Automation device

Abstract

An automated apparatus for joining a first tube to another such tube, thereby forming a fluid pathway therethrough, includes means for engaging the tube and moving the tube to one or more locations to be manipulated, means for clamping a portion of the tube, thereby forming a pinched portion of the tube such that the tube is fluid-sealed upstream of the pinched portion, means for removing an end section of the tube downstream of the pinched portion, thereby forming a new end of the tube within the pinched portion that was not previously in contact with another such tube, and means for joining the pinched portion at the new end of the tube with a corresponding pinched portion of another such tube, the apparatus configured as an end effector for a robotic device.

Description

[Technical field]

[0001] The present invention relates to an automated apparatus that can be used, for example, to manipulate flexible tubing to facilitate fluid transfer between biological samples in an automated bioprocessing system used to perform automated cell therapy. In a preferred embodiment, the present invention relates to an automated apparatus that can be configured as an end effector for a robotic device. [Background technology]

[0002] An increasing number of therapeutics use cells rather than small molecules as a starting point. Approaches to manufacturing these products are rapidly evolving to keep up with new therapies that are constantly emerging. In recent years, we have seen an increase in the use of many new types of cell therapy. One type is autologous cell therapy.

[0003] Autologous cell therapy is a promising type of therapy that has great clinical and commercial potential, ranging from treating cancer to repairing genetic defects. These therapies involve harvesting cells from a patient, manipulating the cells over days to weeks, and reintroducing the cells into the patient's body to produce a therapeutic effect. The steps performed during autologous cell therapy are often complex; for example, a typical CAR-T process may involve a series of steps starting with cryopreserved leukopacks, thawing, washing to remove DMSO, concentrating T cells, activation, transduction, expansion, concentration, filling the formulation into IV bags, and cryopreservation, along with several other intermediate washing steps. To date, these processes have typically been performed in expensive, labor-intensive, manual processes in five-class clean rooms or isolators.

[0004] Due to the complexity of bioprocessing, it is desirable to automate (cell therapy) processes while maintaining a closed system that removes the need to perform steps in such advanced clean rooms. A closed system is one in which the process is not exposed to the surrounding environment and therefore cannot have ingress of contaminants from the environment or cross-contamination from other processes being performed simultaneously. Some systems have attempted to provide a solution to this, but involve complex consumable elements that connect the sample to all other required processing stations, e.g., via tubing fluidly connected to the consumable element, and pumps and valve adjustments to allow the steps to be performed in a specific order. However, these consumable elements are very complex to manufacture and install, and as a result can be relatively expensive and unreliable. Each consumable element must be individually tailored to the process being performed, making the system less flexible to changes and expensive to adapt to new processes. Furthermore, these systems typically only allow one consumable element to be run / operated at a time, making the bioprocess expensive and less space-efficient to scale up for use with multiple patients. Often, systems still cannot perform all the steps required for a complete bioprocessing method, and instead multiple isolated units may be operated in sequence, meaning additional labor and expertise is required to transfer cells (e.g., patient samples) between the isolated units, which also creates an additional risk of cross-contamination, and there is no easy way to verify that contamination has not occurred.

[0005] One method of forming a sterile connection between tubes is tube welding, a process that is performed manually using semi-automated equipment. A sterile tube welder allows the ends to be closed between two tubes to make the connection without exposing the contents of either tube to the environment, and is the only widely accepted means of reusably creating (e.g., reconstructing) a closed connection within a single system. In a typical tube welding device, an operator first inserts and clamps two tubes into the device. The welder then cuts the tubes, aligns them so that they are attached to each other (e.g., by translating or rotating the fasteners), and presses them together so that the tubes are welded. The operator then loosens the tubes, inspects the connection, and manually clamps the tubes to remove any kinks created by the fasteners, thereby allowing fluid to flow through the joint. Overall, the welding process can take between four and seven minutes of operator time.

[0006] However, existing tube welding systems have several drawbacks. These systems are typically very complex, large and heavy, and it is common practice in manufacturing facilities to mount the tube welding machine on a dolly that can be moved to the manufacturing process. Having to transport the tubing to the dolly-mounted tube welding machine often results in a large portion of the tube being discarded by the user during each tube welding operation. Furthermore, conventional tube welding systems are not additionally configured to cut a single tube and reliably reseal the separated tube ends later, which means that the contents cannot be kept sealed when the tube is cut, and separate equipment (RF tube sealer) is typically used for this function.

[0007] In addition, in an automated cell therapy process, hundreds of welds must be performed for each therapy without any of them failing. Even if the success rate for an individual weld is 99%, for example, if performed in series, the success rate for a hundred welds is only 33%. Therefore, to achieve an acceptable 99.9% success rate in such a process, the success rate of the individual welds must be 99.999%. One option is to try to minimize the number of tube welding operations required by the process, and indeed, according to the ISO 23565 standard for the design of equipment systems for cell therapy manufacturing, "equipment should be designed and utilized such that the number of in-process connections, such as tube welds, is minimized to reduce the risk of contamination." However, this approach only avoids the problem of unreliable tube welds and therefore does not promote a flexible, autonomous bioprocessing system capable of performing many therapies, and preferably multiple therapies simultaneously.

[0008] Therefore, automating a manual tube welding system may at first appear impractical. In particular, precise manual operations are required to properly insert the long flexible tube into the welder, to properly remove the tube from the welder, and to remove kinks in the tube after welding. Existing systems also require a visual inspection by the operator after each weld is made to ensure the weld is successful; existing tube welding machines typically remove the tube from the welder to inspect it, which can lead to contamination of the environment or the contents of the tube if the weld is not successful.

[0009] Automating these steps in a manner that would be reliable enough for use in cell therapy processes that involve multiple connections and disconnections is a long way off, and indeed the problems discussed above are particularly evident in systems where reliability and contamination issues are critical, such as bioprocessing systems. Summary of the Invention [Problem to be solved by the invention]

[0010] Thus, there is a need for a reliable method of forming sterile tube welds to enable sealed transfer of fluids and cellular materials, ideally one that can maintain sterility / prevent contamination of consumables and patient samples regardless of whether operations are performed in a sterile or non-sterile atmosphere in such systems. [Means for solving the problem]

[0011] According to a first aspect, an automated device for manipulating a flexible tube (e.g. for joining a first tube to a second / another such tube and thereby forming a fluid pathway therethrough) is disclosed herein, the automated device comprising: means for engaging the (first) tube and moving the (first) tube to one or more positions to be manipulated; means for clamping a portion of the (first) tube, thereby forming a pinched portion of the (first) tube such that the (first) tube is fluid-sealed upstream of the pinched portion; and means for removing an end section of the (first) tube downstream of the pinched portion, thereby forming a new end of the (first) tube within the pinched portion that was not previously in contact with another such (or second) tube.

[0012] Each tube can be fluidly connected to a "consumable" including, for example, a cell sample (of cellular material), a reagent or a fluid, whereby each consumable is fluidly connected to an "upstream" end of the tube, which provides a fluid conduit to a "downstream" (opposite) end of the tube, which is fluidly sealed by a pinched portion when not connected to another such (second) tube. As referred to herein, a "consumable" preferably means a "container" of said cell sample, reagent or fluid, which is intended to be processed, for example, in a cell therapy process using the device. As used herein, the term "engage" preferably refers to gripping the tube without the need for an operator to precisely position the tube within the device.

[0013] In a preferred embodiment, the device can be configured as an automated end effector, more preferably as an end effector for a robotic device. Advantageously, by configuring the device in this manner as an end effector, the device can move toward the tube to be engaged and engage the tubing near the consumable to be welded, reducing the need for long flexible tubing lengths. This significantly reduces the automation challenge and benefits the entire bioprocessing system in terms of reduced dead volume contained within the tubing. Preferably, the end effector is configured to receive power from an external power source via an electrical coupling therebetween. By providing an external power source, the size and weight of the automated device and the end effector can be reduced.

[0014] As used herein, the term "robotic device" preferably means an automated machine or device programmed to perform a specific mechanical function, and the term preferably includes a robot, a collaborative robot (cobot), an xy or Cartesian coordinate robot, a robotic arm, and one or more actuators, which may also include one or more robotic end effectors, and will typically also include one or more sensors, a microprocessor, and a power source. The term "end effector" preferably means a tool, manipulator, or similar device that may form part of any type of "robotic device," such as those described above.

[0015] The apparatus may further comprise means for joining the pinched portion at the new end of the (first) tube with a corresponding pinched portion (e.g. at the corresponding new end) of a second tube / another such tube. The two tubes (i.e. the respective ends) are joined together, preferably forming a butt weld between the two tubes. The means for joining may be configured to force the pinched portion of the first tube into the pinched portion of the second tube, thereby forming the butt weld.

[0016] Preferably, the means for removing the end section of the tube comprises a heated cutting element configured to cut said pinched portion of the (or each) tube, thereby melting said pinched portion at the new end of the tube and forming a butt weld between the ends of the tube when joined together while still melted (i.e. before the material of the tube cools and solidifies). The cutting element may comprise a blade, ribbon, or wire configured to be heated. Preferably, the cutting element is a blade comprising a copper wafer. The heated cutting element may be configured to cut and / or melt the tube for a predetermined period of time and / or may have a predetermined thermal profile. If a heated cutting element is used to cut a tube (without subsequently reconnecting to another such tube), the heated cutting element may be configured to cut and / or melt the tube for a different predetermined period of time and / or may use a different predetermined thermal profile. In other words, the thermal profile for the connection of two tubes may be different from the thermal profile for the cutting of two tubes.

[0017] Preferably, the means for joining the pinched portions is configured to translate the (or each) tube in a direction coaxial with the longitudinal length of the (or each) tube. In this way, the device can engage the tube at one location along its length and clamp the tube at a different location along its length, allowing the length of the end section of the tube to be minimized before removal, thereby reducing the amount of wasted tubing. Furthermore, it may be preferable to engage the tube at a fixed or predetermined location in the space (e.g. where the tube connects to a corresponding container) and then translate the tube until the means for joining reaches the end of the tube, which can increase the reliability of the device in engaging the tube, since it does not have to engage the tube at any location in the space.

[0018] Preferably, the means for clamping a portion of the (first) tube is configured to form a pinched portion of the (first) tube towards an end of the (first) tube In this way, the amount of tubing that is removed can be reduced, thereby reducing the amount of tubing that is wasted.

[0019] Preferably the means for engaging the (first) tube is operable to retain a removed end section of the (first) tube downstream of the pinched portion. Advantageously, this can prevent lengths of discarded downstream tubing from accumulating around the device and thereby interfering with its operation. By retaining the removed end section, the device can be configured to position the end section at a specific, predetermined location.

[0020] Preferably, said means for engaging the (first) tube is configured to align the (first) tube with another such (or second) tube, such that the new ends of each tube, formed by the removal of the end section of each tube, respectively, share a common plane, e.g. the first tube and the second tube are arranged adjacently. Preferably, the first tube and the second tube are arranged such that one of the first tube or the second tube is inverted, e.g. the "downstream" end of the first tube extends towards the "upstream" end of the second tube and vice versa.

