Systems, devices and methods for bioprocessing

Abstract

A frame for holding a bioprocessing consumable, the consumable comprising a plurality of processing elements connected by one or more flexible tubes, the frame comprising: a first subframe configured to retain a first portion of the consumable, the first subframe comprising an engagement feature arranged to enable engagement of the first subframe by a robotic device; and a second subframe configured to retain a second portion of the consumable that is joined to the first portion by a flexible tube; a mounting element for releasably attaching the second subframe to the first subframe, wherein the mounting element is configured to enable manipulation of the first subframe together with the second subframe when the mounting element is in an attached configuration, and to enable manipulation of the second subframe separately to the first subframe when the mounting element is in a released configuration.

Description

[0001] SYSTEMS, DEVICES AND METHODS FOR BIOPROCESSING

[0002] FIELD OF THE INVENTION

[0003] The present invention relates to bioprocessing systems and devices, and methods of operating said systems and devices autonomously.

[0004] BACKGROUND

[0005] Bioprocessing operations such as cell therapy typically involve a large number of steps. For example, in a CAR-T process, the method may involve a sequence of steps starting with a cryopreserved leukopak, thawing, washing to remove DMSO, enrichment of T cells, activation, transduction, expansion, concentration, formulation fill-finish into an IV bag, and cryopreservation, with several intermediate washing steps. Thus, there is a need to transfer fluid and cell material between a plurality of different containers (e.g., through tubing), with different processes being carried out on fluid and cell material in different containers. To date, these processes and transfers are usually performed with labour-intensive manual processes.

[0006] One typical manual approach is to use complex consumable elements where the different types of containers are preconnected together with flexible tubes having a predetermined arrangement and length. This means that an operator can load the complex consumable element into a bioprocessing apparatus, and the apparatus can perform a predetermined sequence of manipulations and transfers on the complex consumable without further operator intervention being required. For example, the tubes of the complex consumable may be loaded into peristaltic pumps on the apparatus, and with the connected containers being installed into predetermined locations such as incubators, centrifuges, sensors or other equipment. However, this loading process of the consumable element into the apparatus is very time consuming, where even an experienced operator may take up to one hour to correctly install the containers and tubes into the apparatus. In addition, since reliability is essential for any operations involving patient samples, several operators are often required to monitor and check that the installation isperformed correctly. Therefore, it is desirable to at least partially automate bioprocessing operations to eliminate these time-consuming manual processes. However, until recently, automation of such operations has not even been considered, due to high standards required for sterility and reliability when handling cell samples. For example, the manipulation of flexible tubes and bags of fluid is not typically considered feasible for robotic devices, since flexible components (such as tubes and fluid bags) are hard to handle and occupy indeterminate positions in 3D space. Furthermore, the bioprocessing apparatus receiving the consumable is designed to be loaded by human operators and not robotic devices, so it has not been considered to try and automate such loading operations due to the precise manual manipulation required.

[0007] Another approach for automation of bioprocessing operations is described in WO2023 / 281257, where the containers are provided individually with flexible tubing that is connected together when required using automated tube welding. This provides a bioprocessing system that can perform any of the bioprocessing steps required and which is reliable and flexible to modifications. However, since many facilities are accustomed to using the complex consumable elements and already own bioprocessing apparatuses that are compatible with the complex consumables, there may be reluctance to make the switch to a type of system where both the consumables and apparatuses are completely replaced. Therefore, there is a desire to provide automated bioprocessing systems, apparatuses and devices that address these problems.

[0008] SUMMARY OF INVENTION

[0009] According to an aspect of the present invention, there is provided a frame for holding a bioprocessing consumable, the consumable comprising a plurality of processing elements connected by one or more flexible tubes, the frame comprising: a first subframe configured to retain a first portion of the consumable, the first subframe comprising an engagement feature arranged to enable engagement of the first subframe by a robotic device; and a second subframe configured to retain a second portion of the consumable that is joined to the first portion by a flexible tube; a mounting element for releasably attaching the secondsubframe to the first subframe, wherein the mounting element is configured to enable manipulation of the first subframe together with the second subframe when the mounting element is in an attached configuration, and to enable manipulation of the second subframe separately to the first subframe when the mounting element is in a released configuration.

[0010] Advantageously, once the consumable is mounted on the frame, minimal manipulation is required by a robotic device to install the consumable into a bioprocessing apparatus. For example, the consumable may be supplied to a facility already mounted in the frame. Then a robotic device may engage the engagement feature to place the frame onto the apparatus (including locating a portion (e.g., the first portion or second portion) of the consumable in its corresponding location in, on, or near the apparatus), disconnect the mounting element, and then, via engagement of the engagement feature, move the other portion of the consumable portion to install it in its corresponding location in, on, or near the apparatus (or in, on, or near a separate apparatus). This means that the installation can be carried out by a robotic arm that only needs to engage the frame at a single location at any given time. Furthermore, when the second subframe is attached to the first subframe using the mounting element, the frame can be in a much more compact arrangement that can be expanded during installation of the consumable into the bioprocessing apparatus(es). This means that the frames can be more efficiently stored and transported and are easier to handle by robotic devices. By allowing movement of the consumable together (rather than different portions individually), the lengths of tubing can be minimized, which reduces risk of entanglement. Additionally, the installation process can be easily reversed to remove the consumable from the apparatus, thereby enabling a further consumable to be quickly installed at the apparatus. Alternatively, the subframes may be transported together without the processing elements being connected by flexible tubes; here the flexible tubes may be connected once installed at the apparatus (such as using tube welding).

[0011] The engagement feature may be a first engagement feature, and the second subframe may comprise a second engagement feature to enable engagement ofthe second subframe by the robotic device. Advantageously, the first and the second subframe can each be manipulated independently with their corresponding engagement feature. Alternatively, the frame may include only a single engagement feature that enables independent manipulation of both the first and second sub-frames. For example, when the mounting element is in the connected configuration, the robotic device may engage the engagement feature and move both the sub-frames so that the second subframe is installed at the bioprocessing apparatus. Then once the second subframe is installed, the robotic device may continue to manipulate the engagement feature, thereby separating the first subframe from the installed second subframe. Subsequently, the first subframe can be installed at its corresponding location at the bioprocessing apparatus.

[0012] The mounting element may be configured to detach the second subframe from the first subframe during manipulation of the second subframe with the second engagement feature. For example, the mounting element may detach when a threshold force is reached. Alternatively, the mounting element may detach when the second subframe is manipulated in a predetermined motion, such as to unclip, unhook or otherwise unfasten the second subframe from the first subframe. Where only a single engagement feature is used, the mounting element may be configured to detach the subframes during manipulation of the first subframe with the (first) engagement feature.

[0013] The mounting element may be a reversible mounting element, preferably wherein the mounting element comprises one or more of: a hook, clip, a magnetic connector. Alternatively, or additionally, the mounting element may include: a spring detent, a friction fit, quick release pins, screw features, a bayonet mount, and / or an adhesive. Alternatively or additionally, the one sub-frame may rest upon a mounting element on another sub-frame (i.e. , by gravity) so that the upper subframe can by lifted off when required.

[0014] Alternatively, the mounting element may be a single use mounting element, preferably wherein the mounting element comprises one or more of: an adhesive, or a snap or break connector. The single use mounting element may move fromthe connected configuration to the released configuration when a threshold force is applied.

[0015] Preferably, the frame further comprises one or more installation features to enable the frame to be installed in or on a bioprocessing apparatus (or in or on different bioprocessing apparatuses within the system). The type of installation feature depends on where the subframe is installed on the apparatus, and the operations being carried out on the subframe. Generally, one or both of the subframes may be installed on the apparatus in slots, grooves or rails. Therefore, the installation features may include elements shaped to fit within the slots, grooves, or rails. The installation features may include, clamps or clips, or components configured to fit within corresponding clamps or clips on the bioprocessing apparatus. The installation features may be passive features. Alternatively, active components may be used to connect the subframes to the apparatus. For example, the installation feature may include a motor or a solenoid.

[0016] The installation features may correspond to the mounting features, which may enable a common connection to be used both between the subframes, and to connect a subframe to the bioprocessing apparatus.

[0017] In some examples, the installation features of the frame may enable the frame to be installed into different apparatuses (e.g., different types of bioprocessing apparatus having different purposes or processing elements). For example, the frame may comprise a plurality of different installation features so that the frame is compatible with different apparatuses. Alternatively or additionally, the frame may comprise at least one installation feature which is itself designed to interface with a plurality of apparatuses. By providing a smaller number of versatile (or universal) installation features, the manufacturing complexity and space required on the frame may be reduced.

[0018] Although the installation features may themselves be sufficient to attach the frames to an apparatus, it will be appreciated that an apparatus may be modified to facilitate the installation of the frame at, on or near the apparatus. For example,an external housing of an apparatus may be modified or supplemented to enable installation features on the frame to be attached thereto.

[0019] Preferably, the frame further comprises a plurality of attachment features, each corresponding to one of the plurality of processing elements, thereby enabling the processing elements to be connected to the frame. As used herein, the term “processing element” preferably refers to an element of the consumable where a particular processing operation takes place. Depending on the particular workflow being performed, many different processes may need to take place, which can occur in various types of container, chamber, tube, or other element. For example, the processing elements may include one or more of: filters, centrifuges, microfluidic chips, valving blocks, pumping tubes (for use with peristaltic pumps, such as tubing made of silicon), bioreactors, cell culture plates, magnetic cell separation columns, electroporation chambers and chips, cell sorting chips, analytics elements (e.g., for cell sorting and cell counting, pH, DO, Biomass sensors), microscope elements, storage chambers or containers, fluid bags for waste or cell material. The processing elements may include ports where liquid or gas can be added or removed from the consumable, such as a port for air.

[0020] The attachment feature may comprise a clip and / or a clamp that retains a processing element in place on the frame.

[0021] Both the first subframe and the second subframe may comprise one of the plurality of attachment features. Advantageously, this allows separate processing elements to be attached to different subframes, thereby enabling them to be installed at different locations of a bioprocessing apparatus (or different apparatuses). Alternatively, in some situations, it may be beneficial to have multiple attachment features provided on the same sub-frame, since this reduces the number of robotic actions required for the installation process and reduces the number of parts and complexity of the frame.

[0022] Preferably, the frame comprises at least one tube storage feature to enable a flexible tube to be secured to the frame. Advantageously, the at least one tube storage feature may keep the tubes fixed in predetermined positions on the frame,which can prevent the tubes from becoming entangled during movement of the frame or the subframes.

[0023] The tube storage feature may comprise a tube routing feature to arrange the flexible tube in a predetermined pathway on the frame. Advantageously, this allows large lengths of tubing to be compactly retained in predetermined positions on the frame. This is particularly advantageous when existing complex consumables are mounted to the frame. Such consumables are largely standardised and include predetermined lengths of tubing so that operations on the consumable can be carried out consistently (e.g., pumping through tubes can be performed for the same duration every time without needing to account for different lengths of tubes). Therefore, by providing a tube routing feature that stores the tubing in a compact manner, there is no need to shorten the flexible tube (e.g., by cutting or sealing) after deployment of the sub-frames. The tube routing feature may comprise grooves and / or slots on the frame. The tube routing feature may comprise a circuitous pathway on the frame, such as a serpentine pathway, zigzag, and / or accordion shape. The tube routing feature may include a concertina rigid frame, and / or kirigami staggered slits in a rubber sheet.

[0024] Alternatively or additionally, the tube storage feature may be a “passive” tube storage feature. For example, the frame may include hooks or a “mushroom” feature, on which a flexible tube can be wrapped (e.g., by a robotic device) for storage. Here, the tube can be pulled out of the passive tube storage feature as required.

[0025] Alternatively or additionally, the tube storage feature may include a tube storage device. The device may store the flexible tube in a coiled configuration, a folded configuration, a helical configuration or any other suitable compact configuration of the tube.

[0026] The tube storage feature may be configured to dispense the tube during manipulation of the second subframe relative to the first subframe. Advantageously, the tube can remain in a stored configuration when the subframes are connected together, and then when the sub-frames are subsequentlyseparated, the flexible tube can be dispensed so that the subframes remain connected by the flexible tube when moved apart.

[0027] Preferably, the tube storage feature enables movement of the flexible tube back to a stored configuration. Advantageously, the subframes can be reconnected together, where the tubing retracts to prevent subsequent entanglement. The tube storage feature may include the tube storage device described herein. The tube storage feature may include a spring-loaded tube spool.

[0028] Alternatively or additionally, the frame may comprise one or more tube guides to constrain movement of the flexible tube during relative movement of the subframes. For example, the frame may include tube clips, runners, and / or pulleys. The tube guides may apply tension to the tubes so that the tube extends in a predetermined pathway between constrained locations. Advantageously, this may reduce the likelihood of entanglement of the tubes with each other and with the subframes.

