Assembly

Abstract

The present invention provides a device that enables the introduction of substances into and the removal of substances from a container by a sterile, automated, or semi-automated method for use in the therapeutic processing of cells and / or genes. [Solution] An assembly for handling biological material is described, comprising a first biological handling element having a first volume having a first port, and a second biological handling element having a second volume having a second port. The assembly also includes a sterile connection element for sterilely fluidizing the first port and the second port, and a sterile disconnection element for sterilely disconnecting the first port and the second port. Furthermore, one or more of the first biological handling element and the second biological handling element are movable so as to align their respective ports with each other to enable sterile fluidizing and sterile fluidizing during use.

Description

Technical Field

[0001] The present invention relates to an assembly for handling biological substances. The present invention also relates to a method of introducing a substance into a component of such an assembly or extracting a substance from a component. More specifically, the present invention relates to an assembly and a method of operating the assembly for use in one or more unit operations in a cell processing method, for example, in the manufacturing process of cell and / or gene therapy.

Background Art

[0002] Biological handling processes such as the manufacturing process of cell and gene therapy (CGT) are often complex and include manual steps across several devices. The equipment systems used in various steps or unit operations in the manufacture of cell-based therapeutic products (CTP) may include devices for various unit operations. Unit operations can include, for example, cell collection, cell separation, selection, cell expansion, cell washing, volume reduction, cell storage, or transportation. Unit operations can vary greatly based on, among other factors, the manufacturing model (i.e., autologous vs. allogeneic), the type of cell, and the intended purpose. Also, cells are "living" entities that are sensitive even to the most simple operations (such as differences in cell transfer procedures). The role of cell manufacturing equipment to ensure scalability and reproducibility is an important factor in cell and gene therapy manufacturing.

[0003] Also, cell-based therapeutic products (CTP) are gaining significant momentum, and thus, there is a need for improved cell manufacturing equipment for various cell manufacturing procedures, for example, but not limited to, stem cell enrichment, generation of chimeric antigen receptor (CAR) T cells, and various cell manufacturing processes such as collection, purification, genetic recombination, culture / harvest, washing, injection into patients, and / or freezing.

[0004] Cell culture or processing typically requires the use of a device to retain cells, for example, in a suitable culture medium. Known devices include shaking flasks, roller bottles, T-flasks, and bags. While such bottles or flasks are widely used, they have several drawbacks. The primary issue is the requirement for the transfer of cells, medium, or other substances without contamination during subculturing or processing.

[0005] A current problem in the development of cell or gene therapies for pharmaceutical use is the lack of a compact, automated, closed system for performing unit operations without contamination. For example, during cell culture, upstream or subsequent cell processing, there is a risk of contamination when adding cells to the incubator, removing cells, or removing liquid samples. Furthermore, current operating systems are largely manual and therefore expensive to operate. Multiple instruments are typically required to cover all non-cell culture steps, which involves many transfers, each of which presents an opportunity for operator error and contamination.

[0006] Furthermore, the increased manual labor increases the risk of manual errors, and therefore, current labor-intensive processes may lack the robustness required to produce clinically rated treatments.

[0007] Therefore, there is a need for assemblies for handling biomaterials or cells, such as multi-stage biomaterials, that allow such processing by automated or at least semi-automated methods, that is, with minimal user intervention and / or operation, while maintaining a sterilized state throughout the entire system. [Overview of the project] [Problems that the invention aims to solve]

[0008] Therefore, the object of the present invention is to provide an improved assembly for handling biological materials, specifically an improved assembly for use in the therapeutic processing of cells and / or genes, and more specifically, an apparatus that enables the introduction of materials into a container and the removal of materials from a container by a sterilized, automated, or semi-automated method.

[0009] It is also an object of the present invention to provide a device that combines the advantages of a cell culture vessel, which avoids the need for a pump and the requirement for periodic subculturing of cells to a new culture device that holds vessels, tubes, etc., with the advantages provided by having individually configurable cell and / or gene therapeutic processing devices.

[0010] A further object of the present invention is to provide an apparatus that enables various biological processes, such as one or more unit operations in cell processing, to be carried out in a single device or apparatus having a smaller footprint and being less complex than existing equipment. Furthermore, the apparatus described herein allows for better compatibility with automated systems. Other advantages will become apparent from the drawings and the following description. [Means for solving the problem]

[0011] According to one aspect of the present invention, an assembly for handling biological materials, A substantially planar joint having at least one port, A component holding element, spaced apart from the substantially planar joint, and configured to hold a component for handling biological material, Equipped with, An assembly is provided in which at least one of the substantially planar joint and the component retaining element is movable such that, when in use, a fluid passage between the component held by the component retaining element and a container associated with the substantially planar joint is provided through the at least one port, thereby aligning the at least one port with the component retaining element.

[0012] Therefore, a substantially planar joint is provided, having a port which is one or more ports formed within a substantially planar joint. The substantially planar joint can be formed substantially in a plane and can take any appropriate size or shape. The substantially planar joint is associated with a container when in use. That is, the substantially planar joint may have a container to which it is connected when in use. The container may be suitable for handling biological materials, such as a bioreactor. Specifically, the container may be a compressible container, such as a container with side walls that are compressible or flexible.

[0013] Accordingly, component retaining elements are also provided that are suitable for holding, receiving, connecting, or suspending components when in use, and are positioned for such purposes. The component retaining elements are either spaced substantially apart from the planar joint or not formed integrally with the planar joint.

[0014] Therefore, during use, the substantially planar joint, the component retaining element, or both the substantially planar joint and the component retaining element are movable such that their ports or their respective ports are aligned with each other. Thus, by aligning such features, the assembly can provide a fluid communication channel between the component held by the component retaining element and the container associated or connected between the substantially planar joint and use, thereby enabling fluid transfer and, consequently, the handling of biological material between the respective components.

[0015] This offers the advantage of providing assemblies for handling biological materials that enable the introduction and extraction of substances using sterilized, automated, or semi-automated methods. Furthermore, such assemblies have a smaller footprint and are less complex than existing equipment.

[0016] In certain embodiments, the substantially planar joint is rotatable about an axis of rotation substantially perpendicular to the plane of the substantially planar joint.

[0017] In certain embodiments, a substantially planar joint is rotatable about the central axis of the substantially planar joint. In some embodiments, the substantially planar joint may be arranged to move laterally within the plane of the substantially planar joint.

[0018] Therefore, during use, the substantially planar joint is rotated so that the port of the component aligns with the subsequent port of the substantially planar joint. This offers the advantage that during use, continuous introduction or extraction of material can be provided by an automated or semi-automated method.

[0019] In certain embodiments, the component retaining element is movable longitudinally along an axis substantially perpendicular to the plane of the substantially planar joint.

[0020] Therefore, in certain embodiments, the component retaining element is movable along the longitudinal axis. The component retaining element is movable along the central longitudinal axis of the component retaining element, or along a portion of the component retaining element, such as the component retaining head.

[0021] This offers the advantage that the component retaining element engages with the component and the ports of the substantially planar joint during use, thereby allowing it to be adapted by automated or semi-automated processing.

[0022] In certain embodiments, the component retaining element is vertically movable when in use to engage the component held by the component retaining element with the at least one port.

[0023] Thus, in certain embodiments, the component holding element is movable along a longitudinal axis so as to engage the component with the at least one port. Thus, the longitudinal axis can be arranged substantially coaxial with the longitudinal axis of the at least one port. The engagement between the component and the port can include an engagement face-to-face between the port of the component and the port of the substantially planar joint.

[0024] This provides the advantage that a sterile, preferably fluid-tight or sealed seal is provided between the component and the port of the substantially planar joint. Thus, a sterile biological handling device is ensured.

[0025] In certain embodiments, the component holding element is substantially non-movable transversely within the plane of the component holding element.

[0026] Thus, in certain embodiments, the component holding element is substantially non-movable or substantially static within the plane defined by the component holding element.

[0027] This provides the advantage that fewer moving parts are included in the device and thus easier and less expensive manufacture of such a device is provided.

[0028] In an alternative embodiment, the component holding element is movable transversely within the plane of the component holding element.

[0029] Thus, in certain embodiments, the component holding element is movable within the plane defined by the component holding element.

[0030] In certain embodiments, the component holding element comprises an arm terminating at a component holding head.

[0031] Therefore, in certain embodiments, the component holding element comprises an arm extending from a distal end to a proximal end. The distal end of the arm may be connected to an interior such as a casing or stand. The proximal end of the arm may be connected to a component holding head. The component holding head may be positioned to hold the component during use.

[0032] In certain embodiments, a component holding head may comprise one or more connecting elements positioned to cooperate with a component during use, such as to hold, receive, connect, or retain the component during use. For example, one or more connecting elements may be rails positioned to cooperate with a protrusion of the component. For example, one or more connecting elements may be fasteners such as clips, bolt and nut configurations, or screws positioned to cooperate with a fastener receiving portion of the component. In one specific example, a component holding head comprises a base and an upwardly extending side wall, the side wall and base providing a volume for receiving the component. The base may comprise an opening or opening through which a portion of the component, such as a port, can protrude or be exposed.

[0033] In certain embodiments, the apparatus further comprises a casing, the component retaining element being formed as part of the casing, and the casing being configured to operably receive the substantially planar joint.

[0034] Therefore, in certain embodiments, there are enclosures in which the component retaining element is formed as part of such an enclosure. In one example, the component retaining element comprises an arm extending from the inner wall of the enclosure and terminating at a component retaining head. Thereafter, the component retaining element may be formed as an integral part of the enclosure. In another example, the component retaining element comprises an arm extending from a stand or structure formed within the enclosure and terminating at a component retaining head.

[0035] In certain embodiments, the substantially planar joint comprises a plurality of ports.

[0036] Therefore, in certain embodiments, a substantially planar joint has more than one port, or two or more ports. In one example, a substantially planar joint has more than 5, 10, 15, 20, 25, or 30 ports. In a specific example, a substantially planar joint has 22 ports.

[0037] In certain embodiments, each port is positioned radially outward from the central longitudinal axis of the substantially planar joint.

[0038] Therefore, in certain embodiments, the substantially planar joint includes a central longitudinal axis, and each port is positioned radially outward from such axis. Specifically, each port is positioned along a radius formed between the central longitudinal axis and the outer edge of the substantially planar joint.

[0039] In certain embodiments, multiple ports are arranged in a circular, semicircular, or arc-shaped configuration.

[0040] This offers the advantage that the substantially planar joint can be rotated to align the component with the subsequent port of the substantially planar joint. Thus, an apparatus adapted by automated or semi-automated processing is provided.

[0041] In certain embodiments, at least one port of the substantially planar joint is a resealable port.

[0042] Therefore, in certain embodiments, the port or each port is resealable so as to return to a sealed configuration after the fluid passage formed through it. For example, a resealable port may comprise a hinged door or valve that returns to a closed position after the fluid passage formed through it, for example, in an open position. Furthermore, in other examples, a resealable port may be a self-sealing port, such as a diaphragm seal that self-seals when the puncture is stopped.

