Automated filling / completion system

Abstract

A closure system (100) for mixed fluids for use in a biological treatment system comprises automated means for operating a tube weld (160) between a first tube fluidly connected to a first consumable (10-1) and another tube fluidly connected to a mixed consumable (10-3), the pipe weld forms a closed fluid connection between the first consumable and the mixed consumable; an automated device for delivering a first fluid contained in the first consumable to the mixed consumable via a fluid connection; and an automated device for determining the amount of fluid delivered to or from the mixed consumable; wherein the system is further configured to operate a tube weld between a second tube fluidly connected to the second consumable (10-2) and another tube fluidly connected to the mixed consumable, and to deliver a second fluid between the second tube and the another tube to mix with the first fluid in the mixed consumable.

Description

Technical Field

[0001] The present disclosure relates to an automated filling / finishing system for use in an automated bioprocessing system, such as for final formulation and filling / finishing of consumable bags prior to cryopreservation. Background Art

[0002] Bioprocessing plays a key role in many industries, including pharmaceuticals, food, biofuels, and other major sectors. It is no wonder that as the bioprocessing industry continues to grow, bioprocessing technologies, including bioprocessing systems, are increasingly relied upon.

[0003] For example, bioprocessing is used in autologous cell therapies. Autologous cell therapies are a promising class of therapies with significant clinical and commercial potential, from treating cancer to repairing genetic defects. These therapies involve extracting cells from a patient, manipulating the cells over a period of days to weeks, and then reintroducing the cells into the patient to produce a therapeutic effect. The steps taken during autologous cell therapy are typically very complex. For example, a typical CAR-T process may include a series of steps: starting with a cryopreserved leukocyte culture bag (leukopak), thawing, washing to remove DMSO, enriching T cells, activating, transducing, amplifying, concentrating, filling / finishing the preparation into an IV bag, cryopreservation, and several other intermediate washing steps.

[0004] Due to the complexity of biological processing, it is desirable to automate the process while maintaining a closed system, thereby eliminating the need to perform these steps in such a high-grade clean room. A closed system refers to a system in which the process is not exposed to the surrounding environment, so that no contaminants from the environment enter, and no cross-contamination from other processes performed simultaneously. Some systems attempt to provide a solution involving complex consumables, which, for example, connects the sample to all other necessary processing stations through a tube connected to the consumable fluid, and provides pumping and valves to allow these steps to be performed in a specific order. The term "consumable" can be used to describe any container containing a sample such as a fluid, such as an intravenous bag. The fluid may include one or more of the following: a cell sample, a reagent, a cryoprotectant, or any other various fluids. However, these consumables are complex to manufacture and install, and are therefore relatively expensive and may be unreliable. Each consumable needs to be individually customized according to the process performed, which makes the system inflexible and the cost of adapting to new processes is high. In fact, the challenge of automating such a system is how to provide a flexibly modifiable system that can also provide a reliable connection between consumables and other fluid containers while maintaining a sterile closed system.

[0005] Tube welding can be used to create fluid connections between tubes connected to individual containers (i.e., "consumables"). Aseptic tube welders allow connections to be made between two tubes with closed ends without exposing the contents of either tube to the environment and are the only widely accepted means of creating connections reusably within a single system. However, tube welding requires precise manipulation to correctly insert the tubes into the welder and requires a visual inspection by the operator after each weld to confirm that the weld was successful.

[0006] Challenges arise in automated systems because the tubes connected to the consumables are typically free-moving, which makes it difficult for the automated bioprocessing system to position the tubes and insert their tube ends into the welder. In addition, tube welding requires very long tubes, which increases the risk of the tubes in the system becoming tangled and / or interfering with other components in the system. Therefore, due to these substantial complexities and the stringent requirements for reliability when applied to bioprocessing systems, there has been little progress in attempting to automate bioprocessing systems that utilize tube welding. In addition, for autologous cell therapies, etc., it is particularly difficult to incorporate the use of consumables into automated bioprocessing systems due to the soft, flexible nature of the consumables and the hardness that varies with the volume of fluid contained in the consumables. This characteristic makes it difficult for automated systems to accurately hold and position consumables during processing.

[0007] One challenge faced when automating a bioprocessing method is the final "fill / finish" stage, in which the cell product is mixed with a cryoprotectant and supplied to a large number of "output consumables" before being cryopreserved for storage and transport. Once the cell product is mixed with the cryoprotectant, the output consumable must be cryopreserved for only a short time (about 1 hour) before the cryoprotectant destroys the cells. Due at least in part to the above-mentioned difficulties in piping and connection while maintaining a closed system, existing systems typically pre-connect the output consumables to a mixing chamber. However, this may limit the number of output consumables to approximately ten, may be space inefficient, and is inflexible for expansion or modification of the processing process. In addition, there may be a risk of cross contamination, and there is no easy way to verify that contamination has not occurred.

[0008] For the reasons stated above, there is a need for an automated system that can efficiently handle and process consumables while maintaining a closed environment. Summary of the invention

[0009] Described herein is a closed system for mixing fluids (e.g., reagents) used in a bioprocessing system, comprising: an automated device for operating a tube weld between a first (e.g., flexible) tube fluidly connected to a first consumable and another (e.g., flexible) tube fluidly connected to the mixing consumable, the tube weld forming a closed fluid connection between the first consumable and the mixing consumable; an automated device for delivering a first fluid contained in the first consumable to the mixing consumable via the fluid connection; and an automated device for determining the amount of fluid delivered to or from the mixing consumable; wherein the system is further configured to operate a tube weld between a second tube fluidly connected to a second consumable and the other tube fluidly connected to the mixing consumable, and to deliver a second fluid between the second tube and the other tube to mix with the first fluid in the mixing consumable.

[0010] Compared to the systems of the prior art, such a system provides fast loading and unloading times of consumables. This is advantageous when mixing the contents of consumables because the mixture may be prone to separation, or, for example, the cryoprotectant is toxic to the cell sample, making it necessary to perform the process quickly. Operating the fluid connections between the consumables reduces internal contamination and reduces the additional labor required to perform the step. Advantageously, the system can be configured as an automated filling / finishing system for a bioprocessing system. The filling / finishing system can be configured to mix the cell product contained in the first consumable with the cryoprotectant contained in the second consumable.

[0011] Preferably, at least a portion (e.g., an end) of the first tube is flexible. Similarly, at least a portion (e.g., an end) of the "other" tube is preferably flexible. In fact, a portion (e.g., an end) of each tube that is operated (as described herein) to form a fluid connection is preferably flexible. Therefore, the tube may be referred to as a "flexible tube", which term may also include flexible portions of the tube, such as the end.

[0012] As used herein, the term "automatic" or "autonomous" preferably means that a particular system or step can be operated and / or controlled by automation (e.g., automatically) without human intervention. For example, a closed system can follow an automated operating sequence.

[0013] As used herein, the term "closed system" may mean a functionally closed system, or more preferably a completely closed system, in which a physical barrier is maintained between the contents of the consumable and the surrounding environment (e.g., other parts of the bioprocessing system). In this way, the risk of contamination of the consumable or the surrounding environment is reduced.

[0014] The device for determining the amount of fluid delivered to or from a mixed consumable can monitor the properties of the mixed consumable, such as its weight or the volume of the fluid contained therein. Alternatively or additionally, the device for determining can monitor the properties of different consumables, such as a first consumable and a second consumable and / or an output consumable that receives fluid from the mixed consumable. Alternatively or additionally, the device for determining the amount of fluid can monitor the flow rate of the fluid through one or more fluid-connected tubes. Advantageously, the device for determining can allow accurate volumes of fluid to be pumped between consumables. For example, it is advantageous for the output consumable to have an accurate volume of a mixture contained therein.

[0015] The automated device for operating the tube weld can be configured to form a closed, sterile and / or sterile tube weld between each tube of two consumables. In other words, the "operating device" can include a "tube welder" or "tube welding equipment".

[0016] The automated apparatus for performing pipe welding may also include means for engaging and / or positioning the pipe, at least a portion of which (eg, the end) is preferably flexible.

[0017] The automated means for conveying may be arranged to convey a fluid between two fluidically connected consumables via tubes which have been welded together to form the fluid connection. The automated means for conveying a fluid may comprise a pumping device configured to apply a pumping action, preferably a peristaltic pumping action, to at least one of the tubes forming the fluid connection. In other words, the means for conveying a fluid may be a "peristaltic pump".

[0018] The system (e.g., automated device) may also be configured to operate a pipe weld between a pipe fluidly connected to the mixing consumable and a pipe fluidly connected to the output consumable, and deliver (at least some) of the mixture (e.g., a mixture of the first fluid and the second fluid) contained in the mixing consumable to the output consumable. The system may also include automated means for disconnecting the fluid connection between the two consumables.

[0019] The system may also include an automated device for sealing each tube once the fluid delivery to or from the mixed consumables is completed. The automated device for sealing may be an RF sealer or a heat sealer. The automated device for sealing may also provide a device for disconnecting the fluid connection between two consumables. The automated device for sealing may be configured to seal a tube connected between the mixed consumables and the first consumable and / or the second consumable. Alternatively, the first consumable and the second consumable may remain connected to the mixed consumables after completing the fluid delivery to the mixed consumables. The automated device for sealing may be configured to seal other consumables, such as output consumables containing a mixture delivered from the mixed consumables. In this way, the filled output consumables may be removed from the system.

[0020] The automated device for operating a pipe weld may also include a device for engaging and / or positioning the pipe, at least a portion of the pipe (e.g., an end portion) being preferably flexible. Alternatively or additionally, at least a portion of the first pipe fluidly connected to the first consumable is (at least partially) maintained along a predetermined path.

[0021] By maintaining a portion of the tube along a predetermined path, the tube can be reliably engaged by a robotic device at any position along the predetermined path. As used herein, the term "predetermined path" preferably means that the position of the tube is known at one and preferably multiple positions along its length, thereby defining a known path between the known positions. It should be understood that the entire tube is not required to have a predetermined path, as long as at least a portion of the tube has a sufficiently known path to allow the tube to be reliably engaged by an automated system (e.g., a robotic device).

[0022] The known position may be defined relative to other components in the system, such as a feature having a fixed position (e.g., a tube holding element having a known position), and / or by one or more identifying marks on the tube. More preferably, the position of the tube is known along at least one continuous length of the tube. The predetermined path may include one or more linear path portions, which may be provided by holding the tube between one or more pairs of tube holding elements, which align the tube substantially along a known axis.