[0029] The frame may comprise one or more further subframes, each configured to retain a respective portion of the consumable, and one or more further mounting elements for releasably attached the subframes to each other. Any of the features discussed above in relation to the second subframe may apply to any of the further subframes. For example, there may be a single “primary” subframe, where one or more “secondary” subframes are attached to the primary subframe by corresponding mounting elements. Alternatively or additionally, the frame may include one or more “tertiary” subframes that are connected to the secondary subframes by corresponding mounting elements. The specific configuration of the subframes depends upon the specific consumable and the specific apparatus. A transportation frame may be used to transport the frame to the apparatus and then may be removed during installation of the subframes in, on, or near the apparatus. For example, the transportation frame may fit around the subframes to keep them fixed relative to each other. Thus, the transportation frame may present the frame to the robotic device with the correct relative positioning, thereby improving the reliability of the installation process.One or more of the subframes may comprise a device for storing and dispensing a flexible tube, the device comprising: a housing having an internal cavity for retaining a portion of the flexible tube in a stored configuration; an opening in the housing for enabling movement of the flexible tube into and out of the cavity; a guide element arranged in the housing to contact a portion of the tube passing through the opening and configured to direct the portion of the tube into the stored configuration inside the cavity. Further features and advantages of the device are discussed below. Any of these features and advantages also apply when the device is part of one of the subframes.

[0030] One or more of the subframes may comprise a device for holding a flexible fluid bag having a flexible tube fluidly connected thereto, the device comprising: a plurality of retaining elements, including a first retaining element configured to retain a first end of the fluid bag, and a second retaining element configured to retain a second end of the fluid bag, the second end being opposed to the first end; a support structure rigidly connecting the plurality of retaining elements; wherein the support structure is arranged to expose at least one face of the fluid bag when the fluid bag is suspended between the plurality of retaining elements. Further features and advantages of the device are discussed below. Any of these features and advantages also apply when the device is part of one of the subframes.

[0031] One or more of the subframes may comprise a retaining device, comprising: a first retaining element configured to retain a first section of the tube, and a second retaining element configured to retain a second section of the tube, said second section of the tube being spaced from the first section of the tube by an intermediate section of the tube, wherein the first and second retaining elements are configured to retain the first and second sections of the tube such that the intermediate section is bent in an arcuate shape that allows it to be loaded into the pumping location in the peristaltic pump, and an engagement feature to enable a robotic device to position the retaining device to locate the intermediate section of the flexible tube adjacent to the pumping location of the peristaltic pump. The retaining device may be part of the system described herein for loading a flexibletube into a pumping location in a rotary peristaltic pump. Any of the further features and advantages of said system also apply when incorporated into the frame.

[0032] One or more of the subframes may comprise: a loading frame comprising a tube receiving member extending between a first support member and a second support member, the tube receiving member having a tube receiving slot that extends between the first and second support members, wherein the tube receiving slot extends at least partially into each of the first and second support members thereby forming tube insertion slots; and an insertion element configured to be inserted into the loading frame thereby to move the tube from a first position, in which the tube is positioned within the tube receiving slot, to a second position, in which the tube is positioned within the tube insertion slots and extends between the first and second support members. The (loading) frame may be part of the system described herein for loading a flexible tube into a processing channel of a bioprocessing apparatus. Any of the further features and advantages of said system also apply when incorporated into the frame.

[0033] According to another aspect of the present invention, there is provided an apparatus comprising the frame as described above and herein, and a bioprocessing consumable, wherein the bioprocessing consumable comprises a first processing element retained on the first subframe, and a second processing element retained on the second subframe, wherein the first processing element and the second processing element are connected together by at least one flexible tube.

[0034] According to another aspect of the present invention, there is provided a method of performing bioprocessing using the frame or apparatus described above and herein, the method comprising using an automated system to: engage the frame using the engagement feature; install one of the first or second subframe at a corresponding location of the bioprocessing apparatus; disconnect the second subframe from the first subframe; and install the other of the first or secondsubframe at a corresponding location of the bioprocessing apparatus (or at a corresponding location of a different bioprocessing apparatus).

[0035] The automated system may comprise one or more robotic devices, and / or any other suitable automated devices such as conveyors. Different steps may be carried out by different parts of the automated system (e.g., different robotic devices).

[0036] The method may further comprise using the automated system to: engage the frame via the engagement feature; uninstall one of the first or second subframe from its location of the bioprocessing apparatus; reconnect the second subframe to the first subframe using the mounting element; and uninstall the other of the first or second subframe from the bioprocessing apparatus.

[0037] According to another aspect of the present invention there is provided a device for storing and dispensing a flexible tube in a bioprocessing system, the device comprising: a housing having an internal cavity for retaining a portion of the flexible tube in a stored configuration; an opening in the housing for enabling movement of the flexible tube into and out of the cavity; a guide element arranged in the housing to contact a portion of the tube passing through the opening and configured to direct the portion of the tube into the stored configuration inside the cavity. Advantageously, a tube can be dispensed from the device (e.g., by pulling it out of the opening in the housing) as well as reloaded into the device by pushing it back into the opening, since the guide element automatically directs the tube into its stored configuration. The device is preferably loadable by pushing the flexible tube into the opening (e.g., without need for further preparation or loading steps). In other words, the pushing of the tube into the opening is sufficient to direct the tube into the stored configuration, preferably where actuation or engagement of the device is not required during the reloading process. The device does not require moving parts in order to direct the tube into the stored configuration. However, it will be appreciated that moving parts may be included to aid in the loading and dispensing of the tube to or from the device. The stored configuration is preferably a predetermined configuration, such as a coiledconfiguration or a folded configuration. Alternatively or additionally, the stored configuration may include a concertina configuration, a helical configuration, and / or any other configuration of tube that enables compact storage. Thus, the housing and / or guide element of the device are preferably configured to define a single repeatable stored configuration that will consistently be reached when a tube is pushed into the opening. By contrast, if a guide element was not included in the housing, any tubing being pushed back into the opening would not necessarily return to a repeatable position and may instead become entangled within the housing, which may inhibit subsequent dispensing of the tube. The flexible tube may be a thermoweldable tube, and / or may be made of silicon. The device may be referred to as a “tube storage device”. The device may be attached to a bioprocessing apparatus or a bioprocessing device.

[0038] Preferably, the guide element is removably attachable to the housing. For example, a base of the cavity may be provided by the guide element. The guide element can be removed from the cavity to allow the tube to be quickly loaded and / or removed.

[0039] Preferably, the stored configuration is a coiled configuration (e.g., where the tube is coiled around a coiling axis). Advantageously, a coiled configuration allows the tube to be compactly stored in the device in a predetermined manner, thereby reducing the likelihood of entanglement within the cavity. Preferably, the guide element is arranged to direct the portion of the tube into a coiled position around the guide element. In other words, when a tube is stored in the device, the tube is coiled around the guide element. Preferably, the opening is located on the coiling axis. In this way, when the tube is reloaded into the cavity by pushing it through the opening, the tube initially passes along the coiling axis before being deflected by the guide element to direct the tube into the coiled configuration. Since the opening is on the coiling axis, the tube is evenly distributed into the coiled position with a consistent amount of force.

[0040] The guide element may comprise a conical (and / or tapered) portion having a tip arranged adjacent to the opening of the housing. Advantageously, when a tube ispushed into the opening, it is directed into the cavity at an angle, which facilitates coiling of the flexible tube during continued movement of the tube into the opening. The tip may be a pointed tip.

[0041] Preferably, the guide element comprises a port arranged at an opposite of the end of the cavity to the opening, such that the tube is insertable into the cavity through the port. This enables the tube to be inserted into the device through either the opening or the port. For example, the port may be used during initial loading of the tube into the device, with the opening being used for subsequent dispensing and reloading of the tube during use. Particularly where the guide element is removable from the housing, the port provides an easy way to install the tube into the device.

[0042] Preferably, the guide element comprises a guide channel connecting the port to the cavity, wherein the guide channel is angled to direct the tube into the coiled position in the cavity around the guide element. Advantageously, when the tube is directed through the guide channel into the cavity, it is urged towards its coiled configuration. This helps to urge the tube back into its coiled configuration, even when the tube is substantially dispensed and reloaded from the cavity.

[0043] Preferably, the internal cavity is defined between an internal surface of the housing and an external surface of the guide element. Advantageously, the housing and the guide element may be used to constrain the position of the tube in the cavity, which may prevent tangling of the tube when dispensed and reloaded through the opening.

[0044] Preferably, the cavity has a ring-shaped cross section defined between the internal surface of the housing and the external surface of the guide element. The external surface of the guide element preferably has a circular cross section, preferably substantially all the way along the length of the cavity. The internal surface of the housing preferably has a circular cross section, preferably substantially all the way along the length of the cavity. Advantageously, the ring-shaped cross section facilitates coiling of the tube in the cavity.Preferably, a spacing between the internal surface of the housing and the external surface of the guide element is substantially the same as a diameter of the opening. The diameter of the opening preferably substantially corresponds to a diameter of the tube. Thus, the spacing between the surfaces of the housing and guide element preferably corresponds to the diameter of the tube. This reduces the likelihood of entanglement of the tube inside the cavity, since it is not possible for two parts of the tube to become crossed. Preferably the surface spacing and / or diameter of the opening is greater than or equal to the diameter of the tube. Preferably, the surface spacing and / or diameter of the opening is less than two times the diameter of the tube. In this way crossing of tubes is prevented in the cavity. Preferably, the flexible tube is substantially constrained to the shape of a coil by the cavity.

[0045] Preferably, the opening has a curved edge. Advantageously, this enables the tube to be pulled out of the device in any direction facing the opening without the tube snagging on a sharp edge of the opening. Other parts of the external surface of the housing may be curved, smoothed and / or radiused to enable smooth movement of the tube thereover. For example, an external (e.g., circular) edge of the device on which the opening is located may also have a curved edge. This may enable the tube to be pulled in any direction in 3D space (including directions not facing the opening) without a substantial risk of snagging.

[0046] Preferably, the device further comprises one or more tube clips located on an external surface of the housing. Advantageously, where the tube is stored (i.e., not being coiled or uncoiled), a portion of the tube extending out of the opening may be clipped into the tube clips to prevent unwanted movement into or out of the device. Furthermore, the tube is retained at a predetermined position relative to the device, which may facilitate engagement of the tube by a robotic device. The tube clips may be passive tube clips. The tube clips may be friction clips. Preferably the one or more tube clips include two tube clips that are spaced a part with a gap between to facilitate engagement of the tube by a robotic device.Also described herein is an apparatus comprising the device as described above and a flexible tube, wherein the flexible tube is positioned in the stored configuration inside the cavity. Also described herein is a bioprocessing system comprising the device or apparatus as described above and herein.

[0047] According to another aspect of the present invention, there is provided a method of storing a flexible tube using the device of any preceding claim, the method comprising: loading a flexible tube at least partially inside the internal cavity, wherein an end portion of the flexible tube extends out of the opening in the housing; and pushing the end portion of the flexible tube into the opening against the guide element, wherein the guide element directs the tube into a stored configuration inside the cavity. Preferably, the stored configuration is a coiled configuration.

[0048] Preferably, the guide element is removably attached to the housing, and the step of loading of the flexible tube comprises: feeding the flexible tube through a port on an external surface of the guide element so that it extends out of a guide channel of the guide element; feeding the flexible tube from the guide channel out of the opening in the housing; and securing the guide element to the housing to define the internal cavity. Thus, when the flexible tube is subsequently pushed into the cavity through the opening in the housing, the tube is automatically directed to a coiled position by the guide element. This is due in part to the contact between the guide element and the tube as it enters the opening, and in part due to the guide channel of the guide element positioning the tube in a coiled position at an opposite end of the cavity to the opening.

[0049] One or more of the steps of the method may be performed manually. For example, the initial loading of the tube into the device may be performed manually. One or more of the steps of the method may be performed by an automated system, such as a robotic device. For example, a roller mechanism may be provided to drive the flexible tube into the cavity to return it to its stored configuration.According to another aspect of the present invention, there is provided a device for holding a flexible fluid bag having a flexible tube fluidly connected thereto, the device comprising: a plurality of retaining elements, including a first retaining element configured to retain a first end of the fluid bag, and a second retaining element configured to retain a second end of the fluid bag, the second end being opposed to the first end; a support structure rigidly connecting the plurality of retaining elements; wherein the support structure is arranged to expose at least one face of the fluid bag when the fluid bag is suspended between the plurality of retaining elements.

[0050] Advantageously, since the device is a rigid device which may have engagement features located thereon, it can be engaged and manipulated by a robotic device. By contrast, if the device was not used to hold the flexible bag, it would be difficult to accurately locate and manipulate the flexible bag to perform bioprocessing operations using a robotic device. Furthermore, the support structure can have a low form-factor which means that the bag can still be inserted into a separate piece of bioprocessing apparatus (which usually fit tightly around the fluid bags). In particular, by suspending the fluid bag with one of its faces exposed, processing (e.g., heating, magnetic manipulation, or similar) can be performed on the bag via its exposed face without needing to remove the bag from the device. Thus, the device enables manipulation of the bag by a robotic device without affecting the ability to process the fluid in the bag with a bioprocessing apparatus.

[0051] As used herein the term “fluid bag” preferably refers to a flexible bag that is capable of being filled with fluid. The term “face” preferably refers to a substantially flat surface of the bag; however, it will be appreciated that due to the flexibility of the bag, the face may still be curved (e.g., when filled with fluid) provided that processing can still be performed on the fluid bag via the exposed face.

[0052] Preferably, the face of the bag that is exposed is substantially exposed. To achieve this, the support structure preferably does not include any side panels that extend across or cover the face of the bag. This face is preferably exposedin at least a central region. For example, the support structure may be configured to expose at least 50% of the face of the fluid bag, preferably at least 75% of the fluid bag, and more preferably at least 80% of the fluid bag, though it will be appreciated that more of the face may be exposed, such as 90%, 95% or 100% of the face.