[0043] This offers the advantage that multiple fluid passages can be provided without compromising the sterilization status of the device.

[0044] In certain embodiments, the resealable port includes a diaphragm seal.

[0045] In specific embodiments, the diaphragm seal may include a silicone material or a thermoplastic elastomer material.

[0046] In a specific embodiment, the outer surface of the diaphragm seal may be substantially coplanar with the upper surface of the substantially planar joint.

[0047] Therefore, in some embodiments, the diaphragm seal and the substantially planar joint are substantially continuous in shape or flush with each other.

[0048] This offers the advantage that the diaphragm seals can come into contact with adjacent diaphragm seals facing each other. Therefore, the sterilization state of the device is ensured during use.

[0049] In specific embodiments, the diaphragm seal may comprise an annular projection wall enclosing a substantially flat portion.

[0050] Therefore, in some embodiments, the diaphragm seal, specifically the annular projection wall, can project above the substantially planar upper surface of the joint. The substantially flat portion of the diaphragm seal can be coplanar with the substantially planar upper surface of the joint.

[0051] This offers the advantage that one diaphragm seal can accommodate the protruding portion of an adjacent diaphragm seal, thereby assisting in the placement of each diaphragm seal during automated or manual processing.

[0052] In certain embodiments, the substantially planar joint and the diaphragm seal are co-molded.

[0053] This offers the advantage of providing increased pull-out force to the diaphragm seal against a substantially planar joint. This is particularly advantageous in needle retraction from the diaphragm seal, otherwise it could pull the diaphragm seal out of the substantially planar joint during retraction. Thus, damage to the substantially planar joint and a potential compromised sterilization state are avoided.

[0054] In a specific embodiment, the substantially planar joint further comprises a removable sterile barrier positioned across the at least one port.

[0055] Therefore, in certain embodiments, a substantially planar joint comprises a removable barrier that ensures the sterilization of its port or each of its ports. Specifically, the port or each of its ports is provided as a sterilization port through gamma irradiation or ethanol wiping, etc. The removable barrier is provided across the sterilization port or each of its ports.

[0056] This offers the advantage that the sterilization state of the port or each individual port is ensured before and during use.

[0057] In certain embodiments, the removable sterile barrier comprises a paper material or a polymer material. The removable sterile barrier may have a handle at one end. The removable sterile barrier may have folds that define a first portion of the barrier and a second portion of the barrier. The first portion of the barrier may be positioned to contact another sterile barrier, and the second portion of the barrier may be positioned across its ports or across each of its ports. Any number of folds may be provided.

[0058] In certain embodiments, the removable sterile barrier comprises a fastening portion operably connected to a sterile outer shell, the sterile outer shell being detachably arranged across at least one port. The fastening portion may be connected to the sterile outer shell by any suitable method, such as a projection of the fastening portion mechanically connected to an opening in the sterile outer shell, by adhesive or by heat welding.

[0059] In certain embodiments, a fastening portion is positioned to connect to a further fastening portion of an adjacent removable sterile barrier. The fastening portion may comprise one or more connecting elements positioned to connect to one or more corresponding connecting elements of an adjacent fastening portion.

[0060] This offers the advantage that adjacent removable sterile barriers can be connected and disconnected simultaneously by the device. Therefore, devices adapted for automated or semi-automated processing are provided. Furthermore, tactile and / or visual feedback may be provided to the user during the manual disconnection process.

[0061] In certain embodiments, the sterile outer layer is positioned in part to be located on its ports or each of its ports, and in another part to connect to a further sterile outer layer of an adjacent removable sterile barrier. In one example, the sterile outer layer may have a fold that defines a first portion of the sterile outer layer and a second portion of the sterile outer layer. The first portion of the sterile outer layer may be positioned to be in contact with the other sterile outer layer, and the second portion of the sterile outer layer may be positioned to be located on its ports or across each of its ports.

[0062] This offers the advantage of ensuring that each port is sterilized before and during use.

[0063] Therefore, during use, removable sterile barriers may be arranged to connect to adjacent removable sterile barriers. For example, a removable sterile barrier positioned across the ports of a substantially planar joint or across each of its ports may be arranged to connect to a removable sterile barrier of a component such as a connector. Subsequently, in the connection of removable sterile barriers, such connected sterile barriers may be removed before a fluid passage is provided.

[0064] It should be noted that the connection of each removable sterile barrier, such as a sterile outer layer, may be through any suitable means, such as mechanical connection, bonding, or thermal welding.

[0065] In certain embodiments, the fastening portion is slidably received in a slot formed in the substantially planar joint, and the fastening portion is movable within the slot between a first configuration in which a sterile sheath is positioned across the at least one port and a second configuration in which the sterile sheath is removed from the at least one port.

[0066] Accordingly, in certain embodiments, a substantially planar joint is provided with a port or a slot adjacent to each port. The slots slidably receive a fastening portion of a removable sterile barrier. The fastening portion is movable, specifically slidable, within the slot between the first and second configurations. In the movement of the fastening portion from the first configuration to the second configuration, the sterile sheath is disengaged, or removed, from its port or each port.

[0067] This offers the advantage that the sterile barrier can be easily removed from each port during use, and that such removal can be adapted by automated or semi-automated processes.

[0068] In certain embodiments, a substantially planar joint comprises one port and one slot adjacent to that port. In certain embodiments, a substantially planar joint comprises a plurality of ports and a plurality of slots, each adjacent to each port.

[0069] In certain embodiments, the apparatus further comprises a sterile barrier removal system, which is configured to operably engage with a portion of the removable sterile barrier and to remove the removable sterile barrier from the at least one port during use.

[0070] Accordingly, in certain embodiments, a sterile barrier removal system is provided. The sterile barrier removal system may include a part configured to connect to or engage with a portion of a removable sterile barrier, such as a fastening portion. In a specific example, the sterile barrier removal system comprises a protruding knob that can engage with an opening in the fastening portion of the removable sterile barrier. In such an example, the protruding knob may be movable between a first configuration in which the protruding knob engages with the fastening portion and a second configuration in which the sterile sheath is removed from a port in a substantially planar joint.

[0071] This offers the advantage that the sterile barrier can be removed using an automated method. Therefore, the sterilized state of the device is ensured during use.

[0072] In certain embodiments, the substantially planar joint comprises a connecting element configured to operably connect to a corresponding connecting element of a container.

[0073] Therefore, in certain embodiments, a substantially planar joint comprises one or more elements arranged to connect to a corresponding element of the container.

[0074] In specific embodiments, the connecting element includes a thread that is positioned to connect to the threads of the container, or a clip portion that is positioned to connect to a corresponding clip portion of the container.

[0075] In specific embodiments, the connecting element of a substantially planar joint and the connecting element of a container cooperate to provide a sterile, fluid-seal, and / or airtight engagement between the substantially planar joint and the container when in use.

[0076] In certain embodiments, the substantially planar joint comprises one or more drive elements arranged to cooperate with a drive mechanism.

[0077] Therefore, in certain embodiments, a substantially planar joint comprises one or more features arranged to be driven by a drive mechanism, such as a drive mechanism for an enclosure.

[0078] This offers the advantage that the drive mechanism can control the location of the substantially planar joint relative to the component holding element, thereby providing an automated or semi-automated device.

[0079] In certain embodiments, the device, or the enclosure housing the device, includes a drive mechanism. For example, the drive mechanism drives a substantially planar joint.

[0080] In certain embodiments, the drive mechanism includes a drive wheel arranged to engage with a plurality of grooves formed on the periphery of a substantially planar joint.

[0081] In certain embodiments, a control device is provided to control the drive mechanism. The control device may include a user interface for receiving user input. For example, the user can provide user input to the user interface regarding the positioning of a substantially planar joint, such as the positioning of one or more ports relating to a component retaining element. In one example, the control device is configured to control the drive mechanism based on user input.

[0082] In certain embodiments, the component holding element includes an actuator configured to actuate at least a portion of the component held by the component holding element when in use.

[0083] Therefore, in certain embodiments, the component holding element comprises an actuator or a system of motion or actuation positioned to actuate a portion of the component when in use.

[0084] In certain embodiments, the actuator is configured to actuate the connector portion of the component when in use. Alternatively, the actuator is configured to actuate the receiving portion of the component to cause fluid distribution when in use. Alternatively, the actuator is configured to actuate the receiving portion of the component to cause fluid to be drawn from a container associated with a substantially planar joint to the receiving portion when in use.

[0085] Therefore, the actuator may be provided as one or more of the following: a connector actuator, a fluid distribution actuator, or a fluid extraction actuator.

[0086] In certain embodiments, a control device is provided to control an actuator. The control device may include a user interface to accept user input. For example, the user can provide user input to the user interface regarding the timing of the component's operation. In one example, the control device is configured to control the actuator based on user input.

[0087] In certain embodiments, the apparatus further comprises a container fluidly connected to the at least one port of the substantially planar joint.

[0088] Accordingly, in certain embodiments, the apparatus further comprises a container to which fluid is connected to the ports of a substantially planar joint or to each of the ports. Thus, a fluid passage may be provided between the ports of the substantially planar joint or to each of the ports and the volume of the container. Specifically, a sealed fluid passage and / or a sterile sealed fluid passage may be provided.

[0089] In certain embodiments, the container comprises flexible or compressible side walls. In such examples, the side walls may be flexible so that the container, specifically the base relative to the top, is compressible along a longitudinal axis parallel to the side walls. To this end, in specific examples, the side walls may comprise a plurality of folds, thereby forming bellows-like side walls. The container may consist of any suitable material, such as a gas-permeable material or a substantially gas-impermeable material, such as low-density polyethylene, high-density polyethylene, silicone, or thermoplastic elastomer.

[0090] In certain embodiments, the apparatus further comprises an expandable receiver operably connected to the substantially planar joint and configured to be in fluid communication with the container through the substantially planar joint.

[0091] Accordingly, in certain embodiments, the apparatus further comprises a receiving portion that is expandable and connected to a substantially planar joint. The expandable receiving portion may be provided in fluid communication with the container, for example, through a fluid passage passing through the substantially planar joint. In some examples, the fluid passage may be provided as an opening in the substantially planar joint or as a port in the substantially planar joint.

[0092] This provides a breathing mechanism for the device, thereby keeping the pressure inside the receiving container substantially constant through use, such as through agitation or mixing.

[0093] In certain embodiments, a fluid passage through a substantially planar joint comprises a winding fluid passage. That is, in certain embodiments, the fluid passage comprises a barrier, wall, shelf, or projection that obstructs at least a portion of the fluid passage. The winding fluid passage may be nonlinear.

[0094] This offers the advantage that gases such as air can easily pass through the passage, while liquids or suspensions, such as media containing biological substances, are substantially prevented from passing through the passage.

[0095] In certain embodiments, a substantially planar joint comprises a central hub with a fluid passage. That is, the fluid passage may extend from its lower surface to its upper surface through the central hub of the substantially planar joint.

