of the base unit 116 is provided with a support surface 116a. The base unit 116 is basically box-shaped / cube-shaped and has a roughly rectangular footprint. The support surface 116a is provided with one or more incubator bases 118, which are placed on the support surface 116a. Each incubator base 118 is configured to have an incubation chamber 110 mounted thereon, and the incubation chamber 110 is configured to accommodate a cell culture chamber 104. This incubation chamber 110 is shown separately in Figure 2 and will be described in more detail later. Therefore, the support surface 116a and the incubator base 118 constitute a part of the incubation system 102 in this embodiment.

[0081] The processing station 100 may include a fluid agitation system for agitating the fluid contained in the cell incubation chamber 110 of incubation. For example, the incubator base 118 may be configured to agitate the incubation chamber 110 mounted thereon, for example, the incubator base 118 may be a rocking plate, which shakes the incubation chamber 110 from one side to the other. Alternatively or additionally, the incubator base 118 may include other devices for agitating the incubation chamber 110 mounted thereon, such as an ultrasonic source, a vibration source and / or an orbital shaker. The fluid agitation system may be configured to agitate the fluid in the incubation cell incubation chamber 110 before the fluid is transferred from the cell culture chamber to an output container and / or a sample container. In this way, the fluid contained in the output container and / or the sample container will represent the contents of the cell incubation chamber 110. Preferably, each incubator base 118 includes a separate agitation device, thereby allowing different cell incubation chambers 110 to be stirred independently such as at different times.

[0082] In this embodiment, the robotic devices 112, 114 are also mounted on a support surface 116a. In addition, the base unit 116 is mounted on wheels 120, such as casters, to allow it to be moved and positioned within the bioprocessing system.

[0083] The frame 122 extends vertically upward from opposite sides of the base unit 116 to form a part of the storage system 106. The frame 122 is substantially rectangular and has a horizontal beam connected between the upper ends of two relative vertical members, and each vertical member is connected to the opposite side of the base unit 116 to form the frame 122. The support member (or track) 124 extends at least partially on the width of the frame 122 to support the consumables 108 (for example, a clip or tab 154 on each consumable 108 is set to hang from the groove of the track), thereby forming a part of the storage system 106. In this way, at least a part of the storage system 106 is raised relative to the incubation system 102. Optionally, the storage system 106 can have a part located below the incubation system, which can be used to store a waste container. In this way, waste is suppressed from flowing back from the waste container to the incubation part.

[0084] The consumable 108 is stored with its tube 108a extending below the main bag portion (e.g., held in place) so that any robotic device 112, 114 can engage and / or manipulate it, for example, to establish a fluid connection between the consumable 108 and a cell culture chamber 104 held within an incubation chamber 110 mounted on an incubator base 118 on a support surface 116a. The consumable 108 can be held by a consumable holder 150 configured to be removably mounted to the frame 122 / support member 124. Figure 3An example of such a consumable holder 150 is shown in FIG. 1 and will be described in more detail later. The tubes 104a, 108a are typically larger than Figure 1 The ones schematically shown in FIG. 1 are longer, in particular the tube 104 a on the cell culture chamber 104 .

[0085] In this embodiment, the cell culture chambers 104 and various consumables 108 will be loaded onto the processing station 100 by a human operator (i.e., "manually") at the beginning of the process, although automated loading may be possible in the future, such as by using a separate robotic device configured to perform this function in the bioprocessing system.

[0086] A power source (not shown), a controller / control unit (not shown), and / or a motor drive (not shown) for each robotic device 112, 114 may be disposed in the base unit 116. These components may be remotely controlled and / or program controlled via a computer network (wired or wireless) to enable the robotic devices 112, 114 to operate autonomously. The base unit 116 may also house one or more mass flow controllers for gas control. The base unit 116 may be configured to direct temperature controlled air into or around the consumables 108 to keep them refrigerated. Other peripheral power, control, and communication components familiar to the skilled artisan may also be provided.

[0087] A tube reel 126 may also be mounted on the frame 122 and configured to deploy similar (weldable) tubes that may be used to supplement (e.g., extend) existing tubes 104a, 108a of the cell culture chamber 104 or consumable 108, respectively. Figure 1 In the illustrated embodiment, additional tubes from the tube reel 126 can be used to connect the consumable 108 to the cell culture chamber 104, or the tubes 104a and 108a can be configured so that their lengths overlap. Optionally, the tube reel 126 can contain lengths of tubes composed of a plurality of different materials (e.g., PVC to Cflex) in sequence, so that the cell culture chamber 104 (wherein a portion of the tube 104a has an end made of Cflex) can be fluidly connected to the consumable 108 (wherein a portion of the tube 108a has an end made of PVC). Alternatively or additionally, a length of tube (optionally comprising a plurality of different materials) can be provided on a frame, such that a robotic device can simply grab it when needed. Preferably, the tubing on the reel and the tubes 104a, 108a of the cell culture chamber 104 and the consumable 108 comprise thermoplastic materials.