[0023] The system may include an automated processing station, more preferably an independent automated processing station. As used herein, the term "processing station" preferably means a station of a bioprocessing system that is configured to perform a specific portion of a bioprocessing method, such as a fill / finish operation. During the bioprocessing method, the processing station may be located at a fixed position in the bioprocessing system. As used herein, the term "independent" preferably means that the processing station is self-sufficient and can perform operations such as fill / finish operations without any external intervention. Alternatively, the processing station can interact with other robotic devices that can move around the bioprocessing system. As used herein, the term "automated" preferably means that at least one processing process is autonomously performed by a processing station. Autonomous processes can occur without operator intervention and can be defined according to a bioprocessing workflow.

[0024] At least one of the automated device for operating the tube weld, the automated device for conveying fluids, and the automated device for sealing may be disposed on the processing station. Alternatively, at least one of the automated device for operating the tube weld, the automated device for conveying fluids, and the automated device for sealing is disposed on a separate mobile unit (e.g., a "mobile operating unit") configured to automatically cooperate with the processing station. The system may include a plurality of mobile operating units; each mobile operating unit is capable of performing one or more of an operation, conveying, sealing, and / or disconnection operation in the bioprocessing system. Preferably, at least one of the automated device for operating the tube weld, the automated device for conveying fluids, and the automated device for sealing comprises a robotic device, such as a robotic arm having an end effector configured to perform one or more operations (i.e., an operation, conveying, sealing, and / or disconnection operation).

[0025] The automated means for delivering may comprise a pumping device configured to apply a pumping action, preferably a peristaltic pumping action, to at least one of the tubes forming the fluid connection. The system may further comprise an automated means for disconnecting a fluid connection between two consumables.

[0026] The system may also include an automated device for mixing the first fluid and the second fluid in the mixing consumable. For example, the system may also include a mixing system arranged on the processing station.

[0027] The means for mixing may include an automated mixing system, which may include a mixing zone in which the mixing consumable is positioned to receive the first fluid and the second fluid from the first consumable and the second consumable, respectively. The mixing system may include means for agitating the mixture of the contents of the first consumable and the second consumable.

[0028] The device for stirring may include a roller arranged to roll on the mixed consumable and / or a shaking plate arranged to shake the mixed consumable, thereby promoting the mixing of the first fluid and the second fluid. The device for stirring may include an ultrasonic source, a vibration source and / or an orbital vibrator. The mixing system may include a device for controlling the temperature of the mixed consumable, such as a Peltier device or plate configured to cool the mixed consumable in the mixing zone.

[0029] The processing station may include a plurality of slots configured to (e.g., releasably) hold the first consumable, the second consumable, and the output consumable. Preferably, the slot is arranged adjacent to the mixing system to facilitate operation of the pipe weld between the first consumable, the second consumable, and the output consumable and the mixing consumable. The slots may be arranged in a linear array. The slots may be arranged above the mixing system. The first consumable, the second consumable, and the output consumable may all be arranged in the apparatus described herein, thereby allowing any consumable to be added, retained, and / or removed from any slot. The slots may be arranged on the forward-facing surface of the processing station to enable operation of the consumable by a robotic device.

[0030] The robotic device may be part of the processing station, or may be a separate robotic device (e.g., a mobile unit or "mobile operating unit") that is capable of moving relative to the processing station. Where the robotic device is a mobile operating unit, the mobile operating unit may be capable of autonomously moving around the floor of the bioprocessing system to access the processing station, or the mobile operating unit may be mounted on tracks (or a mesh system or tracks) to facilitate movement around the bioprocessing system.

[0031] The mobile unit may be configured to deliver at least one of the first consumable and the second consumable to the multiple grooves so that at least one of the first fluid or the second fluid is supplied to the mixing system. The mobile unit may be configured to perform operation, delivery, sealing and / or disconnection operations. Delivery, operation, delivery, sealing and disconnection operations may be performed by the same robotic device (e.g., the same mobile operation unit). Alternatively, these functions may be performed by different robotic devices, which may be part of a processing station or may be separated from the processing station (i.e., a second mobile operation unit). For example, a first mobile operation unit may deliver consumables to multiple grooves (and / or remove consumables from multiple grooves), and a second mobile operation unit (or a robotic device as part of a processing station) may operate a pipe weld, deliver fluids, seal and / or disconnect pipes. Preferably, each mobile operation unit is capable of performing all of the delivery, operation, delivery, sealing and disconnection operations, but it should be understood that during use, these tasks may be allocated between different robotic devices, such as between different mobile operation units.

[0032] The processing station may include a (first) automated delivery system configured to deliver at least one of the first consumable and the second consumable to the mixing system to supply at least one of the first fluid or the second fluid to the mixing system. The first automated delivery system may be referred to as an input delivery system.

[0033] The automated delivery system may also be configured to deliver both the first consumable and the second consumable to the mixing system to supply both the first fluid and the second fluid to the mixing system.

[0034] The input delivery system may deliver other consumables to the mixing system, such as empty output consumables.

[0035] The processing station may also include a (second) automated conveying system configured to remove the output consumable from the mixing system once the output consumable is filled with the resulting mixture of the first fluid and the second fluid. The second automated conveying system may be referred to as the output conveying system. The output conveying system may remove other consumables, such as empty first consumables and second consumables, from the mixing system.

[0036] The automated conveying system or each automated conveying system may be arranged to position the consumables for engagement by a device for operating a pipe weld between each consumable and the mixing system. The conveying system may include a motorized track device in which the consumables are suspended from the track and the consumables can be moved along the track by the motorized track. The automated conveying system or each automated conveying system may be used in conjunction with one or more robotic devices and / or one or more mobile operating units described above. The system may be configured to hold the consumables and their corresponding pipes at one or more predetermined positions. In this way, a device for operating a pipe weld (e.g., a robotic device) can reliably engage the pipe at a predetermined position or on a predetermined path. For example, the system may be configured to engage consumables and pipes held within a device described herein, wherein the device is configured to at least partially hold the pipe along a predetermined path.

[0037] The system may further include means for identifying identification marks on at least one consumable.The system may further include one or more sensors configured to measure one or more parameters of the consumable.

[0038] Also described herein is a closed system for mixing multiple fluids (e.g., reagent fluids) for a bioprocessing system, comprising: an automated device for mixing a first fluid contained in a first (e.g., "input") consumable with a second fluid contained in a second (e.g., "input") consumable within a third (e.g., "mixing") consumable, and then filling a fourth (e.g., "output") consumable with the resulting mixture of the first and second fluids, wherein each consumable comprises a tube (at least a portion (e.g., an end) of which is preferably flexible), the tube being arranged to provide a fluid channel for one or more fluids contained in the consumable; an automated device for operating a closed fluid connection between two of the consumables to transfer fluid therebetween; an automated device for transferring fluid between two fluidically connected consumables; an automated device for determining the weight of the volume of the resulting mixture of the first and second fluids transferred to the fourth consumable; and an automated device for sealing a portion of each tube so that one or more fluids in the consumables are aseptically sealed to be isolated from the surrounding environment before disconnecting the fluid connection operating between the two consumables.

[0039] Also disclosed herein are methods of mixing fluids for bioprocessing comprising using and / or mixing two or more fluids in a closed system as described above and herein.

[0040] The present invention also describes a method for mixing fluids (e.g., reagent fluids) in a closed system of a biological processing system, the method comprising: mixing a first fluid contained in a first consumable and a second fluid contained in a second consumable within a mixing consumable, and then filling an output consumable with the resulting mixture of the first fluid and the second fluid, wherein each consumable comprises a tube (at least a portion (e.g., an end portion) of which is preferably flexible), the tube being arranged to provide a fluid channel for one or more fluids contained in the consumable; operating a fluid connection between two of the consumables to transport fluid between them; determining the weight of the volume of the resulting mixture of the first fluid and the second fluid transported to the output consumable; and sealing a portion of each flexible tube so that the one or more fluids in the consumables are isolated from the surrounding environment before disconnecting the fluid connection operated between the two consumables.

[0041] Preferably, one or more of the above-mentioned "mixing", "operating fluid connection", "determining weight" and "sealing a portion" steps are performed autonomously, and more preferably, all of these steps can be automated, so that the method can be described as an "automated method".

[0042] The present invention also describes a device for holding consumables (e.g., bags) for an automated bioprocessing system, wherein the consumables have at least one flexible tube connected to the fluid of the consumables, the device comprising: a first part for holding the consumables; and a second part configured to hold the flexible tube; wherein the second part is configured to at least partially hold the flexible tube along a predetermined path.

[0043] By holding a portion of the tube along a predetermined path, the tube can be reliably engaged by a robotic device at any position along the predetermined path. As used herein, the term "predetermined path" preferably means that the position of the tube is known at one and preferably multiple positions along its length, thereby defining a known path between the known positions. It should be understood that the entire tube is not required to have a predetermined path, as long as at least a portion of the tube has a sufficiently known path to allow the tube to be reliably engaged by an automated system (e.g., a robotic device).

[0044] The known position may be defined relative to other components of the apparatus, such as a feature having a fixed position (e.g. a tube retaining element or engagement means), or by one or more identifying marks on the tube. More preferably, the position of the tube is known along at least one continuous length of the tube. The predetermined path may include one or more linear path portions, which may be provided by retaining the tube between one or more pairs of tube retaining elements, which align the tube substantially along a known axis.

[0045] Advantageously, the first part provides a device for holding consumables, which is typically a soft and flexible fluid-filled bag, so that the first part provides support for the consumables. In addition, the second part provides a device for holding at least one flexible tube, thereby reducing the free movement of the flexible tube, so that one or more positions of the flexible tube along the predetermined path are known. In fact, by following the predetermined path, a system (such as the system described above and herein) that is programmed to know or identify the predetermined path will also know the position of the held portion of the flexible tube. In this way, the flexible tube can be operated by the system. This operation may include welding the flexible tube to another tube by, for example, an automated robotic arm, which requires the system to find, grasp and operate the end of the tube. For example, the device may be located in a tank, a storage portion, or a conveying system of the system described above and herein. During use, an automated device (such as a tube welder on a robotic arm) for operating a tube weld can engage the tube along a predetermined path, so that a fluid connection and subsequent fluid transmission can be performed. In existing systems, the engagement of the tube may be particularly challenging, because the flexibility of the tube may cause the tube to be generally not located in a defined position in space; therefore, the connection between the flexible tubes may be unreliable.