[0096] In certain embodiments, the central hub may be surrounded by an outer circular wall, or may comprise an inner circular wall concentrically positioned with respect to the outer circular wall. A fluid passage may be formed between the inner and outer circular walls. A projection may be provided extending radially outward from the inner circular wall toward the outer circular wall. A shelf may be provided extending radially inward from the outer circular wall toward the inner circular wall, for example, its base. The projection and / or shelf may define a winding fluid passage.

[0097] In certain embodiments, the projection may form an angle with respect to the horizontal. In specific embodiments, the projection may be angled toward the underside of a substantially planar joint. In more specific embodiments, the projection may be angled toward a shelf extending radially inward from the base of the outer circular wall.

[0098] This is provided so that a medium containing biological material, or a liquid such as a condensate, is returned to the container during use, thereby offering the advantage of minimizing liquid loss from the container.

[0099] In certain embodiments, a plurality of radially extending ribs are provided, each extending between the outer circular wall and the projection, and connecting to the outer circular wall and the projection. Each rib may, if provided, connect to a shelf portion of the outer circular wall. This method provides for a plurality of fluid passages, such as winding fluid passages.

[0100] In certain embodiments, the expandable receiving portion includes a flexible bag.

[0101] In certain embodiments, the expandable support comprises a support having flexible or expandable side walls. In specific embodiments, the support may comprise a base wall, an upper wall, and expandable side walls between the base wall and the upper wall. The expandable side walls may comprise a plurality of folds, thereby forming bellows-like side walls.

[0102] In certain embodiments, the apparatus further comprises components for handling the biological material held by the component holding element.

[0103] In a particular embodiment, the component includes a receiving portion.

[0104] In certain embodiments, the component includes a connector.

[0105] In a particular embodiment, the component includes a connector that is fluidly connected to the receiving portion.

[0106] In certain embodiments, the apparatus further comprises a casing for housing a component retaining element and a substantially planar joint.

[0107] In specific embodiments, the enclosure includes a sliding drawer configured to operably receive the substantially planar joint. For example, the sliding drawer may include a positioning plate positioned to operably receive the substantially planar joint. The sliding drawer may be movable between a first configuration in which the sliding drawer is outside the enclosure and a second configuration in which the sliding drawer is inside the enclosure.

[0108] In specific embodiments, the enclosure may include actuators, drive mechanisms, homing sensors, positioning sensors, etc., depending on the embodiments described herein. Generally, during use, one or more features of the assembly, specifically one or more component holding elements and / or substantially planar joint features, may be housed within the enclosure.

[0109] In a specific embodiment, the enclosure is provided as a culture unit. The culture unit may include a temperature control device and / or a gas supply control device such as an oxygen and / or carbon dioxide control device for controlling the supply of oxygen and / or carbon dioxide.

[0110] According to another aspect of the present invention, a method for introducing a substance into a component of an assembly for handling a biological substance, or for removing a substance from a component of an assembly for handling a biological substance, The steps include providing an assembly as described herein, The steps include: holding a component suitable for handling biological materials and having at least one port in the component holding element; The steps include moving at least one of the substantially planar joint and the component retaining element in order to align the at least one port of the component with the at least one port of the substantially planar joint, The steps include providing the at least one port of the substantially planar joint and the fluid passage through the at least one port of the component, The steps include introducing a substance into the component or removing a substance from the component through the fluid passage. A method including this is provided.

[0111] In a particular embodiment, the assembly further comprises a container fluidly connected to at least one port, and the steps of introducing a substance into the component or removing a substance from the component are: Introducing a substance from the component through the fluid passage into the container, and / or, This includes extracting a substance from the container to the component through the fluid passage.

[0112] In yet another aspect of the present invention, a kit of parts is provided comprising a substantially planar joint as described herein and a component retaining element as described herein. Optionally, the kit of parts further comprises a container, an expandable receiver, and / or components as described herein.

[0113] In yet another aspect of the present invention, a system for handling biological material is provided, comprising an enclosure and an assembly as described herein.

[0114] According to yet another aspect of the present invention, an assembly for handling biological materials, A first biological handling element having a first volume having a first port, A second biological handling element having a second volume having a second port, A sterile connection element is configured to provide sterile fluid communication between a first volume and a second volume by sterilely fluidizing a first port and a second port, A sterile disconnection element is configured to sterilely disconnect the fluid between the first port and the second port in order to prevent sterile fluid communication between the first and second volumes. Equipped with, An assembly is provided in which at least one of the first biological handling element and the second biological handling element is movable so as to align the first port and the second port with each other in order to sterilely fluid connect the first port and the second port to a sterile connecting element when in use, and to sterile fluid disconnect the first port and the second port to a sterile disconnecting element when in use.

[0115] This offers the advantage that biomaterials can be handled in a "just-in-time" manner. That is, the transfer of material between volumes is provided only when the transfer is needed, rather than involving several pre-connected components. This ensures that biomaterials can be handled efficiently in a sterile, automated, or semi-automated manner.

[0116] In one embodiment, the first biological handling element comprises a substantially planar joint as described herein.

[0117] In one embodiment, the first biological handling element comprises a first holding element that holds a first container having a first volume and a first port.

[0118] In specific embodiments, a substantially planar joint comprises at least one port to which a vessel, such as a bioreactor, is fluidly connected, and the vessel contains a first volume. The substantially planar joint may comprise a plurality of ports. Each of the plurality of ports may be fluidly connected to the vessel. The vessel may comprise an upper portion, a base portion, and a flexible or compressible wall element between the upper portion and the base portion. The wall element may comprise a plurality of grooves or spirals, or bellows-like wall elements.

[0119] In one embodiment, the second biological handling element comprises a component holding element as described herein. The component holding element as described herein can hold a container having a second volume and a second port.

[0120] In one embodiment, the second biological handling element comprises a second holding element that holds a second container having a second volume and a second port.

[0121] In specific embodiments, a component holding element is configured to hold a component, or holds a component. The component may comprise a container having a second volume and a second port. The container may comprise an upper portion, a base portion, and a flexible or compressible wall element between the upper portion and the base portion. The wall element may comprise a plurality of grooves or bellows-like wall elements. The container may be a bag, a flexible bag, or a container comprising a plunger.

[0122] The first and / or second ports may comprise an open-end tube, a closed-end tube, or a tube with a removable sterile membrane positioned across the end. The tube may be a flexible tube. Alternatively or in combination, the first and / or second ports may comprise a sealed diaphragm, a sealed membrane, or a Luer-lock port.

[0123] The sterile connection element may be integrated with the sterile disconnection element; that is, an integrated sterile connection and disconnection element may be provided. The integrated sterile connection and disconnection element may comprise a connector, such as a sterile or sterile connector as described herein. Specifically, the connector may comprise a needle. The needle may be operable to engage with or puncture a first port and a second port, such as a first diaphragm seal and a second diaphragm seal, during use.

[0124] The sterile connection element may be a separate component with respect to the sterile disconnection element.

[0125] The sterile connection element may comprise a sterile welding element. Specifically, the sterile connection element may comprise a sterile pipe welding machine configured and / or positioned to sterilely weld a first pipe, such as a first port, to a second pipe, such as a second port. The sterile connection element may comprise a robotic arm terminating at the sterile welding element. The sterile welding element may comprise a sterile welding element configured to apply heat and optionally pressure to each port, such that each port is thermal welded. The sterile welding element may comprise a sterile film covering the closed end of the pipe or the end of the pipe, thereby enabling a fluid passage through each pipe.

[0126] The sterile disconnection element may include a sterile sealing element. Specifically, the sterile disconnection element may include a sterile tube sealing machine configured and / or positioned to sterilely seal a first portion of a tube, such as a first tube or first port, to a second portion of a tube, such as a second tube or second port. The sterile disconnection element may include a robotic arm terminating at the sterile sealing element. The sterile sealing element may be configured to apply heat and optionally pressure to a portion of the connected port to thermally seal that portion, thereby providing a thermally sealed first portion of the connected port from the second portion of the connected port. The sterile sealing element may be further configured to cut or separate the sealed region between the first and second portions of the connected port, thereby allowing the release of each component.

[0127] The apparatus may include component-holding elements as described herein. The component-holding elements may be configured to hold a first biological handling element and / or a second biological handling element.

[0128] The apparatus may comprise one or more robotic arms. One or more robotic arms may be positioned to move a first biological handling element and / or a second biological handling element to align a first port and a second port with respect to each other. One or more robotic arms may comprise a holding portion positioned to hold the first biological handling element and / or the second biological handling element. One or more robotic arms may comprise an actuation portion positioned to actuate a portion of the first biological handling element and / or the second biological handling element to cause the distribution of biomaterial from the first volume and / or the second volume. One or more robotic arms, holding portions, and / or actuation portions may be controlled by a control device. The control device may comprise a user interface. The control device may be positioned to control one or more robotic arms, holding portions, and / or actuation portions in response to user input to the user interface.

[0129] The device may be automated; that is, it does not require manual work or user intervention. The device may also be semi-automated; that is, it may require minimal manual work or user intervention, such as loading biological handling elements into the device.

[0130] The apparatus may include an incubator or a housing that encloses each component of the apparatus.

[0131] In another aspect of the present invention, a method for handling biological substances, A step of moving at least one of a first biological handling element having a first volume having a first port and a second biological handling element having a second volume having a second port, such that the first port and the second port are aligned with each other. The steps include: aseptically fluidizing a first port and a second port, thereby providing fluid communication between a first volume and a second volume; The steps include transferring biological material from a first volume to a second volume, or from a second volume to a first volume, The steps include: sterilely deconnecting a first port and a second port that are fluidly connected, thereby preventing fluid communication between the first volume and the second volume; A method including this is provided.

[0132] This offers the advantage that biomaterials can be handled in a "just-in-time" manner. That is, the transfer of material between volumes is provided only when the transfer is needed, rather than involving several pre-connected components. This ensures that biomaterials can be handled efficiently in a sterile, automated, or semi-automated manner.

[0133] In a particular embodiment, the step of aseptically fluidizing a first port and a second port includes aseptically welding the first port to the second port. In a specific embodiment, the aseptic welding step may be performed by an aseptic pipe welding machine.

[0134] In a particular embodiment, the step of aseptically deflushing the first and second ports includes aseptically sealing the connected first and second ports in order to provide aseptically sealed first and second ports. In a specific embodiment, the aseptic sealing step may be performed by a sterile tube sealing machine.

[0135] It will be understood by those skilled in the art that the method may include one or more components of the apparatus described above or elsewhere in this specification, such as a substantially planar joint, a component retaining element, a sterile tube welding machine, or a sterile tube sealing machine.