[0088] The tube reel 126 includes a housing mounted on the frame 122 and contains a collection of tubes stored on a rotatable reel (not shown) inside the housing. Here, there are two such tube reels 126 disposed in a spaced configuration on the frame 122. In this way, the robotic devices 112, 114 can avoid handling long flexible tube lengths, which are challenging for robotic handling. Furthermore, in this way, when changing between different inputs pumped into the cell culture chamber 104, the tubes do not need to be cleaned, but can be replaced.

[0089] In this embodiment, each consumable 108 includes a bag containing fluid, which has a portion of a flexible tube 108a that allows the fluid to be transferred out of the bag. When not fluidically connected to another tube 104a, the end portion of the consumable tube 108a can be clamped closed to fluidically seal it. In order to open the tube 108a, a portion of the tube 108a in the direction of the bag can be clamped to seal it and remove the clamped end portion, wherein once the tube 108a fluid has been fluidically connected to another tube 104a to establish fluid flow, the clamped portion is released. This process can be performed by a robotic device, as described above.

[0090] Figures 2a to 2c An embodiment of an incubation chamber 110 for incubating a cell culture chamber 104 is shown and will now be described. The incubation chamber 110 shown includes a generally cube-shaped base 130 configured to be mounted on an incubator base 118 that forms part of an incubation system 102. As previously described, in this embodiment, the incubator base 118 is disposed on a support surface 116a of a base unit 116 of the processing station 100.

[0091] The base unit 130 includes a plate 132 for receiving the cell culture chamber 104. The plate 132 is Figure 2b 104, i.e., without the cell culture chamber 104 mounted thereon. For example, the plate 132 can be configured as a ventilated offset shaker base 132.

[0092] In the present embodiment, the cell culture chamber 104 is in the form of a cell culture container having the general shape of a conical flask with an opening at the top. A removable lid 134 (e.g., screws) is mounted on the opening of the cell culture chamber 104 to isolate its contents from the surrounding environment. A plurality of tubes 104a extend through the lid 134 to allow fluid to be introduced into the cell culture chamber 104, such as from the above-mentioned consumables 108, while maintaining a closed system within the cell culture chamber 104. This is possible because the lid 134 is sealed around the tubes 104a, and as described above, the end portions of the tubes 104a are clamped closed to seal them before the robotic device forms a sterile fluid connection by sterile tube welding (similar to the description of the above-mentioned consumables 108).

[0093] The cover 136 is configured to be assembled on the base 130 to enclose the cell culture chamber 104, that is, to provide a chamber 138 in the incubation chamber 110, in which the cell culture chamber 104 can be incubated. For example, the plate 132 can be heated by a heating element (not shown) located below the plate 132. For example, a power supply (not shown) in the base 130 can power the heating element. In this way, the incubation chamber 110 can be temperature controlled. In addition, the incubation chamber 110 can be gas controlled, wherein a gas (e.g., oxygen) can be introduced into the incubation chamber 110 through one or more gas ports (see below). A sterile air filter 144 can also be disposed in the chamber 138.

[0094] exist Figures 2a to 2c In the embodiment of the present invention, heating is achieved by passing heated gas through a heating block 140, which extends into the chamber 138, such as Figure 2c As shown. Arrows indicate the flow of air into chamber 138 through heating block 140, which may include heater 160, heater fan 162, CO2 sensor (board) 164, CO2 sensor pump, thermal sensor (board) 166, and one or more CO2 inlets 170, 172 (or other gas mixtures). One of the inlets 170, 172 may alternatively serve as a sensor hole. Cable inlet 174 may also be provided for powering and / or controlling the above components in heating block 140.

[0095] The incubation chamber 110 may have one or more openings or gaps for allowing one or more tubes 104a of the enclosed cell culture chamber 104 to pass through the cover 136 of the incubation chamber 110 in a defined direction. In this way, the user can install the cell culture chamber 104 at the beginning of the operation (including clamping the tube 104a into the tube routing (not shown)), close the cover 136, and then the automated processing station 100 can still manipulate the tube 104a without opening the cover 136 and possibly losing the temperature control of the chamber 138.