[0046] The first portion may include a structure configured to accommodate the consumable. Advantageously, the structure supports the consumable, thereby reducing the flexibility of the consumable. The structure may be rigid.

[0047] The structure can be configured as a tray with multiple sides that define recessed portions in which consumables are housed. The tray provides further support to the consumables by providing a solid support on the consumables. In this way, the consumables maintain a relatively fixed shape. Since the consumables are held in the tray, the rigidity that varies based on the volume of the fluid in the consumables is no longer detrimental to the function of the system because the tray is movable so that the tray can be easily moved between various positions.

[0048] At least one of the sides defining the recessed portion may have a groove or slot or hole for allowing the tube to pass through. This allows a portion of the tube to be guided to the outside of the tray without causing any deformation of the tube due to the sides of the tray. Thus, a stable and reliable fluid communication can be achieved between the tube and the consumable.

[0049] The second part may include a frame. The second part (e.g., a frame) may have at least one tube retaining element arranged to retain the tube at at least one position along the predetermined path. In this way, the tube is securely held in place by the at least one tube retaining element, thereby reducing undesired free movement of the flexible tube.

[0050] The tube retaining element may be any suitable means for retaining the portion of tube, including a clip, hook or clasp.The portion of tube may be permanently retained by the at least one tube retaining element, or the portion of tube may be removably secured.

[0051] The second part (e.g., a frame) may have a plurality of tube holding elements arranged to hold the tube at a plurality of positions along the predetermined path. By securely holding the flexible tube at a plurality of positions, undesirable free movement of the flexible tube is further reduced. At least one of the plurality of positions may be identified by an identification mark, such as a unique barcode, QR code, RF tag, and / or NFC tag. Each identification mark may be located at the same position as one of the plurality of holding elements. In this way, the position along the predetermined path may be identified by a system having a device for identifying an identification mark, such as the closed system described above and herein. In this way, the system will know the position of the flexible tube being held.

[0052] The frame may be configured as a grid or mesh. The grid or mesh may include a first set of parallel rods that cross with a second set of parallel rods at recurring intervals. The rods may have a rigid structure. The first set of parallel rods and the second set of parallel rods may be at right angles to each other. Advantageously, this arrangement provides ease of movement for an automated system, for example, an automated robotic arm may be programmed for translational movement (i.e., upward and downward movement), enabling it to easily move along the grid or mesh. In addition, the grid is a suitable basis for providing a predetermined path for winding of at least one tube, so that long tubes can be kept in a compact arrangement, thereby saving space.

[0053] At least one tube holding element may be arranged to hold the tube in an intermediate position on the grid or mesh. The term "intermediate position" refers to a position substantially at the midpoint between two intersecting bars. In this way, the robot arm of the automation system can move between multiple positions along a predetermined path using only translational movements.

[0054] The second part may be arranged to provide a cover to the first part so that the consumables are held between the second part and the first part. The cover covering the consumables may be used to stack a plurality of consumable holders on top of each other, thereby saving space. The consumables may be stacked within a closed system, such as in a storage portion of a processing station. In addition, the cover covering the consumables provides protection for the consumables, thereby reducing the likelihood of damage to the consumables and reducing the risk of contamination.

[0055] The second part is slidable relative to the first part. Preferably, the second part is slidable parallel to the longitudinal axis of the first part.

[0056] Alternatively, the second part may be hingedly attached to the first part and configured for hinged movement between an open configuration and a closed configuration. Preferably, when in the open configuration, an axis parallel to the plane of the first part and an axis parallel to the plane of the cover are parallel to each other, thereby improving accessibility of the flexible tube and / or consumables to the robotic device. The robotic device may be programmed to move the consumable holder between the two configurations.

[0057] In the closed configuration, the second part may be secured to the first part. This increases stability when multiple consumable holders are stacked and improves the protection provided to the consumables in the holder when in the closed configuration.

[0058] The apparatus may further comprise means for cooling the consumables held in the first portion. The means for cooling may comprise at least one air port in the first portion and / or the second portion. The air port may be configured to receive a supply of cooling air from an external air source.

[0059] Preferably, the plurality of tube retaining elements comprises a first tube clamp and a second tube clamp, wherein the tube clamps are spaced apart to provide a predetermined path therebetween.

[0060] Alternatively, the first portion may comprise a tray having a cavity shaped to receive the consumable product therein; and a removable cover arranged to enclose the consumable product within the cavity.

[0061] The device may further comprise means for engaging to facilitate operation of the device, the device preferably being arranged on the first portion of the device.

[0062] The device may also include identification indicia to facilitate identification of consumables retained within the device.

[0063] Those skilled in the art will appreciate that any device feature described herein may be provided as a method feature, and vice versa. It will be appreciated that the specific combination of various features described and defined in any aspect described herein may be independently implemented and / or provided and / or used.

[0064] Furthermore, it should be understood that the embodiments are described herein by way of example only and that modifications of detail may be made within the scope of the present disclosure.In addition, as used herein, any "means plus function" feature may be expressed alternatively with respect to its corresponding structure. BRIEF DESCRIPTION OF THE DRAWINGS

[0065] One or more embodiments will now be described by way of example with reference to the accompanying drawings, in which:

[0066] Figure 1 A first embodiment of a closed system is shown;

[0067] Figures 2 to 4 A second embodiment of a closed system is shown;

[0068] Figure 5 A third embodiment of a closed system is shown;

[0069] Figure 6a Some examples of output consumables are shown;

[0070] Figure 6b An example of a cassette frame for holding a plurality of consumables is shown;

[0071] Figure 7 A schematic diagram showing a plurality of consumables fluidly connected to a tube network;

[0072] Figure 8 a schematic diagram showing a first configuration of tools and consumables operable according to a first workflow;

[0073] Fig. 9 a schematic diagram showing a second configuration of tools and consumables operable according to a second workflow;

[0074] Fig.10 A schematic diagram showing another embodiment of a device for delivering a reagent between two fluidly connected consumables;

[0075] Fig.11a and 11b A first embodiment of a device for containing consumables having at least one flexible tube connected thereto is shown in an open and closed configuration, respectively; and

[0076] Fig.12a and 12b A second embodiment of a device for containing consumables having at least one flexible tube connected thereto is shown. DETAILED DESCRIPTION

[0077] In the following description and drawings, corresponding features may preferably be identified using corresponding reference numerals to avoid the need to describe in detail features common to each and every embodiment.

[0078] In general, an automated system (e.g., including a processing station) is described herein, which is configured to connect consumables (e.g., bags) aseptically together to pump fluids between them and aseptically seal them. In more detail, the system is configured to preferably use a robotic tube welder to aseptically connect a first "input" consumable (e.g., containing cells) to a larger mixed consumable, and then preferably use a robotic pumping device (e.g., a pumping mechanism) to deliver the contents from the first consumable to the mixed consumable. Then, the system can use a robotic tube welder to aseptically connect a second "input" consumable (e.g., containing a cryoprotectant) to a larger mixed consumable, and use a robotic pumping device to deliver some or all of the contents from the second consumable to the mixed consumable. Then, the first consumable and the second consumable can be separated from the mixed consumable (while maintaining sterility), preferably using a robotic tube sealer, which can be a part of a robotic tube welder. When the fluid is cooled (e.g., using Peltier), the mixing chamber can be gently shaken to mix the fluid.

[0079] The system may then aseptically connect the mixed consumables to one or more output ("product") consumables in sequence, preferably using a robotic tube welder, after which a controlled transfer of fluid may be performed between the mixed consumables and each output consumable container, preferably using a robotic pumping device. The output consumables may then be disconnected, preferably using a robotic tube sealer. This final "controlled transfer" step may be repeated until all of the fluid contained in the mixed consumables has been dispensed.

[0080] As will be appreciated, in a preferred embodiment, the system may be described as a robotic welding / sealing / pumping and delivery system for performing fill / finish operations.

[0081] In a word, as will be described in further detail with reference to various embodiments, this system comprises the automation device for aseptically connecting consumables together, for pumping fluid between them and for aseptically sealing consumables afterwards.Ideally, this system also comprises the automation device for performing the mixing of the fluid in the mixed consumables and the automation device for accurately measuring the weight of the fluid distributed to the mixed consumables or distributed from the mixed consumables.It is also preferred to be used for cooling the mixed consumables to keep the device of the desired temperature of the mixed fluid, and it is also preferred to be used for keeping the traceability device of input and output fluids.

[0082] As previously mentioned, the consumables referred to herein are preferably bags configured to contain fluids, each bag having a flexible tube providing fluid connection to its contents, the tube being sealed (e.g., clamped shut) prior to connection with the tube of another such consumable.

[0083] The automated "sterile" connection and disconnection technology that provides part of the system described herein enables rapid filling of large quantities of consumables (e.g., bags) that is not possible with existing systems that typically can only fill 10 pre-connected bags at a time. In fact, the system described herein provides much faster loading and unloading times than existing systems that require manual connection of the input consumables at the beginning of the process and then manual disconnection / heat sealing of all output consumables once the transfer of the fluid is complete.

[0084] Figure 1 A first embodiment of a closed system 100 that may form part of a bioprocessing system is shown. Following steps in a cell therapy process such as enrichment, activation, transduction, amplification, and / or concentration, the system 100 may be configured to perform a fill / finish operation in which the cell product is mixed with a cryoprotectant and the mixture is dispensed into a plurality of smaller "output" consumables 10 for subsequent cryopreservation. Thus, the system 100 may be referred to as a fill / finish system 100, but it should be understood that the system 100 may be operated for other purposes. The fill / finish operation must be performed quickly because the cryoprotectant may be toxic to the cells; in particular, all of the output consumables 10 must be filled, sealed, and cryopreserved within one hour. As will be further described in greater detail, the system 100 has several features that enable precise and consistent mixing of the cells with the cryoprotectant, allow control of the temperature of the consumables 10, and are gentle on the cells, which simultaneously enable a large number of output consumables 10 to be filled with the mixture in a short period of time.

[0085] like Figure 1As shown, the system 100 can be configured as a processing station 110, such as a filling / finishing station 110. By implementing the system 100 at a processing station 110, all steps required for a filling / finishing operation can be performed at one location, thereby simplifying the control of the processing station 110 and the transportation of consumables 10 to and from the processing station 110.