[0053] The support structure may be configured to enable the exposed face of the bag to at least partially protrude (e.g., extend or bulge) out of the device. In this way, when the bag is inserted into a bioprocessing apparatus, the exposed face of the bag may contact a processing instrument (e.g., heater) without parts of the support structure being an obstruction. In one possible implementation, a thickness of the fluid bag (e.g., as measured between its opposing faces) may be greater than a thickness of the support structure.

[0054] Preferably, the device is configured to securely retain the fluid bag in any orientation. While alternative implementations may only suspend the bag from one end (with the other end not directly retained by a retaining element), such devices need to remain vertical to keep the bag retained within the device. However, by suspending the bag between two retaining elements at opposing ends, it is possible to hold the bag horizontally (or in any other orientation) while keeping the bag at a consistent position within the device. For example, the device can be used to securely and consistently position the exposed surface of the bag on a horizontal processing surface (e.g. a heating plate or similar surface in a bioprocessing apparatus).

[0055] The bag may be formed from two sheets of material (e.g., plastic) that are joined (e.g., welded) together around at least part of a perimeter of the sheets so that fluid may be contained between the sheets in the unjoined central portion. With this construction, the (outer) surface of an unjoined central portion of the sheets of material may be referred to as the “face” of the bag. For example, the bag may be substantially rectangular (e.g., when not filled with fluid). The shortest opposing edges of the rectangular bag may be referred to as the ends of the bag. The longest opposing edges of the rectangular bag may be referred to as the sidesof the bag. A direction between the ends of the bag may be referred to as a longitudinal direction or longitudinal axis. It will be appreciated that non-rectangular bags may be used with the device.

[0056] Preferably, at least one of the plurality of retaining elements is offset from a longitudinal axis of the support structure. Preferably each of the retaining elements are offset from the longitudinal axis of the support structure. Advantageously, the fluid bag can be suspended between the first and second retaining elements without the support structure obstructing the filling or processing of the bag. Typically, where the bag is filled with fluid, it may expand or bulge towards its centre. Therefore, by offsetting the retaining elements from the support structure, the bag can expand without being adversely affected by the support structure. The offset may be perpendicular to the longitudinal axis, preferably in a direction towards the exposed face of the bag.

[0057] Each of the plurality of retaining elements may comprise one or more of: a clamp, or a hook. For example, a clamp may be provided as the first retaining element. The clamp may attach to a rim or perimeter of the fluid bag. A hook may be provided as the second retaining element. The hook may attach to a corresponding opening or loop at the second end of the bag. Advantageously, the hook can be easily attached and detached from the bag. The device may comprise a plurality of further retaining elements, which may be disposed around the perimeter of the bag. For example, the bag may have several openings or loops around its perimeter, where the device includes a plurality of hooks corresponding to each of these openings or loops.

[0058] In some processes it may be preferable for the retaining elements to be detached during the bioprocessing operation, such as where decreased tension on the bag is required. The detachment may be performed automatically, such as with a robotic device.

[0059] Alternatively or additionally, the retaining elements may include an adhesive (e.g., adhesive pads or beads), magnetic clips (that interface with correspondingmagnetic elements in the bags), straps, zip-ties, a weld, or any other suitable means for retaining the fluid bag on the device. Any of the retaining elements discussed above may be used in any combination with each other.

[0060] The first retaining element may comprise tube management features to retain the flexible tube in a predetermined position on the device. For example, the first retaining element may comprise tube routing features, tube clips, and / or tube guides. The tube clip may be a passive clip, such as a friction clip.

[0061] The device may further comprise means for applying tension to the fluid bag when suspended between the plurality of retaining elements. Advantageously, the face of the bag can be held taught thereby providing a flatter surface for processing by an external apparatus. For example, the first and second retaining elements may be movable parallel to the longitudinal axis to apply tension to the bag. Alternatively, a tube retaining element may pull on the flexible tube to apply tension to the bag. One or more of the retaining elements may comprise a spring. The retaining elements may be spaced from each other so that they only apply tension to the fluid bag when it is filled with fluid.

[0062] The support structure may comprise an elongate strut extending between the first retaining element and the second retaining element such that a face of the bag opposite to the strut is exposed when the bag is suspended between the retaining elements.

[0063] The strut or “support arm” may have a first end connected to the first retaining element, and a second end connected to the second retaining element. The strut may extend between the first and second ends along a longitudinal axis. The strut may comprise a bar, a rod or a beam. The strut may comprise a planar surface. Where the device includes further retaining elements, the support structure can include any number of struts or other elements that extend in any direction to connect them together.Preferably, the strut comprises a bend adjacent to the second retaining element. Advantageously, this bend may provide an offset from the longitudinal axis of the strut, thereby allowing the fluid bag to expand in the device without the strut being an obstruction.

[0064] The support structure may comprise a rim that connects the first retaining element to the second retaining element around at least one side of the bag, such that at least two opposing faces of the bag are exposed when the bag is suspended between the retaining elements. In other words, the rim may extend around at least part of a perimeter of the fluid bag. Advantageously, this may allow for processing of the bag from both of its opposing faces. For example, heating the bag by both of its faces may be more efficient than only heating a single face.

[0065] The rim may connect the first retaining element to the second retaining element around two opposing sides of the fluid bag, such that the fluid bag is suspended around its perimeter. The rim preferably provides a plurality of retaining elements substantially all the way around the perimeter of the bag. Conceptually, this can be considered as providing continuous retention of the fluid bag around its perimeter. Advantageously, by constraining the fluid bag around its perimeter, when the bag is filled with fluid, the bag is forced to expand only in a thickness direction, thereby improving contact between the exposed face of the bag and a bioprocessing apparatus. The rim may be provided in two parts that connect together and clamp the perimeter of the fluid bag therebetween. The two parts may connect together in a clamshell arrangement.

[0066] Preferably, the rim has a thickness that is less than a thickness of the fluid bag when the bag is filled with fluid. Advantageously, this means that when the device is placed into an external bioprocessing apparatus, the rim does not prevent contact between the face of the bag and the apparatus. It will be appreciated that when not filled with fluid, the bag may be substantially flat. However, when filled with fluid, the bag expands and / or bulges around its centre. Preferably, the thickness of the rim is 20% or less than the length of the bag (which maycorrespond to the distance between the retaining elements), more preferably 10% or less, still more preferably 5% or less.

[0067] The support structure may comprise a (e.g., support) plate arranged to substantially cover a face of the fluid bag and expose an opposite face when the fluid bag is suspended between the first and second retaining elements. Advantageously, by covering an opposing face, the plate may provide support to the bag when it is placed into a bioprocessing apparatus. The plate may allow device to apply pressure to the fluid bag against a processing surface (e.g., a heater), thereby increasing surface contact and efficiency of the processing. The device may be used as one of the subframes as described above and herein. Therefore, the device may have any of the features previously described in relation to the subframes, such as tube storage features and / or engagement feature.

[0068] The plate may comprise a ledge (e.g., a rim) configured to surround a perimeter of the fluid bag when it is suspended between the first and second retaining elements. Advantageously, this helps to maintain the shape of the bag when empty, and to increase contact between the exposed face of the bag with the bioprocessing apparatus. Furthermore, when the device is used to place the fluid bag into the apparatus, the plate and the ledge may be used to provide an enclosure around the fluid bag. The enclosure may prevent light from entering the apparatus when installed in the apparatus, which may be beneficial if light sensitive sensors are used to perform processing (e.g., sensing) on the fluid bag. The enclosure may provide thermal insulation, which may be beneficial where the fluid bag is placed into an incubator operating above room temperature (e.g., at 37°C).

[0069] The device may be separable into separate pieces, which may facilitate loading of the flexible bag and flexible tube within the device. Furthermore, this can facilitate assembly, disassembly, cleaning and re-use of the device within a factory setting. For example, the separate pieces may enable the device to be assembled around the bag and / or the tube. One or both pieces of the device may have tubeclips (e.g., a tube storage feature) to keep the tube in position during assembly of the device. The attachment of the tube to the device may serve as a further attachment of the flexible bag to the device. Tension may be applied to the tube to apply tension to the flexible bag.

[0070] The device may further comprise an engagement feature to enable manipulation of the device by a robotic device. The engagement feature may be provided on the support structure, preferably at a central position on the support structure. Advantageously, this means that the device is engaged substantially at the centre of mass of the device, which means that the device is easier to manipulate with a robotic device. Alternatively, the engagement feature may be provided on the first or second retaining element.

[0071] According to another aspect of the present invention, there is provided a system for loading a flexible tube into a pumping location in a rotary peristaltic pump, the system comprising: a retaining device, comprising: a first retaining element configured to retain a first section of the tube, and a second retaining element configured to retain a second section of the tube, said second section of the tube being spaced from the first section of the tube by an intermediate section of the tube, wherein the first and second retaining elements are configured to retain the first and second sections of the tube such that the intermediate section is bent in an arcuate shape that allows it to be loaded into the pumping location in the peristaltic pump, and an engagement feature to enable a robotic device to position the retaining device to locate the intermediate section of the flexible tube adjacent to the pumping location of the peristaltic pump.

[0072] Advantageously, the retaining device can position the intermediate section of tube in the correct shape, which means that subsequent steps to install the intermediate section of tube into the pumping location (e.g., using an installation device) can be relatively simple. The term “pumping location” preferably refers to a location in the peristaltic pump where a pumping operation occurs. For example, the peristaltic pump may have a pair of jaws that are movable between an open configuration where the tube can be inserted therebetween, and a closedconfiguration, where the pump is operable to effect a peristaltic pumping action on the tube. The pump is preferably a rotary peristatic pump, where the first jaw comprises a curved plate, and the second jaw comprises a roller. When in the open configuration, an arcuate (or curved) gap or channel may be present between the jaws. When in the closed configuration, the roller may rotate, thereby compressing the flexible tube against the curved plate and urging fluid through the flexible tube. The arcuate shape of the intermediate section corresponds to the arcuate shape of the gap between the jaws. The arcuate shape preferably substantially corresponds to an arc of a circle; however, it will be appreciated that other arcuate or curved shapes may be used, provided that they enable a flexible tube to be inserted within a corresponding pumping location in a peristaltic pump.

[0073] The engagement feature advantageously enables the flexible tube to be loaded into the pumping location using a robotic device (i.e., without the need for a human operator to position the flexible tube or retaining device). The engagement feature may comprise a protrusion or indentation (or any other suitable feature) that is specifically shaped to interface with an end effector of a robotic device (e.g., on a robotic arm), thereby enabling the precise position of the retaining device to be controlled by movement of the end effector. Due to the difficulties in handling and loading flexible tubes, loading operations are typically performed manually by human operators. However, by providing a robotically engageable retaining device that correctly positions the tube for installation into the peristaltic pump, it is possible to consistently load a flexible tube into a pumping location of a peristaltic pump without the need for any operator intervention. The engagement feature may correspond to any of the engagement features described herein (e.g., those discussed in relation to other aspects of the present disclosure). For example, the engagement feature may comprise a substantially triangular element.

[0074] The first retaining element and / or the second retaining element of the retaining device may comprise a clip, groove or slot to retain the respective sections of the tube. The clip, groove or slot may be a passive element that retains the section of the tube with friction (e.g., a friction clip).The first and second retaining elements of the retaining device may be spaced apart such that the intermediate section of the flexible tube is substantially exposed between the first and second retaining elements. Advantageously, the intermediate section of the tube can be directly manipulated by the installation device to load it into the channel. Thus, the system can load the tube into the pumping location of the peristaltic pump in a simple and quick manner.

[0075] The retaining device may further comprise an intermediate retaining element connecting the first retaining element to the second retaining element, the intermediate retaining element configured to retain the intermediate section of the tube in the arcuate shape. Advantageously, by providing an intermediate retaining element, the intermediate section of the tube is constrained to the arcuate shape, which increases the reliability of the insertion of the intermediate section into the pumping location of the peristaltic pump. The first retaining element, second retaining element, and the intermediate retaining element may be integrally formed or may be separate components.

[0076] The system may further comprise an installation device configured to insert the intermediate section of the tube into the pumping location of the peristaltic pump. Advantageously, the installation device can move the flexible tube from a position adjacent to the pumping location to a position inside the peristaltic pump. Alternatively, the retaining device may be manipulated to locate the intermediate portion of tube inside the peristaltic pump without manipulation by a separate installation device.

[0077] The installation device may be attached to the peristaltic pump. In other words, the installation device may be a “local” device arranged at a fixed position relative to the peristaltic pump. Alternatively, the installation device may be separate to the peristaltic pump, such as a tool on an end effector of a robotic arm, which directly manipulates the flexible tube into the pumping location.The installation device may comprise an arm movable to press the intermediate section of the tube into the pumping location when the tube is arranged adjacent to the peristaltic pump by the retaining device. The arm may pivot and / or may follow an arcuate pathway when pressing the intermediate section of the tube into the pumping location.

[0078] The installation device may comprise one or more motors or actuators to move the arm. The actuators may comprise linear actuators.