[0096] like Figure 2b As shown, air channels 142 are provided to deliver air down and around the plate 132. The air paths are particularly advantageous for gas permeable cell culture chambers (or "bioreactors") to ensure air access thereunder.

[0097] Figure 3An embodiment of a holder 150 for consumables 108 is shown and will now be described. The consumable holder 150 includes a substantially rectangular frame 152 in which the consumables (bags) 108 are suspended by clips / tabs 154 mounted on the frame 152. Legs 156 extend downward from one side of the frame 152 and then substantially span the width of the frame 152 to provide support for the frame 152, for example if the legs 156 are received in holes or bores of corresponding size in the device. The frame 152 and the legs 156 can be made of a metal material, preferably stainless steel. A tube clamp 158 is connected to one side of the frame 152 for holding a portion of a tube 108a that is fluidically connected to the consumable 108. The tube clamp 158 ensures that at least the portion of the tube 108a is maintained in a predetermined position, for example so that it can be easily found and / or engaged by a robotic device.

[0098] Figure 4A and 4B A second embodiment of a closed processing system 20 is shown and will now be described.

[0099] Similar to the first embodiment, the processing system 20 includes an automated processing station 200, which in turn includes an incubation system 202 (which is configured to facilitate incubation of one or more cell culture chambers 204), and a storage system 206 (which is configured to facilitate storage of one or more fluid-containing consumables 208). The storage system 206 is in an elevated position relative to the incubation system 202.

[0100] The incubation system 202 and the (consumable) storage system 206 are co-located at the processing station 200 to enable robotic equipment to manipulate sterile tube welding between tubes 208a storing consumables 208 and tubes 204a connected to the incubated cell culture chamber 204, as previously described.

[0101] Similar to the first embodiment, the processing station 200 includes a first robot device 212 and a second robot device 214, which together help to automate the processing system 20. However, in the present embodiment, the robot devices 212, 214 are mounted on a mobile system, and the mobile system includes a movable platform 260, which is arranged to move relative to the processing station 200. The processing station 200 includes a base unit 216, which has a support surface 216a. One or more incubator bases 218 are located on the support surface 216a. The movable platform 260 is mounted on a track system 262, and the track system 262 includes one or more tracks (not shown), and the track extends along the lower side of the support surface 216a of the base unit 216. Therefore, more specifically, the movable platform 260 (and therefore the robot devices 212, 214 mounted thereon) is configured so that it can move relative to the incubator base 218, so that the robot devices 212, 214 can access each incubator base 218 individually when needed.

[0102] As with the first embodiment, each incubator base 218 is arranged to have an incubation chamber 110 mounted thereon, therein or therein, which is configured to accommodate a cell culture chamber 104, as shown in Figure 2. Similarly, in this embodiment the support surface 216a and the incubator base 218 form part of the incubation system 202. Each incubator base 218 is separated from its neighbor by a partition wall 264.

[0103] The first and second robotic devices 212, 214 may include robotic arms with attached end effectors for manipulating the tube, as previously described in the first embodiment.

[0104] In this embodiment, the storage system 206 includes a plurality of slots 224 configured to receive and store consumables 108. The consumables 108 may be held in a cartridge 50 that is configured to be installed into the slots 224 by a human operator, as shown. Fig. 6A and 6B and will be discussed in more detail later.

[0105] The consumable 108 is stored so that its tube 108a extends below the main bag portion so that the robotic devices 212, 214 can engage and / or manipulate it, for example to create a fluid connection between the consumable 108 and a cell culture chamber 104 held within an isolation chamber 210 on an incubator base 218 mounted on a support surface 216a.

[0106] The user interface 266 is configured to control the autonomous operation of the movable platform 260 and the robotic devices 212, 214. A power source (not shown), a control unit (not shown), and / or a drive mechanism (not shown) for the movable platform 260 and the robotic devices 212, 214 may be provided in the base unit 216, respectively. These components may communicate with the user interface 266, respectively, which may include a touch screen or similar programmable computer device to enable the robotic devices 212, 214 to operate autonomously. Additionally or alternatively, one or more of these components may be remotely controlled and / or programmed via a computer network (wired or wireless) to enable the robotic devices 212, 214 to operate autonomously. Other peripheral power, control, and / or communication components known to the skilled person may also be provided.

[0107] Other peripheral power, control and / or communication components known to skilled artisans may also be provided.