[0021] The means for clamping the tube can be further configured to seal the tube. For example, it may be advantageous to provide a seal of the tube during the cutting process (in addition to the seal provided by the heated cutting element). It may be advantageous to seal the tube (preferably the downstream "end" section) during the connection process, such as before the end section is discarded. In addition, if the joint is not successful, the tube can be fully sealed before loosening and rewelding, thereby reducing the risk of contamination. By sealing the tube with the clamping means, the tube can be sealed over a larger area, thereby providing a more robust seal of the tube. The means for clamping can include a heat source that melts the tube once clamped, thereby heat sealing the clamped tube. The heat source may be a resistive element or may be an electromagnetic source, such as an RF source.

[0022] The apparatus may further include a sensor configured to determine whether the first tube and / or the second tube are engaged and / or aligned with the means for engaging the tube. The sensor may include a camera for visually inspecting the engagement and / or alignment of the tube. The sensor may include a mechanical sensor, a pressure sensor, a capacitive sensor, or any suitable sensor or combination of sensors capable of determining the presence and / or position of the tube in the means for engaging.

[0023] Preferably, the apparatus further comprises means for manipulating the tube once joined with said other such tube to release the pinched portion and thereby establish a fluid pathway between the joined tubes, thus allowing fluid to pass through the joined tubes as well, allowing controlled transfer of fluid between corresponding containers.

[0024] The device may maintain engagement with the tube during operation of one or more of the means for engaging the tube, the means for clamping, the means for removing, the means for joining, and / or the means for manipulating the tube to release the pinched portion. Advantageously, the device may join a first tube to a second tube without having to release and re-engage either or both of the tubes. This reduces the risk of the tubes becoming misaligned during any part of the joining operation. For example, by maintaining engagement throughout the process, it may be unnecessary to realign the pinched portion of the tube with the means for manipulating the tube to release the pinched portion.

[0025] More preferably, the means for manipulating the tubes includes an automated pinch-release mechanism configured to press on an edge of the pinched portion of the tubes, thereby releasing the pinched portion and opening the welded tubes, thereby forming a fluid pathway therethrough.

[0026] According to a second aspect, disclosed herein is an apparatus for releasing a pinched portion of a tube, the apparatus including an automated pinch release mechanism configured to press an edge of the pinched portion of the tube, thereby releasing the pinched portion and opening the welded tube, thereby forming a fluid pathway therethrough.

[0027] The term "automated pinch release mechanism" as used herein preferably means a mechanism that can function without any operator intervention, more specifically, the operator is not required to push (directly or indirectly) the pinched portion and preferably does not need to initiate or trigger the pinch release mechanism to release a particular pinched portion. As used herein, "edge of pinched portion" refers to the boundary (or "crease") between two opposing sides of the tube once pinched or flattened by the clamping means. By automating the pinch release mechanism, the entire tube welding operation can be completed fully autonomously. The automated pinch release mechanism can be located on an end effector of a robotic device, which may be the same end effector and robotic device described above, or may be a separate end effector and / or separate robotic device.

[0028] The following optional features may be applied to the apparatus of either the first or second aspect (or both).

[0029] Preferably, the pinch release mechanism is configured to compress the pinched portion of the tube against one or more seats of the means for engaging and moving the tube and the means for clamping a portion of the tube. The seats thus provide a counter force against the tube during use of the pinch release mechanism. Additionally, the seats can maintain alignment of the tube during unpinching of the tube and / or other operation of the device.

[0030] Preferably, the pinch release mechanism includes a first release element and a second release element configured to engage opposite edges of the pinched portions of the tubes at an interface between the new ends of the first and second tubes when joined together, and the first and second release elements are capable of gripping (engaging) the tube when the tube is fully released by the means for engaging the tube.

[0031] The pinch release mechanism may be configured to push against the edge of the pinched portion by moving along a linear path. In this manner, the pinch release mechanism may release the pinched portion without subjecting the tube to shear or twisting forces that may damage the weld. Preferably, the linear path is perpendicular to the direction in which the tube is clamped by the means for clamping the tube.

[0032] Preferably, the apparatus further comprises means for stretching the interface between the new ends of the first and second tubes when joined together (e.g. by applying tension to each tube and slowly pulling them apart) to verify the integrity of the bond, and preferably said means for joining is further configured to provide said means for stretching and thereby perform a quality control or quality assurance (QC) check.

[0033] Preferably, the apparatus further comprises means (e.g. a machine vision system) for inspecting the interface between the new ends of the first tube and another such (or second) tube when joined together, for example to verify the integrity of the joint, thereby performing a quality control or quality assurance (QC) check, said joint being preferably a butt weld. The means for clamping can be configured to keep the clamped tubes closed on at least one side, preferably both sides, of the joint during inspection, thereby maintaining a closed system until the integrity of the joint is verified. The apparatus can be configured to hold the joint in a fixed location relative to the means for clamping during inspection of the joint, thus reducing the risk of damaging the joint before inspection and reducing the risk of fluid migration between the upstream and downstream sections of the tube. The means for inspecting the interface can also provide a sensor configured to determine whether the first tube and / or the second tube are engaged and / or aligned with the means for engaging the tube. Alternatively, separate sensors can be provided for inspecting the interface and for verifying engagement and alignment.

[0034] Preferably, the means for engaging the tube is provided by a tube gripping mechanism including a pair of jaws operable for relative movement between an open configuration for receiving the tube between the pair of jaws and a closed configuration for the tube between the pair of jaws. Means for clamping a portion of the tube may also be provided by the tube gripping mechanism, the closed configuration of the pair of jaws being configured to clamp the tube between the pair of jaws. When the closed configuration of the jaws is used to clamp the tube, a position between the open and closed configurations may be used to engage the tube. Alternatively, the means for clamping may be provided in other ways and / or may be provided by a different gripping mechanism than the means for engaging the tube.

[0035] More preferably, the tube gripping mechanism may include multiple pairs of adjacently arranged gripping elements, each pair including a first gripping element and a second gripping element, and each pair of gripping elements configured to move between the open and closed configurations.

[0036] According to a third aspect, disclosed herein is a tube gripping mechanism including a plurality of adjacently arranged pairs of gripping elements, each pair including a first gripping element and a second gripping element, the first gripping element and the second gripping element operable for relative movement between an open configuration for receiving a tube between the first gripping element and the second gripping element and a closed configuration for engaging and clamping a portion of the tube between the first gripping element and the second gripping element, each pair of gripping elements configured to move between said open and closed configurations.

[0037] As used herein, the terms "gripping" or "gripping" can mean both a light gripping (e.g., for engaging or manipulating a tube) and a tight gripping (e.g., clamping or pinching a tube closed for a welding operation), depending on the context. It will be understood that each pair of gripping elements can be operated in intermediate positions between the open and closed configurations.

[0038] The following optional features may be applied to the device of the first or second aspect (or both) or the arrangement of the third aspect.

[0039] Preferably, the tube gripping mechanism includes a seat which abuts the tube when placed between the opposing pair of gripping elements. In this way, the seat can maintain alignment of the tube when placed on the gripping mechanism. This means that the tube is always engaged and clamped in the same way between the opposing pair of gripping elements, thereby improving the consistency and reliability of the bond between the tubes.

[0040] Preferably, both gripping elements of an opposing pair are configured to move to allow the tube to remain centered throughout its movement between the open and closed configurations, thereby ensuring consistent alignment of the tube when gripped and / or clamped.

[0041] Preferably, at least one of the gripping elements is moved by a corresponding cam. Using a cam to actuate the gripping elements may allow for more reliable and accurate positioning of the gripping elements.

[0042] Preferably, the first pair of gripping elements and the adjacent second pair of gripping elements are spaced to provide a gap for receiving the means for removing the end section of the tube between the first pair of gripping elements and the adjacent second pair of gripping elements, such that there is no need to adjust the gripping elements of the pairs to make space for the means for removing the end section (e.g. a cutting blade).

[0043] Preferably, a first pair of gripping elements is configured to engage a first portion of the end section of the tube before a second pair of gripping elements is configured to engage an adjacent second portion of the end section of the tube, thereby forcing fluid within the tube away from the first portion of the tube and towards the second portion of the tube before the operation of the means for removing the end section of the tube, which is configured to remove a portion of the end section of the tube on the other side of the first pair of gripping elements. Additionally or alternatively, the first pair of gripping elements closer to the gap are configured to clamp the tube before the second pair of gripping elements further from the gap, thereby removing fluid from the clamped portion of the tube prior to the operation of the means for removing the end section of the tube. By removing (or "pumping") the fluid from the clamped portion of the tube in this manner, fluid loss is reduced and the likelihood of the fluid interfering with the welding process is reduced. This increases the reliability of the device or mechanism when creating a wet weld (i.e. a weld between tubes that still contain some liquid).

[0044] Preferably, the gripping mechanism is controllable to clamp different portions of said portion of the tube while releasing other portions of said portion of the tube. For example, the gripping elements of adjacent opposing pairs may be in different intermediate positions between said open and closed configurations such that some portions are gripped (engaged or clamped) and other portions are released. Furthermore, the gripping elements of adjacent opposing pairs may be opened and closed at different times (e.g. in a predetermined sequence). In other words, the gripping elements of multiple opposing pairs may move out of phase with each other. This may be achieved by actuating the gripping elements of each opposing pair with a separate cam, each cam being rotationally offset with respect to the adjacent cam.

[0045] Advantageously, by providing a gripping mechanism that can selectively grip some of the tube sections while releasing other sections, the gripping mechanism can gradually engage the tube and straighten the tube rather than bunch it. Preferably, the gripping mechanism is controllable to hold the tube section between at least one pair of gripping elements in a closed configuration, while at least one different pair of gripping elements is moved to an open configuration to release a portion of said tube section, such that said portion of said tube section is exposed. The device or mechanism can further comprise means for inspecting said released or exposed portion of said tube section. In this way, it is possible to determine whether the weld has been successful while keeping the upstream portion of the tube isolated from the joint, thereby preventing exposure of the contents of the tube to the environment. This also allows inspection of the joint without removing the tube from the device or mechanism, which allows the tube to be immediately re-clamped and re-welded without the need to re-engage the tube.

[0046] Preferably, the means for manipulating the tube to release the pinched portion is configured to compress (e.g. apply a compressive force) the released or exposed portion of the tube. In this manner, it may be possible to release the pinched portion without completely releasing the tube from the device or mechanism and without having to re-engage the tube. As the pinch mechanism can be configured in this manner to always act on the same portion of the weld, this can substantially increase reliability and substantially reduce the risk of the tubing kinking or otherwise shifting prior to release of the pinch.

[0047] Preferably, the pairs of gripping elements of the gripping mechanism are controllable to move the engaged tube in a direction substantially perpendicular to the longitudinal length of the tube relative to the gripping mechanism. In this way, the distance between the first tube and the second tube (e.g., held by the second gripping mechanism) can be changed before and / or after removing the corresponding end sections, which may allow a smaller blade to be used to cut both tubes simultaneously. This may also prevent the tubes from being accidentally welded due to being too close to each other, preferably the first tube is at least 4 mm away from the second tube during welding. In addition, this may reduce the subsequent time it takes to align and join the tubes after the end sections have been removed, which may improve the quality of the weld (e.g., ensuring that the tubes are hot when joined together).