[0136] Herein, an example embodiment of the present invention will be described below with reference to the accompanying drawings. [Brief explanation of the drawing]

[0137] [Figure 1] This is an overall perspective view of the system comprising the assembly, enclosure, and components according to the present invention. [Figure 2] Figure 1 shows a perspective view of the assembly, enclosure, and components during use. [Figure 3] This is a perspective view of the planar joint, including the attached container. [Figure 4] This is a side view cross-sectional view of the assembly shown in Figure 3, which includes an expandable receiving portion and a cover attached to a planar joint. [Figure 5] This is a perspective view of another planar joint, including the attached container. [Figure 6(a)] This is a perspective view of the other planar joint, including the attached container. [Figure 6(b)] Figure 6(a) is a cross-sectional view of the planar joint. [Figure 6(c)] This is an enlarged cross-sectional view of the planar joint shown in Figure 6(a). [Figure 6(d)] This is another cross-sectional view of the planar joint in Figure 6(a). [Figure 7] Figure 5 is a perspective view of the assembly, further including the component holding elements of the assembly. [Figure 8(a)] Figure 5 is a perspective view showing the planar joint being mounted onto the drawer of the enclosing body. [Figure 8(b)] This is a perspective view of the planar joint portion that is mounted on the drawer shown in the open position. [Figure 8(c)] This is a perspective view of the enclosure with the drawer in the closed position. [Figure 9(a)] This is an enlarged perspective view of Figure 8(b). [Figure 9(b)] This is a partially cropped perspective view of Figure 8(c). [Figure 9(c)] This is an enlarged perspective view of Figure 8(b), which shows the drive mechanism. [Figure 10(a)] This is a perspective view of another enclosure showing the location features of other planar joints and the withdrawal of the enclosure. [Figure 10(b)] Figure 10(a) is a perspective view showing the planar joint portion mounted on the drawer. [Figure 11] Figure 8(c) is a partially cut front view of the enclosure, including component holding elements formed as part of the enclosure. [Figure 12(a)] This is a cross-sectional view of the component from the side. [Figure 12(b)] Figure 12(a) is a perspective view of the cross-section of the connector of the component. [Figure 13(a)] This is a partially cropped perspective view of Figure 8(c), with the component holding elements omitted. [Figure 13(b)] Figure 13(a) is a perspective view of the cross-section. [Figure 13(c)] This is another perspective view of Figure 13(a), which shows the stirring mechanism and its stirring modes. [Figure 13(d)] This is a side view of Figure 13(a) showing another stirring mode of the stirring mechanism shown in Figure 13(c). [Figure 14(a)] This is a perspective view of another encircling body. [Figure 14(b)] This is a perspective view showing the planar joint in Figure 5 being mounted onto the enclosing body in Figure 14(a). [Figure 14(c)] This is an enlarged view of Figure 14(b). [Figure 15(a)] Figure 14(a) is a perspective view of the enclosure having an upward access door in the closed position. [Figure 15(b)] Figure 14(a) is a perspective view of the enclosure with an access door in the open position. [Figure 16(a)] This is a perspective view of the components and surrounding body shown in Figure 14(a) before installation. [Figure 16(b)] This is an enlarged perspective view of Figure 15(b), showing the components mounted on the component holding elements of the assembly. [Figure 16(c)] This is an enlarged perspective view of Figure 15(b), showing the components mounted on the component holding elements of the assembly. [Figures 17(a)-17(b)]Figure 17(a) is a perspective view of a component held by a component holding element as shown in Figure 16(c), and Figure 17(b) is a perspective view of the initial operation of the component by the component holding element. [Figure 17(c)] This is a perspective view of the further movement of a component by a component retaining element for engaging the component with a planar joint. [Figure 18(a)] This is a schematic side view of a component held by a component holding element, as shown in Figure 16(c). [Figure 18(b)] This is a schematic side view of the engagement of components to planar joints that are aligned with each other. [Figure 18(c)] This is a schematic side view of the components for engaging each port with each other and the removal of the sterile barrier at the planar joint. [Figures 19(a)-19(c)] Figure 19(a) is a perspective view of the first step in activating the sterile barrier removal system, specifically the sterile barrier removal system; Figure 19(b) is a perspective view of the second step in activating the sterile barrier removal system; and Figure 19(c) is a perspective view of the third step in activating the sterile barrier removal system. [Figure 20(a)] This is a perspective view of the component, including the connector, held by the component retaining element as shown in Figure 17(c), before the connector is operated. [Figure 20(b)] This is a perspective view of the component, including the connector, after the connector has been operated, and which is held by a component retaining element as shown in Figure 17(c). [Figure 21(a)] Figure 20 shows a side cross-sectional view of the connector during the various steps of connector operation, prior to the connector's operation. [Figure 21(b)] Figure 20 shows a lateral cross-sectional view of the connector during various steps of its operation, after the initial operation of the connector. [Figure 21(c)] Figure 20 shows a lateral cross-sectional view of the connector during various steps of connector operation, after further operation of the connector. [Figure 21(d)] Figure 20 shows a side cross-sectional view of the connector during various steps of connector operation, in which the connector stops operating. [Figures 22(a)-22(b)] Figure 22(a) is a perspective view of the component held by a component retaining element as shown in Figure 17(c), further including a distribution actuator, before distribution, and Figure 22(b) is a perspective view of the component held by a component retaining element as shown in Figure 17(c), further including a distribution actuator, after distribution. [Figure 23] This is a schematic side view of a component held by a component retaining element, as shown in Figure 17(c), after being removed from a planar joint. [Figure 24(a)] This diagram illustrates a method for aseptically connecting and disconnecting biologically handled components, as an example. [Figure 24(b)] This diagram illustrates a method for aseptically connecting and disconnecting biologically handled components, as an example. [Figure 24(c)] This diagram illustrates a method for aseptically connecting and disconnecting biologically handled components, as an example. [Figure 24(d)] This diagram illustrates a method for aseptically connecting and disconnecting biologically handled components, as an example. [Modes for carrying out the invention]

[0138] The embodiments described relate to assemblies for handling biological materials. Specifically, some embodiments relate to assemblies that are sterile or sterilized. It should be noted that the terms “sterile” and “sterilized” may be used interchangeably throughout this disclosure. References to fluids in the detailed description are not intended to limit the scope of protection to such substances. As will be understood by those skilled in the art, the fluids described herein are merely examples of suitable substances for use with such assemblies. Similarly, references to containers or receptacles may be made, but such references are not intended to limit the scope of protection to such containers or receptacles. As will be understood by those skilled in the art, containers or receptacles are described herein merely as examples.

[0139] Certain terms are used in the following description for convenience only, but are not limited to them. The terms “up” and “down” indicate the direction in the drawing from which the reference is made, relating to the component being assembled and mounted. The terms “inside,” “inward,” “outside,” and “outward” refer to the direction toward and away from a specified centerline or geometric center (e.g., central axis) of the element being described, and their specific meanings are readily apparent from the context of the description. Furthermore, the terms “proximal” (i.e., closer to) and “distal” (i.e., further away from) specify the position relative to an axis or mounting point.

[0140] Furthermore, as used herein, terms such as “connection,” “adhesion,” and “linking” are intended to include not only direct connections between two members without any other material interposed between them, but also indirect connections between two members in which one or more other members are interposed between them. The terms include the words explicitly mentioned above, their derivatives, and words of a similar nature.

[0141] Furthermore, unless otherwise specified, the use of order adjectives such as “first,” “second,” and “third” is not intended to refer to different examples of similar objects, or to imply that the objects described in this way must be in a given order in time, space, order, or any other manner. Similar symbols are used throughout to describe similar characteristics.

[0142] As shown in Figure 1, a biomaterial handling system 1, comprising an assembly 10, for handling biomaterials according to the present invention is shown. Specifically, the system 1 comprises a casing 12, a component holding element 14, a planar joint 16, a container 18, and a component 20. In this specific example, component 20 is a connector 22 having a fluidly attached receiving portion 24. Component 20 may also be other components, such as an additional component one of the following: a cell loading component 20a for loading cells into the container 18, a bead loading component 20b for loading beads such as magnetic beads into the container 18, a virus loading component 20c for loading viruses into the container 18, or a medium loading component 20d for loading a medium such as a biological medium suitable for cell retention into the container 18. Furthermore, component 20 may be an extraction component, for example, one of the following: a cell extraction component 20e for extracting cells from container 18 to a suitable container; a sample component 20f for drawing in a sample of the contents of container 18; or a medium extraction component 20g for extracting some, most, or all of the medium or contents of container 18. Generally, in the embodiments described, component 20 comprises a connector 22 and a receiving portion 24, the receiving portion 24 being positioned for appropriate use as an additional or extraction component 20a-20g.

[0143] Referring further to Figure 2, the enclosure 12 forms an internal volume for housing the component holding element 14, the planar joint 16, the container 18, and the component 20. The enclosure 12 generally takes the form of a culture unit. The component holding element 14 is provided integrally with the enclosure 12, that is, the component holding element 14 is formed as part of the enclosure 12 in its internal portion and is positioned to hold, receive, or retain the component 20 during use. Furthermore, as shown in Figure 1, the planar joint 16 is connected to the container 18, such as a bioreactor, which may have flexible walls or be foldable, so as to be connected fluidly sterile. During use, the planar joint 16 and the container 18 are housed within the enclosure 12, as shown in Figures 1 and 2.

[0144] Figure 3 shows a portion of the assembly of the present invention. Specifically, Figure 3 shows a planar joint 116 having a container 118, such as a bioreactor, attached thereto. Specifically, the planar joint 116 is equipped with threads for connection to complementary threads of the container 118, as discussed below in relation to Figure 4. Thus, a sterile, fluid-seal or airtight seal is formed between the planar joint 116 and the container 118. The planar joint 116 is equipped with a plurality of ports 150 formed in this example as 22 diaphragm seals, the ports 150 which allow themselves to be punctured by a needle, thereby enabling the handling of biological material or fluids. Any number of diaphragm seals may be used. Such use may include, for example, sampling the contents of the container 118 during use, adding to the container 118 during use, and / or removing, i.e., discarding, the contents of the container 118 during use. Generally, each port 150 is positioned to provide a fluid passage to the container 118 through the planar joint 116 during use, as described below. Those skilled in the art will recognize that other ports having openings, doors, valves, etc., may be used to enable selected fluid communication.

[0145] As shown in this example, each individual port 150 has a sterile barrier 152 positioned over it. The sterile barrier 152 is generally removablely attached to the port 150 on the surface of each port 150. The sterile barrier 152 ensures the sterile state of each port 150 before use and is generally removed before making a connection to each port 150. The sterile barrier 152 generally takes the form of a sterile sheath made of paper or polymer material in this example. As further described below, each sterile barrier 152 is positioned to be removed by a part of the enclosure 12 (see enclosure in Figure 1), such as a barrier removal system, or by the user.

[0146] The planar joint 116 in this example further comprises a central hub 154 including a plurality of connecting elements 156 that rise upright from the upper surface of the planar joint 116 and are formed as clips in this embodiment, the connecting elements 156 being arranged to receive and connect an expandable receiver, as described in relation to Figure 4.