[0079] Alternatively or additionally, the arm may comprise an interface to enable movement of the arm by a robotic device. For example, the arm may comprise an engagement feature so that the robotic device can engage (e.g., grip) the arm and move it along a predetermined (e.g., arcuate) pathway to push the intermediate section of the flexible tube into the pumping location.

[0080] The retaining device may be a first retaining device for loading a first flexible tube into a first rotary peristaltic pump, and the system comprises a second retaining device for loading a second flexible tube in a second peristaltic pump, wherein the first and second retaining device are connected to each other by a frame. One or more additional retaining devices may be provided on the frame. Some bioprocessing apparatuses include several peristaltic pumps, so that pumping steps can be performed on flexible tubes simultaneously. While these pumps could be loaded separately, by using a frame that connects the retaining devices (e.g., so that they are located at predetermined positions relative to each other), a single loading operation may be used to load tubes into all of the peristaltic pumps. The relative position of the retaining devices on the frame preferably corresponds to the relative position of the peristaltic pumps on the apparatus.

[0081] The system may further comprise a closing device attached to the peristaltic pump, wherein the closing device is operable to move the peristaltic pump between an open position, in which the flexible tube is movable into the pumping location, and a closed position, in which the peristaltic pump is configured to effect a peristaltic pumping action on the flexible tube. Where the bioprocessing systemincludes a plurality of peristaltic pumps, a single closing device may be used to move all of the pumps to their closed position at the same time. Alternatively, different closing devices may be used for different peristaltic pumps.

[0082] The closing device may comprise one or more motors or actuators. Alternatively or additionally, the closing device may comprise an engagement feature to enable manipulation of the closing device by a robotic device to move the peristaltic pump between its open and closed positions.

[0083] The system may further comprise a loading device, the loading device comprising a curved channel corresponding to the arcuate shape, whereby the loading device can be positioned between the first and second retaining elements of the retaining device so that the flexible tube can be positioned therein with its intermediate section supported in the arcuate shape.

[0084] The loading device may be moved during loading of the tube into the retaining device. For example, the loading device may be slidably mounted to the retaining device so that it contacts the pump during loading. Advantageously, the loading device ensures that the tube is always loaded into the retaining device with its intermediate section in the same arcuate shape. Where the loading device is not used for this, the tube may be loaded with its intermediate section following a different pathway between the first and second retaining elements. Depending on how much this pathway differs from the preferred arcuate shape, correct loading of the flexible tube into the pumping location may be inhibited. Thus, by using a loading device, the tube can be more reliably inserted into the peristaltic pump. Alternatively or additionally, markers may be provided on the tubing (e.g., a fixed distance apart) to aid insertion of the tube into the retaining device. The markers may identified by an automated system (e.g., a machine vision system) to confirm that the tube is correctly loaded into the retaining device.

[0085] According to another aspect of the present invention, there is provided a system for loading a flexible tube into a processing channel of a bioprocessing apparatus, the system comprising: a frame comprising a tube receiving member extending between a first support member and a second support member, the tube receivingmember having a tube receiving slot that extends between the first and second support members, wherein the tube receiving slot extends at least partially into each of the first and second support members thereby forming tube insertion slots; and an insertion element configured to be inserted into the frame thereby to move the tube from a first position, in which the tube is positioned within the tube receiving slot, to a second position, in which the tube is positioned within the tube insertion slots and extends between the first and second support members.

[0086] Advantageously, the system can be operated by a robotic device to load a flexible tube into a processing channel. As used herein, the term “processing channel” preferably refers to any channel, indentation, groove or slot where processing steps in the bioprocessing operation may be carried out. The processing includes manipulation of the flexible tube (e.g., applying heat, or light), as well as sensing of the tubing. Thus, the processing channel may be a sensor on a bioprocessing apparatus. The alignment of the tube with the processing channel is facilitated with the frame, and movement of the tube is facilitated with the loading element, where the tube remains supported by both of the tube insertion slots as it moves from its first position to its second position. These elements are easy to position and operate using a robotic device, thereby allowing a flexible tube to be loaded into a processing channel autonomously without the need for a human operator to perform the precise manipulation steps.

[0087] Preferably, the insertion element is a plate configured for insertion into the tube receiving slot.

[0088] Preferably, the insertion element is configured to form a seal with the tube receiving slot when the flexible tube is in the second position. Advantageously, the insertion element can act as a light guard, which may be preferable if optical measurements are taken in the processing channel.

[0089] The system may further comprise a manipulation tool having an engagement feature to facilitate movement of the manipulation tool by a robotic device, wherein the manipulation tool comprises the insertion element. In this way, the roboticdevice (e.g., robotic arm), can pick up the manipulation tool and push the insertion element on the tool into the tube receiving slot, thereby moving the tube to its second position to load it in the processing channel. The robotic device can release the manipulation tool to leave it in place while processing on the tube takes place; thus, the manipulation tool can act as a light guard when optical measurements are carried out. Then the robotic device can re-engage the engagement feature to remove the insertion element from the frame.

[0090] The system may further comprise an insertion guide to retain the insertion element adjacent to the flexible tube in its first position. Advantageously, the tube may be initially inserted into its first position in the frame. Then the insertion guide can be mounted onto the frame, so that the insertion element is retained adjacent (e.g., above) to the flexible tube. In other words, the insertion guide supports the insertion element adjacent the tube. Subsequently, the insertion element can be manipulated (e.g., with an external robotic device) to push the insertion element through the insertion guide and through the tube receiving slot, thereby urging the flexible tube from the first position to the second position.

[0091] Preferably, the insertion guide has a lower surface with a shape corresponding to an upper surface of the tube receiving member, preferably wherein a seal is formed between the insertion guide and the tube receiving member. Advantageously, the insertion guide (e.g., in combination with the insertion element) can act as a light guide.

[0092] The system may further comprise a manipulation tool having an engagement feature to facilitate movement of the manipulation tool by a robotic device. The manipulation tool may comprise a protrusion configured to extend into the insertion guide to press the insertion element against the flexible tube.

[0093] According to another aspect of the present invention there is provided a method of using the system of any preceding claim, the method comprising: position the frame on a bioprocessing apparatus to align a processing channel of the apparatus between the first support member and the second support member; place a flexible tube into a first position in the frame where a central portion of thetube is retained in the tube receiving slot of the frame; insert an insertion element into the frame to urge the tube through the insertion slots so that the flexible tube is moved to a second position where the central portion of the tube is loaded into the processing channel between the support members. Preferably, at least the placing and inserting steps are performed autonomously by a robotic device.

[0094] It will be understood by a skilled person that any apparatus feature described herein may be provided as a method feature, and vice versa. It will also be understood that particular combinations of the various features described and defined in any aspects described herein can be implemented and / or supplied and / or used independently.

[0095] Moreover, it will be understood that the present invention is described herein purely by way of example, and modifications of detail can be made within the scope of the invention.

[0096] BRIEF DESCRIPTION OF DRAWINGS

[0097] One or more embodiments will now be described, purely by way of example, with reference to the accompanying figures, in which:

[0098] Figure 1 shows a schematic diagram to illustrate the steps of a bioprocessing operation;

[0099] Figures 2A and 2B show an automated bioprocessing system, and a robotic device that is part of the automated bioprocessing system;

[0100] Figures 3A to 3C schematically show the installation of a first frame comprising two subframes in a bioprocessing apparatus;

[0101] Figures 4Ato 4C schematically show the installation of a second frame comprising two subframes in a bioprocessing apparatus;

[0102] Figures 5A to 5E show a particular example of a frame comprising three subframes being installed in a bioprocessing apparatus;

[0103] Figures 6A and 6B show external views of a tube storage device;Figures 7A to 7E show exploded views and cross-sectional views of the tube storage device in Figures 6A and 6B;

[0104] Figures 7F to 7H show an alternative tube storage device where an outer surface of the housing is rounded;

[0105] Figures 8A to 8E show a first example of a device for holding a flexible fluid bag; Figures 9A to 9D show a second example of a device for holding a fluid bag; Figures 10Ato 10D show a third example of a device for holding a fluid bag; Figures 11 A to 11 C show a first example of a system for loading a flexible tube into a processing channel such as a sensor;

[0106] Figures 12A to 12C show a second example of a system for loading a flexible tube into a processing channel such as a sensor;

[0107] Figures 13A and 13B show a system for loading a flexible tube into a rotary peristaltic pump, where the system includes a retaining device for holding the flexible tube;

[0108] Figures 14A to 14D show further features of the system, where an installation device is included to press the tube into the rotary peristaltic pump;

[0109] Figures 15A and 15B show an alternative retaining device that may be used to install a flexible tube into a peristaltic pump;

[0110] Figures 16A to 16D show a loading device that may be used with the retaining device in Figures 13Aand 13B to install the flexible tube into the peristaltic pump; Figures 17A and 17B show a closing device that may be used in the system so that the peristaltic pump can be closed by a robotic device; and

[0111] Figures 18A and 18B show a system where a frame is used to facilitate simultaneous loading of two peristaltic pumps.

[0112] DETAILED DESCRIPTION

[0113] The present disclosure relates generally to bioprocessing systems and methods. A bioprocessing method usually includes a large number of steps to be carried out in a specific sequence. For example, a process may involve steps such as thawing a cryopreserved sample, enrichment of T-cells, activation, transduction, expansion, concentration, formulation fill-finish into IV bags, and cryopreservation.A schematic diagram showing exemplary steps of this process is shown in Figure 1. At a cell washing and concentration stage, cell material and buffer are added (from containers 60-1, 60-2) to a chamber 60-3 for washing, and waste material is removed to waste bag 60-4. Then the sample may be transferred via intermediate container 60-5 to an activation transduction and expansion stage, where the material is mixed with reagents (from containers 60-11 ) and media (from container 60-12) in an expansion chamber 60.13. Waste is removed to another waste container 60-14, and the expanded cell culture is moved to a harvest chamber 60-15. From here the process proceeds to a fill finish stage, where the cell culture is mixed with a final formulation 60-21 in a mixing chamber 60-22. The final product is then moved to several product bags 60-23, 60-24, 60-25 and a quality control QC bag 60-26.

[0114] In many existing bioprocessing systems, several of these steps are performed using corresponding bioprocessing apparatuses, into which a complex consumable element is installed. In one possible example, the entire process discussed above may be performed with a single consumable, having preconnected containers. Alternatively, there may be separate consumables corresponding to the cell washing and concentration stage, the activation and transduction stage, and the fill finish stage, respectively. These consumables typically have a predetermined format having a particular arrangement of “processing elements”. The term “processing element” includes any component where processing (e.g., sensing or manipulation) occurs in the consumable. The processing elements include the respective containers (e.g., fluid bags, chambers), together with other components such as filters, centrifuges, microfluidic chips, valve manifolds, pumping tubes (for use with peristaltic pumps, such as tubing made of silicon), bioreactors, cell culture plates, magnetic cell separation columns, electroporation chambers and chips, cell sorting chips, analytics elements (e.g., for cell sorting and cell counting, pH, DO, Biomass sensors), and / or microscope elements. These processing elements are fl uidically connected together by flexible tubes with a predetermined length. This ensures that the apparatus can manipulate the consumable in the same way every time sothat consistent bioprocessing operations can be performed on every patient sample.

[0115] During use, the consumable is installed at a corresponding bioprocessing apparatus. This installation process depends on the specific configuration of the consumable and the process being performed, but it may include mounting the containers (e.g., fluid bags) in certain positions (e.g., in incubators, rocking devices or cooling plates), inserting tubes into processing devices (e.g., into sensors or analytics components) in the apparatus, inserting tubes into peristaltic pumps, clipping flexible tubing into certain locations, inserting processing devices such as syringes, spinning membrane filters and centrifuge chambers into their operational elements, and similar installation steps. Some processing elements require external actuation during use. For example, centrifuge chambers and spinning membrane filters may be connected to a motor (or similar) on the apparatus so that they can be operated during a bioprocessing operation. Thus, the processing elements may include an interface (e.g., pneumatic, electrical, motor driven) which needs to be correctly installed at the apparatus. In existing bioprocessing systems, a human operator needs to manually install each consumable into its corresponding bioprocessing apparatus. Due to the complexity of the consumable elements and the strict requirements for sterility and reliability, this installation process can take more than an hour and often requires more than one human operator to ensure that all the installation steps are performed correctly. Therefore, the present invention aims to enable automation of this process to remove the need for human operators.

[0116] However, automating the installation of the complex consumables into the bioprocessing apparatuses has a number of challenges.

[0117] Firstly, the complex consumables are difficult to handle by robotic devices, since they include a large number of containers and flexible tubes, which occupy indeterminate positions in space and thus can by hard to locate and engage using robotic devices. For example, it is difficult for robotic devices to consistently engage and move flexible bags of fluid, since they occupy different positions in space depending on the amount of contained fluid. Furthermore, since theapparatuses can be relatively large, long lengths of flexible tubes are needed to connect the containers when they are installed in the apparatus. This could lead to entanglement of the tubes with each other or with the apparatus, and / or may result in a tube being misidentified by the robotic device and installed incorrectly.

[0118] Secondly, since each consumable is designed specifically to be connected to a particular apparatus by a human operator, there is limited design freedom to modify either the consumable or the apparatus to aid with automation. For example, the consumable may include fluid bags that are designed to fit tightly within an incubation chamber. Likewise, the consumable may include flexible tubes that are designed to fit within narrow channels when loaded into sensors and peristaltic pumps. In either case, it is not a simple task to add engagement features to the bags or flexible tubes to aid with automated manipulation, since doing so may prevent them from fitting within the chambers or channels of the apparatus. Similarly, it has not been considered to modify the apparatus itself to accommodate modified consumables, since doing so may prevent the apparatus from operating correctly.