[0108] In this embodiment, everything is facing forward, so it can be easily wiped clean. The individual incubation chambers 110 can be spaced apart with some kind of separation between them, preferably also utilizing partition walls 264, so that if a single incubation chamber 110 has a leak, then while the other incubation chambers 110 remain operational, the area can also be completely cleaned.

[0109] Having two robotic devices 212, 214 allows complex tasks to be performed in parallel, for example, the first robotic device 212 can manipulate some tubes 104a, 108a, while the second robotic device 214 contacts the fluid-connected tubes 104a, 108a to pump liquid between the consumables 108 and the cell culture chamber 104. In addition, in the event of a welding failure, the second robotic device can fluid-seal the upstream and downstream pipes of the weld, so that a t (or T) weld can be performed. By mounting the robotic devices 212, 214 on a movable platform 260, which is mounted on a track system 262, the robotic devices 212, 214 can be shared with other processing stations or modules in a larger system. In another example (not shown), the robotic device can be driven directly on the track system 262 (e.g., using a linear track or the like), or alternatively the track can simply serve as a guide and the robotic device can be a mobile robot running on wheels, where the robot is hung on the track. The latter option could be advantageous because it might be easier to daisy chain more systems together while using the same robot, but without having to deal with the complexity of a fully autonomous robot.

[0110] FIG5 shows a third embodiment of a closed processing system 30, which will now be described. The processing system 30 includes an automated processing station 300, which is similar in all respects to the automated processing station 200 of the second embodiment (described above), except that with respect to the processing station 300, a single robotic device 312 is provided on a movable platform 360, which helps to automate the processing system 30. In this embodiment, the robotic device 312 is configured to have interchangeable end effectors (not shown) that are stored in an exchange station 368 located behind a user interface 366. A robotic tool changer (not shown) can be hidden behind the user interface 366, and the robotic device 312 can select appropriate tools as needed. The end effectors can include a tube welder, a peristaltic pump, a tube sealer, and / or a tube disconnector (e.g., a heated cutting element, such as a blade or wire). Advantageously, due to the cost of the robotic device, this "single robotic device" arrangement should be cheaper than the processing station 200 of the second embodiment having "multiple robotic devices". Additionally, a single robotic device 312 will take up less space, so the movable platform 360 can be smaller than would be required for two robotic devices.

[0111] Fig. 6A and 6B An exemplary embodiment of a cartridge 50 (or "device") for holding consumables 108 is shown. Fig. 6A In the example shown, the consumables 108 are connected to two flexible tubes 108a. The consumables 108 can be pre-installed into such a box 50, which is configured to hold the tubes 108a in a defined orientation. The box 50 includes a housing 70, which is configured to hold the consumables 108; in other words, the housing 70 provides a first portion of the box 50 to hold the consumables 108. The box 50 can also provide insulation and / or thermal conduction to the consumables 108, so that the temperature of each consumable 108 can be adjusted individually.

[0112] The housing 70 may be provided with an upper surface and a lower surface, separated by a pair of opposing side walls 73a, 73c (i.e., first and second side walls 73a, 73c) and at least one end wall 73b, thereby forming a cubic shape. The housing 70 may have a longitudinal axis having a first end 70a and a second end 70b.

[0113] The housing 70 may include a tray 70 having a cavity 71 shaped to receive therein the consumable 108. The upper surface of the housing 70 may be a removable cover 72 that substantially encloses the consumable 108 within the cavity 71; in this manner, the consumable 108 may be conveniently added to and / or removed from the cartridge 50. Furthermore, this means that the cartridge 50 has a rigid outer surface that protects the consumable 108 and enables the cartridge 50 to be securely mounted in the storage system 206, 306 of the processing station 200, 300, such as in the slot 224, 324.

[0114] Preferably, the size of the cavity 71 is comparable to the size of the consumable 108, so that the consumable 108 fits tightly into the cavity 71, thereby keeping the consumable 108 in place. This reduces the flexibility of the consumable 108 by keeping the consumable 108 in a given shape. The housing 70 can be rigid and can be made of any suitable material, such as plastic or metal. In other examples, the housing 70 can include a material with a certain flexibility, such as any material with elastic properties. In this way, the consumable 108 can be forced into the cavity 71 by slightly stretching the cavity 71 when inserted. Once the consumable 108 is inserted, the housing 70 will elastically return to its original shape, thereby fixing the consumable 108.

[0115] Advantageously, using a box 50 to contain a bag containing consumables 108 can prevent the bag from expanding outward when filled. The housing 70 can also include external insulation and a path for internal cooling air flow so that the consumables within the housing 70 can be maintained at a specified temperature. A thermistor (not shown) can also be built into the housing 70 to monitor the temperature.