[0147] Furthermore, the container 118 in this example, formed as a bioreactor having an internal chamber, a base wall, and a compressible side wall, has a maximum volume of 1.5 L. Generally, the base of the container 118, i.e., the cell growth area, can be 150 square cm. Also, in some embodiments not shown, the container 118 can accommodate a 0.2 micron filter, which in some embodiments is formed as part of the base or side wall of the container 118, or alternatively, as part of a planar joint 116. The filter can provide gas exchange between the surrounding environment, such as a surrounding body, and the internal chamber of the container 118. The container 118 can generally be manufactured using blow molding methods such as extrusion molding or injection blow molding, which provide a simplified manufacturing of the container 118 having a single-piece container, i.e., no joints, and therefore no leak paths, and having a flatter base, and also provide a reduction in plastic for entering the medical waste flow. The container 118 may be made of any suitable material such as low-density polyethylene (LDPE), high-density polyethylene (HDPE), thermoplastic elastomer (TPE), or silicone.

[0148] Figure 4 shows a portion of the assembly of Figure 3, including a planar joint 116 and a container 118. As shown, the planar joint 116 connects to the container 118 thanks to a threaded portion 160 of the planar joint 116 that is complementary to the threaded portion 162 of the container 118. Furthermore, in this example, a cover 164 is provided positioned across the top surface of the planar joint 116 and connected to its top surface, for example, by a clip fastener, and can be removed before use or retained during use. The central hub 154 of the planar joint 116 is shown in Figure 4 as connected to an expandable receiver 166, which is shown in a compressed configuration. The expandable receiver 166 includes a connecting element, such as a clip, that is complementary to the connecting portion 156 of the central hub 154 and connects to the connecting portion 156. In a specific example, the expandable receiver 166 has threads that are complementary to the threads formed on the central hub 154. The expandable receiver 166 is fluidly connected to the container 118 thanks to fluid passages 168 indicated by dotted lines. The fluid passages 168 may be formed by ports (not shown) or openings (not shown) in the planar joint 116 that communicate with each port or opening (not shown) of the expandable receiver 166. In this way, a fluid such as air from the container 118 can enter the expandable receiver 166 during the compression of the container 118, thereby providing a breathing mechanism that causes the expandable receiver 166 to expand into its expanded configuration. Similarly, during use, a fluid such as air from the expandable receiver 166 can be drawn into the container 118 during its expansion, thereby causing the expandable receiver 166 to compress into its compressed configuration. Thus, the pressure inside the container 118 is maintained at a substantially constant level during the compression and decompression of the container 118. In other embodiments not shown, the expandable receiver 166 can be replaced by a filter, which, if necessary, provides a breathing mechanism by allowing a fluid such as air to escape into or be drawn into the container 118. Such a filter may be gas-permeable, or oxygen-permeable and / or carbon dioxide-permeable, and liquid-impermeable.

[0149] Figure 5 shows another planar joint 216 for use in the present invention, as further described below. The planar joint 216 is substantially the same as the planar joint 116 of Figures 3 and 4, in that it comprises several ports (not shown) having a sterile barrier 152 that is removablely attached across itself. The planar joint 216 further comprises a periphery 250 having several drive elements 252 arranged to cooperate with the drive mechanism of the enclosure, as further described below. The planar joint 216 also comprises a central hub 254 erected from the top surface of the planar joint 216, the central hub 254 is shown not connected to the expandable receiver, but may have features that allow connection to an expandable receiver or filter, such as those described in relation to Figures 3 and 4.

[0150] Figures 6(a) to 6(c) show yet another planar joint 216a for use in the present invention, as will be further described below. The planar joint 216a is substantially the same as the planar joints 116, 216 in Figures 4 and 5, and therefore similar features such as the periphery 250 and the container 118 will not be further described.

[0151] The planar joint 216a comprises a central hub 254a having an inner circular wall 254b and a concentrically positioned outer circular wall 254c. The outer circular wall 254c is positioned to allow connection of the expandable receiver 166 during use, as shown in Figure 6(b). For example, the outermost surface of the outer circular wall 254c may have threads or clip portions, etc., to allow connection of the expandable receiver 166.

[0152] The inner circular wall 254b includes a radially extending projection 255 that extends radially outward from the inner circular wall 254b toward the outer circular wall 254c. The projection 255 may extend around the entire perimeter of the inner circular wall 254b, but is shown as C-shaped. In this example, the central hub 254a is further provided with a dividing wall 257 that extends from a portion of the outer circular wall 254c toward a portion of the inner circular wall 254b, connecting a portion of the outer circular wall 254c to a portion of the inner circular wall 254b, for example, a portion of the inner circular wall 254b and a portion of the outer circular wall 254c do not include the C-shaped projection 255. Thus, the dividing wall 257 may connect opposite ends of the C-shaped projection 255.

[0153] The outer circular wall 254c includes a shelf 259 extending radially inward from the base 259a toward the inner circular wall 254b. Generally, the shelf 259 and the protruding edge 255 define a fluid passage 168 between them, specifically, as best shown in Figures 6(b) and 6(c), between the lower surface of the planar joint 216a to which the container 118 is attached and the upper surface of the planar joint 216a, specifically the upper surface of the central hub 254a to which the expandable receiver 166 is attached. In this way, the central hub 254a defines a fluid passage 168 from the attached container 118 to the attached expandable receiver 166 to allow breathing or air pressure compensation between the respective containers 118, 166. More specifically, the shelf portion 259 and the protruding edge 255 define a winding or nonlinear fluid passage 168 such that air or gas can pass through the passage 168, while preventing fluids such as a medium containing biological material from passing through such passage 168 to the expandable receiving portion 166.

[0154] A series of radially extending ribs 261 are provided, connecting the protruding edge 255 to the inner surface of the outer circular wall 254c, with each rib 261 spaced apart from one another. Each adjacent pair of ribs 261 defines individual fluid passages 168 between them. Furthermore, as best shown in Figure 6(c), the protruding edge 255 forms an angle with respect to the horizontal, i.e., with respect to the horizontal plane in which the protruding edge 255 is positioned, so that it is oriented or angled downward or toward the shelf portion 259 of the outer circular wall 254c. In this manner, any liquid or condensate generated from the container 118 is directed toward returning to the container 118 so that no substance is lost from the container 118 to the expandable receiving portion 166 during use.

[0155] Furthermore, the planar joint 216a has several ports 150 (see Figure 6(b)), each port 150 having a removable sterile barrier 152 that is removablely attached and positioned across the ports 150 to provide a sterile seal. Specifically, the removable sterile barrier 152 comprises a fastening portion 152a connected to a sterile outer shell 152b, which is sterilely connected to each port 150 (see Figure 6(b)). The fastening portion 152a is positioned in a space 263 formed between each guide wall 265 and is held in place using clips 267 attached to adjacent guide walls 265. Thus, the fastening portion 152a is slidable within the space 263 so that the sterile outer shell 152b can be removed from the ports 150 during use, as will be described in more detail below.

[0156] Referring particularly to Figure 6(d), the planar joint 216a further comprises a downward volume sampling element 150a extending from the lower surface of the planar joint 216a. More specifically, the downward volume sampling element 150a is formed integrally with one or more of the ports of the planar joint 216a. The downward volume sampling element 150a is formed as a hollow, tubular member 150b containing an elastic material such as thermoplastic elastomer or silicone, and has a through-hole extending from the distal end to the proximal end, communicating with each port 150. Specifically, the hollow, tubular member 150b is connected to the lower surface of the planar joint 216a adjacent to the port 150 using a screw cap 150c having threads that screw into the corresponding threads of the hollow, tubular member 150b. The screw cap 150c may be connected to the lower surface of the planar joint 216a by suitable means such as adhesive or clips.

[0157] During use, the container 118 and / or the planar joint 216a may move so that the hollow, tubular member 150b extends into the liquid held within the container 118, allowing for sampling of the container 118. Additionally, due to the elastic nature of the hollow, tubular member 150b, it may be positioned to contact the base of the container 118 without damaging it. Specifically, the hollow, tubular member 150b, being made of an elastic material, may be positioned to curve at a corner of the container 118, specifically at a corner where the base of the container 118 is adjacent to the side wall of the container 118, or curve toward that corner. Thereafter, a sample, even a small amount, can be taken from the container 118 without risk of damaging the container 118. More specifically, in this particular example, the connector's needle is inserted through port 150 such that the through-hole of port 150 is in fluid communication with the through-hole of the hollow, tubular member 150b, as will be considered below. Thus, the component connected to the other end of the connector's needle can be operated to draw fluid from the container 118, through the hollow, tubular member 150b, through the connector's needle, to or toward the component. This allows a sample to be taken from the container 118.

[0158] Furthermore, as shown in Figures 6(b) and 6(d), in this example, the container 118 is connected to the planar joint 216a using a retaining ring 269. The retaining ring 269 has a projection 269a that frictionally engages with the outer surface of the container 118, and the container 118 is secured between the projection 269a of the retaining ring 269 and a connecting wall 271 that extends distally from the lower surface of the planar joint 216a. The retaining ring 269 is connected to the planar joint 216a using a plurality of fasteners 269b, such as screws or bolts. Alternatively, the container 118 may have threads that engage with the threads of the planar joint 216a, thereby eliminating the need for the retaining ring 269.

[0159] Furthermore, as shown in Figures 6(b) and 6(d), an expandable receiver 166 is provided, connected to the central hub 254a. The expandable receiver 166 comprises an upper portion 166a, a base portion 166b, and a wall portion 166c extending between the upper portion 166a and the base portion 166b. The wall portion 166c is formed as a bellows with a plurality of foldable folds, thereby allowing the receiver 166 to expand and compress. The upper portion 166a of the expandable receiver 166 includes an air filter 273 that communicates with the internal volume of the expandable receiver 166 and the external environment. The air filter 273 is positioned to allow air to pass into the expandable receiver 166 or out of the expandable receiver 166 without allowing liquid to pass into or out of the expandable receiver 166. The air filter 273 may be gas-permeable, such as oxygen-permeable or carbon dioxide-permeable, and liquid-impermeable. Generally, the air filter 273 is a sterile air filter, thereby filtering out bacteria, viruses, or other substances, thereby creating a sterile environment within the container 118 and / or the expandable receiver 166. The base portion 166b of the expandable receiver 166 is an open end and comprises a circular base wall 166d positioned to connect to the central hub 254a of the planar joint 216a. Specifically, the circular base wall 166d is connected to the outer circular wall 254c of the central hub 254a using spring fasteners or spring clips (not shown). Alternatively, the circular base wall 166d may have male threads configured to engage with threads in the outer circular wall 254c of the central hub 254a.

[0160] Figure 7 shows an assembly 100 comprising the planar joint 216 of Figure 5 and a container 118. Alternatively, the planar joint 116 of Figure 3, Figure 4, or Figure 6(a) may be used. The assembly includes a component receiving element 114, such as a component receiving element 14 formed as part of the enclosure 12 of Figures 1 and 2, for holding a component 120, such as the component 20 of Figures 1 and 2. Specifically, the component receiving element 114 is formed by an arm 114a extending from inside the enclosure (not shown) and terminating at a component holding head 114b. The component holding head 114b includes a holding element for holding, receiving, or holding the component 120 during use. For example, the component holding head 114b may include a rail for receiving a portion of the component 120 so that the component 120 slides within the component holding head 114b as needed. In another example, the component holding head 114b holds the component 120 thanks to a friction fit. In a further example, the component retaining head 114b comprises a base and one or more side walls, thereby forming a volume from which the component 120 is received, specifically, from which the component 120 presses or leans against the base during use. As will be recognized by those skilled in the art, a suitable mechanism for retaining the component 120 to the component retaining element 114 has been considered.