[0048] Preferably, said means for manipulating the tube to release the pinched portion is configured to engage the tube between gaps provided between adjacent gripping elements, for example a gap for receiving said means for removing an end section of the tube therebetween. The means for removing an end section of the tube may also provide the means for manipulating the tube to release the pinched portion, for example where a heated blade is used to remove the end section of the tube, allowing the blade to cool before passing through the gap to release the pinched portion.

[0049] According to a fourth aspect, disclosed herein is an automated and / or robotic system comprising any of the apparatus or mechanisms described herein. The robotic system can include one or more robotic devices.

[0050] Any of the apparatus or mechanisms described herein can be configured as an automated end effector, for example a robotic end effector for a robotic device.

[0051] As used herein, the term "automated system" preferably means a system that is operated and / or controlled by automation, which term preferably includes one or more of the following: a robotic device, a conveyor, one or more actuators configured to engage and / or move containers, or indeed any combination of these features that can move and / or manipulate containers and / or tubes within the system.

[0052] As used herein, the term "bioprocessing" preferably includes cell therapies, such as autologous and allogeneic cell therapies, as well as, for example, vaccines and (small batch) bioprocessing.

[0053] As used herein, the term "sterile connection" preferably refers to a connection in which the contents of each connected container are not exposed to the ambient air or atmosphere. The term "sterile connection" can be equivalently referred to, for example, as a "sealed connection" or a "sterile connection."

[0054] As used herein, the term "fluid" preferably means liquid and / or gas, and may further include materials such as cellular material contained therein.

[0055] It will be understood by one of ordinary skill in the art that any apparatus feature described herein may be provided as a method feature, and vice versa. It will also be understood that specific combinations of the various features described and defined in any embodiment described herein may be independently implemented and / or provided and / or used.

[0056] It will also be understood that the invention has been described herein by way of example only, and modifications of detail may be made within the scope of the invention. Furthermore, as used herein, any "means-plus-function" feature may be alternatively expressed in terms of its corresponding structure.

[0057] One or more embodiments will now be described, by way of example only, with reference to the accompanying drawings. [Brief description of the drawings]

[0058] [Figure 1] FIG. 1 is a schematic diagram of an automated (bioprocessing) system. [Figure 2a] FIG. 1 illustrates one embodiment of an apparatus including a robotic arm with an end effector in accordance with the present invention. [Figure 2b] FIG. 2b is a cutaway (inner view) of the end effector of FIG. 2a. [Figure 3a] 3A-3C are cutaway views of the end effector of FIG. 2 at various stages of manipulating a flexible tube. [Figure 3b]3A-3C are cutaway views of the end effector of FIG. 2 at various stages of manipulating a flexible tube. [Figure 3c] 3A-3C are cutaway views of the end effector of FIG. 2 at various stages of manipulating a flexible tube. [Figure 3d] 3A-3C are cutaway views of the end effector of FIG. 2 at various stages of manipulating a flexible tube. [Figure 3e] 3A-3C are cutaway views of the end effector of FIG. 2 at various stages of manipulating a flexible tube. [Figure 3f] 3A-3C are cutaway views of the end effector of FIG. 2 at various stages of manipulating a flexible tube. [Figure 3g] 3A-3C are cutaway views of the end effector of FIG. 2 at various stages of manipulating a flexible tube. [Figure 3h] 3A-3C are cutaway views of the end effector of FIG. 2 at various stages of manipulating a flexible tube. [Figure 3i] 3A-3C are cutaway views of the end effector of FIG. 2 at various stages of manipulating a flexible tube. [Figure 3j] 3A-3C are cutaway views of the end effector of FIG. 2 at various stages of manipulating a flexible tube. [Figure 3k] 3A-3C are cutaway views of the end effector of FIG. 2 at various stages of manipulating a flexible tube. [Figure 3l] 3A-3C are cutaway views of the end effector of FIG. 2 at various stages of manipulating a flexible tube. [Figure 3m] 3A-3C are cutaway views of the end effector of FIG. 2 at various stages of manipulating a flexible tube. [Figure 4a] FIG. 4 is a cutaway rear view of the end effector of FIG. 3. [Figure 4b] FIG. 1 illustrates a set of cams configured to control multiple jaws of an end effector. [Figure 4c] FIG. 1 illustrates a set of cams configured to control multiple jaws of an end effector. [Figure 5a]4A-4C are schematic diagrams showing gripping elements forming the jaws of the end effector of FIGS. 2 and 3 at various stages of cutting a flexible tube. [Figure 5b] 4A-4C are schematic diagrams showing gripping elements forming the jaws of the end effector of FIGS. 2 and 3 at various stages of cutting a flexible tube. [Figure 5c] 4A-4C are schematic diagrams showing gripping elements forming the jaws of the end effector of FIGS. 2 and 3 at various stages of cutting a flexible tube. [Figure 5d] 4A-4C are schematic diagrams showing gripping elements forming the jaws of the end effector of FIGS. 2 and 3 at various stages of cutting a flexible tube. [Figure 5e] 4A-4C are schematic diagrams showing gripping elements forming the jaws of the end effector of FIGS. 2 and 3 at various stages of cutting a flexible tube. [Figure 5f] 4A-4C are schematic diagrams showing gripping elements forming the jaws of the end effector of FIGS. 2 and 3 at various stages of cutting a flexible tube. [Figure 6a] FIG. 13 is a schematic diagram showing a gripping element of the end effector for moving a tube longitudinally through the end effector. [Figure 6b] FIG. 13 is a schematic diagram showing a gripping element of the end effector for moving a tube longitudinally through the end effector. [Figure 6c] FIG. 13 is a schematic diagram showing a gripping element of the end effector for moving a tube longitudinally through the end effector. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0059] An exemplary bioprocessing system 1 is shown in Figure 1. The system 1 has a series (e.g., "plural") of processing stations 20 configured to perform processing steps for bioprocessing, and an (automation) system for automating (at least part of) the process.

[0060] In this exemplary system 1, processing stations 20 include a thawing station 4, a centrifuge 6, a magnetic cell separator 8, a controller rate freezer 10, and a refrigerator 11, although additional and alternative stations 20 (not shown) for processing may be provided depending on the particular process being performed by system 1.

[0061] The processing stations 20 can include any combination of concentration stations, cryopreservation units, washing stations, cell concentration stations, cell proliferation stations, cell selection stations, stations for determining cell count, cell viability or cell type, or stations for any other suitable processing or analysis steps. The system 1 also has an incubator 12 large enough to contain and culture multiple consumables 13 at a time, including under perfusion.

[0062] For example, the incubator 12 may be capable of storing 20 consumables 13 and may operate at approximately 37° C., although the number of consumables 13 may be selected to meet the needs of the particular bioprocessing to be performed. Each consumable 13 may contain a cell sample, a reagent or a fluid, and each consumable 13 connects to a first "upstream" end of a tube (150, not shown), which first "upstream" end connects to a second "downstream" end of the tube 150, and which second "downstream" end is fluid-sealed when unconnected (or "free"). Thus, as referred to herein, a "consumable" may be in the form of a "container," which may hold, for example, cellular material to be processed in a cell therapy process.

[0063] All of the consumables 13 and reagents may be preloaded into the system 1 before a particular bioprocess begins, although additional reagents may be added throughout the process if required (e.g., on day 7 of a 10 day therapy process). Additional reagents may be required for reactivation of cells or to add additional media to the consumables 13, for example.

[0064] A particular bioprocess can be defined by a bioprocessing workflow, and preferably the system 1 can be configured to perform several bioprocessing workflows. For example, the system 1 can perform the same bioprocessing workflow on multiple patient samples in parallel, or can perform different bioprocessing workflows on multiple patient samples in parallel. Each bioprocessing workflow can use a different subset of the processing stations 20 in the system 1. In a preferred embodiment, the system 1 includes stations 20 that perform enrichment, washing and incubation processes.

[0065] The system 1 includes an automation system configured to place one or more consumables 13 at each of a series of processing stations 20, and to move the consumables 13 between the stations 20. The automation system includes a robotic device 2 capable of moving the consumables 13 between the various stations 20, and can manipulate tubing 150 (e.g., fluid conduits) connecting each of the consumables 13.

[0066] The robotic device 2 can be mounted on rails 18, allowing the robotic device 2 to access all areas of the system 1, such as stations 20. The robotic device 2 can also be mounted on an autonomous mobile robot, such that it can autonomously move around the factory floor to perform tasks, such as sampling from a bioreactor. The robotic device 2 can be configured as a collaborative robot ("cobot"). The robotic device 2 can be, for example, an XY or Cartesian coordinate robot, or a robot on a gantry. The robotic device 2 can have a robotic arm 3 for manipulating consumables 13 and tubes 150, as shown here, or can include a conveyor belt, one or more actuators, or any combination of the above aspects.

[0067] The automated system is configured to manipulate a fluid connection between a first consumable 13 and a separable second consumable, thereby creating a sterile connection that allows for the controlled transfer of fluid or cellular material between the first consumable 13 and the second consumable 13. Here, the robotic device 2 is used to form (or manipulate) a fluid connection between tubing 150, allowing separate consumables 13 to be connected to one another.

[0068] The connection between the two tubes 150 is preferably performed by a device such as a tube welder, which may be located in one of the processing stations 20. The device may be configured as an end effector 100, for example, located on the robot arm 3 and / or on an XY or Cartesian coordinate robot or robot in a gantry. The device (e.g., end effector 100) may be equivalently referred to as a "manipulator" or "tool" or more generally as a "tube connection means". It will be understood that any feature of the tube connection means (e.g., end effector 100) described herein may be implemented as a static tube welding device, which may form part of the bioprocessing system 1 or may be provided as a separate piece of equipment. The connection between the separate tubes 150 is performed aseptically, such that the consumable 13 and the contents of the tubes 150 are never opened or exposed to the ambient air or atmosphere at any stage.

[0069] The fluid connections are also reconfigurable, such that two separate tubes 150, once joined together, can be later disconnected and reconnected to different consumables 13 as many times as necessary to perform the required bioprocessing method. In other words, the automated system is configured to create a sterile connection that can be disconnected after the transfer of fluid or cellular material is completed, and to allow for further such fluid connections to be operated between a first consumable and a separable third consumable. Preferably, a subsequent connection is made at a different location along the tube 150 than the previous connection. As noted above, during both connection and disconnection, the consumables 13 and their respective tubes 150 are never exposed to the ambient air or atmosphere, such that controlled transfer of fluids and / or cellular material occurs only between the consumables 13 that are connected to each other via their respective tubes 150. As a result, it is not strictly required to have a sterile atmosphere around the station 20, the consumables 13, or the robotic device 2, although an enclosure 14 can be provided to prevent access by an operator and / or to provide a sterile atmosphere or otherwise control the environment, for example by controlling temperature, light levels or other conditions.

[0070] The system 1 preferably also has a pumping unit (not shown) configured to pump the fluid along the tube 150 after the robotic device 2 has successfully connected the two consumables 13 via the respective tubes 150. The pumping unit may be located on the robotic arm 3 or may be a static component located at one of the stations 20 where the tube 150 is placed by the robotic arm 3 for pumping. Although a pumping unit is preferred, the transfer of fluids and cellular material can also be performed by gravity or by the addition of gas, for example, through a sterile filter.