[0119] To address the problems above, Figure 2A shows an example of a bioprocessing system 1. The bioprocessing system 1 includes a plurality of apparatuses 10 that each carry out at least part of a bioprocessing operation on a corresponding consumable (not shown). The bioprocessing system 1 includes an automated system so that the bioprocessing operations can be carried out autonomously without any operator intervention. The automated system may include one or more robotic devices 20, and / or any other suitable automated devices such as conveyors. An example of a robotic device 20 is shown further in Figure 2B. The robotic device 20 has an end effector 24 to manipulate various components in the system 1 , such as each of the consumables and each of the apparatuses. In this example, the robotic device 20 is a mobile robotic device that can move across the floor of the bioprocessing system 1 to access the apparatuses 10 as required. This robotic device 20 has two robotic arms 22 with two end effectors 24 so as to perform different functions, such as tube welding, pumping, and / or sealing steps. Suitable robotic devices and robotic arms are discussed further inWO2023 / 281257, WO2023 / 281258, and WO2023 / 187414. However, it will be appreciated that there are other configurations of robotic device may be used (such as x-y robots, and / or robots on cables and / or rails), and that other end effectors may be used to manipulate the components.

[0120] Separable sub-frames

[0121] As discussed above, a challenge of automating bioprocessing using the consumables relates to the fact that the flexible containers and tubes occupy indeterminate positions in space. To address this, a rigid frame may be used, where the containers and flexible tubes may be attached to the frame. Since the frame is rigid, it can be engaged at well-determined positions in space, thereby allowing the frame (and the consumable mounted thereon) to be manipulated autonomously in the bioprocessing system. In one example, a single rigid element may be provided, with portions that arrange the containers and tubes relative to a particular bioprocessing apparatus. This approach may allow the consumable to be automatically installed in the apparatus. However, since only a single rigid frame is used to retain the consumable, the frame needs to be very large so that all the parts of the consumable can reach the respective parts of the apparatus. This makes it difficult to handle by the robotic device, particularly if there is limited space around the apparatus. Likewise, these frames are impractical to store and transport. Furthermore, the frame may not have the degrees of freedom needed to allow installation by robot of the consumable kit into an apparatus. For example, some installation steps may require certain components to move in different directions (e.g., when inserted into slots or mounting elements on the apparatus), which may not be possible where the frame is a single rigid element.

[0122] Examples of frames that address these problems will now be described. Figures 3A to 3C show schematic diagrams where a frame 100 is used to install a consumable into a bioprocessing apparatus 10. The frame 100 includes a first subframe 110 and a second subframe 120. Each of these subframes 110, 120 is configured to retain a respective portion of a consumable (which is not shown in Figure 3 for clarity). A first portion of the consumable is retained in the first subframe 110, where the first portion of the consumable includes at least oneprocessing element where a bioprocessing step may be carried out. A second portion of the consumable is retained in the second subframe 120, where the second portion of the consumable includes at least one processing element where a bioprocessing step may be carried out. The first portion is connected to the second portion by a flexible tube 55. The particular processing elements depend on the operations being performed on the consumable by the apparatus. For example, the processing elements may include pumping tubes, containers, filters, and / or centrifuges.

[0123] The first subframe 110 has a (first) engagement feature 111 to enable manipulation of the subframe 110 by a robotic device. The first subframe 110 also has an installation feature 115 to enable the first subframe 110 to be inserted at a predetermined position 10-1 in a bioprocessing apparatus. The second subframe 120 has a (second) engagement feature 121 to enable manipulation of the subframe 120 by a robotic device. The first subframe 120 also has an installation feature 125 to enable the first subframe 120 to be inserted at a predetermined position 10-2 in a bioprocessing apparatus. The second subframe 120 is attached to the first subframe 110 using a mounting element. In this example, the first subframe 110 has a hook 112 that fits within an opening (not shown) on the second subframe 120. Thus, when the robotic device manipulates the first engagement feature 111 , both the first and second subframes 110, 120 can be moved together. Furthermore, the second subframe 120 can be lifted the by robotic device via the engagement feature 121 to disconnect the mounting feature and allow the second subframe 120 to be manipulated independently to the first subframe 110. In Figure 3A, the robotic device engages the first engagement feature 111 to manipulate both of the subframes together. In Figure 3B, the robotic device installs the first subframe 110 into its predetermined position 10-1 in the apparatus. Then the robotic device can release the first engagement feature 111 , engage the second engagement feature 121 , and disconnect the second subframe 120 from the first subframe 110. In Figure 3C, the second subframe 120 can be installed into its predetermined position 10-2 in the apparatus.In the example above, both the first subframe 110 and the second subframe 120 include an engagement feature 111, 121 so that they could both be manipulated independently. However, this is not strictly necessary for installing both of the subframes 110, 120 in the apparatus. Figures 4A to 4C show an alternative example, where the second subframe 120 does not include an engagement feature.

[0124] As shown in Figure 4A, the first subframe 110 includes an engagement feature 111. The second subframe 120 is attached to the first subframe 110 by a mounting element (not shown). In the attached configuration shown in Figure 4A, the robotic device can engage the first engagement feature 111 to manipulate both of the subframe 110, 120 in combination. In Figure 4B the robotic device installs, via manipulation of the first engagement feature 111, an installation feature 125 of the second subframe 120 into a predetermined position 10-2 in the apparatus. As shown in Figure 4B, this may involve placing a protrusion on the second subframe 120 into a corresponding slot in the apparatus. In Figure 4C, the robotic device manipulates the first engagement feature 111 to move the mounting element to a released configuration. Subsequently, the first subframe 110 can be manipulated independently to the second subframe 120, so as to install the first subframe 110 into a corresponding predetermined position 10-1 in the apparatus (e.g., at an installation feature, not shown in Figure 4C).

[0125] Figures 5A to 5E show a specific implementation of a frame 100 being installed on a corresponding apparatus 10. While not described in detail, the frame 100 holds a consumable 50, which has several processing elements connected by flexible tubes 55 (not all labelled). In this example, the processing elements include syringes 52, and an incubation bag (not visible in Figure 5), among other elements. The processing elements are attached to the frame by attachment features, such as clips or clamps, though these are not shown or described in detail herein. These processing elements are connected together by flexible tubes so that, once the frame 100 and consumable 50 are installed in the apparatus 10, a bioprocessing method can be performed by transferring fluid between the processing elements in a particular sequence.The frame 100 has a first subframe 110, a second subframe 120, and a third subframe 130. The first subframe 110 has a (first) engagement feature 111 to enable it to be picked up and manipulated by a robotic device, such as by using an end effector on a robotic arm. The second subframe 120 is mounted to the first subframe 110 with a mounting element (not shown). Likewise, the third subframe 130 is mounted to the second subframe 120 with a respective mounting element (not shown). The third subframe also includes an engagement feature 131 to enable the third subframe 130 to be engaged and manipulated by the robotic device. In this example, the second subframe 120 does not have an engagement feature, but in alternative examples, all of the subframes may have a corresponding engagement feature.

[0126] Each of the subframes is configured to be installed at a particular location at the apparatus 10. To facilitate this, each subframe has installation features that enable installation at a particular location on the apparatus 10. In particular, the first subframe 110 has protrusions 115 that fit within corresponding slots 10-1 on the front surface of the apparatus 10. The second subframe 120 has respective protrusions 125 that fit within respective slots 10-2 on the front surface of the apparatus 10 above the installation features 115. The third subframe 130 is configured to fit within an incubator 13 of the apparatus 10. Therefore, the third subframe 130 has installation features such as a rim 135 to enable the third subframe 130 to be securely installed within the incubator 13.

[0127] In the position shown in Figure 5A, the frame 100 is not yet installed in the apparatus 10. In this position, the frame 100 may be held by a robotic device by the engagement feature 111 on the first subframe 110. Due to the mounting elements, both the second subframe 120 and third subframe 130 remain connected to the first subframe 110 when the robotic device holds the engagement feature 111. There are several ways in which the mounting elements may be implemented. In this example, the third subframe 130 has a clip 132 that hooks into a slot 123 on the second subframe 120 so that they remain in place due to gravity (see Figure 5D in particular). While not visible in the figures, a similar arrangement may be used to hook the second subframe 120 onto the firstsubframe 110. However, clips, clasps, hooks and / or any suitable mounting element may be used to releasably attach the subframes together. The mounting elements may be active or passive elements, and / or may allow for reversible or irreversible connections.

[0128] In Figure 5B, the robotic device moves the frame 100 (via the engagement feature 111) towards the apparatus 10 so that the protrusions 125 of the second subframe 120 extend into the slots 10-2 on the front of the apparatus 10, thereby installing the second subframe 120 in its predetermined position. Subsequently, as shown in Figure 5C, the robotic device moves the first subframe 110 downward so that its protrusions 115 are inserted into the slots 10-1 on the apparatus, thereby inserting the first subframe 110 in its predetermined position. Since the second subframe 120 is already installed and held in place by the slots 10-2, the first subframe 110 detaches from the second subframe 120 during this movement (i.e. , at the mounting element). The third subframe 130 remains hooked onto the second subframe 120 during movement of the first subframe 110 by its corresponding mounting element.

[0129] In Figure 5D, the robotic device releases the engagement feature 111 of the first subframe 110, and engages the engagement feature 131 of the third subframe 130. Then the robotic device detaches the third subframe 130 from the second subframe 120 (i.e., at the mounting element 132) so that it can be manipulated independently by its engagement feature 131. During this manipulation, the first subframe 110 and second subframe 120 remain installed in their respective predetermined positions in the apparatus 10.

[0130] In Figure 5E, the robotic device installs the third subframe 130 into the incubator 13. During this process, the rim 135 of the third subframe 130 is fitted within the incubator 13 thereby installing it in its predetermined position in the apparatus 10.

[0131] Once in this position, the frame 100 is installed at the apparatus 10, together with the corresponding processing elements of the consumable 50. Subsequently, the apparatus may perform a bioprocessing operation on the consumable 10, which may involve several steps (e.g., those discussed above in relation to Figure 1).For example, fluid may be pumped through the syringes 52 and through the flexible tubes 55. The incubator 13 may be operated to incubate cell material in the fluid bag in the third subframe 130. Once the operation is complete, the installation process described above may be reversed, where the subframe 130 is reattached to the second subframe 120 using the corresponding mounting features 123, 132 (i.e., to the position shown in Figure 5C), and the second subframe 120 is reattached to the first subframe 110 using the corresponding mounting features (i.e., to the position shown in Figure 5B). This may allow for the entire frame 100 and consumable 50 to be removed from the apparatus 10 in a single operation using the first engagement feature 111 (i.e., to the position shown in Figure 5A). Alternatively, the subframes may be separated from each other (e.g., by sealing and cutting any connecting tubing) prior to removal from the apparatus 10, so that they can be transported to different locations separately for further processing.

[0132] One of the benefits of the frame 100 is that the existing consumable 50 and existing apparatus 10 may still be used to carry out bioprocessing operations. However, since the existing consumables were originally designed to be handled and connected by human operators, they may include long lengths of tubing to allow different processing elements of the consumable to be freely manipulated. Since the frame 100 arranges the processing elements ready for installation in their correct positions, these long lengths of tubing are no longer required for the installation process. However, rather than modify the consumable 50 to remove excess tubing (which would require corresponding modifications to the processing steps carried out by the apparatus 10, such as pumping volumes and duration), the frame 10 includes tube storage features to secure the flexible tube to the frame. This reduces the likelihood of entanglement without requiring modification to the consumable or the apparatus. Different types of tube storage feature may be provided.

[0133] For example, as indicated in Figure 5E, the first subframe 110 includes a tube routing feature 116, where the tube 55 is clipped into a channel in the frame along a circuitous pathway. The third subframe 130 also includes a tube routing feature136 to store excess tubing in a compact arrangement on the frame 100. The second subframe 120 includes pairs of tube clips 126, where a length of tubing is held between the tube clips 126.

[0134] While the above types of tube storage feature enable compact storage of tubes on each of the subframes, it is also beneficial to handle the tubes during relative movement of the subframes. As described above, during the installation of the frame 100 into the apparatus 10, the subframes 110, 120, 130 are separated from each other, thereby moving the frame from a compact configuration to a deployed configuration. During this deployment process, the processing elements (e.g., the syringes 52 and fluid bag) also need to move further apart, so any tubes extending between the processing elements need to move to accommodate the movement of the subframes. Therefore, a tube storage feature may be provided that dispenses a flexible tube from a stored configuration, when required. As shown in Figures 5A and 5E, five tube storage devices 200 (only two labelled) are provided which deploy the tube from a stored configuration (see Figure 5A) to a deployed configuration (see Figure 5E). An example of a tube storage device 200 that achieves this is described below, but it will be appreciated that there are other tube storage devices that allow for movement between a stored configuration (e.g., coiled, folded) and a deployed configuration.