[0116] The housing 70 may include at least one clip 75 to hold the consumable 108 in the cavity 71. In this example, the housing 70 has a clip 75 in the cavity 71 near the first end 70a of the housing 70. The clip 75 may be a tab or a hook. The consumable 108 may be mounted through a hanging hole on the bag.

[0117] The housing 70 may include an engagement device 76 disposed on an outer surface of the housing 70. In this example, the engagement device 76 is a handle 76 connected to the first side wall 73a. The handle 76 may allow the box 50 to be manipulated and moved by a human operator and / or robotic equipment.

[0118] For example, the handle 76 may allow the box 50 to be carried and installed into the storage system 206 , 306 of the processing station 200 , 300 , such as into the slot 224 , 324 .

[0119] One or more ribs 78 are provided around the perimeter of the housing 70, extending between the upper and lower surfaces of the housing 70. Identification indicia, such as a barcode, a QR code, an RFID, or an NFC code, may be provided on the cartridge 50 to allow the cartridge 50 to be easily loaded into the storage system 206 in a plug / play manner, and / or to allow the cartridge 50 to be identified and tracked. For example, when the cartridge 50 is inserted into the slot 224, 324 of the storage system 206, 306, the cartridge 50 may be automatically identified.

[0120] The housing 70 may include at least one groove (e.g., gap or opening) in an end portion (e.g., second end 70b) of the housing 70 through which the tube 108a may pass. The groove 74 is preferably aligned with the portion of the consumable 108 connected to the flexible tube 108a. There may be multiple grooves 74 on the housing 70 so that the consumable 108 is fluidly connected to multiple tubes 108a.

[0121] The box 50 includes a second portion 80 configured to hold a flexible tube 108a connected to the consumable 108. The second portion 80 can extend from the second end 70b of the housing 70, preferably near the groove 74. The second portion 80 may include a plurality of tube holding elements 81 (e.g., tube clamps) to hold the flexible tube 108a at a plurality of positions along a predetermined path. In this example, the second portion 80 has a pair of tube holding elements 81 that are spaced apart so that a portion of the tube 108a can be held between them in a substantially taut manner to facilitate engagement of the robotic device. In this way, the robotic device can engage the tube 108a at a position between the pair of tube holding elements 81.

[0122] The tube 108a can be fixed to each tube holding element 81 by applying a force to the tube 108a to push it into the tube holding element 81, so that the tube holding element 81 fixes the tube 108a in a given position. The tube holding element 81 can alternatively include any suitable means for connecting the tube 108a portion to the second part 80, such as a hook or a buckle. The tube 108a portion held by the tube holding element 81 can be permanently retained or can be removably fixed.

[0123] The cartridge 50 may include a cooling device 77 for cooling the consumable 108 held within the housing 70. In this example, the cooling device 77 is at least one air port 77 (or "air duct") in the first portion 70 and / or the second portion 80 of the cartridge 50; in this manner, cool air may be supplied to the at least one air port 77 to cool the consumable 108. Specifically, the cartridge 50 includes a first external air port 77a in communication with an internal air port 77b to facilitate the introduction / extraction of air into / from the cavity 71. A second external air port 77c is provided in the housing 70 in fluid connection with the cavity 71 to allow air to flow out / into the housing 70. Alternatively, a Peltier and a fan (not shown) may be provided within the consumable.

[0124] A single incubator base may be provided on a support surface, configured to have a single incubation chamber or multiple incubation chambers mounted thereon. Rather than configuring each incubation chamber to contain a single cell culture chamber, a single incubation chamber may be configured to contain (and thus incubate) multiple cell culture chambers.

[0125] The processing station can process multiple (e.g., patient) samples simultaneously, or can distribute the contents of a single (e.g., patient) sample to multiple cell culture chambers (e.g., expansion chambers) to allow for experimental design of the chambers, adjusting conditions such as feed time / rate, reagent type, temperature, pH, etc. If the processing station includes a cell analyzer (e.g., a "cell analysis unit" or similar device), the incubation chamber (bioreactor) conditions or parameters (i.e., feed rate, etc.) can be automatically adjusted in response to measured parameters (e.g., cell number). The cell analyzer can be a cell counter, cytometer, or any other device for cell analysis or culture medium analysis.

[0126] As a further alternative, the pumping (and / or valving) device can be provided as a separate device or apparatus on the processing station (perhaps one pumping device for each incubation chamber), and the robotic device can insert the tubing forming the fluid connection into the pumping device. In this way, control of the fluid can be maintained while the robotic device operates other incubation chambers.