[0071] Automating the tube welding process is not a simple task, as can be seen from the following challenges that must be addressed: Indeed, there are several reasons why tube welding may at first appear to be incompatible with automation.

[0072] First, tube welding requires the handling of long flexible tubes, which are very difficult for automated equipment to handle. In particular, flexible tubing, once moved, for example by a robotic device, does not always stay within a well-defined, definitive location, making tube engagement, alignment and orientation difficult. In particular, it is very difficult to engage flexible tubing in free space and automatically load the tubing into a tube welding machine without human intervention. When the end of a sufficiently long flexible tube, restrained at one end, is manipulated at the other, the path defined by the tube will have many non-unique solutions as to what the path between the restrained end and the manipulated end will occupy, depending on the internal stresses in the tube. Such a system has many degrees of freedom. While such applications are ideal for humans, they are very difficult to automate and are therefore usually left to human operators. Furthermore, since the weld strength is very dependent on the exact placement and compression of the tube, any error in the robot's engagement of the tubing can lead to a weld failure. Therefore, it has not been feasible to simply take existing tube welding equipment and automate it on a robotic end effector to engage the tube.

[0073] Second, the size and weight of typical tube welders make them highly unsuitable for incorporation into end effectors for robotic arms. A typical tube welder weighs at least 2.5 kg, and typically heavier than 5 kg. Robotic arms suitable for use in bioprocessing systems are typically not designed to be capable of handling heavy payloads (e.g., heavier than 5 kg), so any allowable weight used to carry the weight of the end effector may limit the effectiveness of the robotic device when manipulating tubes and other objects in the bioprocessing system. Furthermore, a typical tube welder typically measures over 30 cm in length, and when incorporated into an automated bioprocessing system, the end effector needs to be relatively small to engage tubing and other equipment in the bioprocessing system.

[0074] Third, the tube welding operation requires multiple steps that must all be completed reliably and be fully automated without any manual intervention. This means that the end effector must include features to engage the tubing (as discussed above), detect the presence of the tube, clamp the tubing in a fluid-free area, weld the tube, unclamp the tube, and perform quality control (QC) of the weld. As previously mentioned, precise manual operations are required to properly insert the tube into the welder, properly remove the tube from the welder, and remove kinks in the tube after welding.

[0075] A preferred embodiment of an automated apparatus 100 for joining a first tube 150a to another such tube 150b, thereby forming a fluid pathway therethrough, will now be described with reference to the robotic device 2 shown in Fig. 2a. In this exemplary embodiment, the robotic device 2 includes a robotic arm 3 equipped with an end effector 100 configured to provide said apparatus 100. Additionally or alternatively, the apparatus 100 may also be described as suitable for manipulating a fluid sterile connection between two tubes 150, thereby forming a fluid pathway therethrough.

[0076] The internal components of the end effector 100 are shown in a cutaway view in FIG. 2b. The end effector 100 has two gripping mechanisms 110a, 110b for gripping respective tubes 150a, 150b. The end effector 100 is configured to fluidly connect the first tube 150a and the second tube 150b to each other while maintaining a seal between the inside of the tubes 150a, 150b and the surroundings (i.e., the tubes and the contents of the consumable 13 are not exposed to the atmosphere). Each tube 150a, 150b can be fluidly connected to a respective consumable 13 (not shown).

[0077] As used herein, the term "upstream" refers to a direction along the tubes 150a, 150b toward the respective consumables 13. Similarly, the term "downstream" refers to a direction along the tubes 150a, 150b toward the "free" ends of the tubes 150a, 150b. The first gripping mechanism 110a and the second gripping mechanism 110b can also be used to perform other steps in a cell therapy process, such as moving the consumables 13 between processing stations 20. As described in more detail below, the end effector 100 also includes a blade 140 attached to a blade arm 145 that can move along a cutting plane 141 (not shown), thereby cutting the tubes 150a, 150b. When the cut is made, the tubes 150a, 150b are preferably oriented parallel to each other and perpendicular to the cutting plane 141. The direction parallel to the tubes 150a, 150b can be referred to as the longitudinal direction.

[0078] The operation of the end effector 100 will now be described in detail with reference to Figures 3a-3m. As shown in Figures 3a and 3b, the first gripping mechanism 110a has a first jaw 112a and a second jaw 114a. Similarly, the second gripping mechanism 110b has a first jaw 112b and a second jaw 114b. The jaws 112, 114 are operable to grip a respective tube 150a, 150b therebetween. The terms "clamping" or "engaging" may also be used to refer to gripping the tube 150a, 150b between the jaws 112, 114.

[0079] When the gripping mechanisms 110a, 110b operate to join (e.g., butt weld) two tubes 150a, 150b together, they may be tightly gripped or "clamped" between the jaws 112a, 114a, 112b, 114b formed by each of the gripping mechanisms 110a, 110b to pinch the tubes 150a, 150b completely closed. On the other hand, the tubes 150a, 150b may instead be lightly gripped or "engaged" between the jaws 112a, 114a, 112b, 114b of the gripping mechanisms 110a, 110b so that fluids can still pass through the gripping areas of the tubes 150a, 150b when they are being manipulated inside the bioprocessing system 1.

[0080] Each jaw 112, 114 of each gripping mechanism 110 may include a plurality of gripping elements 115 (also referred to herein as "finger elements" or "fingers") that may be individually actuated to grip a tube 150. An opposing pair of gripping elements 115 may thus be referred to as forming a pair of said jaws 112, 114. A pair of jaws 112, 114 may further include a plurality of opposing pairs of gripping elements 115. The gripping elements 115 on the jaws 112, 114 may be positioned adjacent to one another, thereby providing an "array" of adjacent gripping elements 115 that form the pair of jaws 112, 114. As shown in Figures 3a-3m, each pair of jaws 112, 114 includes five opposing pairs of gripping elements 115. However, while any number of opposing pairs of gripping elements 115 can be used, preferably each gripping mechanism 110 includes at least one pair of opposing gripping elements 115 disposed on either side of the cutting surface 141. For example, if only one pair of opposing gripping elements 115 is provided on each side of the cutting surface 141, a separate gripping unit (not shown) can be used to engage and / or manipulate the tubes 150a, 150b to position them between a pair of jaws 112, 114 on the device 100.

[0081] Each opposing pair of gripping elements 115 is movable between a closed configuration in which the gripping elements 115a, 115b pinch or "clamp" the tube 150a, 150b, and an open configuration in which the tube 150a, 150b is received or released by the gripping elements 115a, 115b. Each opposing pair of gripping elements 115 can be moved to any position between the open and closed configurations to engage the tube 150 without pinching it closed.

[0082] In FIG. 3a, the tubes 150a, 150b are each disposed between a pair of jaws 112, 114 of a respective gripping mechanism 110, but the jaws 112, 114 have not yet been actuated to grip the tubes 150a, 150b. In other words, all of the opposing pairs of gripping elements 115a, 115b are in an "open configuration." The end effector 100 includes a first base plate 102 and a second base plate 104. The end effector 100 can also include a first mounting plate 106 and a second mounting plate 108, which can move relative to the base plates 102, 104. The first gripping mechanism 110a is mounted to the first mounting plate 106, and the second gripping mechanism 110b is mounted to the second mounting plate 108. As described below, motors or other actuators may be mounted on the base plates 102, 104 or on the mounting plates 106, 108 to actuate parts of the end effector 100. Alternatively, the actuators and other parts of the end effector 100 may be mounted elsewhere without affecting its overall operation. The orientation of the end effector 100 may be changed by the robot arm 3. For example, Figures 2a and 2b show the end effector 100 holding the tubes 150a, 150b horizontally, while Figures 3a-3l show the end effector 100 holding the tubes 150a, 150b vertically.

[0083] FIG. 3b shows a cross section through the end effector 100. The cutting plane 141 where the tube 150 will be cut by the blade 140 is shown using a dotted line. Both the first gripping mechanism 110a and the second gripping mechanism 110b have a pair of opposing gripping elements 115 on either side of the cutting plane 141. In other words, both gripping mechanisms 110a, 110b have at least a gripping element 115a, 115b from the first jaw 112a, 112b and the second jaw 114a, 114b, respectively, on either side of the cutting plane 141. The space between adjacent gripping elements 115 may be larger for gripping elements 115, 115' located on either side of the cutting plane 141 than for gripping elements 115 located on the same side of the cutting plane 141 to allow a gap for the blade 140 to pass therebetween. As will be explained in more detail below with reference to FIG. 3i, a lifting mechanism 120 can be used to increase or decrease this gap.

[0084] In this embodiment, there is one gripping element 115a', 115b' on each pair of jaws 112, 114 that is located downstream of the cutting surface 141 for the respective tube 150a, 150b, which may hereinafter be referred to as the "downstream" gripping element 115a', 115b'. This embodiment has four opposing pairs of gripping elements 115a, 115b on each of the jaws 112, 114 that are located "upstream" of the cutting surface 141, which may hereinafter be referred to as the upstream gripping elements 115a, 115b. There may be a different number of upstream gripping elements 115a, 115b and / or downstream gripping elements 115a', 115b' forming a pair of jaws 112, 114 on either or both of the gripping mechanisms 110a, 110b.

[0085] The "gripping elements" may hereafter be referred to as "fingers" and the areas of the fingers 115 that contact the tube 150 may be referred to as "fingertips". Optionally, the fingertips may be removable from the rest of the fingers 115 so that they can be cleaned without replacing the entire fingers 115. To allow for this, any suitable releasable connector may be used to insert and remove the fingertips from the rest of the fingers 115. Additionally, the length of the fingers 115 may be increased to reduce ingress of contaminants from the fingertips into the remainder of the respective gripping mechanism 110. The range of motion of the fingers 115 may also be increased to create a larger opening to accommodate misalignment of the tube 150 when gripped by the fingers 115.

[0086] 3c and 3d show a pair of jaws 112, 114 formed by a pair of opposing fingers 115 in closed and open configurations, respectively. Each of the fingers 115 has a proximal end 115-1, a distal end 115-2 at which the fingertips are located, and both fingers 115 rotate about a common pivot 115-3 located between the proximal and distal ends 115-1, 115-2. An actuation mechanism moves the fingers 115 between the closed and open configurations. In this embodiment, the actuation mechanism includes a cam 116 located between the proximal ends 115-1 of the opposing pair of fingers 115. The fingers 115 can be resiliently biased toward the cam 116 using a resilient member 117, such as a spring 117, such that the cam 116 remains in contact with the proximal ends 115-1 of the fingers 115.

[0087] In the position shown in FIG. 3c, the cam 116 urges the proximal ends 115-1 of the fingers 115 away from each other against the force of the elastic member 117. Thus, the distal ends 115-2 of the fingers 115 are urged toward each other to a closed configuration via rotation about the pivot 115-3. When the cam 116 is in the position shown in FIG. 3d, the proximal ends 115-1 of the fingers 115 move toward each other, thereby moving the distal ends 115-2 of the fingers away from each other to an open configuration via rotation about the pivot 115-3. The cam 116 can be rotated to any intermediate position so that the fingers 115 can be moved to any configuration between the open and closed configurations. In this manner, the opposing pair of fingers 115 can fully clamp the tube 150 in a closed configuration, or fully release the tube 150 in an open configuration, or lightly grip or engage the tube 150 in an intermediate configuration. The cam 116 may be rotationally driven using, for example, a motor 118 .