[0161] In general, the component retaining element 114 and / or the planar joint 216 are movable so as to align or position the ports of the component 120 with one of the ports of the planar joint 216. In this specific example, as indicated by arrow A, the planar joint 216 is rotatable about its central longitudinal axis L. The component retaining element 114 is also substantially immobile laterally, i.e., within the plane formed by the component retaining element 114, but is movable longitudinally along the longitudinal axis L1 of the component retaining element 114, specifically the component retaining head 114b, such as in the direction indicated by arrow B. Therefore, during use, as further described below, the planar joint 216 is rotated around a central longitudinal axis L so that the ports of component 120 held by the component holding head 114b of the component holding element 114 are aligned with the ports of the planar joint 216, and then the component holding head 114b, or alternatively the entire component holding element 114, is moved along axis L1 in direction B to engage the ports of component 120 with the ports of the planar joint 216, specifically, the sterile barrier 152 in the first example. Subsequently, the component holding head 114b, or the entire component holding element 114, is moved along axis L1 in the direction opposite to direction B to disengage the engagement between the respective ports. Then, the planar joint 216 is rotated around a central longitudinal axis L so that the next port of the planar joint 216 is aligned with the port of component 120 in a continuous manner. The process can then be repeated any number of times. The detailed operation of assembly 100 is described below. In general, the described assembly 100 provides an assembly that is more suitable for automation and requires less manual intervention or operation. As will be understood by those skilled in the art, this is an example of the present invention, and therefore in other examples, the arms may be rotatable and movable to align their respective ports, and the planar joints may be substantially immovable.Further examples may include both a movable arm and a movable planar joint.

[0162] Figures 8(a) to 8(c) show how the planar joint 216 and container 118 of Figure 7 are mounted onto the enclosure 112. As shown in Figure 8(a), the enclosure 112 is equipped with a sliding drawer 180, which has a mounting plate 182 and is slidable on an extension rail between an open configuration (see Figures 8(a) and 8(b)) in which the planar joint 216 can be mounted onto the drawer 180, and a closed configuration (see Figure 8(c)) in which the drawer 180 is positioned and housed within the enclosure 112. Generally, during use, the user slides the drawer 180 open in a direction perpendicular to the central vertical axis of the planar joint 216, mounting the planar joint 216 onto the mounting plate 182, and thereby mounting it onto the drawer 180 (Figure 8(a)). Once installed, the user slides the drawer 180, and consequently the planar joint 216, into the closed configuration in the indicated direction C (Figure 8(b)). In the closed configuration, the planar joint 216 and the receiving part 118 are installed in the enclosure 112 and housed within the enclosure 112, specifically within the internal volume of the enclosure 112 (Figure 8(c)), and the system can be used.

[0163] Figures 9(a) to 9(c) show more detailed diagrams of the enclosure 112, the planar joint 216, and the drive mechanism 184 of the enclosure 112. As shown in Figures 9(a) and 9(b), the planar joint 216 is mounted onto the drawer 180 of the enclosure 112, as previously described. Once mounted, as shown in Figure 9(c), the drive mechanism 184, specifically the grooved drive wheel 186, engages with the periphery 250 having a plurality of drive elements 252. The grooved drive wheel 186 and the drive elements 252 of the periphery 250 mesh during use to act as a gear configuration, thereby providing rotation of the planar joint 216 around its central longitudinal axis during use. Specifically, the drive wheel 186 can be driven clockwise by a motor, as indicated by arrow D, thereby driving the planar joint 216 counterclockwise around its central longitudinal axis.

[0164] The drive mechanism 184, specifically the drive wheels 186, can be driven by a control device (not shown) of the enclosure 112, which may be connected to several sensors (not shown) for sensing the positioning of the planar joint 216 within the enclosure 112. For this purpose, the planar joint 216 may be equipped with several magnets and the enclosure 112 may be equipped with Hall effect sensors, or the enclosure 112 may be equipped with several magnets and the planar joint 216 may be equipped with Hall effect sensors. The control device can control the positioning of the planar joint 216 with respect to component holding elements during use, specifically during use, in order to position each port of the planar joint with the component. Thus, control or automated homing and / or rotation of the planar joint 216 is provided within the enclosure 112 without manual intervention or operation. In this method, the planar joint 216 can be mounted on the enclosure 112 without the user having to precisely align the planar joint 216; that is, the planar joint 216 can be placed on the enclosure without having to align it with the ports of the component that are held in place by the component holding elements. The planar joint 216 is then positioned and rotated by a control device that controls the drive wheel 186 to align the respective ports of the planar joint 216 and the component, in response to user input such as the selection of specific ports of the planar joint 216 in the user interface of the enclosure 112. Subsequently, the drive wheel 186 can control the subsequent movement of the planar joint 216 to align another port of the planar joint 216 with a port of the component in a sequential manner as described below, thereby providing an automated system.

[0165] Figures 10(a) and 10(b) show other planar joints 316 and other enclosures 212. Planar joints 316 are substantially the same as the planar joints 216 in Figures 5, 6, and 7, except that they include several positioning features 352 formed on the underside of the planar joint 316. In this particular example, the positioning features 352 are formed as sinusoidal shaped portions, such as notches on the underside. Furthermore, planar joints 316 do not have a periphery with a grooved outer surface as shown in the planar joints 216 in Figures 5, 6, and 7, but instead have a smooth periphery 350. In other embodiments, planar joints 316 may include both positioning features 352 on the underside of the planar joint 316 and a grooved periphery.

[0166] The enclosure 212 similarly comprises a drawer 280, as described in relation to Figures 8(a) to 8(c). However, in this example, the drawer 280 comprises a mounting plate 282 having a corresponding positioning feature 284 on its upper surface. In this specific example, the positioning feature 284 is formed as a sinusoidal shaped portion, such as a notch on the upper surface. Thus, the positioning feature 284 is complementary to the positioning feature 352 of the planar joint 316. In this way, the user is provided with tactile feedback that the planar joint 316 is seated inside the drawer 280. During use, the assembly 212 can be made to rotate the planar joint 316 in a manner as described in relation to Figures 9(a) to 9(c), or alternatively, the drawer 280, specifically the mounting plate 282, can be rotated by a drive mechanism as indicated by the arrow in Figure 10(a). Therefore, the positioning features 284 and 352 can provide the user with confidence that the planar joint 316 is seated on the drawer 280, while eliminating the need for the user to mount the planar joint 316 in a specific orientation.

[0167] Figure 11 shows the assembly 100 of Figure 6 housed within an enclosure 312, which may be one of the previously considered enclosures. Specifically, as shown in Figure 11, the assembly 100 is formed in this example as part of the interior portion of the enclosure 312 and includes a component holding element 114 that holds the component 120.

[0168] Referring further to Figure 11, the component holding element 114 is shown to further comprise an actuator 170 positioned to actuate component 120, specifically its connector 122 (see Figures 12(a) and 12(b)). Referring, for example, to Figures 11, 12(a), and 12(b), the actuator 170 can provide a fluid connection between the second diaphragm seal 128b of the connector 122 and the port of the planar joint 116, as further described below. The planar joint 116 is housed within a casing 312, specifically between a stirring plate 350 that can engage with the base surface of a container 118 attached to the planar joint 116, and a plate 352 that can house or receive the planar joint 116 and / or may have a drive mechanism (not shown) for driving the planar joint 116. The planar joint 116 can be housed within the enclosure 312, for example, thanks to a drawer, according to one of the examples discussed earlier.

[0169] Referring further to Figures 12(a) and 12(b), component 120 in this example includes a connector 122 to which a receiving part 124, such as a blood collection tube, is attached. Thus, this specific example of component 120 provides a sample collection component 20e (see Figure 1). As will be apparent to those skilled in the art, this is merely one example of a component that can be used in the assembly present herein.

[0170] The connector 122 of component 120 is described with reference to Figures 12(a) and 12(b). The connector 122 is generally positioned to connect two volumes of fluid. The connector 122 comprises a housing comprising an upper housing portion 123a and a lower housing portion 123b. The housing extends along the longitudinal axis between a distal end 125a and a proximal end 125b. The upper housing portion 123a is axially movable or slidable relative to the lower housing portion 123b, as further described below.

[0171] The housing has a threaded portion 126 at its distal end 125a for connecting to a corresponding threaded portion of a receiving portion, such as a threaded screw cap 127 of a receiving portion 124 shown in Figure 12(a), and the receiving portion contains a first volume of fluid. As will be apparent to those skilled in the art, the housing may be provided without the threaded portion 126, or instead, other suitable connection mechanisms may be provided for connecting to a portion of the receiving portion. Furthermore, the receiving portion may be directly attached to the distal end 125a by any suitable mechanism, for example, the receiving portion may be pre-connected or sealed, for example, through an adhesive. In one embodiment, a receiving portion comprising a connector 122 is manufactured.

[0172] In this embodiment, the connector 122 comprises a first port formed as a first diaphragm seal 128a and located at the distal end 125a of the housing, and a second port formed as a second diaphragm seal 128b and located at the proximal end 125b of the housing. The housing further comprises a hollow needle 129 mounted inside the housing and, in this specific example, biased and mounted. The hollow needle 129 is generally coaxial with the longitudinal axis of the connector 122. The hollow needle 129 comprises a first end 130a facing the first diaphragm seal 128a and a second end 130b facing the second diaphragm seal 128b. The first end 130a is configured to penetrate and perforate the first diaphragm seal 128a during use, and the second end 130b is configured to penetrate and perforate the second diaphragm seal 128b during use. The first diaphragm seal 128a, the second diaphragm seal 128b, or both the first and second diaphragm seals 128a and 128b may optionally be provided with a sterile barrier 131 positioned across them. The sterile barrier 131 is generally configured to fit with the corresponding sterile barrier 152 (see Figure 3) of the planar joints 116, 216, 216a, 316 (see Figures 3-7 and 8). The sterile barrier 131 may be positioned to adhere to, or otherwise connect with, the corresponding sterile barrier 152 so that both barriers 131 and 152 can be removed simultaneously, as further described below.