[0127] Although the processing station shown in the drawings shows consumables (e.g., media / reagent bags) stored in the storage system at room temperature, a portion of the storage system can be configured to refrigerate the consumables. For example, this can be achieved by blowing cold air into the air ducts of each consumable (controlling the temperature of each consumable individually by changing the amount of air passing through each consumable), or by blowing cold air around all consumables (similar to refrigerators with opening or sliding doors in supermarkets).

[0128] The processing station can transfer samples between different cell culture chambers (e.g., that have been preloaded onto the processing station). For example, it may be necessary to perform activation in one chamber and transfection / amplification in a subsequent chamber coated with fibronectin (retronectin). Additionally or alternatively, it may be necessary to start amplification in a small chamber and then transfer the culture to a larger chamber. The processes or operations performed at the processing station can be "reconfigurable", that is, a human operator can program a sequence of sampling, medium changes, harvesting times, etc. for a specific use, and then reprogram the processing station for another use.

[0129] The robotic device can also have probes that can interrogate key analytes in separate cell culture chambers, thereby enabling online monitoring of analytes. For example, a robotic device can carry probes for Raman spectroscopy (to detect metabolites such as glucose or lactate) or optical probes for fluorescence lifetime (using "presens" sensors to measure pH and CO2) or microscopes (to measure cell morphology in adherent cell cultures) and move the probes between each cell culture chamber. This approach may be advantageous because the cost of the Raman system can be amortized over multiple patient samples. It should be understood that these probes do not need to directly contact the cells to collect data, so that cells can be monitored while maintaining a closed system.

[0130] The processing system described herein may also include one or more cameras or sensors, such as a machine vision system, which enables all consumables 108 to be tracked throughout a particular process. In other words, the system may include a device for maintaining the traceability of consumables 108. One or more cameras or sensors may be located on a robotic device. One or more cameras or sensors may be configured to identify identification marks on at least one of the consumables 108, the cell culture chamber 104, and the tubes 104a, 108a. One or more cameras or sensors may be optical to detect barcodes and / or QR codes, or may be non-optical to detect RFID or NFC tags.

[0131] Bioprocessing systems that include one or more such processing stations are easy to adopt and easy to expand. For example, the system may initially have a single processing station, but as demand grows, additional processing stations can be added. A fully automated system can be achieved by incorporating multiple processing stations, optionally where the robotic device is not located at the processing station, but rather on an autonomous mobile "manipulation" unit / mobile robotic device that can access multiple processing stations when needed.

[0132] Thus, a bioprocessing system may include a plurality of processing stations as described herein operating in parallel, each processing station comprising: a means for aseptically connecting a consumable (e.g., a cell bag) to an amplification chamber (e.g., a cell culture chamber) and transferring cells to the amplification chamber (i.e., seeding cells); a means for aseptically connecting a different consumable (e.g., a culture medium bag) to the amplification chamber and transferring fluid to the amplification chamber (i.e., feeding cells); a means for agitating the amplification chamber (e.g., to make the sample representative) and taking samples from the amplification chamber; a means for aseptically connecting another consumable (e.g., an output bag) to the amplification chamber and transferring fluid to the output bag (i.e., harvesting cells) - agitating the amplification chamber prior to transfer to ensure that all cells are distributed; and a means for disconnecting consumables (e.g., cell bags, culture medium bags, and output bags); and a means for controlling an automated sequence of operations.

[0133] The device for controlling the automated operation sequence can be provided by a processing and control unit (not shown). The processing and control unit can be part of a closed system or a part of the entire bioprocessing system. The processing and control unit can be used to control multiple closed systems in parallel. The automated operation sequence can be controlled according to one or more predetermined workflows, preferably one or more reconfigurable workflows. In this way, the ad hoc method performed by the bioprocessing system can be easily modified or adjusted without modifying the bioprocessing system itself.

[0134] The device for controlling the automated sequence of operations can be configured to automatically schedule the sequence of actions to be followed by the closed system. The sequence of actions can be automatically updated based on input received from at least one sensor of the bioprocessing system and / or the closed system. In this way, the closed system can process multiple cell culture chambers simultaneously while minimizing the risk of conflicts between their respective workflows. For example, the sequence of operations can be scheduled to minimize and preferably prevent any robotic device or other part of the closed system or bioprocessing system from being required by different workflows at the same time. If conflicts cannot be avoided, the device for controlling the automated sequence of operations can delay one of the conflicting operations based on a preprogrammed or user-configurable priority list.