[0135] Tube storage device

[0136] As discussed above, one challenge associated with automation of bioprocessing operations concerns the long lengths of flexible tubes that are required to connect between different parts of the system. Unless these tubes are carefully managed in 3D space, entanglement may occur, which can lead to bioprocessing operations being performed incorrectly. This challenge may be also present when operating the frame 100 discussed above in relation to Figures 3 to 5. For example, when the sub-frames are in their deployed configuration to connect to the apparatus 10, long lengths of tubing may be required to extend between the sub-frames 110, 120, 130. However, if the sub-frames are subsequently moved to their stored configuration (e.g., so the frame can be removed from the apparatus 10), theselong lengths of tubing become slack, which may be problematic during any subsequent manipulation or storage.

[0137] In view of the above, a device 200 for storing and dispensing a flexible tube will now be described with reference to Figures 6 and 7. As discussed below, the device 200 allows for the flexible tube to be dispensed and retracted as many times as required without risk of entanglement. While the device 200 may be used in combination with the sub-frames (e.g., mounted to one or more of the subframes 110, 120, 130), it will be appreciated that the device 200 may be completely separate to the sub-frames and may be advantageous for other operations elsewhere in the bioprocessing system.

[0138] Figures 6A and 6B show external views of the device 200. The device has a housing 210 with an internal cavity 212 (not shown in Figures 6A and 6B) for storing the flexible tube. As particularly shown in the cross-sections and exploded views in Figures 7Ato 7E, the housing 210 is formed from an outer element 220 and an inner element 250 that are assembled to define the cavity 212 therebetween.

[0139] The outer element 220 is substantially cylindrical, extending along a longitudinal axis from a first end 220a to a second end 220b. The outer element has an opening 222 at its first end 220a to allow the flexible tube 55 to pass into and out of the cavity 212 in the housing 210.

[0140] The housing 210 also includes a tube retaining portion 230 that is attached to the cylindrical outer element 220. The tube retaining portion 230 comprises a pair of tube clips 232 located adjacent to the opening 222 at the first end 220a of the outer element 220. This means that when the flexible tube extends out of the opening 220, it can be held at a predetermined location on the device 200, which facilitates engagement of the flexible tube 55 by a robotic device. In this example, the tube retaining portion 230 includes two tube clips 232 with a gap therebetween, where a length of the tube can be held taut. This means that the robotic device can consistently engage the tube 55 along the line extending between the tube clips 232. The tube clips 232 are passive clips or friction clips.The inner element 250 and the cavity 212 will now be described further with reference to Figures 7A to 7E. The inner element 250 includes a guide portion 260 that fits inside the cylindrical shape of the outer element 260, and a base portion 270 that provides an external surface of the housing 210. The guide portion 260 tapers from its widest point adjacent to the base portion 270 towards a tip 264 adjacent to the opening 222 of the outer element. The tip 264 is pointed so that the tube 55 is always deflected into the cavity 212 when pressed against the tip 264. In other words, the tube 55 cannot rest on the tip 264 without being deflected into the cavity 212. Thus, at least part of the guide portion 260 may have a substantially conical shape. The internal surface of the outer element 220 has a shape corresponding to the guide element 260, such that the cavity 212 defined therebetween has a substantially constant thickness. A cross section of the cavity 212 (perpendicular to the longitudinal axis) is thus ring shaped. The thickness substantially corresponds to the outer diameter of the tube and is preferably no greater than twice the outer diameter of the tube. In this way, the tube cannot become crossed within the cavity, which prevents any entanglement from occurring.

[0141] Figure 7C shows a cross section along a longitudinal axis of the device 200 to show how the tube 55 may be positioned when stored in the cavity 212. When the tube 55 is pushed into the device through the opening 222, it contacts the tip 264 of the guide portion 260, which deflects the tube 55 away from the longitudinal axis into a coiled position inside the ring-shaped cavity. Since the cavity 212 constrains the tube 55 in a coiled shape, it is not possible for the tube 55 to become entangled in the cavity 212. Therefore, when a length of tube 55 needs to be dispensed, the tube 55 can be pulled out of the opening 222, thereby uncoiling the necessary length of tube from the ring-shaped cavity 212. Furthermore, since the opening 222 has a curved edge, the tube 55 does not need to be pulled out directly along the longitudinal axis. Rather, it can be pulled in any direction away from the first end 210a of the housing 210 without the tube 55 become snagged on the edge of the opening 222. As shown in the alternative device 200’ shown in Figures 7F to 7H (which is otherwise the same as the device 200 and thus will not be described in detail), the circular outer edge of thecylindrical outer element 220’ may also be rounded at its second end 220a’. This means that the tube 55 can be pulled out of the device 200’ in any direction in 3D space from the opening 222’ without snagging on the edges of either the opening 222’ or the end of the outer element 220’.

[0142] The base portion 270 of the inner element 250 also includes a port 272 to allow the tube 55 to be inserted into the cavity 212. The port 272 is positioned in the centre of the base portion 270 (i.e., aligned with the longitudinal axis). The port 272 connects to the cavity 212 through a guide channel 276 in the inner element 250. Rather than connect to the cavity 212 in a purely radial direction, the guide channel 276 is curved so that the tube enters the cavity 212 at an angle, as shown particularly in Figure 7E. In this way, the tube 55 is urged into a coiled configuration adjacent to the base portion 270 of the inner element. This means that even when the tube 55 is substantially pulled out of the device 200, if the tube 55 is subsequently pushed back into the device 200 through the opening 222, it will still return into its coiled configuration.

[0143] The outer element 220 and inner element 250 can be removably attached to facilitate loading of the flexible tube in the device 200. A method of operating the device 200 will now be described. The inner element 250 and the outer element 220 may initially be separated from each other. Then, the flexible tube 55 may be fed through the port 272, through the guide channel 272, and then out of the opening 222 (i.e., from the inside to the outside of the outer element 220). Then the inner element 250 is attached to the outer element 220 to define the cavity 212. At this stage in the method, the tube 55 extends into the device through the port 272, through the cavity 212, and out of the opening 222. Then, the portion of the tube 55 extending out the opening 222 may be pushed into the opening 222, where it is deflected by the guide element 260 into the coiled configuration inside the cavity.

[0144] The steps described above may be used to load the device 200 prior to use. Once loaded and positioned within the bioprocessing system, the following further steps may be performed. The end of the tube 55 extending out of the device 200 may be pulled to dispense a portion of flexible tube 55. During this step, the tube 55uncoils within the cavity 212. In the device 200, the tube 55 may be pulled in any direction from the second end of the outer element 220 that lies in a half-sphere without risk of the tube 55 snagging. Where the device 200’ is used, the tube 55 can be pulled in any direction in 3D space without risk of the tube 55 snagging. The tube 55 may be pulled by a human operation during a bioprocessing operation. Preferably, the tube 55 is pulled during an automated operation, such as by a robotic device. The robotic device may directly engage the end of the tube to pull it out of the device 200. Alternatively, the robotic device may indirectly cause the tube 55 to be dispensed, such as during the movement of subframes away from each other (such as shown during the movement from Figures 5B to 5C).

[0145] During use, or following a bioprocessing operation, the tube may be pushed back into the device 200. For example, if the two subframes 110, 120 are moved closer to each other, the tube 55 may be pushed back into the opening 222 to reload the tube in its coiled configuration, thereby removing excess slack tubing. This reduces the chance of entanglement during any subsequent operations.

[0146] Bag holding device

[0147] As discussed previously, the manipulation of consumables is a challenge when automating bioprocessing operations, since the consumables typically include flexible fluid bags 60 that are difficult to manipulate by robotic device. For example, as particularly shown in Figure 8B, the fluid bags 60 are typically formed from two sheets of material that are joined together around their perimeter. Here, the sheets are joined at a first end 61, a second end 62, a first side 63 and a second side 64, which defines a substantially rectangular bag 60 having two opposing faces 65, 66. The bag 60 has an opening or loop at its second end 62 to allow it to be suspended from a hook for storage. This type of bag 60 is particularly suitable for installation into a bioprocessing apparatus such as an incubator, since the faces 65, 66 provide a large flat surface to allow for efficient heat transfer when placed in contact with a heating or cooling plate in the incubator. For example, this type of fluid bag 60 may be used in the third subframe 130 discussed above in relation to Figures 5A to 5E. Although the bag 60 ispreferably substantially rectangular, it will be appreciated that other shapes may be used for the bag. For example, the bag may have a tapered or pointed shape at either or both of the first end 61 or second end 62.

[0148] However, these bags are designed to fit tightly within the incubator, so it is challenging to add further structures to the bag to aid with manipulation without obstructing the installation process. It is important that the bag has uniform contact with the flat plate in the incubator to ensure uniform temperature distribution of the cel Is / fluids in the bags. To address this, various examples of devices will now be described that allow the flexible bag to be held within a rigid frame (e.g., to facilitate manipulation by a robotic device), without obstructing the installation of the bag into the apparatus (e.g., into an incubator, where a face of the bag must remain exposed for heat transfer).

[0149] Figures 8A to 8E show a first example of a device 300 for holding a flexible fluid bag. As particularly shown in Figures 8A and 8B, the device 300 includes a support arm 310 extending from a first end 311 to a second end 312 along a longitudinal axis. The support arm 310 may be referred to as a “bar”, “strut”, “rod” or “beam”. The first end 311 of the support arm 310 includes a clamp 321 configured to retain the first end 61 of the fluid bag 60. The second end 312 of the support arm 310 includes a hook 322 configured to retain the second end 62 of the fluid bag 60 (shown particularly in Figure 8E). In this way, the device 300 can suspend the fluid bag 60 between the clamp 321 and the hook 322, with a front face 65 of the bag 60 remaining exposed, without substantially increasing the size. This means that the device 300 can be used to insert the fluid bag 60 into the incubator without the support arm 310 obstructing the insertion or preventing access to the front face 65 of the fluid bag 60.

[0150] As shown in the side view of Figure 8C, the clamp 321 and the hook 322 are offset from the longitudinal axis of the support arm 310. To enable this, the support arm 310 is bent at its second end 312 adjacent to the hook 322 (as shown in Figure 8E). This means that the when the fluid bag 60 is suspended between the clamp 321 and the hook 322, it can expand when filled with fluid without the support arm 310 being a substantial obstruction.Figure 8D shows a close up of the first end 311 of the support arm 310. The first end 311 includes a clip 305 so that the device 300 can be releasably attached to other devices in the bioprocessing system, and / or engaged by a robotic device. The first end 311 includes tube management features to retain the flexible tube in a predetermined position on the device 300. In particular, the device 300 includes an opening 314 through which a flexible tube (e.g., connected to the first end 61 of the bag) extends. Here, the flexible tube is enclosed within the opening 314 between an upper portion 315a and a lower portion 315b. To enable the tube to be removed from the device 300, the upper portion 315a is releasably attached to the lower portion 315b using screws 316. The tube management features include a channel 317. Aplastic Y-junction (not shown) may be inserted into this channel 317 to position a flexible tube at the first end 311 of the support arm 310. Alternatively, the flexible tube can be clipped directly into a channel or tube routing feature during use.

[0151] Figures 9A to 9D show a second example of a device 330 for holding a flexible fluid bag. This device 330 has a support structure 340 that extends all the way around the perimeter of the bag 60. More specifically, the support structure 340 includes a first end portion 341 for retaining a first end 61 of the fluid bag 60, a second end portion 342 for retaining a second end 62 of the fluid bag 60. The support structure 340 also includes a first side portion 343 for retaining the first side 63 of the fluid bag 60 and a second side portion 344 for retaining the second side 64 of the fluid bag 60. In this way, the support structure 340 provides a rim that connects the first end 61 of the bag to the second end 62 of the bag around its perimeter. The support structure 340 has a thickness of 10mm or less. This means that when the bag 60 is filled with fluid (thereby causing it to expand), the front and back faces of the bag 60 can contact the apparatus (e.g., a heat plate) without the rim preventing said contact.

[0152] As shown in Figures 9A and 9B, the support structure 340 is separable into a first piece 340a that substantially surrounds the perimeter of the bag 60, and a second piece 340b that includes tube management features for retaining the flexible tube 55 connected to the fluid bag 60. The tube management features are not shownor described in detail but may include openings and / or grooves similar to those described above in relation to the device 300. Likewise, an engagement feature (e.g., a clip) may be included on the support structure 340, such as on the second piece 340b to enable the device 330 to be manipulated by a robotic device. To attach around the perimeter of the bag, the first piece 340a and / or the second piece 340b may be formed from two separate parts that attach together around the perimeter of the bag (e.g., in a clamshell arrangement). This is particularly shown in the cross-section in Figure 9D, where the first side portion 343 and the second side portion 344 can be seen pinching the respective sides 63, 64 of the bag 60 within a slot. It will be appreciated that this slot continues around the rim so as to provide continuous retention of both ends 61 , 62 and both sides 63, 64 of the bag 60. To facilitate loading of the bag into this slot, the first piece 340a may be separable into a front part and bag part in a clamshell arrangement, where the perimeter of the bag is pinched between the front and back part during assembly.

[0153] Figures 10A to 10D show a third example of a device 360 for holding a flexible fluid bag. In this example, the device 360 is configured as the subframe 130 described in relation to Figures 5Ato 5E. Figures 10Aand 10B show the device 360 in isolation, and Figures 10C and 10D show the device 360 positioned in an incubator 13 (similarly to as shown in Figure 5E). Therefore, the device 360 includes a mounting element in the form of a clip 393 that enables it to be mounted to the slot 123 on the second subframe 120 (see Figure 5D).