[0088] Either or both of the fingers 115 can have a seat 115-4 arranged to abut the tube 150 when disposed between the fingers 115. In this way, a "reference" or "datum" is provided so that the tube 150 is consistently gripped at the same position between the fingers 115 as they move from the open to the closed configuration. To ensure that the seat 115-4 contacts the tube 150 in both the open and closed configurations, the fingers 115 are arranged to overlap each other, as shown by the dotted lines in Figures 3c and 3d. In addition, both opposing fingers 115 can move simultaneously during the rotation of the cam 116, meaning that the tube 150 can remain centered throughout the movement between the open and closed configurations. This ensures that the tube 150 is consistently aligned between the fingers 115.

[0089] Each of the opposing pairs of fingers 115 can be actuated using an actuation mechanism as described above. Because each opposing pair of fingers 115 is actuated using a separate cam 116, each opposing pair of fingers 115 can act (e.g., open and close) independently of the other pairs of fingers 115 in a predetermined manner. In other words, because each pair of fingers 115 is driven by a separate cam 116, a pair of fingers can be controlled (through the arrangement of the respective cams 116) to open and close at different times (e.g., in a predetermined sequence) than the other (e.g., adjacent) pairs of fingers 115. The sequence in which each pair of fingers 115 opens and closes can be preconfigured and fixed because the separate cams 116 controlling each opposing pair of fingers 115 are controlled by a common motor 118. With a small number (e.g., three) pairs of fingers 115, their (e.g., three) corresponding cams 116 can provide a sufficient number of rest points between them to allow for "on-the-fly" individual control of each pair of fingers 115. This can be achieved by rotating a common motor 118 that controls them all to a rest point on the cam 116 that corresponds to a corresponding pair of fingers 115 in an open configuration while the other pair of fingers 115 is in a closed configuration. Such individual control becomes more difficult as the number of pairs of fingers 115 (and therefore corresponding cams 116) increases, due to the increasing number of possible open / closed configurations required, and consequently, rest points.

[0090] The movement of each pair of fingers 115 between the open and closed configurations can be actuated in other ways, for example, by using a linear screw or linear actuator, or by directly moving the fingers 115 with a separate servo. In an alternative embodiment (not shown), the fingers 115 can be replaced by a linear actuator.

[0091] 3e, clamping of tube 150a, 150b by gripping mechanisms 110a, 110b will now be described. In operation, each of fingers 115 of first jaw 112 and second jaw 114 move toward each other using the actuation mechanism described above, thereby squeezing and clamping the respective tube 150. Optionally, the actuation mechanism first moves first jaw 112 and second jaw 114 to an intermediate configuration to engage but not clamp tube 150 so that tube 150 can be manipulated in bioprocessing system 1. The portions of each of the fingertips that contact tube 150 preferably have flat surfaces so that tube 150 is evenly pinched by gripping mechanisms 110a, 110b.

[0092] The opposing pairs of fingers 115 preferably do not move simultaneously, i.e., can move independently, when gripping the tube 150. The upstream pair of fingers 115 can be moved first, starting with the finger 115 closest to the cutting surface 141 and ending with the finger 115 furthest from the cutting surface 141. The downstream pair of fingers 115' can then be moved. In an embodiment with multiple pairs of downstream fingers 115', they can also be moved starting with the one closest to the cutting surface 141. In this way, any fluid contained in the tube 150 can be removed from the gripped portion of the tube 150 and pushed towards the consumable 13 instead. This prevents any loss of fluid and inhibits the fluid from interfering with the welding process. Optionally, the pumping unit can be operated to pump the fluid upstream towards the consumable 13. This can help ensure that the tube 150 is empty at the cutting surface 141, which helps keep the tube 150 pinched closed.

[0093] In FIG. 3e, the tube 150a is shown in the middle of the above-mentioned process, with each of the fingers 115a of the first gripping mechanism 110a in different positions. In particular, the downstream finger 115a' is still open, while the upstream finger 115a is in the process of moving. The tube 150b is shown after the clamping process is completed, with all fingers 115b, 115b' on the second gripping mechanism 110b fully actuated towards each other. In this position, the tube 150b is fully pinched closed, preventing fluid from passing through the gripped portion. The clamping of the tubes 150a, 150b may be performed simultaneously or at different times. For example, the robot arm 3 may move the end effector 100 to clamp one side of the tube 150 and then move the end effector 100 to clamp the other side of the tube 150. If both tubes 150 are already present between the first jaw 112 and the second jaw 114 of both gripping mechanisms 110a, 110b, clamping can occur simultaneously.

[0094] Optionally, the robotic device 2 includes force, torque, and / or compliance sensors (not shown) to ensure that the tubes 150a, 150b are not preloaded prior to welding. One or more of these sensors can be located in the robot arm 3, in the end effector 100, or in one or both of the gripping mechanisms 110a, 110b. For example, if the force / torque / compliance sensor determines that the force exceeds a predetermined value (such as 10 Newtons) or that the tube 150 is twisted, the gripping mechanisms 110a, 110b can release and re-grip one or both of the tubes 150a, 150b until the measured force is at a level suitable for welding. A machine vision system, which can include a camera (not shown) and a processing unit (not shown), can also be used to verify whether the tubes 150a, 150b are engaged.

[0095] In FIG. 3f, the second gripping mechanism 110b can be moved toward the first gripping mechanism 110a to move the tubes 150a, 150b toward each other. In other words, the tubes 150a, 150b move in a direction substantially perpendicular to the longitudinal direction of the tubes 150a, 150b. In this example, the rotation of the first cam 132-1 (seen in FIG. 4a) causes the second mounting plate 108 to rotate about a pivot (not shown), thereby moving the second gripping mechanism 110b toward the first gripping mechanism 110a. The second mounting plate 108 is biased by the spring 134 toward the first cam 132-1 which rotates the second mounting plate 108 to maintain contact therebetween. In this example, the first gripping mechanism 110a is stationary. Alternatively, the first gripping mechanism 110a may be moved towards the second gripping mechanism 110b, or both gripping mechanisms 110a, 110b may be moved towards each other. In other embodiments, neither gripping mechanism 110a, 110b moves.

[0096] The first jaw 112b and the second jaw 114b of the second gripping mechanism 110b are both mounted to the second mounting plate 108 so that they move simultaneously without changing their relative positions. Thus, the tubes 150a, 150b are pinched closed and remain parallel to each other during movement. A first stopper 130a (seen in FIG. 3i) is attached to a downstream finger 115a' on the second jaw 114a of the first gripping mechanism 110a. A second stopper 130b is attached to a downstream finger 115b' on the first jaw 112b of the second gripping mechanism 110b. As the first gripping mechanism 110a moves relative to the second gripping mechanism 110b, the first stopper 130a abuts the second mounting plate 108. Similarly, the second stopper 130b abuts the first mounting plate 106. In this manner, the second gripping mechanism 110b always moves a constant, predetermined distance from the first gripping mechanism 110a.

[0097] The blade 140 can then be heated to between 300° C. and 400° C. to sterilize and depyrogenate the blade 140. The blade 140 or the mounting block 142 in contact with the blade 140 can be heated using resistive heating, where power is supplied to resistive elements in the blade 140 and / or the mounting block 142.

[0098] Alternatively, the blade 140 can be heated by a separate heat source or can be heated without direct contact, for example through a laser heater. The blade 140 may be partially cooled before being used to cut the tube 150. The power source and / or transformer for heating the blade 140 can be located outside (e.g., external to) the end effector 100 to reduce the weight and size of the end effector 100. For example, the power source and / or transformer can be located elsewhere in the robotic system 2 and wires can be used to transfer power to the end effector 100. This power can also be used to operate other components such as actuators or motors of the end effector 100. In this embodiment, the end effector 100 can weigh as little as 1.8 kg and measure (e.g., have this "footprint") as little as 20 cm by 10 cm, which is a substantial improvement over the size and weight of existing tube welding machines.

[0099] The movement of the blade 140 to cut the tubes 150a, 150b can be actuated in a number of ways. In this embodiment, FIG. 3f shows the blade arm 145 in a retracted position that does not affect the operation of the gripping mechanisms 110a, 110b described above. The blade arm 145 includes a first end plate 143 that extends on an outer surface of the first base plate 102. The blade arm 145 can also include a second end plate (not shown) that extends on an outer surface of the second base plate 104. The actuation and movement of the second end plate can correspond to the actuation and movement of the first end plate 143 and will therefore not be described in detail.

[0100] On the first base plate 102 is a pin 143-1 that extends into a slot 143-2 in the first end plate 143. Thus, the first end plate 143 can rotate about the pin 143-1 and can translate parallel to the first base plate 102 in the direction of the slot 143-2. ​​A link arm 144 is pivotally coupled to a proximal end of the first end plate 143 by a rod 144-1. The rod 144-1 can extend through a slot 144-4 in the link arm 144 into a slot or groove 144-2 in the first base plate 102. The slot or groove 144-2 can have a contour that limits the movement of the rod 144-1 along a particular path.

[0101] When driven by a motor 146 (seen in FIG. 4a), and preferably via a gearbox 147, the link arm 144 rotates about the shaft 144-3, moving the rod 144-1 through the curved portion of the slot 144-2. This motion causes the first end plate 143 to rotate about the pin 143-1 first, which pivots the blade arm 145 so that the mounting block 142 and the blade 140 are positioned adjacent to the tubes 150a, 150b. As the link arm 144 continues to rotate, the rod 144-1 moves through the straight portion of the slot 144-2. This causes the first end plate 143 to move in a straight direction, and the pin 143-1 moves through the slot 143-2 in the first end plate 143. This causes the first end plate 143 and the blade arm 145 to translate, moving the blade 140 along the cutting surface 141 to intersect with the tubes 150a, 150b. The final position of the blade arm 145 is shown in FIG. 3g, with the arrows indicating the above-mentioned movement of the blade arm 145.

[0102] As a result, the first tube 150a can be cut into an upstream section 150a that connects to the consumable 13 and a downstream section 150a' that previously formed the end of the tube 150a. Similarly, the second tube 150b can be cut into an upstream section 150b that connects to the consumable 13 and a downstream section 150b' that previously formed the end of the tube 150b. In this way, the new ends of the upstream portions 150a, 150b formed by the removal of the downstream sections 150a', 150b' share a common plane.

[0103] The blade 140 may be a copper wafer with high thermal conductivity to allow the temperature of the blade 140 to be changed quickly. The blade 140 may be replaced between each tube welding operation to ensure a clean surface for each weld. A cartridge of wafers may be placed on the mounting block 142 or elsewhere to replace the blade 140. Alternatively, the blade 140 may be provided by a ribbon of material such that a new portion of the ribbon can be moved into place after each welding operation.

[0104] In Figure 3h, the upstream fingers 115a, 115b have been moved to longitudinally align the upstream sections of the tubes 150a, 150b. To do so, the first cam 132-1 (not shown), which rotates the second mounting plate 108, continues to rotate, thereby urging the second mounting plate 108 and the second gripping mechanism 110b towards the first gripping mechanism 110a. The stopper 130b abuts against the first mounting plate 106, preventing further movement of the downstream finger 115b' of the second gripping mechanism 110b, but allowing the upstream finger 115b to continue moving.