[0135] The apparatus for controlling an automated sequence of operations can be configured to simulate an automated sequence of operations before the bioprocessing system executes the sequence. The apparatus for controlling an automated sequence of operations can communicate at least one result of the simulation to an operator. The at least one result can include an indication when a particular operation occurs, an indication when a manual step may need to be performed, and / or an indication that a conflict may (or may not) occur between two concurrent operations. The bioprocessing system can also include a monitoring system to verify whether the automated sequence of operations has occurred. The monitoring system can be provided by the apparatus for controlling the automated sequence of operations of the processing station.

[0136] The processing system can include a cell analyzer (e.g., a "cell analysis unit"), such as a cell counter / flow cytometer (or other cell analysis / culture medium analysis) and a device for transferring a sample from a cell culture chamber to the cell analyzer. For example, a cytometer station configured to hold an analysis chamber (or analysis unit) can be mounted on a support surface of a base unit. The analysis chamber can have a flexible tube connected thereto. A tube welder can form a tube weld between corresponding tubes of the cell culture chamber and the analysis chamber, and a peristaltic pump can transfer a sample of the contents of the cell culture chamber to the analysis chamber for analysis. Based on the measurements of the cell analyzer, one or more processing parameters of the closed system can be adjusted. For example, the temperature of the incubation chamber can be changed, and / or the feed rate of the incubation chamber can be changed.

[0137] It is also possible to aseptically connect a waste bag (i.e., consumables) to the cell culture chamber at the processing station and remove spent media from the top of the cell culture chamber (i.e., reduce media volume without removing cells, whether for concentration or media exchange purposes).

[0138] Advantageously, the processing station is capable of performing each of the following steps of the cell therapy process at a single location (e.g., at a stand-alone station): activation, transfection, and expansion. In addition, simple process development is possible due to the ability to simultaneously perform parallel processes and automate sampling and cell counting. Due to the automation of the processing station, samples can be sampled 24 hours a day. In addition, the processing station can automatically maintain traceability between consumables (e.g., bags) and cell culture chambers (i.e., expansion chambers) in a space-efficient manner.

[0139] Although the foregoing is directed to exemplary embodiments of the present invention, it should be understood that the present invention is described herein by way of example only, and that the details may be modified within the scope of the present invention. In addition, it will be understood by those skilled in the art that the present invention may not be limited to the embodiments disclosed herein, or any details shown in the accompanying drawings that are not described in detail herein or defined in the claims. In fact, these redundant features may be removed from the accompanying drawings without affecting the present invention.

[0140] Moreover, other and further embodiments of the present invention will be apparent to those skilled in the art from consideration of the specification and may be devised without departing from the basic scope as determined by the appended claims.

Claims

1. An automated system for performing biological processing, comprising: an incubation system configured to house at least one incubation chamber for incubating a cell culture chamber having a flexible tube fluidly connected thereto; as well as a storage system configured to store at least one fluid-containing consumable having a tube fluidly connected thereto; Wherein, the incubation system and the storage system are arranged together to enable a robotic device to manipulate the tube welding between the flexible tube of the incubated cell culture chamber and the tube for storing consumables, thereby forming a sterile fluid connection between the cell culture chamber and the consumables to maintain a closed system.

2. The system according to claim 1, wherein: The system is configured as a bioreactor system for a bioprocessing system.

3. The system according to claim 1 or 2, wherein: The incubation system is further configured to store a cell culture chamber in each incubation chamber with the flexible tube in a predetermined orientation, optionally wherein a portion of the flexible tube is retained outside the incubation chamber, such as by one or more tube clamps.

4. The system according to any one of claims 1 to 3, wherein: The storage system is further configured to store each consumable, with the tube of each consumable being held in a predetermined orientation, for example, by one or more tube clamps.

5. The system according to any one of claims 1 to 4, wherein: The incubation system is configured to accommodate a single incubation chamber.

6. The system according to any one of claims 1 to 4, wherein: The incubation system is configured to house a plurality of incubation chambers, each of the incubation chambers being arranged to incubate a single cell culture chamber in physical isolation from adjacent incubation chambers.

7. The system according to any of the preceding claims, further comprising a cell analysis unit, wherein at least one of the robotic devices is further configured to manipulate a fluid connection between the cell analysis unit and the incubated cell culture chamber.