[0086] System 100 includes an automated device 120 for mixing the first reagent and the second reagent contained in the third consumable 10-3 before filling the fourth consumable 10-4 with the resulting mixture of the first reagent contained in the first consumable 10-1 and the second reagent contained in the second consumable 10-2. The first consumable 10-1 and the second consumable 10-2 can be referred to as "input consumables". The third consumable 10-3 can be referred to as a "mixing consumable". The fourth consumable 10-4 can be referred to as an "output consumable", such as a "vial" or a "container".

[0087] In the case where system 100 is configured to fill / complete system 100, the first consumable 10-1 may include a cell product, and the second consumable 10-2 may include a cryoprotectant and optionally any preparation for infusion. It should be understood that the first consumable 10-1 and the second consumable 10-2 are interchangeable within the scope of the present disclosure. In addition, the first consumable 10-1 and the second consumable 10-2 may include different reagents and / or additional reagents or a mixture of reagents. As used herein, the term "fluid" may refer to any liquid or gas, including reagents, cell samples, infusion preparations, cryoprotectants and / or any mixture thereof. Additional input consumables 10-1, 10-2 may be provided to deliver their contents to the mixed consumable 10-3.

[0088] Mixed consumables 10-3 preferably have a larger volume than input consumables 10-1, 10-2, so that the first reagent and the second reagent can be completely contained in the mixed consumables 10-3. For filling / finishing operation, the mixture of the first reagent and the second reagent is distributed among multiple output consumables 10-4, for example, 4 to 100 output consumables 10-4. Therefore, output consumables 10-4 may have a smaller volume than input consumables 10-1, 10-2 and / or mixed consumables 10-3. Where appropriate, the term "consumable" may refer to any one of the first, second, third and / or fourth consumables 10. The operation of fluid connection and the delivery of reagents between each consumable 10 will be described in more detail below.

[0089] Each consumable 10 includes a flexible tube 11, which is arranged to provide a fluid passage to one or more reagents contained in the consumable 10. The flexible tube 11 has an "upstream end" that is fluidly connected to the corresponding consumable 10 and a "downstream end" that defines a sealed end or closed end of the tube 11. Optionally, the consumable 10 can be connected to more than one tube 11, so that multiple connections and / or transfers of reagents can occur simultaneously. As will be discussed in more detail below, the tube welder 160 can be used to form a closed fluid connection between the consumables 10 via their respective tubes 11.

[0090] Multiple fluid connections can be formed between the mixed consumable 10-3 and multiple output consumables 10-4. Therefore, the mixed consumable 10-3 should have a tube 11 of sufficient length to allow multiple connections and disconnections by the tube welder. In order to prevent this length of tube 11 from being entangled with other parts of the system 100, and to facilitate engagement by the tube welder 160, the mixed consumable 10-3 can be contained in the device 1 that keeps the tube 11 along a predetermined path. The example of such a device 1 will be further discussed in conjunction with Figure 11. Other (input and / or output) consumables 10 can also be contained in a device (such as a rigid tray) with a tube alignment feature to assist robot movement and tube positioning. The example of another device 50 for accommodating consumables 10 will be described in conjunction with Figure 12.

[0091] The automated device 120 for mixing may include a mixing system 120 disposed on a processing station 110, which may be a "stand-alone" station 110 (or "device") for a bioprocessing system. The mixing system 120 may include a mixing zone 122 in which the third consumable 10-3 is positioned to receive the first reagent and the second reagent from the first consumable 10-1 and the second consumable 10-2, respectively.

[0092] Mixing system 120 may include a device for stirring a mixture of the contents of the first and second (input) consumables 10-1, 10-2. For example, the device for stirring may include a roller (not shown), which is arranged to roll on the mixed consumable 10-3, thereby promoting the mixing of the first reagent and the second reagent. Alternatively, or in addition, the device for stirring may include a shaking plate (not shown) on the mixing zone 122, which is arranged to shake the mixed consumable 10-3, thereby promoting the mixing of the first reagent and the second reagent. Other examples of stirring devices can be ultrasonic sources, vibration sources or orbital vibrators. Any of these stirring devices can be provided in any suitable combination as required.

[0093] The mixing system 120 may include a device for controlling the temperature of the mixed consumable 10-3. For example, the mixing zone 122 may include a Peltier device or a cooling plate (not shown) configured to cool the mixed consumable 10-3 when located in the mixing zone 122. The device for controlling the temperature may be configured to maintain the mixed consumable 10-3 at a temperature of about 4 degrees.

[0094] The system 100 (preferably the processing station 110) may include a first automated ("input") delivery system 130 configured to deliver at least one of the first consumable 10-1 and the second consumable 10-2 to the mixing system 120 so as to supply at least one of the first reagent and the second reagent to the mixing system 120.

[0095] Preferably, the (first) automated delivery system 130 is also configured to deliver both the first consumable 10-1 and the second consumable 10-2 to the mixing system 120, so that both the first reagent and the second reagent are supplied to the mixing system 120. The delivery system 130 may also deliver an empty fourth consumable 10-4 to be filled with a mixture of the first reagent and the second reagent from the mixing system 120. The delivery system 130 may include a track system 132, which includes one or more tracks, and the consumable 10 (e.g., the first consumable 10-1 and / or the second consumable 10-2) may be configured to move along the track. The delivery system 130 may include a device (not shown) for moving the consumable 10 along the track 132, so that the consumable 10 is positioned in sequence adjacent to the mixing system 120. For example, the track system 132 may include a motorized track (not shown), whereby the consumable 10 may be suspended on the track 132, and the consumable 10 may be moved along the track 132 by the motorized track.

[0096] The processing station 110 may also include a second automated ("output") conveying system 140, which is configured to remove the fourth consumable 10-4 from the mixing system 120 once the fourth consumable 10-4 is filled with the resulting mixture of the first reagent and the second reagent. The (second) conveying system 140 can remove other consumables 10 from the mixing system 120, such as an empty first consumable 10-1 and an empty second consumable 10-2. Similar to the (first) "input" conveying system 130, the (second) "output" conveying system 140 may include a track system 142, which includes one or more tracks, and the consumable 10 (e.g., the fourth consumable 10-4) is configured to move along the one or more tracks. The conveying system 140 may include a device for moving (not shown) consumables 10 along the track 142 so as to position the consumables 10 adjacent to the mixing system 120 in sequence. As with the (first) conveyor system 130 , the track 142 may include a motorized track (not shown), whereby the consumables 10 may be suspended on the track 142 and the consumables 10 may be moved along the track 142 via the motorized track.

[0097] The track 142 of the conveyor system 140 may be contained within a refrigeration tunnel / section to maintain the temperature of the output consumables 10 - 4 at approximately 4 degrees.

[0098] The processing station 110 may also include a storage portion 190 configured to accommodate a plurality of mixed consumables 10-3. The storage portion 190 may have a first portion 192 configured to store unused mixed consumables 10-3 and a second portion 194 configured to store used mixed consumables 10-3. Figures 2 to 4 An example of the storage portion 290 is described in more detail.

[0099] By providing an input delivery system 130 and an output delivery system 140, each consumable 10 can be positioned adjacent to the mixing section 120, wherein fluid connections between the consumables 10 can be operated and reagents can be delivered. In other words, the delivery systems 130, 140 (also referred to as "carousels") are able to quickly manage the inflow and outflow of consumables 10. This rapid management allows a large number of continuous fluid connections between the consumables 10 and the mixing system 120 via their respective tubes 11 without collisions or congestion in the system 100.

[0100] The system 100 includes an automated device 160 for operating a closed fluid connection between two consumables 10. The automated device 160 for operating can form a closed fluid connection by producing a (sterile) tube weld between the respective flexible tubes 11 of the two consumables 10. In other words, the automated device 160 for operating can include an automated tube welding device or an automated "tube welder" 160.

[0101] As used herein, the term "tube welder" 160 refers to any device configured to join (i.e., weld) a first tube to a second such tube (preferably at their free ends) to provide a sterile (and preferably closed) fluid connection between the tubes. The weld formed between the two tubes is preferably a sterile weld.

[0102] In short, the automated tube welder 160 may include a first clamping unit and a second clamping unit. Each clamping unit may include a pair of jaws movable between an open position and a closed position, the open position being used to receive a flexible tube between the jaws, and the closed position being used to clamp 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 preventing any fluid from flowing through. The clamping unit may be operated to grasp the tube without clamping them closed, which may enable the tube to be engaged and positioned without inhibiting fluid flow. 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 may be heated and moved to intersect the clamped portions 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. 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 is moved to position each tube of the upstream portion adjacent to each other. The downstream portion may be discarded. Once the blades are removed, the upstream portions can be pressed into each other, thereby welding the tubes together to form a single tube. The joint can be referred to as a butt weld. At this stage, the joint between the tubes can remain clamped closed; a clamp release mechanism can be operated to remove the clamped portion, thereby establishing a fluid path through each connected tube. In addition, a quality control (QC) mechanism can be provided to verify the integrity of each weld. The tube welder 160 allows a closed connection to be quickly formed between the tubes 11. The system 100 may include an additional tube welder 160, which may be particularly advantageous if tube welding is a rate limiting step.

[0103] The automated device 160 for operation may further include a device for engaging and / or positioning the flexible tube 11. For example, the system 100 may include at least one robotic arm 162 having an end effector for grasping the tube 11. For example, the device 160 for operation may include an end effector on a robotic arm 162 configured as a tube welder, wherein the clamping unit of the tube welder 160 is configured to grasp the tube 11 without clamping them closed, thereby allowing the tube 11 to be positioned. In this way, the robotic arm 162 can move to engage a first tube 11 connected to the first consumable 10 and a second tube 11 connected to the second consumable 10, and then produce a tube weld therebetween. Alternatively, the device 160 for operation may include a static tube welder located on the processing station 110, whereby the robotic arm with the gripping unit can engage and position the tube 11 into the static tube welder 160.

[0104] The system 100 includes an automated device 170 for conveying a reagent between two fluidically connected consumables 10. The automated device 170 for conveying may be arranged to convey a reagent between two fluidically connected consumables 10 via their respective flexible tubes 11 once the flexible tubes 11 are welded together to form a fluid connection. The automated device 170 for conveying may include a pumping device 170 configured to apply a pumping action to the flexible tube, preferably applying a peristaltic pumping action by a peristaltic pumping mechanism. For example, the system 100 may include a peristaltic pump 170.