[0173] In this particular example, the hollow needle 129 is mounted in the housing via a ring 132 that is spring-biased by a first helical spring 133a and a second helical spring 133b. In other embodiments, the hollow needle 129 may be mounted by other suitable methods, for example, the hollow needle 129 may be mounted statically, i.e., so as not to move, and the housing may be movable relative to the hollow needle 129. In a further alternative, the hollow needle 129 may be axially movable via the ring 132, and the upper housing portion 123a may be axially movable while the lower housing portion 123b remains statically, i.e., so as not to move. To this end, the upper housing portion 123a may be provided with an operable knob, and the ring body 132 may be provided with an operable knob, and each set of operable knobs is operable by an actuation mechanism arranged to move the hollow needle 129 and the upper housing portion 123a in order to cause puncture of the respective diaphragm seals 128a and 128b. In this example, the order of puncture of the diaphragm seals 128a and 128b is controlled by the spring forces of springs 133a and 133b, respectively. Specifically, the first spring 133a provides a first biasing force to the hollow needle 129 via the ring body 132 in the direction toward the proximal end 125b of the housing, and the second spring 133b provides a second biasing force to the hollow needle 129 via the ring body 132 in the direction toward the distal end 125a of the housing. The first biasing force can be greater than, equal to, or less than the second biasing force to control the continuous puncture of the diaphragm seals 128a and 128b. In this example, the first biasing force is greater than the second biasing force thanks to the larger wire diameter of the first spring 128a compared to the second spring 128b.

[0174] During use, as will be recognized by those skilled in the art, the hollow needle 129 is caused to engage with and puncture the respective ports 128a, 128b to fluidize the receiving portion 124 (see Figure 12(a)) into a second volume of fluid, such as a container 118 connected to planar joints 116, 216, 216a (see, for example, Figures 3, 5, and 6), such as a container 118. To achieve such puncture, the connector 122 is provided with an operating mechanism, in this example provided as an outer cover 133 surrounding the upper housing portion 123a and the lower housing portion 123b. The outer cover 133 is rotatable about the central longitudinal axis of the connector 122. On its inner surface, the outer cover 133 has projections (not shown) that engage with slots (not shown) on the outer surface of the upper housing portion 123a. The protrusions and slots provide a cam mechanism such that rotation of the outer cover 133 causes axial translation of the upper housing portion 123a relative to the lower housing portion 123b. Generally, during use, the second diaphragm seal 128b is positioned to cooperate with ports such as the diaphragm seal of the planar joint, as described below. To this end, the hollow needle 129 can puncture both the second diaphragm seal 128b and the diaphragm seal of the planar joint to provide a fluid passage through the diaphragm seal of the joint during puncture. The method of fluid connection is provided below with reference to Figures 21(a) to 21(d).

[0175] Figures 13(a) to 13(d) show alternative views of the assembly 100 and enclosure 312 of Figure 11. Specifically, several linear actuators 354 are provided as part of the enclosure 312, positioned to move the stirring plate 350 during use. As shown in Figures 13(b) and 13(c), the linear actuators 352 are configured to move the stirring plate 350 along the longitudinal axis L2 in the direction of arrow E. There may be four linear actuators 354, specifically pairs of linear actuators 354a, 354b, positioned on the opposite side of the assembly 100, specifically on the opposite side of the planar joint 116 and the container 118. The linear actuators 354a, 354b are positioned and configured to act synchronously. For example, a pair of linear actuators 354a act in one direction, and the other pair of linear actuators 354b act in the same direction. In this method, the linear actuators 354a and 354b are positioned to cause linear compression, i.e., axial translation, of the container 118 during use. Such motion may be useful, among other things, for removing material from the container 118 and / or for mixing material within the container 118. Furthermore, as best illustrated in Figure 13(d), the opposing pairs of linear actuators 354a and 354b are positioned and configured to act asynchronously, for example, as indicated by arrows E and F in Figure 13(d), the pair of linear actuators 354a act in one direction and the other pair of linear actuators 354b act in the opposite direction, thereby imparting a oscillating or wave-like motion to the container 118. Such motion may be useful, among other things, for mixing material within the container 118, such as resuspended biomaterials, such as cells, in a medium.

[0176] Figures 14(a) to 14(c) show other enclosures 412 for use with assemblies as described herein. Specifically, Figures 14(a) and 14(b) show an enclosure 412 comprising a hinged door 450 arranged to rotate in direction G around an axis between a closed configuration (Figure 14(a)) that encloses the contents of the enclosure 412 and an open position (Figure 14(b)) that allows access to the contents of the enclosure 412. In this specific example, the planar joint 116 and container 118 are slidable into the enclosure 412 as indicated by arrow H (Figures 14(b) and 14(c)), and the periphery of the planar joint 116 is slidably received into a slot 452 in a plate of the enclosure 412 (see, for example, plate 352 in Figure 13(a)). Furthermore, the positioning feature portion 454 may be provided on the stirring plate of the surrounding body 412 to assist in mounting the container 118 attached to the planar joint portion 116 onto the surrounding body 412.

[0177] Figures 15(a) and 15(b) show other enclosures 512 for use with assemblies such as those described herein. Specifically, the enclosure 512 comprises a pair of sliding doors 550 that are movable away from each other in their own plane. Thus, the sliding doors 550 may be movable between a closed position in which the contents of the enclosure are enclosed (Figure 15(a)) and an open position in which the contents of the enclosure 512 can be accessed (Figure 15(b)). In this specific example, the doors 550 are openable in direction I to allow access to the component retaining element 114, the component 120, and / or the upper surface of the planar joint 116. In this method, the upper components of the enclosure 512, namely the component holding element 114, the upper surface of the planar joint 116, and component 120, are accessible thanks to the door 550, while the lower components of the enclosure 512, namely the container (not shown) and the lower part of the planar joint 116, are accessible thanks to the drawer or hinged door 554, as described in the previous example. Thus, various accessible parts are separated, and user access may be limited to specific parts of the system during use.

[0178] Here, the use of assemblies and their components, as well as the exemplary enclosure, will be illustrated with reference to Figures 16(a) to 23, as a non-limiting example.

[0179] Referring first to Figure 16(a), the component 120 held by the component retaining element is provided as an enclosure 512, as described in relation to Figures 15(a) and 15(b), although such an enclosure may be any of the enclosures described herein. The enclosure 512, specifically its upper sliding door 550, is opened (Figure 16(b)), thereby exposing the component retaining element 114 of the assembly 100 within the enclosure 512. The component 120 is shown as a connector 122 having a receiving portion 124 with a compressible plunger 124a, and is located within the component retaining element 114, specifically within the component retaining head, as indicated by arrows J and K, and is held by the component retaining head (Figure 16(c)). The component retaining element 114 can hold the component 120 by any suitable means as previously described, but in this example, the component retaining element 114 holds the component 120 thanks to a rail formed in the component retaining head that cooperates with a portion of the component 120, such as a protrusion. In this specific example, the planar joint 116 and container (not shown) are pre-mounted in the enclosure 512. As will be understood by those skilled in the art, the planar joint 116 and container (not shown) can be mounted according to any of the examples previously described. Following mounting, the user can close the sliding door 550 to enclose the contents of the enclosure 512.

[0180] Referring to Figures 17(a) to 17(c), a method is shown for engaging a component held by a component holding element with a planar joint. As shown in Figure 17(a), when component 120 is mounted on component holding element 114, the control device acts on actuator 170. To this end, the user can provide input to the control device's user interface. Specifically, actuator 170, formed as part of component holding element 114, has a notch and comprises a rotatable disc 171 housed in actuator housing 173. Housing 173 similarly has a notch. Each notch is arc-shaped to provide a crescent-shaped notch. Thus, with the respective notches aligned as shown in Figure 17(a), component 120 can be mounted on component holding head 114b before use. Referring further to Figure 17(b), in operation, the rotatable disc 171 rotates around the central longitudinal axis of the component holding head 114b in a specified direction L to expose the engaging surface of the disc 171 that is positioned to engage with the component 120. In this example, the engaging surface is provided as a segment of the rotatable disc 171. The rotatable disc 171 is also axially movable, as shown in Figure 17(c), so that the engaging surface engages with the upper surface of the component 120, thereby allowing the component 120 to move axially within the component holding head 114b due to a cooperative rail configuration between the component holding head 114b and the component 120. For this purpose, the component 120 is slidably received and therefore may be slidable or axially movable within the component holding head 114b. Component 120 is moved axially in the indicated direction M until the sterile barrier 131 of the connector 122 of component 120 (see Figure 12(b)) engages with the corresponding sterile barrier 152 of the planar joint 116. Specifically, the sterile barriers 131 and 152 are made to engage in a facing manner.

[0181] Referring to Figures 18(a) to 18(c), schematic diagrams of an example of a component retaining element 114, a component 120, and a planar joint 116 housed within a casing 512. In this example, another example of a sterile barrier 650 is provided across a port 150 of the planar joint 116. The sterile barrier 650 comprises a sterile sheath 652 positioned across the port 150 and terminates at a fastening portion 654a. The fastening portion 654a is generally received in a slot (not shown) of the planar joint 116 so as to be slidable within the slot between a first configuration in which the sterile sheath 652 is positioned across the port 150 and a second configuration in which the sterile sheath 652 is removed from the port 150. The fastening portion 654a is generally made of a rigid plastic material, while the sterile sheath 652 is made of paper or polymer material. The fastening portion 654a is connected to the sterile outer shell 652 by any suitable method, such as through mechanical connection of a projection to the opening of the sterile outer shell 652 (see Figures 19(a) to 19(c)), or by adhesion to the sterile outer shell 652.

[0182] Furthermore, in this specific example, the sterile barrier 131 of the connector 122 (see also Figure 12(b)), which is positioned across the port 128b of the connector 122, further comprises a sterile sheath connected to the fastening portion 654a. However, in other examples, as will be understood by those skilled in the art, the fastening portions 654a, 654b may be provided on only one of the component 120 or the joint plate 116. In this example, the fastening portions 654a, 654b have corresponding features, such as the configuration of protrusions and openings, so that they are positioned to be connected to each other during use. Referring further to Figures 18(b) and 18(c), as will be further described below, in facing engagement with the planar joint 116 of the connector 122, the fastening portions 654a, 654b are connected to each other, and their respective sterile sheaths are also connected to each other (see Figure 18(b)). Subsequently, the sterile barriers 131 and 650 are removed primarily by the detachment of the connected fastener portions 654a and 654b from component 120 and planar joint 116, respectively (see Figure 18(c)). In this method, the lateral movement of the fastener portions 654a and 654b connected to their respective sterile outer layers detaches the sterile outer layers from their respective ports 150 and 128b, thereby engaging the ports 150 and 128b with each other in opposing engagements.

[0183] Referring to Figures 19(a) to 19(c), the sterile barrier removal system 600 is shown, and its operation is illustrated. The sterile barrier removal system 600 comprises a laterally extending beam 602 with rails 604 on its side walls. A slidable arm member 606 is also provided, which is slidably received within the rails 604, slidable along the rails 604, and terminates at a longitudinally extending operating projection 608.