8. The system according to claim 7, wherein: The cell analysis unit has at least one tube fluidically connected thereto, and at least one of the robotic devices is further configured to manipulate a fluid connection between a tube fluidically connected to the cell analysis unit and a tube fluidically connected to the incubating cell culture chamber.

9. The system according to claim 8, wherein: One or more processing parameters of the system are configured to be adjusted based on the measurements of the cell analysis unit.

10. The system according to any of the preceding claims, further comprising an automated processing station, preferably configured as a stand-alone processing station, comprising a support platform forming part of the incubation system.

11. The system according to claim 10, wherein: At least one robotic device is disposed on the processing station.

12. The system of claim 11, further comprising a movement system for the at least one robotic device, the movement system configured to move the robotic device relative to at least one of the incubation system and the storage system.

13. A biological treatment system comprising: An automated processing station according to any one of claims 10 to 12, and A separate robotic device is configured to move independently relative to the automated processing station.

14. A system according to any one of claims 11 to 13, wherein: the robotic device being configured to manipulate the fluid connection to create a tube weld between the flexible tube of the incubating cell culture chamber and the flexible tube of the storage consumable to transfer fluid therethrough, The tube weld is a sterile tube weld formed between the free ends of the respective tubes.

15. A system according to any one of claims 11 to 14, wherein: The robotic device is configured to manipulate the fluid connection to disconnect the flexible tube of the incubating cell culture chamber from the flexible tube of the storage consumable.

16. A system according to any one of claims 11 to 15, wherein: The robotic device is configured to manipulate the fluid connection to seal one or both of the flexible tubes, preferably prior to disconnecting the fluid connection.

17. A system according to any one of claims 11 to 16, wherein: The robotic device is configured to manipulate the fluid connection to pump fluid between the consumable and the incubated cell culture chamber through the fluid connection.

18. The system of claim 17, wherein: The robotic device is further configured to pump the fluid by applying a peristaltic pumping action to at least one flexible tube forming the fluid connection.

19. A system according to any one of claims 11 to 18, wherein: The robotic device is configured to manipulate the fluid connection so that at least one flexible tube of the corresponding incubating cell culture chamber and at least one flexible tube of the storage consumable are engaged and / or positioned relative to each other to form the fluid connection.

20. The system according to any one of claims 11 to 19, wherein: The at least one robotic device is further configured to manipulate a fluid connection between the first incubating cell culture chamber and the second incubating cell culture chamber.

21. A system according to any one of claims 11 to 20, wherein: The robotic device is configured to use interchangeable end effectors, and the system further includes an end effector storage system for storing one or more interchangeable end effectors for use by the robotic device.

22. A system according to any one of claims 11 to 21, wherein: The robotic device includes an end effector on a robotic arm, and the robotic device further includes at least one of a probe or a sensor located on the end effector.

23. A system according to any preceding claim, further comprising a controller for controlling an automated sequence of operations of the system.

24. The system of claim 23, wherein: The controller is configured to automatically schedule a sequence of actions to be followed by the system.

25. The system of claim 23 or 24, further comprising a user interface configured to enable a user to program a predetermined workflow to be followed by the system.

26. A system according to any one of claims 23 to 25, wherein: The controller is configured to simulate the automated operation sequence before the system executes the sequence.

27. The system according to any of the preceding claims, further comprising a fluid agitation system for agitating a fluid contained within the incubated cell culture chamber.

28. The system of claim 27, wherein: The fluid agitation system is configured to agitate fluid within the or each incubating cell culture chamber prior to transferring the fluid from the cell culture chamber to an output container and / or a sample container.

29. A system according to claim 27 or 28, when dependent on any one of claims 11 to 22, wherein: At least one of the robotic devices is configured to manipulate the fluid connection to facilitate transfer of fluid from at least one incubating cell culture chamber to a waste container prior to agitating the incubating cell culture chamber by the fluid agitation system.

30. A system according to any preceding claim, wherein: The storage system includes a refrigeration or heating unit for regulating the temperature of one or more consumables.

31. A system according to any preceding claim, further comprising a tube supply arranged to provide replenishment of tubes to at least one cell culture chamber or consumable, preferably the tube supply comprising a tube supply reel.

32. The system of any preceding claim, further comprising means for identifying identification marks on at least one of the following: a consumable, a tube, a cell culture chamber.

33. A system according to any preceding claim, wherein: The system includes a self-contained processing station arranged to facilitate the transfer of fluids from storage consumables to incubated cell culture chambers at the processing station.

34. A bioprocessing system comprising a plurality of automated systems according to any preceding claim.

35. A method comprising performing a bioprocess using a system according to any preceding claim.

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