[0105] As a result, the upstream section 150b of the second tube moves out of alignment with the downstream section 150b' of the second tube and into alignment with the upstream section 150a of the first tube. As this occurs, the stopper 130a (seen in FIG. 3i) abuts the second mounting plate 108, which also pushes the downstream finger 115a' of the first gripping mechanism 110a, causing the downstream section 150a' of the first tube to be pushed out of alignment with the upstream section 150a of the first tube.

[0106] The blade 140 remains between the tubes 150a, 150b, thereby transferring heat from a heat source to melt the new ends of the tubes 150a, 150b. The blade 140 can be held between the tubes 150a, 150b for a predetermined period of time and can have a predetermined thermal profile. The predetermined period and predetermined thermal profile can be selected such that the tubes 150a, 150b are melted sufficiently for subsequent welding, but are not so hot that they destroy biological material contained within the tubes 150a, 150b or compromise the structural integrity of the tubes 150a, 150b.

[0107] An infrared camera or infrared laser can be used in a closed loop to verify that the ends of the tubes 150a, 150b have reached a suitable temperature for welding and that a uniform temperature has been reached. Alternatively, thermistors, thermocouples, or resistance temperature detectors (RTDs) can be mounted on components such as the blade 140, the mounting block 142, or the heat source to monitor temperature. Alternatively, or in addition, the resistance of a resistive element can be measured directly to detect and control the temperature of the blade 140.

[0108] As depicted in FIG. 3h, the downstream fingers 115a' (not shown), 115b' gripping the downstream portions 150a', 150b' of the tubes 150a, 150b can remain in place. Optionally, the downstream fingers 115a', 115b' can be moved away from the upstream fingers 115a, 115b to prevent the upstream tubes 150a, 150b from being inadvertently welded to the downstream tubes 150a', 150b'. If the upstream tubes 150a, 150b were inadvertently welded to the downstream tubes 150a', 150b', the force required to separate the tubes 150 could tear the weld between the upstream tubes 150a, 150b. To prevent this, the tubes 150 are preferably held at least 4 mm apart.

[0109] The blade 140 can then be removed from between the upstream fingers 115a, 115b and the downstream fingers 115a', 115b'. As seen in FIG. 3i, the lifting mechanism 120 can be actuated to move the upstream finger 115b of the second gripping mechanism 110b towards the upstream finger 115a of the first gripping mechanism 110a. This position can be referred to as the "up" position. The downstream fingers 115a', 115b' can also be moved by the lifting mechanism 120. This movement pushes the upstream portion 150b of the second tube 150b into the upstream portion 150a of the first tube 150a. Preferably, the lifting mechanism 120 is actuated soon enough after the removal of the blade 140 so that the ends of the tubes 150a, 150b are still molten when they come into contact. The lifting mechanism 120 can be any type of actuator that urges the upstream fingers 115b of the second gripping mechanism 110b toward the upstream fingers 115a of the first gripping mechanism 110a. For example, a linear actuator or a screw mechanism can be used to move either or both sets of upstream fingers 115a, 115b toward each other. The fingers 115a, 115b can be configured to move, for example, continuously or in a series of predetermined movements.

[0110] In this embodiment, the lifting mechanism 120 is a lifting pad 120 mounted to the second base plate 104 of the end effector 100. When actuated by a motor 135, as described below in connection with FIG. 4a, the lifting pad 120 can rotate relative to the second base plate 104 and the upstream finger 115a of the first gripping mechanism 110a. The rotation of the lifting pad 120 can be translated into linear motion of the second mounting plate 108 through a cam mechanism. Because the upstream finger 115b is mounted to the second mounting plate 108, the linear motion of the second mounting plate 108 moves the upstream finger 115b of the second gripping mechanism 110b towards the upstream finger 115a of the first gripping mechanism. A spring 122 can be used to return the lifting pad 120 to its initial position. Additionally, springs 124 (visible in FIG. 4a) can bias the upstream fingers 115a, 115b away from each other when the lifting pads return to their initial positions. For example, springs 124 can bias the second mounting plate 108 toward the second base plate 104.

[0111] In this manner, the position of the upstream finger 115a of the first gripping mechanism 110a relative to the upstream finger 115b of the second gripping mechanism 110b can be monitored to determine if the weld is successful. For example, if a sensor (not shown) determines that the second mounting plate 108 has returned to its initial position, the weld is not strong enough to overcome the force from the spring 124 and is therefore unsuccessful. On the other hand, if the weld is strong enough to hold the second mounting plate 108 in its "up" position against the force of the spring 124, the weld is successful.

[0112] The lifting mechanism 120 may equally be mounted to the first base plate 102, or may instead move the upstream finger 115a of the first gripping mechanism 110a via linear motion of the first mounting plate 106. In other embodiments, separate lifting mechanisms 120 may be mounted to both the first base plate 102 and the second base plate 104. By actuating the relative motion of the mounting plates 106, 108, out-of-plane movement of the fingers 115 is eliminated. Alternatively, the lifting mechanism 120 may move the upstream fingers 115a, 115b directly relative to each other.

[0113] When the lifting mechanism 120 is actuated to press the upstream tubes 150a, 150b together, the heat previously transferred to the tubes 150a, 150b by the blades 140 welds the upstream tubes 150a, 150b together, causing the tubes 150a, 150b to form a single tube 150. The joint or "interface" between the joined tubes 150a, 150b may further be referred to as a "butt weld."

[0114] In FIG. 3j, the upstream fingers 115a, 115b can be partially retracted so that the tube 150 is still engaged between the fingers 115a, 115b but is not tightly clamped by the fingers 115a, 115b. Similarly, the downstream fingers 115a', 115b' can be partially retracted so that they engage the downstream tube 150b', 150b' but are not tightly clamped. The opposing pair of fingers 115a, 115b closest to the cutting surface 141 can be moved to a fully open configuration to expose the butt weld between the tubes 150a, 150b. The opposing pair of fingers 115a, 115b furthest from the cutting surface 141 can remain in place to engage the tube 150 and preferably fluidly seal the butt weld from the section of the tube 150 that leads to the consumable 13. This means that even if the weld is unsuccessful, the consumable 13 or any fluid contained within the tube 150 will not be exposed to the atmosphere.

[0115] When the butt weld is exposed by moving the upstream fingers 115a, 115b closest to the cut surface, a portion of the tube 150 remains pinched at the connection between the upstream tubes 150a, 150b. This pinched portion is sometimes called a "kink" and must be removed before any fluid can pass through the tube 150. Before this occurs, a machine vision system can be used to inspect the connection between the two tubes 150a, 150b. By moving the upstream fingers 115a, 115b closest to the cut surface 141 to an open configuration, a portion of the pinched portion of the tube 150 is exposed and can be inspected.

[0116] The camera of the machine vision system preferably has a microscope lens and is connected to a processing unit (not shown), which identifies whether the weld is successful. The camera can be located at any suitable location for observing the weld, and depending on the location of the camera, can include one or more mirrors, allowing the camera to observe the weld via reflection in the mirror. For example, the mirror can be located on the blade arm 145. The camera can detect visible light, infrared (IR) and / or ultraviolet (UV) radiation. The processing unit can inspect the physical alignment of the tube 150 to determine whether the weld is successful. Alternatively or additionally, the "burr" around the weld can be inspected to determine the integrity of the weld. The lifting pad 120 can be used to apply a tensile force to the tube 150 via the fingers 115, which can also provide a measurement of the stress-strain profile of the tube 150. The stress-strain profile can also be analyzed by the processing unit to determine whether the weld is successful.

[0117] Other mechanical tests can also be used, such as torsion or vibration tests. Ultrasonic or x-ray sources can also be used to test for the presence of voids in the connections. Fluid can also be pumped through the tube 150, and a camera can be used to detect the presence of leaks.

[0118] Alternatively or additionally, gas sensing methods can be used to inspect the welds, with the connection placed in a sealed container or volume. For example, the volume can be first filled with an inert gas, and the container can have a water vapor or oxygen sensor that detects any leakage from the weld into the volume. Alternatively, the volume can be filled with a tracer gas, such as helium, which is subsequently removed from the volume. A sensor in the volume can then detect leakage of the tracer gas from the weld. The container can be fitted with a pressure sensor that indicates leakage by detecting a pressure change inside the container. For example, if the container is first pressurized, a decrease in pressure can indicate gas is leaking into the weld. A camera can also be used to observe if air is leaking into the connection. Alternatively, air can be pumped into the tubes 150a, 150b before welding, and then a vacuum can be applied to the sealed container to see if air escapes.

[0119] Inspection of the connection can be performed before the kinks are removed from the tube 150. By inspecting the tube 150 before the kinks are removed, even if there is a leak in the connection, the contents of the consumable 13 still remain isolated from the surrounding air and atmosphere. If the processing unit determines that the weld is not successful, the tube 150 can be re-clamped and re-welded. This can be done in a number of ways, for example, the robotic device 2 can take the tube 150a, 150b to an external clamp before re-gripping at a different location further upstream for re-welding. Alternatively, the tube 150a, 150b can be moved longitudinally through the gripping mechanism (as further described in connection with Figures 5a-5c) such that the joint is formed further upstream.

[0120] To remove the kinks (i.e., release the pinched portion of tube 150) and open tube 150, a pinch release mechanism 170 can be used. The pinch release mechanism 170 pushes against the edges of the pinched portion at the joint between tubes 150a, 150b. Preferably, the pinch release mechanism 170 pushes against the butt weld in a direction perpendicular to the direction in which tube 150 is clamped by jaws 112, 114, which causes the pinched portion to "pop open" due to the effect of Poisson's ratio.

[0121] There are many ways in which the pinch release mechanism 170 can be implemented. For example, there may be a separate arm with a popper plate that moves along the cutting surface 141 to press the tube 150 against the seat 115-4 of the fingers 115. There may be a separate set of jaws (e.g., including a first release element and a second release element) that grip and compress the edges of the pinched portion of the tube 150 to remove kinks. This pair of jaws can grip the tube 150 even when the tube is released by the gripping mechanism 110a, 110b. As a further alternative, the blade 140 can be cooled before being pressed against the butt weld through the actuation of the blade arm 145.

[0122] In this embodiment, the pinch release mechanism 170 includes a popper heel 170 disposed on a mounting block 142. The mounting block 142 is connected to the blade arm 145 by a pin 171 about which the mounting block 142 can rotate. To operate the pinch release mechanism 170, the blade arm 145 pivots so that the mounting block 142 is adjacent to the pinched portion of the tube 150. The pivoting of the blade arm 145 occurs in the same manner as already described in connection with Figures 3f and 3g. The mounting block 142 also rotates about the pin 171 so that the popper heel 170 is disposed adjacent the tube 150, as will be described below in connection with Figure 4a. The blade arm 145 then translates using the same mechanism already described in connection with Figures 3f and 3g, thereby compressing the tube 150 between the popper heel 170 and the seat 115-4 of the finger 115. As the upstream fingers 115a, 115b closest to the cutting surface 141 have moved to the open configuration, the popper heel 170 can fit between the opposing pair of fingers 115a, 115b to compress the joint between the tubes 150a, 150b. Alternatively, the popper heel 170 may be a plate that fits into the gap between the upstream fingers 115a, 115b of the first gripping mechanism 110a and the second gripping mechanism 110b.