[0105] As used herein, the term "peristaltic pump" may refer to a rotary peristaltic pump or a linear peristaltic pump. A peristaltic pump may be configured to compress a portion of the flexible tube 11 and then translate the compressed portion along the length of the tube 11 in a pumping direction, thereby forcing fluid through the tube 11.

[0106] Advantageously, the peristaltic pump 170 can allow fluid to be pumped quickly through the tube 11 with minimal wear and tear on the tube 11 and minimal potential for contamination. In addition, the pumping action of the peristaltic pump 170 is gentle on the cells. The peristaltic pump 170 can be configured as an end effector of a robotic arm 172. The end effector and / or robotic arm 172 can be the same as the end effector and robotic arm 162 of the device 160 for operating a closed fluid connection. Preferably, the system 100 includes a first robotic arm 162 and a second robotic arm 172, the first robotic arm 162 having an end effector providing the tube welder 160 and the second robotic arm 172 having an end effector providing the peristaltic pump 170. The system 100 can include an additional peristaltic pump 170, which can be particularly advantageous if fluid transfer is a rate limiting step.

[0107] System 100 also includes (not shown) an automated device 180 for sealing a portion of each flexible tube 11, so that one or more reagents in the consumables 10 can be aseptically sealed to be isolated from the surrounding environment before disconnecting the fluid connection between two consumables 10. The device 180 for sealing can be called a "tube sealer". The device 180 for sealing can be arranged on the end effector identical with any one or both of the tube welder 160 and / or the peristaltic pump 170. The device 180 for sealing is preferably an RF sealer, but it can also be a heat sealer of any type that melts the flexible tube 11 to prevent fluid from flowing through. Advantageously, providing a device 180 for sealing can help prevent leakage of the consumables 10. This is particularly important for the output consumables 10-4 that can be stored for a considerable period of time and transported to other places once frozen.

[0108] The system 100 may also include an automated device for disconnecting a fluid connection between two consumables 10. The automated device for disconnecting may be provided by an automated device for sealing 180, preferably an RF sealer. Alternatively, the tube welder 160 may provide a device for disconnecting a fluid connection, such as by using a heated cutting blade. In this way, once the fluid is transferred between the two consumables 10, the device for disconnecting may allow the consumables 10 to be disconnected, thereby allowing them to be transported to a different location for storage or processing.

[0109] System 100 includes an (automatic) device for determining the amount of fluid delivered to or from mixed consumables 10-3, such as the amount of fluid delivered from input consumables 10-1, 10-2 or delivered to output consumables 10-4. For example, the device for determining can determine the weight of the volume of the resulting mixture of the first reagent and the second reagent delivered to the fourth consumable 10-4. The device for determining the amount of the fluid can be a weight sensor and / or can include any combination of a gravity sensor, an ultrasonic sensor, a flow sensor and / or a liquid level sensor. For example, a weight sensor may include a gravity sensor configured to monitor the weight of the output consumable 10-4, thereby determining the weight of the mixture delivered from the mixed consumable 10-3 to the output consumable 10-4.

[0110] Alternatively, or in addition, the weight sensor may include a gravity sensor configured to monitor the weight of the mixed consumable 10-3; the weight sensor may calculate the weight of the fluid delivered to the output consumable 10-4 based on the change in weight of the mixed consumable 10-3 during delivery.

[0111] Alternatively, or in addition, the weight of the mixture in the output consumable 10-4 can be calculated based on the volume of fluid pumped by the automated device 170 for delivering reagents; the volume of the pumped fluid can be determined by a flow sensor, for example in combination with Fig.10 The flow sensor 175 is described. The flow sensor can determine the flow rate by monitoring the speed at which bubbles move through the tube 11. A gravity sensor can be located on a platform of the system 100, wherein the weight sensor determines the weight of the consumable 10 placed on the platform; in particular, the gravity sensor can be located on the mixing zone 122 of the mixing system 120, thereby measuring the weight of the mixed consumable 10-3 placed thereon.

[0112] Alternatively, or in addition, a gravity sensor may be located on the track 142 of the output conveyor system 140 and may measure the weight of the consumable 10 held on the track 142. Optionally, the track 132 of the input conveyor system 130 may also have a gravity sensor.

[0113] Each consumable 10 may include an identification mark, such as a QR code or a barcode. Alternatively, or in addition, an RF tag or an NFC tag may be used. The identification mark may allow each consumable 10 to be uniquely identified and tracked during the filling / finishing operation and during the subsequent storage and distribution stages. The system 100 may have a device for identifying the identification mark on each consumable 10. The device for identifying may include at least one image capture device, which may be located on one or more robotic arms 162, 172. The device for identifying may be a machine vision system.

[0114] System 100 may include one or more sensors configured to measure one or more parameters of consumables 10. For example, one or more sensors may include gravity sensors, ultrasonic sensors, flow sensors and / or liquid level sensors discussed previously, and may include sensors for measuring the temperature of mixed consumables 10-3. One or more sensors may include a camera (not shown) for measuring the mixing progress in mixed consumables 10-3. The camera may be the same camera as the device for identifying the identification mark on each consumable 10 provided, or may be a different camera.

[0115] An exemplary filling / finishing operation performed in the system 100 will now be described. First, a plurality of consumables 10 are loaded into the system 100. For example, at least one first consumable 10-1 and at least one second consumable 10-2 may be loaded onto the input conveying system 130, each consumable containing a respective first reagent and a second reagent. A plurality of empty fourth consumables 10-4 may also be loaded onto the input conveying system 130. At least one third consumable 10-3 may be loaded into the storage portion 190, such as being loaded into the first portion 192. The loading of the consumables 10 may be performed by a human operator, or may be performed by a separate robotic device in a bioprocessing system. When the consumables 10 are loaded into the system 100, the device for identification may scan each of their corresponding identification marks so that each consumable 10 may be identified and tracked throughout the filling / finishing operation.

[0116] The third consumable 10-3 can be moved from the storage portion 190 to the mixing zone 122 of the mixing portion 120, for example, by the end effector of one of the robotic arms 162, 172. The tube welder 160 automatically welds the tube 11 connected to the first consumable 10-1 to the tube 11 connected to the third consumable 10-3. The peristaltic pump 170 automatically pumps a fluid (e.g., a cell material) from the first consumable 10-1 to the third consumable 10-3. The fluid connection between the first consumable 10-1 and the third consumable 10-3 is disconnected, and the corresponding tube 11 is sealed, thereby maintaining a closed system. In a similar manner, the tube welder 160 welds the tube 11 connected to the second consumable 10-2 to the tube 11 connected to the third consumable 10-3. The peristaltic pump 170 pumps a fluid (e.g., a cryoprotectant) from the second consumable 10-2 to the third consumable 10-3. The fluid connection between the second consumable 10 - 2 and the third consumable 10 - 3 is disconnected and the corresponding tubes 11 are sealed, thereby maintaining a closed system.

[0117] It should be understood that the above steps may occur in a different order, and some steps may occur simultaneously. For example, before the tube welder 160 connects the second consumable 10-2 to the third consumable 10-3, the first consumable 10-1 does not need to be disconnected from the third consumable 10-3. In the case where two input consumables 10-1, 10-2 remain connected to the mixed consumable 10-3 during pumping, a valve may be present on the pipe 11 to suppress the backflow of the fluid. In addition, the delivery of the fluid to the second consumable 10-2 can be used to flush any residual fluid (and vice versa) left in the first consumable 10-1. The pumping of the peristaltic pump 170 to the reagent may occur at any time when the corresponding consumable 10 is connected. In addition, the disconnection of the input consumable 10-1, 10-2 and the mixed consumable 10-3 may occur at a later stage in the filling / finishing operation, or may not occur at all; For example, the input consumable 10-1, 10-2 and the mixed consumable 10-3 may be removed from the system 100 to be processed when still connected.

[0118] The third consumable 10-3 can be stirred to mix reagents. This can occur during one or both reagents are pumped into the third consumable 10-3, and / or can occur after both reagents are pumped into the third consumable 10-3. Any device for stirring described previously can be used to achieve stirring, such as a rocking plate and / or a roller. Similarly, the third consumable 10-3 can be cooled using a Peltier device or a cooling plate in a mixing zone 122. Once the first reagent and the second reagent are fully mixed (this can be determined by one or more sensors in the system 100), the pipe welder 160 and the peristaltic pump 170 are repeatedly connected in sequence and conveyed to multiple fourth consumables 10-4.

[0119] More specifically, the tube welder 160 welds the tube 11 connected to the third consumable 10-3 to the tube 11 connected to the fourth consumable 10-4. Then, based on the measurement of the weight sensor and / or the flow sensor, the peristaltic pump 170 pumps a predetermined weight of the mixture from the third consumable 10-3 to the fourth consumable 10-4. Then, the fluid connection between the fourth consumable 10-4 and the third consumable 10-3 is disconnected, and the corresponding tube 11 is sealed, thereby maintaining a closed system.

[0120] Repeat the above steps with multiple additional fourth consumables 10-4 until the mixture in the third consumable 10-3 has been dispensed. The third consumable 10-3 can be moved to the second portion 194 of the storage portion 192, for example, by the end effector of one of the robotic arms 162, 172. Once each fourth consumable 10-4 is filled with the mixture, the fourth consumable 10-4 is removed from the mixing portion 120 using the output conveying system 140. Similarly, the empty first consumable 10-1 and the second consumable 10-2 can be removed from the mixing portion 120 using the output conveying system 140. In this way, 4 to 100 fourth consumables 10-4 can be filled with the mixture contained in the third consumable 10-3 without crowding the consumables 10 near the mixing portion 120 or causing entanglement of the tubes 11.

[0121] Then, the consumables 10 can be unloaded from the system 100. The consumables 10 can be unloaded by a human operator, or can be unloaded using a robotic device in a bioprocessing system. The empty first consumable 10-1 and the second consumable 10-2 can be removed from the output conveying system 140 for processing. The empty third consumable 10-3 can be removed from the second portion 194 of the storage portion 190 for processing. A plurality of filled fourth consumables 10-4 can be transported from the output conveying system 140 to a cryopreservation unit. In the case where the consumables 10 are unloaded by a robotic device, the identification mark on each consumable 10 can allow them to be distinguished by a machine vision system.