[0154] Similarly to the device 300, the device 360 has retaining elements (such as a clamp and a hook) to suspend the fluid bag between its first and second end. However, the device 360 differs from device 300 in that it includes a support plate 370 that connects the retaining elements. The support plate 370 is arranged to substantially cover the back face of the fluid bag (not shown in Figures 10A to 10D). By covering the entire back surface of the fluid bag, the device 360 can seal the fluid bag within the incubator (as shown in the loaded position in Figures 10C and 10D), which may provide improved efficiency of heat transfer to the contents of the fluid bag. The device 360 also includes a ledge 375 that surrounds the perimeter of the fluid bag when it is suspended. The ledge 375 ensures thatthe bag remains in a predetermined position relative to the support plate 370 which may improve reliability of insertion into the apparatus. This ledge 375 may also act as an installation feature to connect the device 360 to the incubator in the apparatus.

[0155] The device 360 also includes a tube routing feature 396 to store an excess length of tubing connected to the fluid bag. The tube routing feature 396 stores the flexible tube in a serpentine pathway on the support plate 370. In this example, the tube routing feature 396 includes a first pathway 396a and a second pathway 396b. Each pathway retains a respective flexible tube connected to the fluid bag during use. This enables separate samples to be extracted from the fluid bag at different stages of the process. The flexible tubes are connected to the device 360 at a tube clip 397 on the upper surface of the support plate 370. The tubes pass through the pathways 396a, 396b and to the underside of the support plate 370, where the pass through another tube storage feature 398 that retains a length of each tube in a stored configuration in a respective hourglass-shaped element 398a, 398b (see Figure 10B). After passing through this tube storage feature 398 the tubes connect to the flexible fluid bag.

[0156] This arrangement facilitates a sampling process, which may be performed as follows. First, a robotic device may pick up one of the flexible tubes from one of the pathways 396 and pull the tube away from the support plate 370, which deploys the tubing from the tube storage feature 398 (e.g., by unfolding the tube). Then, a central portion of the tube can be installed in a peristaltic pump, and an end (opposite to the end connected to the fluid bag) may be welded to a separate sample bag, so that fluid can be pumped from the bag in the device 360 to the sample bag. Once the sample is extracted, the tube can be sealed. This process may be repeated using the other tube (in the other pathway) at a later stage in the bioprocessing operation. Advantageously, by providing tube routing and storage features in this way, there is no need to reroute or reinstall tubing once the bioprocessing operation has started.Automated tube loading

[0157] As explained previously, in existing manual processes, an operator may need to install the flexible tubes into instruments on the bioprocessing apparatus. For example, some sections of the tubes may be loaded into processing instruments such as sensors (e.g., flow sensors or fluid sensors) so that a bioprocessing operation can be carried out. Such sensors usually include a processing channel within which the tube is retained for processing. The processing may include light measurements (e.g., using infrared sensors) where it is also necessary to block light entering the channel above the flexible tube. Therefore, the installation process of tubes into these processing channels involves a large number of precise steps that are difficult to carry out using robotic devices.

[0158] In view of the above, systems 400 that address these challenges. A first example of such a system 400-1 is described in relation to Figures 11 A to 11 C.

[0159] As shown particularly in Figure 11 A, the system 400-1 includes a frame 410. The frame 410 includes a tube receiving member 420 having a first end 420a extending along a longitudinal axis to a second end 420b. The tube receiving member 420 is connected at its first end 420a to a first support member 430a. The second end 420b of the tube receiving member 420 is connected to a second support member 430b. The support members 430 extend away from the longitudinal axis of the tube receiving member 420. In this example, the support members 430 extend in a perpendicular direction, though it will be appreciated that they may extend from the tube receiving member 420 at other angles. In this example, the frame 410 has a substantially U-shaped construction.

[0160] The tube receiving member 420 includes a tube receiving slot 425 that extends from the first end 420a to the second end 420b of the tube receiving member 420. The first support member 430a includes a first insertion slot 435a that connects to the tube receiving slot 425 at the first end 420a of the tube receiving member 420. The second support member 430b includes a second insertion slot 435b that connects to the tube receiving slot 425 at the second end 420b of the tubereceiving member 420. Thus, the tube receiving slot 425 and the insertion slots 435 can be considered to provide a continuous slot on the U-shaped construction.

[0161] Figure 11 A shows a tube 55 positioned within the tube-receiving slot 425. Here the tube 55 is in a first position in the frame 410. As shown more clearly in Figure 11 C, the slot 425 includes a pair of rails 426 (only one labelled) upon which the tube 55 may rest when in the first position. The rails 426 extend parallel to each other through the slot parallel to the longitudinal axis. The portion of the slot 425 without the rails 426 has a width that is equal to or greater than the outer diameter of the flexible tube 55, thereby allowing the tube to move freely into the first position in the frame 410. The rails 426 have a spacing that is less than the outer diameter of the flexible tube 55 so that the flexible tube 55 can rest upon the rails 426 when no external force is applied but can be pushed past the rails 426 when an external force is applied (as will be discussed further later).

[0162] The edges of the tube receiving slot 425 on the upper surface of the tube receiving member 420 include a chamfer 428 (only one of which is visible in Figure 11A). The chamfer 428 means that the upper surface of the tube receiving member 420 slopes downwardly into the tube receiving slot 425.

[0163] As shown in Figures 11 B and 11 C, the system 400-1 includes a manipulation tool 450. The manipulation tool 450 has an engagement feature 453 so that it can be manipulated with the robotic device. In this example, the engagement feature 453 is a substantially triangular element, though it will be appreciated that other configurations of engagement feature 453 may be used provided that they enable manipulation of the manipulation tool 450 by a robotic device. The manipulation tool 450 has a body 452 and a lower plate 454 that extends from a first end 454a to a second end 454b along a longitudinal axis. The lower plate 454 has a length that substantially corresponds to the length of the tube-receiving slot 425 so that the lower plate 454 can substantially cover the tube receiving slot 425 during use (as shown in Figure 11 C). The manipulation tool 450 includes an insertion plate 455 that extends from the first end 454a to the second end 454b of the lower plate 454 in a perpendicular direction. The insertion plate 455 has a thickness that isless than or equal to the width of the tube receiving slot 425 so that it can be inserted through the tube receiving slot 425, during use.

[0164] Figures 11 B and 11 C show two states of the system 400-1 during use of the frame 410 and the manipulation tool 450. While not depicted in these figures, the frame 410 is positioned above a processing channel in a processing instrument (e.g., a sensor). When in position, the support members 430 are located either side of the processing channel, with the tube retaining slot 425 aligned above the processing channel. While not depicted in Figures 11 B and 11C, the steps described below are performed using the robotic device via manipulation of the engagement feature 453.

[0165] In Figure 11 B, the tube 55 is in its first position, where it rests upon the rails 426 in the tube-receiving slot 425. In this position, the robotic device has engaged the engagement feature 453 of the manipulation tool 450 and is holding the manipulation tool 450 so that the insertion plate 455 is held against the flexible tube 55. Subsequently, as shown in Figure 11 C, the robotic device moves the manipulation tool 450 to insert the insertion plate 455 further into the tube receiving slot 425, pushing the flexible tube 55 past the rails 426 into a second position in the frame 410. In this second position, the tube 55 is positioned within the tube insertion slots 435 of the support members 430 (at a lower end thereof) and thus extends between the support members 430. Thus, when the frame 410 is aligned with a processing channel, movement of the flexible tube 55 to its second position loads the flexible tube 55 into the processing channel. Optionally, the manipulation tool 450 can be removed from the frame 410. However, where the processing channel requires light sensitive measurements or operations to be performed with the tube, the robotic device may release the engagement feature 453 to leave the manipulation tool 450 in place until the measurements are taken.

[0166] The system 400-1 described above allows a flexible tube 55 to be reliably installed into a processing channel. This system 400-1 advantageously requires few parts (only the frame 410 and the manipulation tool 450).However, in other situations it may be desirable for the robotic device to use a manipulation tool to load other flexible tubes elsewhere, while light sensitive measurements are still ongoing.

[0167] Therefore, Figures 12Ato 12C show an alternative example of a system 400-2 for loading a flexible tube 55 into a processing channel.

[0168] This system 400-2 includes a frame 410. The frame 410 corresponds to the frame already described above, and therefore will not be described again in detail. The system 400-2 also includes an insertion plate 465. Unlike the first system 400-1 the insertion plate is not connected to a manipulation tool, but is a separate component that can move within the tube receiving slot 425 (as discussed above). However, if the frame 410 was only provided with the insertion plate 465, the plate 465 may not be able to rest in a stable position on top of the flexible tube 55, which may lead to difficulties during subsequent manipulation by the robotic device. Therefore, the system 400-2 also includes an insertion guide 470 to hold the insertion plate 465 in position within the tube receiving slot 425. The insertion guide 470 is shaped to fit on the upper surface of the frame 410. In particular, a lower surface of the insertion guide 470 has bevels (not shown) that correspond to the chamfers 428 of the tube receiving member 420. In this way, when the insertion guide 470 rests upon the tube receiving member 420, a seal is formed therebetween that prevents light from entering the processing channel, during use. The insertion guide 470 extends along a longitudinal axis from a first end 470a to a second end 470b, which correspond to the respective first and second ends 420a, 420b of the tube receiving member 420. The insertion guide 470 includes a slot 475, within which the insertion plate 465 can be retained. Additionally, the insertion guide 470 includes a first notch 476a proximal to its first end 470a and a second notch 476b proximal to its second end 470b. These notches 476 are formed in the upper surface of the insertion guide 470 perpendicular to the slot 475. As described below, these notches 476 facilitate interlocking of the insertion guide 470 with a manipulation tool 480.

[0169] The manipulation tool 480 is shown in Figure 12B and 12C, which depict two states of the system 400-2 during use. The manipulation tool 480 shares severalfeatures with the manipulation tool 450 already described above, such as the body 482, and engagement feature 483. However, this manipulation tool 480 differs in that it does not include a lower plate. Instead, the lower surface of the manipulation tool 480 is shaped to fit within the insertion guide 470 and push the retained insertion plate 465 against the flexible tube 55, thereby urging the flexible tube towards its second position (shown in Figure 12C). To achieve this, the manipulation tool 480 includes a longitudinal protrusion 485 on its lower surface that can fit within the slot 475 of the insertion guide 470. When the manipulation tool 480 is pushed downward onto the insertion guide 470, this longitudinal protrusion 485 presses against the insertion plage 465 retained in the insertion guide 470, which presses against the tube 55, pushing it past the rails 426 and into its second position. As already discussed above in relation to the first system 400-1, this movement from the first position to the second position, loads the flexible tube 55 into the processing channel. Additionally, the manipulation tool includes two lateral protrusions 486a, 486b which fit within the respective first and second notches 476a, 476b of the insertion guide 470. When the manipulation tool 480 is pushed downward into the insertion guide 470, the longitudinal and lateral protrusions 485, 486 interlock with the slot 475 and notches 476 of the insertion guide, thereby ensuring consistent alignment of the manipulation tool 480.

[0170] Advantageously, when the manipulation tool 480 is removed from the insertion guide 470, the insertion plate 465 and the insertion guide 470 provide a seal with the frame 410 thereby preventing light from entering the processing channel. This means that the same manipulation tool 480 can be used to perform similar tube insertion steps elsewhere in the bioprocessing system.

[0171] Peristaltic pump loading

[0172] As well as the loading of flexible tubes into processing channels, many bioprocessing operations and apparatuses 10 require flexible tubes to be loaded into peristaltic pumps. As shown in Figures 13A and 13B, a peristaltic pump 70 includes a first jaw 72 in the form of a curved plate, and a second jaw 74 that is spaced form the first jaw 72 to define an arcuate gap 76 therebetween. The jaws72, 74 are movable between an open position (shown in Figures 13A and 13B) where the flexible tube 55 is insertable into the arcuate gap 76, to a closed position (not shown) where the jaws compress the tube 55 therebetween for a pumping operation to occur. The peristaltic pump 70 is a rotary peristaltic pump, where the second jaw 74 includes at least one roller 75. The at least one roller 75 presses the flexible tube 55 against the curved plate of the first jaw 72 and moves along the length of the tube 55, thereby moving fluid through the tube 55.

[0173] However, loading of such peristaltic pumps 70 is difficult for automated systems including robotic devices, due to the curvature of the arcuate gap 76. Since the arcuate gap 76 is relatively narrow in the open position of the jaws 72, 74, it can be difficult for a robotic device to reliably insert a flexible tube into the peristaltic pump so that pumping can occur.

[0174] Therefore, systems will now be described that address this problem. A first example of a system 500 will now be described in relation to Figures 13 to 15.

[0175] The system includes a retaining device 510. The retaining device 510 has a first retaining element 512 for holding a first section of the tube 55. The retaining device 510 has a second retaining element 514 for holding a second section of the tube 55. The first and second retaining elements 512, 514 are provided by tube clips. The retaining device 510 includes a support bar 516 that rigidly attaches the first retaining element 512 to the second retaining element 514. The retaining elements 512, 514 extend away from an axis of the support bar 516, so that the retaining elements 512, 514 can be positioned either side of the arcuate gap 76 of the pump 70 without the support bar 516 colliding with the pump 70.