[0123] In Figure 3l, the blade arm 145 has returned to its retracted position. The tube 150 remains lightly engaged by the upstream fingers 115a, 115b furthest from the cutting surface 141, and the downstream tube 150a', 150b' remains engaged by the downstream fingers 115a', 115b'. The aforementioned inspection step may be performed after any kinks in the tube 150 have been removed, which may provide a better functional test of the tube 150. Preferably, the inspection step is performed both before the tube 150 is partially released by the upstream fingers 115a, 115b, and after the tube 150 has been removed to allow fluid flow.

[0124] In FIG. 3m, the fingers 115 move to a fully open configuration to drop the tubes 150, 150a', 150b'. This may be done simultaneously or the tubes 150, 150a', 150b' may be released separately so that they can be moved to separate locations before being released. The downstream tubes 150a', 150b' remain closed at both ends and can therefore be discarded without exposing the inside of the downstream tubes 150a', 150b' to the environment. The downstream tubes 150a', 150b' can be discarded in a specific container in the bioprocessing system 1, such as a container for waste disposal. The tube 150 between the two consumables 13 can also be placed by the end effector 100 in a specific location in the bioprocessing system 1. This can be done to allow the robotic system 2 to perform other steps in the bioprocessing method and to allow the tube 150 to be quickly positioned at a later time. With the connection between original tubes 150a, 150b complete, the pumping unit can be operated to pump fluid through tube 150 between consumables 13 to perform a step in the cell therapy process. Optionally, tube 150 may remain engaged by end effector 100 during pumping.

[0125] A rear view of the end effector 100 is shown in FIG. 4a, with components such as mounting plates 106, 108 and gripping mechanism 110 removed for clarity. A motor 146 is shown driving the rotation of shaft 144-3 and link arm 144 via gearbox 147. Once actuated, this motor 146 is used to pivot and translate blade arm 145 in the manner already described. Also shown is a first cam 132-1 which drives second gripping mechanism 110b towards first gripping mechanism 110a, as previously described. The first cam 132-1 is rotated by motor 135 via gearbox 132. In this embodiment, motor 135 is a different motor than motor 146, and gearbox 132 is different from gearbox 147. The second cam 132-2 is also driven by motor 135 via gearbox 132. The second cam 132-2 is used to actuate the lifting mechanism 120 and rotate the mounting block 142 so that the popper heel 170 can be positioned adjacent to the tube 150. Due to the contour of the second cam 132-2, both the lifting mechanism 120 and the mounting block 142 can be actuated using only the rotation of the second cam 132-2. Alternatively, separate cams and / or motors may be used to actuate each of the lifting mechanism 120 and the mounting block 142.

[0126] To actuate the lifting mechanism 120, the second cam 132-2 pushes against the lift plate drive arm 121. The lift plate drive arm 121 pushes against the lifting pad 120 against the force of the spring 122, as previously described in connection with FIG. 3i. To rotate the mounting block 142, the second cam 132-2 pushes against the popper engagement arm 172, which rotates the mounting block 142 against the force of the spring 173.

[0127] FIG. 4b shows a series of cams 116 disposed along a camshaft 116-1 on which a worm gear wheel 116-2 is mounted to receive a rotational drive input from a motor 118. An alignment disk 116-4 having a notch 116-5 is also disposed on the camshaft 116-1. The location of the notch 116-5 can be detected by an alignment detector 116-6 to determine the rotational position of the camshaft 116-1 and the cam 116. There may also be additional notches, series of notches and / or additional alignment detectors 116-6 so that the position of the fingers 115 can be confirmed. For example, the alignment detector 116-6 can confirm whether the fingers 115 are in a fully gripped position, a fully open position, or any combination. FIG. 4c shows the camshaft 116-1 and cam 116 configured to drive the gripping mechanism 110, with the worm gear wheel 116-2 configured to receive a rotational drive input from a motor 118 configured to output rotation via the worm gear 116-3. During rotation of the cam 116 by the motor 118, the fingers 115 move between the open and closed configurations in the manner previously described. Both gripping mechanisms 110a, 110b are actuated as described above using separate motors 118. Alternatively, the gripping mechanisms 110a, 110b may be actuated by a common motor, for example.

[0128] The above method can be improved to further minimize the chance of any leakage when the tube 150 is cut as follows: When the tube 150a, 150b is first gripped by the gripping mechanism 110a, 110b, the lifting mechanism 120 can be actuated to increase the distance between the upstream finger 115a, 115b and the downstream finger 115a', 115b', thereby applying tension to the tube 150a, 150b. Then, when the tube 150a, 150b is cut by the blade 140 and the upstream tube 150a, 150b is aligned, the lifting mechanism 120 can decrease the distance between the upstream fingers 115a, 115b to press the tube 150a, 150b together (i.e., provide compression between the tube 150a, 150b) and weld them together. Preferably, the lifting mechanism 120 can move the finger 115 through a range of positions and apply a predetermined force. For example, the lifting mechanism 120 can be configured to have at least three predefined positions, namely, an initial reference position where the tube 150 is simply held, a position where the clamped tube 150 is stretched, and a position where the ends of the two tubes 150a, 150b are pressed against each other.

[0129] The cutting process of the two consumables 13 (e.g., reconstituting the tube 150) will now be described with reference to Figures 5a to 5f, which depict the fingers 115 of the end effector 100 shown in Figure 3b. In Figure 5a, the welded tube 150 connecting the two consumables 13 is positioned between the upstream fingers 115a, 115b of the first and second gripping mechanisms 110a, 110b, but the gripping mechanisms 110a, 110b have not yet been activated to clamp the tube 150. The downstream fingers 115a', 115b' are not used during the cutting process.

[0130] In Fig. 5b, the upstream fingers 115a, 115b are moved to grip and clamp the tube 150 closed. Similar to the connecting process, the upstream fingers 115a, 115b can engage (and thereby clamp) the tube 150 at different times. For example, the upstream fingers 115a, 115b closest to the cutting surface 141 can be moved first, followed by the one furthest from the cutting surface 141. In this way, any fluid contained in the tube 150 can be removed from the gripped portion of the tube 150 and pushed towards one of the consumables 13 instead. This prevents any loss of fluid and inhibits the fluid from interfering with the welding process.

[0131] The blade 140 is then heated by a heat source (not shown) to between 300°C and 400°C to sterilize and / or depyrogenate the blade 140. To better seal the tube 150, the heating profile used during cutting may be different from the heating profile used during connection. The blade 140 is partially cooled. Similar to the connection process, the blade 140 is moved along the cutting surface 141 to intersect with the tube 150, as shown in FIG. 5c. This cuts the tube 150 into a first tube 150a that connects to the first consumable 13 and a second tube 150b that connects to the second consumable 13. The blade 140 remains between the tubes 150a, 150b for a predetermined period of time to melt the ends of the tubes 150a, 150b, thereby sealing the tubes 150a, 150b. The predetermined period of time used to melt the ends of the tubes 150a, 150b during cutting may be different than the predetermined period of time used to melt the ends of the tubes 150a, 150b during connecting. The predetermined period of time may be longer during the cutting process. In Fig. 5d, the blade 140 is removed from between the first tube 150a and the second tube 150b.

[0132] Alternatively, it may be desired to separate the sealing and cutting functions and seal the tube 150 to be cut over a greater length than can be achieved using the blade 140 alone. The tube 150 will first be sealed by application of either heat or RF energy generated by the fingertips. To heat seal the tube 150, the individual fingertips can be made from resistive elements and powered while compressing the tube 150, with heat being conducted through the tube 150 to melt the inner surfaces together. Preferably, the fingertips will be coated with a non-stick material. Alternatively, the individual fingers 115 may be used as a means to provide an RF heat seal. The fingertips can be made from ceramic and supplied with alternating current operating in the MHz or GHz frequency range, preferably 40.68 MHz. The RF method is advantageous because the tube material melts over a larger area and with a more uniform temperature distribution throughout the cross section of the tube 150, thus allowing a wider and more robust seal of the tube 150.

[0133] In Figure 5e, the upstream finger 115a of the first gripping mechanism 110a moves away from the upstream finger 115b of the second gripping mechanism 110b, thereby separating the first tube 150a from the second tube 150b. Thus, the upstream fingers 115a, 115b realign with the downstream fingers 115a', 115b'.

[0134] In FIG. 5f, the tubes 150a, 150b are released by the first gripping mechanism 110a and the second gripping mechanism 110b. The release of the tubes may occur simultaneously or at different times. For example, the first tube 150a and the second tube 150b may be moved to different locations by the robot arm 3 before being released by the first gripping mechanism 110a and the second gripping mechanism 110b. This may be to facilitate subsequent steps in the cell therapy method. Optionally, the first tube 150a and the second tube 150b may be released before the tubes are separated. The upstream fingers 115a, 115b may thus be released after removal of the blade 140, but before the upstream fingers 115a, 115b are aligned with the downstream fingers 115a', 115b'.

[0135] The above-described connection and disconnection process can be performed as many times as required for a particular bioprocessing method. During each connection step, a portion of the downstream tubing 150a', 150b' is discarded, so that the length of the tubing 150 between the downstream end and the consumable 13 will shorten over time. With this in mind, the bioprocessing system 1 can be provided with a reserve supply of tubing 150, and the end effector 100 can be operated to extend the existing tubing 150 by welding it to tubing from the reserve supply. Optionally, the reserve supply of tubing can be built directly into the end effector 100, so that new tubing is always available when the tube 150 needs to be extended. Preferably, during the connection process, the gripping mechanisms 110a, 110b grip the tubing 150a, 150b near the downstream end, such that the length of the downstream tubing 150a', 150b' that is discarded is minimized.

[0136] The gripping mechanisms 110a, 110b can also be operated to move the tube 150 longitudinally while it is held by the gripping mechanisms 110a, 110b. The term "longitudinal" refers to a direction parallel or "coaxial" to the axis of the tube, which allows the location on the tube 150 gripped by the gripping mechanisms 110a, 110b to be adjusted to be closer to the respective consumable 13 or closer to the downstream end of the tube 150. This increases the degree of control of the gripping mechanisms 110a, 110b and reduces the amount of wasted downstream tube 150a', 150b' generated during the connection process. Longitudinal movement of the tube 150 is accomplished in a manner similar to an inch-worm drive, where the tube 150 is gradually dragged through the gripping mechanisms 110 without the gripping mechanisms completely releasing the tube 150.

[0137] 6a to 6c, longitudinal movement of tube 150 will now be described. Although only one of gripping mechanisms 110 is shown, it will be understood that both gripping mechanisms 110 enable longitudinal movement and can do so simultaneously.

[0138] To move the tube 150 longitudinally, the fingers 115 grip and release the tube 150, for example sequentially or in a predetermined sequence, periodically out of phase with each other. FIG. 6a depicts the gripping mechanism 110 at a first stage in the process, with the downstream fingers 115' moving relative to each other so as to squeeze the tube 150. The downstream fingers 115' may fully pinch the tube 150, or may be in a position where the tube 150 is lightly squeezed but not fully pinched. The upstream fingers 115 move gradually away from the downstream fingers 115'. FIG. 6b depicts the gripping mechanism 110 at a later stage in the process, with the downstream fingers 115' beginning to move apart and the opposing pair of upstream fingers 115 squeezing the tube 150. The opposing pair of upstream fingers 115 may fully pinch the tube 150, or may be in a position where the tube 150 is lightly squeezed but not fully pinched. FIG. 6 c depicts the gripping mechanism 110 at a later stage in the process, with the downstream fingers 115 ′ moving apart and the upstream fingers 115 at the opposite end of the gripping mechanism 110 squeezing the tube 150 .