[0122] It should be understood that the loading and unloading steps may occur during other steps of the filling / finishing operation. For example, during the distribution of the mixture from the third consumable 10-3 to a plurality of fourth consumables 10-4, empty fourth consumables 10-4 may be added to the input conveying system 130 and removed from the output conveying system 140. Advantageously, this means that the conveying systems 130, 140 do not need to have the capacity to accommodate all consumables 10 at the same time.

[0123] At least one of an automated device 160 for operating fluid connections, an automated device 170 for transporting reagents, and an automated device 180 for sealing may be provided on the processing station 110. Figure 1In the illustrated embodiment, all of the device 160 for operation, the device 170 for conveying, and the device 180 for sealing are arranged on the processing station 110. In particular, the processing station has a base unit 111 divided into a first part 111a and a second part 111b. On the upper surface of the first part 111a, mechanical arms 162, 172 can be installed. The upper surface of the second part 111b can support the mixing system 120 and / or the storage system 190. The housing 115 can be mounted to the second part 111b of the base unit 111 and extend vertically therefrom. The housing 115 can have a portion configured to provide a mixing zone 122 for supporting mixed consumables 10-3. The conveying system 130, 140 can be mounted to the housing 115 laterally. Specifically, the input conveying system 130 may include an input conveyor housing 134, and the track 132 extends from the side of the input conveyor housing 134. The input conveyor housing 134 may have a front portion configured to hold the first input consumable 10-1 and the second input consumable 10-2 when the first input consumable 10-1 and the second input consumable 10-2 are fluidly connected to the mixing consumable 10-3 supported in the mixing zone 122. In other words, the input conveyor system 130 is arranged to position the consumables 10 for engagement by means 160 for operating a fluid connection between each consumable 10 and the mixing system 120.

[0124] Likewise, the output conveyor system 140 may include an output conveyor housing 144 with tracks 142 extending from the sides of the output conveyor housing 144. The output conveyor housing 144 may have a front portion configured to hold at least one of the output consumables 10-4 when the output consumable 10-4 is fluidly connected to the mixing consumable 10-3. In other words, the output conveyor system 140 is arranged to position the consumables 10 for engagement by means 160 for operating a fluid connection between each consumable 10 and the mixing system 120. Figure 1 As shown, three output consumables 10-4 (two full and one empty) are held at the front of the output conveyor housing 144. In this manner, the robotic arms 162, 172 are positioned adjacent to both the mixing consumables 10-3 and the delivery systems 130, 140, thereby allowing closed fluid connections and fluid delivery to be operated between the consumables 10 without requiring a large length of tubing 11.

[0125] Alternatively, in Figures 2 to 4 In the second embodiment of the closed system 200 shown, at least one of the automated device 260 for operating fluid connections, the automated device 270 for transporting reagents, and the automated device 280 for sealing can be arranged on a separate mobile unit 250 that cooperates with the processing station 210 in an automated manner. Figure 1The described closed systems 100 share several features, which will not be described in detail for the sake of brevity. However, in the system 200, the autonomous mobile unit 250 provides all of the means 260 for operation, the means 270 for transport, and the means 280 for sealing. In this way, the mobile unit 250 can also perform other operations within the overall bioprocessing system and can facilitate the loading and / or unloading of consumables 10 to the system 200, such as loading to or unloading from external storage areas, other processing stations, and / or cryopreservation units.

[0126] System 200 also includes a storage portion 290. Although not incorporated Figure 1 Detailed description will be given, but it should be understood that the system 100 of the first embodiment may also include a storage portion 190 similar to the storage portion 290 of the second embodiment. The storage portion 290 is configured to store a plurality of third "mixed" consumables 10-3. The mixed consumables 10-3 may be retained in the device 1, for example in combination with Fig.11a and 11b The device described in 1. Figure 4 As particularly shown in the figure, the storage portion 290 may have a first portion 292 and a second portion 294, wherein the first portion 292 is configured to store a plurality of devices 1 holding unused mixed consumables 10-3, and the second portion 294 is configured to store a plurality of devices 1' holding used mixed consumables 10-3. It should be understood that these portions 292, 294 are interchangeable without affecting the present invention.

[0127] The first part 292 may have a first hatch 293 to allow the hybrid consumable 10-3 to be inserted into the first part 292 and / or removed from the first part 292. For example, a user may load one or more unused hybrid consumables 10-3 into the first hatch 293 before one or more filling / finishing operations occur. The second part 294 may have a second hatch 295 to allow the hybrid consumable 10-3 to be inserted into the second part 294 and / or removed from the second part 294. For example, a user may unload one or more used hybrid consumables 10-3 from the second hatch 295 after completing one or more filling / finishing operations. Alternatively, or in addition, the hybrid consumable 10-3 may be inserted into or removed from the storage portion 290 during the filling / finishing operation. As will be described later in conjunction with FIG. 11, the device 1 may allow consumables to be stacked to be compactly stored in the storage portion 290, and the device 1 may be moved from a closed configuration to an open configuration during the filling / finishing operation.

[0128] Figure 5A third embodiment of a closed system 300 is shown, comprising a processing station 310 and a mobile unit 350. The mobile unit 350 provides a means for manipulation 360, a means for transport 370 and a means for sealing 380 via a first robot 362 and a second robot 372. The robots 362, 372 are mounted to a base unit 352 that is autonomously movable relative to the processing station 310. Alternatively, the robots 362, 372 may be arranged in a manner similar to that of a mobile unit 350. Figure 1 The first embodiment is shown mounted to a processing station 310 .

[0129] In this third embodiment, a plurality of slots 312 are arranged in the processing station 310, each slot being configured to receive and store consumables 10. As shown, the processing station 310 includes ten slots 312, but it should be understood that any (reasonable) number of slots 312 may exist to accommodate any number of consumables 10. It can be seen that the first consumable 10-1 for accommodating the first reagent is maintained in the first slot 312, and the second consumable 10-2 for accommodating the second reagent is maintained in the second slot 312. The processing station 310 also includes a mixing system 320 with a mixing zone 322 for supporting the third "mixed" consumable 10-3. As previously discussed, the mixing system 320 may include a device for stirring and a device for cooling. It can be seen that the fourth "output" consumable 10-4 for receiving a mixture of the first reagent and the second reagent from the mixing system 320 is maintained in the tenth slot 312, but it should be understood that additional output consumables 10-4 may exist in other slots 312. Each tank 312 may have a weight sensor, allowing the amount of fluid in each output consumable 10-4 to be determined.Consumables 10 such as input and output consumables 10-1, 10-2, 10-4 may be held within an apparatus such as the apparatus 50 described in conjunction with FIG.

[0130] In this way, when following the previously discussed method, consumables 10 can be added to and / or removed from the slot 312 when needed. For example, input consumables 10-1, 10-2 and multiple empty output consumables 10-4 can be installed into the slot 312, for example, by a human operator or a robotic device (such as a mobile unit 350). Conceptually, the mobile unit 350 can be considered to provide another form of automated delivery system because it delivers consumables 10 to the slot 312 of the processing station 310. The mixed consumables 10-3 can be installed in the mixing area 322 of the mixing system 320 from the storage portion 390 (not shown) on the processing station 310 or from an external storage area. The mobile unit 350 can then operate the fluid connection and fluid delivery in the manner previously described, and the consumables 10 are added to / removed from the slot 312 when needed. For example, once the reagents are transferred from the input consumables 10-1, 10-2 to the mixing consumables 10-3, the input consumables 10-1, 10-2 can be removed from the slots 312. The filled output consumables 10-4 can be removed from the slots 312 and moved to an external cryopreservation unit. Empty output consumables 10-4 can be added to available slots 312, for example to replace the removed input consumables 10-1, 10-2 and / or filled output consumables 10-4.

[0131] Figure 6a An example of a plurality (e.g., 10) of output consumables 10-4 (only some of which are labeled) is shown, wherein the plurality of output consumables 10-4 are housed within the housing 2. These output consumables 10-4 may be referred to as vials 10-4. Each of the vials 10-4 has a tube 11 (only some of which are labeled) to facilitate welding to other tubes in the closed system 100, 200, 300, such as the tube 11 connected to the mixing consumable 10-3.

[0132] Figure 6b An example of a "cassette" (or "cartridge") frame 3 is shown, which can be used to accommodate multiple output consumables 10-4 in corresponding openings 3-1 (only some of which are marked). In this way, when all output consumables 10-4 have been filled with a mixture from a mixed consumable 10-3, the frame 3 can be moved to a cryopreservation unit, rather than transporting all output consumables 10-4 individually. In addition, by storing the output consumables 10-4 in a single frame 3, only one identification mark may be required to identify all stored output consumables 10-4.

[0133] Figure 7A pipe network 11-1 is shown in which a plurality of (e.g., five) output consumables 10-4 are connected to a single filling portion 11-2. In this way, the pipe welder 160 only needs to form a single connection between the pipe 11 connected to the mixed consumable 10-3 and the filling portion 11-2, which can accelerate the filling / finishing process. Then, the peristaltic pump 170 can deliver the mixture to all pre-connected output consumables 10-4. When each of the output consumables 10-4 receives the mixture of the required weight, the pipe network 11-1 can be sealed. Then, the output consumables 10-4 can be disconnected so that each output consumable 10-4 is only connected to a single pipe 11.

[0134] Now refer to Figure 8 A first workflow for delivering a mixture from a mixing consumable 10-3 to a plurality of output consumables 10-4 is described. In this example, the closed system 100, 200, 300 has a first tool 101 providing a peristaltic pump 170 and a second tool 102 providing a tube welder 160 and a tube sealer 180, however, it will be understood that these may be provided as separate tools. In this example, the first tool 101 may be a static tool and the second tool 102 may be movable, for example, on a robotic arm. The mixing consumable 10-3 has a single tube 11 connected thereto.

[0135] As shown in the figure, the tube welder 160 connects the mixed consumable 10-3 to the first output consumable 10-4a by their respective tubes 11. Then, the peristaltic pump 170 performs the controlled fluid delivery from the mixed consumable 10-3 to the first output consumable 10-4a. Then, the second tool 102 uses the tube sealer 180 to seal the first output consumable 10-4a, and the second output consumable 10-4b is welded to the mixed consumable 10-3 via their respective tubes 11. Then, the process can be repeated so that the fluid is delivered to a plurality of other output consumables 10-4. More specifically, then, the peristaltic pump 170 delivers the mixture to the second output consumable 10-4b. When this occurs, the second tool 102 can be moved to the position of the second output consumable 10-4b ready to be sealed, and the third output consumable 10-4c is welded to the mixed consumable 10-3. The time spent in one cycle of performing this process can be about 30 seconds for pumping, 30 seconds for sealing, and 1 minute for welding. This would therefore allow 30 output consumables 10-4 to be filled in one hour.