[0176] The first and second retaining elements 512, 514 are angled relative to the support bar 516 to bend an intermediate section of the tube 55 (i.e. , a section connected between the retaining elements 512, 514) into an arcuate shape that corresponds to the shape of the arcuate gap 76 of the peristaltic pump 70. This means that when the tube 55 is retained by the retaining device 510, it can be positioned adjacent the pump (as shown in Figure 13A) and subsequently installed into the pump 70 simply by movement of the retaining device 510 (as shown in Figure13B). To facilitate movement of the retaining device 510, it may include an engagement feature (not shown in Figures 13A and 13B) so that a robotic device can engage and manipulate the retaining device 510 relative to the pump 70. In this way, the retaining device 510 may be operated by a robotic device to load the flexible tube 55 into the peristaltic pump 70.

[0177] Figures 14A to 14D show further features of the system 500. In particular, a installation device 550 is included to insert the flexible tube 55 into the arcuate gap 76 of the peristaltic pump 70. In this example, the installation device 550 is attached to the peristaltic pump, though in other examples it can be an independent device. While not shown in Figures 14Ato 14D, a retaining device 510 such as the one described above (in relation to Figures 13Aand 13B) may be used to arrange the flexible tube 55 in a position adjacent to the arcuate channel 76.

[0178] The installation device 550 includes an arm 552 that is movable to press the intermediate section of the flexible tube 55 into the pumping location in the pump 76. Figure 14A depicts the arm 552 in a first position where it is moved away from the peristaltic pump. This allows the flexible tube to be positioned adjacent the arcuate channel 76 without the arm 552 from being an obstruction. Once in this position, the arm 552 is moved to a second position, where an end 553 of the arm presses against the intermediate section of the flexible tube 55, thereby moving it into the arcuate channel 76 of the peristaltic pump, as shown in Figure 14B. As depicted, the installation device 550 includes an interface 560 which is arranged for engagement by a robotic device. The interface 560 protrudes away from the peristaltic pump 70 so that it can be easily engaged by a robotic device (e.g., without obstruction from other parts of the pump 70 or the retaining device 510). The interface 560 may include engagement features that enable manipulation by the end effector of the robotic device.

[0179] The actuation of the arm 552 via the interface 560 will now be described further with reference to Figures 14C and 14D. As depicted, the arm 552 is actuated using a rack and pinion system. The interface 560 is connected to a rack 562 having teeth that interlock with a pinion gear 564. The pinion gear 564 isconnected to an arm gear 566 using a common shaft, so that movement of the rack 562 rotates both the pinion gear 564 and the arm gear 566. The arm gear 566 has teeth that interlock with teeth on the arm 552 (although these teeth are not visible in the Figures). In this way, motion of the rack 562 is converted to motion of the arm 552, thereby allowing the arm to move between its first and second positions to install the tube 55 in the peristaltic pump 70. While the rack and pinion system is used in this example to facilitate movement of the arm 552 through manipulation of the interface 560, it will be appreciate that other mechanisms may exist that achieve this.

[0180] While the retaining device 510 described above retains the flexible tube at a first section and second section, where the intermediate section is substantially unsupported, Figures 15A and 15B show an alternative retaining device 580 that the intermediate section of the tube is also retained in the device 580. This device 580 can be considered as including a first retaining element 582, a second retaining element 584, and an intermediate retaining element 585 that retains the intermediate section of tube in the arcuate shape. In this example, these retaining elements 582, 584, 585 are provided as a single piece of material, though in other examples the intermediate retaining element 585 may be separate from the first and second retaining elements 582, 584. The retaining elements are mounted on a support plate 586, which may have engagement features to facilitate manipulation by a robotic device.

[0181] As shown in Figures 16A to 16D, the system 500 may include a loading device 570 to facilitate loading of the tube 55 into the retaining device 510. Without the loading device 570, it may be possible for an operator to include too much (or not enough) slack tubing between the first and second retaining elements 512, 514, which may cause the intermediate section of the tube to misalign with the desired arcuate shape. Therefore, when the tube is loaded into the retaining device 510, the loading device 570 may be attached to the retaining device 510 (e.g., positioned between the retaining elements 512, 514). The loading device 570 may include a groove or channel having a shape corresponding to the arcuate gap 76. In Figures 16A and 16B, the loading device 570 is shown attached to theretaining device 510 to facilitate loading of the flexible tube into the correct position in the retaining device 510. The loading device 570 may be slidably attached to the retaining device 510 such as by using protrusions 577, 578 on the loading device 570 that slide through corresponding slots 517, 518 on the retaining device 510. As shown in Figures 16C and 16D, when the retaining device 510 is moved towards the pump 70 to load the tube, the loading device 570 contacts the pump 70 such that continued motion of the retaining device 510 causes the loading device 570 to slide within the slots 517, 518. In this way, the tube only leaves the groove or channel of the loading device 570 (i.e., which is open on a lower surface of the loading device 570) at the moment when the tube is loaded into the arcuate gap 76 in the peristaltic pump 70.

[0182] As shown in Figures 17Aand 17B, the system 500 may include a closing device 590. The closing device 590 has an arm 592 that is coupled to the first jaw 72 of the pump. For example, the arm 592 may be rigidly attached to the pump housing adjacent the first jaw 72. The closing device 590 also has pump mount 594 that is coupled to the first jaw 74 of the pump 70. Here the pump mount 594 is a substantially U-shaped element that extends around the pump 70. The arm 592 is pivotally mounted to the pump mount 594, so that movement of the arm 592 moves the first jaw 72 relative to the second jaw 74 to move the pump 70 between its open and closed positions. The closing device 590 has an engagement feature 596 to enable manipulation of the arm 592 by the robotic device to move the pump 70 between its open and closed positions. In this example, the engagement feature 596 is a bar 596 rigidly attached to the arm 592. The bar 596 extends outwardly from the arm 592 so that it can be easily engaged by a robotic device.

[0183] While the description above generally relates to loading of a flexible tube 55 into a single peristaltic pump 70, some bioprocessing apparatuses have several peristaltic pumps that each require a respective flexible tube to be installed. One way to achieve this would be to use a plurality of separate systems 500 as disclosed above. However, one particularly efficient way to load multiple tubes into multiple peristaltic pumps is to provide a system with a plurality of retaining devices 510 attached to a frame. Such a configuration is shown in Figures 18Aand 18B, where steps during the loading of two peristaltic pumps 70-1, 70-2 are depicted. A frame 140 is provided that connects a first retaining device 510-1 to a second retaining device 510-2. Here, the frame 140 also provides the function of the loading device discussed above, where corresponding slots and protrusions allow movement of the retaining devices 510-1, 510-2 in the frame 140. Figure 18A shows the frame 140 prior to loading respective tubes in the pumps 70-1, 70-2, and Figure 18B shows the position of the frame 140 following loading of the tubes, where the frame slides relative to the retaining devices 510-1, 510-2 in respective slots (similarly to as described above in relation to Figures 16Ato 16D).

[0184] The position of the retaining devices 510-1, 510-2 on the frame 140 aligns with the position of the peristaltic pumps 70-1, 70-2 on the apparatus, so that movement of the frame 140 (by a robotic device) enables loading of both the pumps 70-1 , 70-2 with a respective tube simultaneously.

[0185] Similarly, where the closing device 590 discussed above is present in this system, all of the pumps 70-1, 70-2 may be closed simultaneously using a single (common) closing device. For example, the engagement feature 596 may connect to the arms of several closing devices arranged side by side, so that a single movement of the engagement feature closes all the pumps. Alternatively, separate closing devices may be used for each pump.

[0186] While the foregoing is directed to exemplary embodiments of the present invention, it will be understood that the present invention is described herein purely by way of example, and modifications of detail can be made within the scope of the invention. Furthermore, one skilled in the art will understand that the present invention may not be limited by the embodiments disclosed herein, or to any details shown in the accompanying figures that are not described in detail herein or defined in the claims. Indeed, such superfluous features may be removed from the figures without prejudice to the present invention.

[0187] Moreover, other and further embodiments of the invention will be apparent to those skilled in the art from consideration of the specification and may be devisedwithout departing from the basic scope thereof, which is determined by the claims that follow.

Claims

CLAIMS1. A frame for holding a bioprocessing consumable, the consumable comprising a plurality of processing elements connected by one or more flexible tubes, the frame comprising:a first subframe configured to retain a first portion of the consumable, the first subframe comprising an engagement feature arranged to enable engagement of the first subframe by a robotic device; anda second subframe configured to retain a second portion of the consumable that is joined to the first portion by a flexible tube;a mounting element for releasably attaching the second subframe to the first subframe, wherein the mounting element is configured to enable manipulation of the first subframe together with the second subframe when the mounting element is in an attached configuration, and to enable manipulation of the second subframe separately to the first subframe when the mounting element is in a released configuration.

2. The frame of claim 1, wherein the engagement feature is a first engagement feature, and the second subframe comprises a second engagement feature to enable engagement of the second subframe by the robotic device.

3. The frame of claim 2, wherein the mounting element is configured to detach the second subframe from the first subframe during manipulation of the second subframe with the second engagement feature.

4. The frame of any preceding claim, wherein the mounting element is reversible mounting element, preferably wherein the mounting element comprises one or more of: a hook, clip, a magnetic connector.

5. The frame of any of claims 1 to 3, wherein the mounting element is a single use mounting element, preferably wherein the mounting element comprises one or more of: an adhesive, or a snap or break connector.

6. The frame of any preceding claim, further comprising one or more installation features to enable the frame to be installed in or on a bioprocessing apparatus.

7. The frame of any preceding claim, further comprising a plurality of attachment features, each corresponding to one of the plurality of processing elements, thereby enabling the processing elements to be connected to the frame.

8. The frame of claim 7, wherein both the first subframe and the second subframe comprise one of the plurality of attachment features.

9. The frame of any preceding claim, further comprising at least one tube storage feature to enable a flexible tube to be secured to the frame.

10. The frame of claim 9, wherein the tube storage feature comprises a tube routing feature to arrange the flexible tube in a predetermined pathway on the frame.

11. The frame of claim 9 or 10, wherein the tube storage feature is configured to dispense the tube during manipulation of the second subframe relative to the first subframe.

12. The frame of any preceding claim further comprising one or more further subframes, each configured to retain a respective portion of the consumable, and one or more further mounting elements for releasably attached the subframes to each other.

13. The frame of any preceding claim, wherein one or more of the subframes comprises a device for storing and dispensing a flexible tube, the device comprising:a housing having an internal cavity for retaining a portion of the flexible tube in a stored configuration;an opening in the housing for enabling movement of the flexible tube into and out of the cavity;a guide element arranged in the housing to contact a portion of the tube passing through the opening and configured to direct the portion of the tube into the stored configuration inside the cavity.

14. The frame of any preceding claim, wherein one or more of the subframes comprises a device for holding a flexible fluid bag having a flexible tube fluidly connected thereto, the device comprising:a plurality of retaining elements, including a first retaining element configured to retain a first end of the fluid bag, and a second retaining element configured to retain a second end of the fluid bag, the second end being opposed to the first end;a support structure rigidly connecting the plurality of retaining elements; wherein the support structure is arranged to expose at least one face of the fluid bag when the fluid bag is suspended between the plurality of retaining elements.

15. The frame of any preceding claim, wherein one or more of the subframes comprises a retaining device, comprising:a first retaining element configured to retain a first section of the tube, anda second retaining element configured to retain a second section of the tube, said second section of the tube being spaced from the first section of the tube by an intermediate section of the tube,wherein the first and second retaining elements are configured to retain the first and second sections of the tube such that the intermediate section is bent in an arcuate shape that allows it to be loaded into the pumping location in the peristaltic pump, andan engagement feature to enable a robotic device to position the retaining device to locate the intermediate section of the flexible tube adjacent to the pumping location of the peristaltic pump.

16. The frame of any preceding claim, wherein one or more of the subframes comprises:a loading frame comprising a tube receiving member extending between a first support member and a second support member, the tube receiving member having a tube receiving slot that extends between the first and second support members, wherein the tube receiving slot extends at least partially into each of the first and second support members thereby forming tube insertion slots; and an insertion element configured to be inserted into the loading frame thereby to move the tube from a first position, in which the tube is positioned within the tube receiving slot, to a second position, in which the tube is positioned within the tube insertion slots and extends between the first and second support members.

17. An apparatus comprising the frame of any preceding claim, and a bioprocessing consumable, wherein the bioprocessing consumable comprises a first processing element retained on the first subframe, and a second processing element retained on the second subframe, wherein the first processing element and the second processing element are connected together by at least one flexible tube.

18. A method of performing bioprocessing using the frame of claims 1 to 16, or the apparatus of claim 17, the method comprising using an automated system to:engage the frame using the engagement feature;install one of the first or second subframe at a corresponding location of the bioprocessing apparatus;disconnect the second subframe from the first subframe; andinstall the other of the first or second subframe ata corresponding location of the bioprocessing apparatus or a different bioprocessing apparatus.

19. The method of claim 18, further comprising using the automated system to:engage the frame via the engagement feature;uninstall one of the first or second subframe from its location of the bioprocessing apparatus;reconnect the second subframe to the first subframe using the mounting element; anduninstall the other of the first or second subframe from the bioprocessing apparatus.

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