[0139] 6a-6c are repeated multiple times, resulting in the tube 150 moving in the direction of arrow 190. This motion can be referred to as a drive wave of the fingers 115 pinching the tube 150. By reversing the above process, the tube 150 will move in the opposite direction. The motion of each of the fingers 115, 115' may be a sinusoidal motion, and adjacent fingers 115, 115' may be shifted by a certain phase angle. This phase angle may depend on the total number of fingers 115, 115' present in the gripping mechanism 110.

[0140] Alternatively, longitudinal movement of the tube 150 can be achieved by using the lifting mechanism 120. In a first step, the upstream fingers 115 can initially grip (but not completely pinch) the tube 150. In a subsequent step, the downstream fingers 115' grip the tube 150 and the upstream fingers 115 retract. The lifting mechanism 120 is then actuated to move the (closed) downstream fingers 115' closer to the (open) upstream fingers 115. The upstream fingers 115 then grip the tube 150 again and the downstream fingers 115' release the tube 150. The lifting mechanism 120 is then turned off and the (open) downstream fingers 115' move away from the (closed) upstream fingers 115. Thus, the gripping mechanism 110 returns to its original position while the tube 150 moves longitudinally relative to it. This can be repeated many times to move the tube 150 through the gripping mechanism 110. The process can also be reversed to move tube 150 in the opposite direction.

[0141] When the gripping mechanism 110 is operated to move the tube 150 longitudinally, the pinch release mechanism 170 can be positioned in front of the fingers 115 to hold the tube 150 to the gripping mechanism 110. Alternatively, the gripping mechanism 110 can be moved to a particular orientation when the tube 150 is moved longitudinally to prevent the tube 150 from falling off the gripping mechanism 110.

[0142] Any of the features described in connection with the end effector 100 described herein can be implemented in a static tube welding apparatus. For example, the pinch release mechanism 170 can be combined with any tube welder, whether located on the robot arm 3 or otherwise, or can be supplied as a separate component. The tube welder can have a machine vision system or camera as described herein to verify whether the tubes are properly engaged. A machine vision system or camera can also be used before and / or after releasing the pinch of the tube 150 to verify whether the weld was successful. Such a tube welder may require manual operation (or a separate robotic device) to place the tube between the jaws 112, 114. However, subsequent steps such as clamping, cutting, alignment, inspection, and operation of the pinch release mechanism 170 can be operated autonomously by the tube welder.

[0143] Similarly, gripping mechanisms 110a, 110b with pairs of gripping elements 115, whether static or disposed on the end effector 100, can be separately provided or used in both manual and automatic tube welding machines. Such gripping mechanisms 110a, 110b can be operated according to any of the steps described herein, for example, to longitudinally move the tube 150 or to remove fluid from near the cut surface 141.

[0144] As used herein, the gripping mechanisms 110a, 110b may be collectively referred to as a "clamping unit." The first jaw 112a, 112b of each of the gripping mechanisms 110a, 110b may be equivalently referred to as a first jaw of a clamping unit. Similarly, the second jaw 114a, 114b of each of the gripping mechanisms 110a, 110b may be equivalently referred to as a second jaw of a clamping unit.

[0145] The upstream finger 115a of the first jaw 112a of the first gripping mechanism 110a and the downstream finger 115b' of the first jaw 112b of the second gripping mechanism 110b can be collectively referred to as a first part of the first jaw. The downstream finger 115a' of the first jaw 112a of the first gripping mechanism 110a and the upstream finger 115b of the first jaw 112b of the second gripping mechanism 110b can be collectively referred to as a second part of the first jaw. The upstream finger 115a of the second jaw 114a of the first gripping mechanism 110a and the downstream finger 115b' of the second jaw 114b of the second gripping mechanism 110b can be collectively referred to as a first part of the second jaw. The downstream finger 115b' of the second jaw 114a of the first gripping mechanism 110a and the upstream finger 115b of the second jaw 114b of the second gripping mechanism 110b can be collectively referred to as a second portion of the second jaw.

[0146] Although the above relates to exemplary embodiments of the invention, it will be understood that the invention is described herein purely by way of example and modifications of detail can be made within the scope of the invention. Moreover, those skilled in the art will understand that the invention cannot be limited to the embodiments disclosed herein or to any details shown in the accompanying figures that are not detailed herein or defined in the claims. In fact, such extraneous features can be omitted from the figures without detracting from the invention. It will also be understood that specific combinations of the various features described and defined in any aspect described herein can be independently implemented and / or provided and / or used. Any apparatus features described herein can be incorporated as method features and vice versa.

[0147] Additionally, other and further embodiments of the invention will become apparent to those skilled in the art from a consideration of the specification and can be devised without departing from its basic scope as determined by the appended claims. [Explanation of symbols]

[0148] 1. Bioprocessing System 2. Robot Devices 3. Robot Arm 4. Thawing Station 6. Centrifuge 8. Magnetic Cell Separator 10 Controller Rate Freezer 11. Refrigerator 12. Incubator 13 Consumables 14. Chassis 18 Rail 20 Processing Stations 100 End Effector 102 First Base Plate 104 Second Base Plate 106 First Mounting Plate 108 Second Mounting Plate 110a First gripping mechanism 110b Second gripping mechanism 112a First Joe 112b First Joe 114a Second Joe 114b The Second Joe 115 Finger 115-1 Proximal end 115-2 Distal end 115-3 Pivot 115-4 Seat part 115a Upstream Finger 115a' downstream finger 115b Upstream finger 115b' downstream finger 116 Cam 116-1 Camshaft 116-2 Worm gear wheel 116-4 Alignment disc 116-5 Notch 116-6 Alignment detector 117 Elastic Members 118 Motor 120 Lifting Mechanism 121 Lift plate drive arm 122 Spring 124 Spring 130a First stopper 130b Second stopper 132 Gearbox 132-1 First Cam 132-2 Second Cam 134 Spring 135 Motor 140 Blade 141 Cut surface 142 Mounting Block 143 First End Plate 143-1 pin 143-2 Slot 144 Link Arm 144-1 Rod 144-2 Groove 144-3 Shaft 144-4 Slot 145 Blade Arm 146 Motor 147 Gearbox 150 tubes 150a upstream section 150a' downstream section 150b upstream section 150b' downstream section 170 Clamp release mechanism 171 Pin 172 Popper engagement arm 173 Spring 190 Arrow

Claims

1. An automated device for joining a first tube to another such tube to thereby form a fluid path therethrough, means for engaging the tube and moving the tube to one or more positions to be operated, means for clamping a portion of the tube, thereby forming a clamped portion of the tube and causing the tube to be fluid-tight upstream of the clamped portion, means for removing an end section of the tube downstream of the clamped portion, thereby forming a new end of the tube within the clamped portion that has not heretofore been in contact with another such tube, means for joining the clamped portion at the new end of the tube to a corresponding clamped portion of another such tube, comprising, wherein the automated device is configured as an end effector for a robotic device, Automated device.

2. The automated device according to claim 1, wherein the end effector is configured to receive power from an external power source via an electrical coupling provided therebetween.

3. The device according to claim 1 or 2, further comprising a sensor configured to determine whether the first tube and / or the second tube is engaged and / or aligned with the means for engaging the tube.

4. The device according to any one of claims 1 to 3, further comprising means for operating the tube once joined to another such tube to release the clamped portion, thereby establishing a fluid path between the joined tubes.

5. The device according to claim 4, wherein the means for operating the tube comprises an automated pinch release mechanism configured to push an edge of the clamped portion of the tube, thereby releasing the clamped portion and opening the welded tube, thereby forming a fluid path through the welded tube.

6. The device according to claim 5, wherein the automated pinch release mechanism is configured to compress the clamped portion of the tube against one or more seats of the means for engaging and moving the tube and the means for clamping a portion of the tube.

7. The automated clamping release mechanism includes a first release element and a second release element, and the first release element and the second release element are configured to engage both edges of the clamped portion of the tube at an interface between the new ends of the first tube and the second tube when joined to each other. The device according to claim 5 or 6.

8. The automated clamping release mechanism is configured to push an edge of the clamped portion by moving along a linear path. The device according to any one of claims 5 to 7.

9. The device according to claim 1 further includes means for stretching an interface between the new ends of the first tube and the second tube when joined to each other to verify the integrity of the joint, and preferably the means for joining is further configured to provide the means for stretching.

10. The device according to claim 1 further includes means for visually inspecting the interface between the new ends of the first tube and the second tube when joined to each other to verify the integrity of the joint.

11. The means for engaging the tube is provided by a tube gripping mechanism including a pair of jaws, and the pair of jaws is operable to move relative to each other between an open configuration for receiving the tube between the pair of jaws and a closed configuration for engaging the tube between the pair of jaws. The device according to any one of claims 1 to 10.

12. The means for clamping a portion of the tube is also provided by the tube gripping mechanism, and the closed configuration of the pair of jaws is configured to clamp the tube between the pair of jaws. The device according to claim 11.

13. The tube gripping mechanism includes a plurality of pairs of gripping elements arranged adjacent to each other, each pair of gripping elements includes a first gripping element and a second gripping element, and each pair of gripping elements is configured to move between the open configuration and the closed configuration. The device according to claim 12.

14. The first pair of gripping elements and the adjacent second pair of gripping elements are spaced apart to provide a gap for receiving between them means for removing an end section of the tube. The device or mechanism according to claim 13.

15. The means for removing the end section of the tube, configured such that after the first pair of gripping elements are configured to engage a first portion of the end section of the tube, a second pair of gripping elements are configured to engage an adjacent second portion of the end section of the tube, thereby forcing fluid within the tube away from the first portion of the tube and then extruding it towards the second portion of the tube, and then operating to remove a portion of the end section of the tube on the other side of the first pair of gripping elements, as claimed in claim 13.

16. The apparatus or mechanism according to any one of claims 13 to 15, wherein the gripping mechanism is controllable to tighten different portions of the portion of the tube while releasing other portions of the portion of the tube.

17. The apparatus or mechanism according to claim 16, wherein the gripping mechanism is controllable to hold the portion of the tube between at least one pair of gripping elements in the closed configuration, while at least one different pair of gripping elements move to the open configuration to release a portion of the portion of the tube such that the portion of the portion of the tube is exposed.

18. The apparatus or mechanism according to claim 17, further comprising means for inspecting the released or exposed portion of the portion of the tube.

19. The apparatus or mechanism according to claim 17 or 18, wherein one or more of the means for operating the tube to release the clamped portion are configured to compress the released or exposed portion of the portion of the tube.

20. The apparatus or mechanism according to any one of claims 13 to 19, wherein the plurality of pairs of gripping elements of the gripping mechanism are controllable to move the engaged tube in a direction substantially perpendicular to the longitudinal length of the tube with respect to the gripping mechanism.

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