[0136] Now refer to Fig. 9Describe the second workflow for conveying a mixture from a mixed consumable 10-3 to a plurality of output consumables 10-4. In this workflow, a tube welder 160 and a pump 170 operate in parallel, allowing more output consumables 10-4 to be filled in one hour. However, since the output consumables 10-4 operate in two different lines (or similar lines) to avoid tying a plurality of tubes 11, the workflow is more complicated. In this example, each system 100, 200, 300 has a first tool 101 providing a peristaltic pump 170 and a tube sealer 180, and a second tool 102 providing a tube welder 160, but it should be understood that the peristaltic pump 170 and the tube sealer 180 can be arranged on separate tools. Mixed consumables 10-3 have a first flexible tube 11a and a second flexible tube 11b connected thereto. The first tube 11a and the second tube 11b can have a pinch valve to prevent fluid from flowing through.

[0137] In the first step, the first tool 101 pumps the fluid through the first tube 11a into the first output consumable 10-4a and seals the first output consumable 10-4a. At the same time, the tube welder 160 welds the second tube 11b to the second output consumable 10-4b. The third output consumable 10-4c and the fourth output consumable 10-4d can enter the position for the subsequent steps.

[0138] In the second step, the second tool 102 having the tube welder 160 moves to the third output consumable 10-4c and welds the first tube 11a to the third output consumable 10-4c. The first tool 101 moves to pump fluid into the second output consumable 10-4b through the second tube 11b and then seals the second output consumable 10-4b.

[0139] In the third step, the second tool 102 having the tube welder 160 moves to the fourth output consumable 10-4d and welds the second tube 11b to the fourth output consumable 10-4d. The first tool 101 moves to pump the fluid into the third output consumable 10-4d through the first tube 11a and then seals the third output consumable 10-4c. The fifth and sixth output consumables (not shown) may enter positions for subsequent steps.

[0140] In the fourth step, the second tool 102 having the tube welder 160 moves to the fifth output consumable and welds the first tube 11a to the fifth output consumable. The first tool 101 moves to pump fluid into the fourth output consumable 10-4d through the second tube 11b and then seals the fourth output consumable 10-4d.

[0141] In order to deliver fluid to a plurality of additional output consumables 10-4, the above steps can be repeated. The time taken to fill one output consumable 104 can be about 30 seconds for movement, and longer for pumping and sealing time and welding time, which can be about one minute. This means that about 40 output consumables 10-4 can be filled in one hour.

[0142] Fig.10 An alternative device 170 for delivering reagents between two fluidically connected consumables 10 is shown. The device 170 for delivering can be applied to any one of the systems 100, 200, 300 described herein. The device 170 for delivering can include a valved air source 173, which is connected to the mixed consumable 10-3 via a sterile air filter 174. The flexible tube 11 connected between each of the mixed consumable 10-3 and a plurality of output consumables 10-4 includes a flow sensor 175. The flow sensor 175 is preferably a disposable medical grade flow sensor 175. Preferably, welding, sealing and / or disconnection occur on the flexible tube 11 between the flow sensor 175 and the output consumable 10-4 (rather than between the mixed consumable 10-3 and the flow sensor 175).

[0143] Advantageously, the flow sensor 175 allows a precise volume of fluid to be delivered to each output consumable 10-4. In this way, air can be pumped into the mixing consumable 10-3 through the valved air source 173, so that the mixture in the mixing consumable 10-3 is forced to be discharged into the output consumable 10-4 through the flexible tube 11 due to the increase in pressure. It should be understood that pumping air through the sterile air filter 174 meets the requirements of a functionally closed system, which is considered sufficient to prevent contamination between the contents of the consumable 10 and the surrounding environment.

[0144] Now refer to Fig.11a and 11b An apparatus 1 for holding a consumable 10 is described. The apparatus 50 is configured to hold a consumable 10, which is fluidly connected to at least one flexible tube 11. The apparatus 1 includes a structure 20 ("first portion") for holding the consumable 10. The structure 20 may have a longitudinal axis with a first end 20a and a second end 20b.

[0145] The structure 20 may be configured as a tray 20. As such, the tray 20 may define a recess 21 shaped to receive therein the consumable product 10. The tray comprises a pair of opposing side walls 23a, 23c and at least one end wall 23b which together generally define the recess 21, which here is generally rectangular.

[0146] The recess 21 is desirably of comparable size to the consumable 10 so that the consumable 10 fits tightly into the recess 21, thereby holding the consumable 10 in place. This reduces the flexibility of the consumable 10 by holding the consumable 10 in a given shape.

[0147] The tray 20 may be rigid and may be made of any suitable material, such as plastic or metal. In other examples, the tray 20 may include a material that has a certain degree of natural flex, such as a material with elastic properties. In this way, the consumables 10 may be forced into the recesses 21 by slightly stretching one or more sides of the tray 20 during insertion. Once released, the sides of the tray 20 tighten back to their original shape as the consumables 10 are inserted, thereby securing the consumables 10.

[0148] In an alternative embodiment, the tray 20 may include a rectangular plate with a hole through its center, thereby forming an "open" structure. The structure 20 may also include at least one clamp configured to secure the consumables 10 to the plate. At least one clamp may be located on the structure so as to hold the consumables 10 against gravity. When there is more than one clamp, the clamps may be located on more than one side of the structure 20. This may allow the device 1 to be positioned in different orientations while still holding the consumables 10 in place and minimizing changes in their shape.

[0149] The device 1 includes a cover 30 ("second portion") configured to cover the consumables to secure them within the recess 21 of the tray and further to hold the flexible tube 11 connected to the consumables 10. The cover 30 may include a frame 40 having a plurality of tube holding elements 41 arranged to hold the flexible tube 11 at a plurality of positions along a predetermined path. The frame 40 may be configured as a grid comprising a first set of parallel bars that cross (or intersect) a second set of parallel bars at recurring intervals.

[0150] Since each tube holding element 41 is located at an intermediate position on the grid 40, such as at the midpoint of two intersections, the predetermined path followed by the tube 11 can be a curved (e.g., serpentine) path as shown. This is advantageous because it allows long tubes to be held by the apparatus 1 in a compact arrangement, avoiding entanglement of the tubes 11 with each other and with other components in the bioprocessing system or processing station 110 or other tubes 11. This further allows the tubes 11 to be long, which is ideal for tube welding because it allows many connections and disconnections to be made at different locations along the length of the tube 11.

[0151] The tube 11 may be secured to each of the plurality of tube retaining elements 41 by exerting a force on the tube 11 to push the tube 11 into the tube retaining element 41, so that the tube retaining element 41 secures the tube 11 in a given position. Alternatively, the tube retaining element 41 may include any suitable means for coupling a portion of the tube 11 to the frame 40, such as a hook or clasp. The portion of the tube 11 retained by the tube retaining element 41 may be permanently retained or may be removably secured.

[0152] The cover 30 may be fixed at the first end 20a of the tray 20. The width dimension of the cover 30 may be smaller than the width dimension of the tray 20, so that the tray 20 may receive a portion of the cover 30 through the third recess on its upper surface. This provides an overlap of the opposing side walls 23a, 23c of the tray 20 and the opposing side walls 31a, 31c of the frame 40. In this way, each side wall 23a, 23c of the tray 20 may be attached to the corresponding side wall 31a, 31c of the frame 40.

[0153] A second recess 24 (e.g., a gap or slot) is provided in the side of the cover 30 attached to the first end 20a of the tray 20, and the tube 11 can pass through the second recess 24. The second recess 24 is preferably aligned with the portion of the consumable 10 connected to the flexible tube 11. When the consumable 10 includes more than one tube 11, there may be more than one such second recess 24 on the side of the cover 30.

[0154] Preferably, the lid 30 is hingedly attached to the tray 20 for hinged movement between an open configuration and a closed configuration. Fig.11a An open configuration is shown in which the longitudinal axis of the tray 20 is aligned with the longitudinal axis of the lid 30, such that the lid 30 lies in a plane parallel to the tray 20. In other words, in the open configuration, the device 1 can provide a generally flat panel. Fig.11b , the device 1 is shown after the lid 30 has been hingedly moved to a closed configuration in which the lid 30 has been rotated about the first end 20a of the tray 20 to fold inwardly over the upper surface of the tray 20.

[0155] The lid 30 may be attached to the first end 20a of the tray 20 using a pair of screws 22 located on opposite sides. Each screw 22 may be inserted perpendicularly to the longitudinal axis of the tray 20 through one of the side walls 23a, 23c of the tray 20 and through one of the corresponding side walls 31a, 31c of the frame 40 so as to hingedly connect the tray 20 and the lid 30 to each other. The tray 20 and the lid 30 may pivot about the screws 22 to hingedly move between an open configuration and a closed configuration. The lid 30 may be fixed to the tray 20 to maintain the device 1 in the closed configuration.

[0156] In other examples, the lid 30 can be hinged to the tray 20 by other means. This can include at least one of a butt hinge, a ball bearing hinge, a piano hinge, and a strap hinge. In these examples, the connection means can be substantially located at the center of the first end 20a of the tray 20, or alternatively located on the opposite side of the first end 20a of the tray 20. Alternatively, the lid 30 can slide relative to the tray 20, for example parallel to the longitudinal axis of the tray 20.

[0157] Now refer to Fig.12a and 12b Another device 50 for holding a consumable 10 is described. The device 50 is configured to hold a consumable 10, which is fluidically connected to at least one flexible tube 11. Fig.12a In the example shown, the consumables 10 are connected to two flexible tubes 11. The device 50 includes a housing 70 configured to house the consumables 10; in other words, the housing 70 provides a first portion of the device 50 for holding the consumables 10. The device 50 may also provide insulation and / or thermal conduction to the consumables 10 so that the temperature of each consumable 10 can be adjusted individually.

[0158] 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., a first side wall 73a and a second side wall 73c) and at least one end wall 73b, thereby forming a cubic shape. The housing 70 may have a longitudinal axis with a first end 70a and a second end 70b.

[0159] The housing 70 may include a tray 70 having a cavity 71 shaped to receive the consumable 10 therein. The upper surface of the housing 70 may be a removable cover 2 that substantially encloses the consumable 10 within the cavity 71; in this manner, the consumable 10 may be conveniently added to and / or removed from the device 50. Furthermore, this means that the device 50 has a rigid outer surface that protects the consumable 10 and enables the device 50 to be securely inserted into the slot 312 in the processing station 310 of the closed system 300.

[0160] Preferably, the cavity 71 has a size comparable to that of the consumable 10, so that the consumable 10 fits tightly into the cavity 71, thereby keeping the consumable 10 in place. This reduces the flexibility of the consumable 10 by keeping the consumable 10 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 some flexibility, such as any material with elastic properties. In this way, by slightly stretching the cavity 71 when inserting, the consumable 10 can be forced into the cavity 71. Once the consumable 10 is inserted, the housing 70 will tighten back to its original shape, thereby fixing the consumable 10. Advantageously, using the device 50 to accommodate the consumable 10 including the bag can prevent the bag from expanding outward when it is full. The housing 70 can also include an external insulation layer and a path for internal cold air flow, so that the consumable 10 contained in the housing 70 can be maintained at a specified temperature. A thermistor (not shown) can also be embedded in the housing 70 to monitor the temperature.

[0161] The housing 70 may include at least one clamp 75 to hold the consumable 10 in the cavity 71. In this example, the housing 70 has a clamp 75 in the cavity 71 toward the first end 70a of the housing 70. The clamp 75 may be a tab or a hook. The consumable 10 may be mounted through a hanging hole provided in the bag of the consumable 10.

[0162] 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 attached to the first side wall 73a. The handle 76 may allow the device 50 to be operated and moved by a human operator and / or a robotic device such as a robotic arm 162, 172. For example, the handle 76 may allow the device 50 to be carried, installed, and / or removed from a slot 312 in a processing station 310 of a closed system 300 described herein.

[0163] One or more ribs 78 may be disposed around the perimeter of the housing 70, extending between the upper and lower surfaces of the housing 70. An identification mark, such as a barcode, QR code, or NFC code, may be disposed on the device 50 to allow a machine vision system to identify the device 50. For example, when the device 50 is inserted into the slot 312 of the processing station 300, the device 50 may be automatically identified.

[0164] The housing 70 may include at least one recess 74 and a housing end (e.g., second end 70b) through which the tube 11 may pass. The recess 74 is preferably aligned with the portion of the consumable 10 connected to the flexible tube 11. When the consumable 10 is fluidically connected to more than one tube 11, there may be multiple recesses 74 on the housing 70.

[0165] The device 50 includes a second portion 80 configured to hold the flexible tube 11 connected to the consumable 10. The second portion 80 may extend from the second end 70b of the housing 70 and is preferably located adjacent to the recess 74. The second portion 80 may include a plurality of tube retaining elements 81 (e.g., tube clamps) to hold the flexible tube 11 at a plurality of positions along a predetermined path. In this example, the second portion 80 has a pair of tube retaining elements 81 that are spaced apart so that a portion of the tube 11 can be held between them in a substantially taut manner to facilitate engagement by a robotic device. In this way, the robotic device can engage the tube 11 at a position between a pair of tube retaining elements 81.

[0166] The tube 11 can be fixed to each tube holding element 81 by exerting a force on the tube 11 to push the tube 11 into the tube holding element 81, so that the tube holding element 81 fixes the tube 11 in a given position. Alternatively, the tube holding element 81 may include any suitable means for connecting a portion of the tube 11 to the second portion 80, such as a hook or a clasp. The portion of the tube 11 held by the tube holding element 81 may be permanently held or may be removably fixed.

[0167] The device 50 may include means 77 for cooling the consumables 10 held within the housing 70. In this example, the means 77 for cooling is at least one air port 77 (or "air duct") in the first portion 70 and / or the second portion 80 of the device 50; in this way, cool air can be supplied to the at least one air port 77 to cool the consumables 10. Specifically, the device 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 to allow air to flow out / into the housing 70.

[0168] 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, nor to any details shown in the accompanying drawings, not described in detail herein, or not defined in the claims. In fact, these redundant features may be removed from the accompanying drawings without impairing the present invention. In addition, by considering this specification, other and more embodiments of the present invention will be apparent to those skilled in the art, and may be designed without departing from the basic scope of the present invention, which is determined by the appended claims.

Claims

1. A closed system for mixing fluids for use in a biological treatment system, comprising: an automated device for operating a tube weld between a first tube fluidly connected to a first consumable and another tube fluidly connected to a mixing consumable, the tube weld forming a closed fluid connection between the first consumable and the mixing consumable; an automated device for delivering a first fluid contained in the first consumable to the mixed consumable via the fluid connection; as well as an automated device for determining an amount of fluid delivered to or from the mixed consumable; Wherein, the system is further configured to operate a pipe weld between a second pipe fluidly connected to a second consumable and another pipe fluidly connected to the mixed consumable, and to transport a second fluid between the second pipe and the other pipe to mix with the first fluid in the mixed consumable.

2. The system according to claim 1, wherein: The system is further configured to operate a pipe weld between the other pipe fluidly connected to the mixing consumable and another pipe fluidly connected to an output consumable, and to deliver at least a portion of a mixture of the first fluid and the second fluid contained in the mixing consumable to the output consumable.

3. The system according to claim 1 or 2, further comprising: Automated means for sealing and / or disconnecting each tube once fluid transfer to or from the mixing consumable is complete.

4. A system according to any preceding claim, wherein: The system comprises an automated processing station, more preferably comprises a stand-alone automated processing station.

5. The system according to claim 4, wherein: At least one of the automated device for operating a pipe weld, the automated device for conveying a fluid, and the automated device for sealing is disposed on the processing station.

6. The system according to claim 4, wherein: At least one of the automated device for operating a pipe weld, the automated device for conveying a fluid, and the automated device for sealing is disposed on a separate mobile unit configured to perform automated cooperation with the processing station.

7. A system according to any preceding claim, wherein: At least one of the automated apparatus for operating a pipe weld, the automated apparatus for conveying a fluid, and the automated apparatus for sealing comprises a robotic device, such as a robotic arm having an end effector configured to perform one or more operations.

8. A system according to any preceding claim, wherein: The automated means for conveying comprise pumping means configured to apply a pumping action, preferably a peristaltic pumping action, to the flexible tube.

9. A system according to any preceding claim, further comprising: An automated device for mixing the first fluid and the second fluid in the mixing consumable.

10. The system according to claim 9, wherein: The means for mixing includes an automated mixing system having a mixing zone in which the mixing consumable is positioned to receive the first fluid and the second fluid from the first consumable and the second consumable, respectively.

11. The system according to claim 10, wherein: The mixing system comprises means for agitating a mixture of the contents of the first consumable and the second consumable.

12. A system according to any one of claims 9 to 11, wherein: The mixing system comprises means for controlling the temperature of the mixing consumable, such as a Peltier device or plate configured to cool the mixing consumable located in the mixing zone.

13. A system according to any one of claims 4 to 12, wherein: The processing station comprises a plurality of slots configured to hold the first consumable, the second consumable and the output consumable, preferably wherein: The slot is disposed adjacent the mixing system to facilitate operation of the first consumable, the second consumable, and tube welds between the output consumable and the mixing consumable.

14. The system of claim 13 when dependent on claim 6, wherein: The moving unit is configured to transport at least one of the first consumable and the second consumable to the plurality of tanks to facilitate supplying at least one of the first fluid or the second fluid to the mixing system.

15. A system according to any one of claims 4 to 14, wherein: The processing station includes an automated delivery system configured to deliver at least one of the first consumable and the second consumable to the mixing system to supply at least one of the first fluid or the second fluid to the mixing system.

16. The system of claim 15, wherein: The automated delivery system is further configured to deliver both the first consumable and the second consumable to the mixing system to supply both the first fluid and the second fluid to the mixing system; the system also includes an automated delivery system configured to remove the output consumable from the mixing system once the output consumable is filled with the resulting mixture of the first fluid and the second fluid.

17. The system according to claim 15 or 16, wherein: The or each automated conveying system is arranged to position said consumables for engagement by means for operating a tube weld between each consumable and said mixing system.

18. A system according to any one of claims 15 to 17, wherein: The conveying system includes a motorized track device, in which each of the consumables is suspended on a track, and each of the consumables moves along the track via the motorized track.

19. A system according to any preceding claim, further comprising: Means for identifying identification markings on at least one consumable item.

20. A system according to any preceding claim, further comprising: One or more sensors configured to measure one or more parameters of each of the consumables.

21. A method of mixing fluids for bioprocessing comprising mixing two or more fluids using a closed system according to any one of the preceding claims.

22. An automated method for mixing fluids in a closed system of a bioprocessing system, the method comprising: mixing a first fluid contained in a first consumable and a second fluid contained in a second consumable within a mixing consumable, and thereafter filling an output consumable with the resulting mixture of the first fluid and the second fluid, wherein each consumable comprises a flexible tube arranged to provide a fluid passage for one or more fluids contained in the consumables; operating a pipe weld between two of said consumables to convey a fluid therebetween; determining a weight of a volume of a resulting mixture of the first fluid and the second fluid delivered to the output consumable; and A portion of each flexible tube is sealed so that one or more fluids in the consumables are isolated from the surrounding environment before the fluid connection between the two consumables is disconnected.

23. The method of claim 22, wherein at least one of the mixing, manipulating, determining, and sealing steps is automated.

24. An apparatus for holding consumables for an automated bioprocessing system, the consumables having at least one flexible tube fluidically connected to the consumables, the apparatus comprising: A first part, for holding the consumables; as well as a second portion configured to retain the flexible tube; Wherein the second portion is configured to at least partially retain the flexible tube along a predetermined path.

25. The apparatus of claim 24, wherein: The first part includes: a tray having a cavity shaped to receive the consumable product therein; A removable cover is arranged to enclose the consumable product within the cavity.

26. The apparatus according to claim 24 or 25, further comprising: Means for engaging to facilitate operation of the device, said means being preferably provided on said first part of the device.

27. The apparatus according to any one of claims 24 to 26, further comprising: Identification markings to facilitate identification of consumables held within the device.

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