[0184] In this example, the sterile barriers 131 and 650 shown in Figures 18(a) to 18(c) are provided for use with a sterile barrier removal system 600. During use, the sterile barrier removal system 600 is positioned to remove the sterile barriers 131 and 650 from the connector 120 and the planar joint 116 (see Figure 18(a)), which are integrally connected to cooperate as previously described. Specifically, in this example, the working projection 608 is moved along the rail 604 in direction N to engage with the connected fastener portions 654a and 654b, as shown in Figure 19(a). More specifically, the fastener portions 654a and 654b may have an introduction edge 655 (see Figure 19(a)) for guiding the projection 608 to the opening 657 (see Figure 19(b)) of the fastener portions 654a and 654b. In the engagement of the operating projection 608 with the fastening portions 654a and 654b, the operating projection 608 is retracted, i.e., moved away from the component 120 along the rail 604 in direction O, so as to apply a release force to the fastening portions 654a and 654b. In this manner, the fastening portions 654a and 654b are pulled outward away from the component 120 and the planar joint 116, respectively, thereby causing their respective sterile sheaths to be pulled outward and removed from their respective ports 128b and 150 (see Figure 18(a)). In this manner, the port 150 of the planar joint 116 and the port of the connector 122, i.e., the second diaphragm seal 128b, can be engaged in a face-to-face manner (see Figure 18(c)). Furthermore, when the sterile barriers 131 and 650 are removed, they fall into the waste chute 660, as indicated by arrow P in Figure 19(c). The waste chute 660 may provide a passage to, for example, a trash can, for the direct or indirect removal of the sterile barriers into the medical waste workstream.

[0185] Referring to Figures 20(a) and 20(b), and further to Figures 21(a) to 21(d), a method for operating the components to provide fluid communication through a planar joint is described.

[0186] As shown in Figure 20(a), before fluid communication is provided, component 120, specifically its ports, is aligned with the planar joint 116, specifically its ports. As shown in Figure 20(b), actuator 170 is positioned to actuate component 120, specifically the connector 122, in order to provide fluid communication through the respective ports of component 120 and the planar joint 116. More specifically, actuator 170 is positioned to rotate in direction Q around the longitudinal axis of component 120, specifically the connector 122, as described below. To this end, actuator 170 may include a pair of gripping fingers (not shown) to enable rotation of the connector 122. In this method, fluid communication is provided between component 120, specifically its receiving portion 124, and a receiving portion (not shown) attached to the planar joint 116.

[0187] Referring to Figures 21(a) to 21(d), the various steps of the component's operation are described. Figure 21(a) shows the port of component 120, i.e., the second diaphragm seal 128b of connector 122, aligned with the port 150 of planar joint 116. That is, ports 128b, 150 are coaxial or aligned. Figure 21(b) shows the first step in the operation of connector 122, specifically the initial rotation of the outer cover 133 by an actuator of a component retaining element (not shown). Following such a first step in the operation of connector 122, the second end 130b of the hollow needle 129 is punctured through the second diaphragm seal 128b of connector 122 and through the port 150 of planar joint 116. This is achieved through the rotation of the outer cover 133, which causes the upper housing 123a to drop relative to the lower housing 123b, thereby allowing the hollow needle 129 to puncture the second diaphragm seal 128b and port 150 at its second end 130b. As illustrated, the first diaphragm seal 128a opposite the connector 122 remains punctured due to the spring biasing discussed in relation to Figure 12(b).

[0188] Figure 21(c) shows a second step in the operation of the connector 122, specifically a further rotation of the outer cover 133 by an actuator of a component retaining element (not shown). Following such a second step in the operation of the connector 122, i.e., by the further rotation of the outer cover 133, the first end 130a of the hollow needle 129 is punctured through the first diaphragm seal 128a of the connector 122 into the receiving portion 124. In this specific example, the receiving portion 124 also includes a diaphragm seal 124a having a trapezoidal cutout, through which the first end 130a of the hollow needle 129 is also punctured. As shown in Figure 21(c), fluid communication through the hole of the hollow needle 129 is provided between the receiving portion 124 and the internal volume of the planar joint 116, such as the attached receiving portion. At this point, the fluid, such as a medium or biological material, can be passed between the receiving portion 124 and the container attached to the planar joint in either direction. When it is desired that fluid communication be stopped, the outer cover 133 is rotated in the opposite direction to the rotation that would cause the hollow needle 129 to puncture each diaphragm seal, thanks to an actuator of a component holding element (not shown). Thus, as shown in Figure 21(d), the puncture of each diaphragm seal 128a, 128b is stopped when the hollow needle 129 returns to its original configuration. Specifically, the order in which the punctures are stopped in each diaphragm seal 128a, 128b is the reverse of the order in which they were punctured. In other words, in this specific example, the first end 130a of the hollow needle 129 is made to stop puncturing the first diaphragm seal 128a first, and then the second end 130b of the hollow needle is made to stop puncturing the second diaphragm seal 128b. As will be understood by those skilled in the art, the order of punctures and the stopping of punctures can be altered by controlling the spring biasing force and / or by providing an alternative operating mechanism for the connector 122.

[0189] Figures 22(a) and 22(b) illustrate how fluid distribution to the receiving portion 124 of component 120 is provided while fluid communication is established through the respective ports of component 120 and the planar joint 116, such as the fluid communication shown in Figure 21(c). Specifically, fluid communication between component 120 and the receiving portion 124 through the planar joint 116 is established to a container (not shown) attached to the planar joint 116, as shown in Figures 21(c) and 22(a). Once fluid communication is established, a distribution actuator 172, formed as part of the component holding element 114, acts on the plunger 124a of the receiving portion 124, thereby driving the piston 124b axially downward in direction R, i.e., toward the connector 122 and the planar joint 116. In this example, the distribution actuator 172 is formed as a motor-driven spatula. In other examples, the distribution actuator 172 may be formed as part of the previously considered actuator 170 (Figures 17(a) to 17(c)), thereby providing a single actuator for operating the connector 122 and the receiving portion 124. When the piston 124b is biased downward, the contents of the receiving portion 124 are distributed from the receiving portion 124 through the hollow needle of the connector 122 (see also Figure 21(c)), through the connector 122 and the planar joint 116, to a container (not shown) attached to the planar joint 116. Thus, additional fluid is supplied from component 120 to the container (not shown) attached to the planar joint. Similarly, as will be recognized by those skilled in the art, the distribution actuator 172 may be replaced by a removal actuator positioned to act on the plunger 124a in the opposite direction to that described above, that is, to move the plunger 124a and piston 124b axially upward, that is, axially away from the connector 122 and the planar joint 116. Thus, a negative pressure configuration may be provided so that the contents of a receiving (not shown) attached to the planar joint 116 are drawn out, or pulled in, to the receiving 124.Similarly, as will be recognized by those skilled in the art, the actuator 172 may be configured and positioned for both distributing fluid from the receiving portion 124 and drawing fluid into the receiving portion 124.

[0190] Figure 23 outlines the final steps in the use of the assembly and other associated components. Specifically, once fluid distribution is complete and component 120 is disconnected from the planar joint 116, the component retaining element 114, specifically its actuator 170 (see Figure 17(b)), detaches component 120 from the planar joint 116 by axially translating component 120 away from the planar joint 116 in direction S. Component 120 can then be removed from the component retaining element 114 by a user or a robotic arm of the encirclement, and may be replaced with another component. The operation of the assembly and similar features can then be repeated as many times as desired by using subsequent ports of the planar joint 116. Specifically, the planar joint 116 is rotated so that the ports of the new components align with the subsequent ports of the planar joint 116, as shown in Figures 7 and 9(c).

[0191] Other embodiments of the assembly 1000 for handling biological materials are disclosed, as shown in Figures 24(a) to 24(d). As shown in Figure 24(a), the assembly 1000 comprises a component holding element 1002 for holding a container 1004 having a tube 1006. The tube 1006 may have a sterile membrane (not shown) connected to its distal end. The component holding element 1002 is formed as a robotic arm 1008 terminating at a holding portion 1010 formed by a gripping arm 1012. The gripping arm 1012 is configured to grip and hold the container 1004 during use. The robotic arm 1008 is movable to move the container 1004 during use. The assembly 1000 also comprises a substantially planar joint 1014, such as those described herein, for example with respect to Figures 3 to 7, which is connected to a bioreactor 1016. However, in this specific embodiment, the substantially planar joint 1014 comprises a plurality of tubes 1018 to which sterile membranes (not shown) are connected at their ends.

[0192] As shown in Figures 24(b) and 24(c), the assembly 1000 also includes a sterile tube welding machine 1022 and a sterile tube sealing machine 1024. The sterile tube welding machine 1022 is formed at the end of a robotic arm. Similarly, the sterile tube sealing machine 1024 is formed at the end of another robotic arm. Thereafter, each robotic arm is movable to operate the sterile tube welding machine 1022 and the sterile tube sealing machine 1024 during use. The robotic arms can also bring about the operation of the respective sterile tube welding machine 1022 or the sterile tube sealing machine 1024.

[0193] Here, the assembly 1000 is described in relation to its use in connection with Figures 24(a) to 24(d). As shown in Figures 24(a) and 24(b), the component holding element 1002 is movable to align the tube 1006 of the container 1004 with the tube 1018 of the planar joint 1014. Once the tubes 1006 and 1018 are aligned with each other, as shown in Figure 24(b), the sterile tube welding machine 1022 is operated to form a sterile weld between the respective tubes 1006 and 1018, as shown in Figure 24(c). If connected, the sterile membrane may be removed during this step as part of the welding process, i.e., through thermal welding or melting, or in another removal operation operated by the sterile tube welding machine 1022 or another operating component. Therefore, the sterile tube welding machine 1022 forms a sterile weld between the tubes 1006 and 1018, fluidly connecting the lumens of each tube 1006 and 1018. In this method, a sterile fluid passage 1026 is provided through the connected tubes 1006 and 1018 to connect the container 1004 and the bioreactor 1016 through a planar joint 1014, as shown in Figure 24(c). The biomaterial is then transferred from the container 1004 to the bioreactor 1016, for example, by the method described earlier. Once the biomaterial has been transferred, as shown in Figure 24(d), the sterile tube sealing machine 1024 is operated to form a sterile seal between the connected tubes 1006 and 1018. In this method, the sterile fluid passage 1026 is sealed between the container 1004 and the bioreactor 1016 by a thermal seal 1027. The sterile tube sealing machine 1024 may also have cutting elements positioned to cut the sealed tubes 1006, 1018 along the heat seal 1027 in order to release each component, or it may provide the user with the necessary cuts in a manual step. The container 1004 is then removed from the planar joint 1014.Next, container 1004 may be discarded, and the component holding element 1002 can hold the next container 1004 for the next addition to or removal from the bioreactor 1016 via the planar joint 1014, and the process can be repeated starting from Figure 24(a). Generally, aseptic tube welding machines and aseptic tube sealing machines are familiar to those skilled in the art and will not be described further here. This example provides an automated or at least semi-automated method for aseptically connecting and disconnecting fluid volumes, suitable for the “just-in-time” addition of a medium to a bioreactor or the “just-in-time” removal of a medium from a bioreactor.

[0194] In general, it will be understood by those skilled in the art that the embodiments described above are presented only as examples and not in a restrictive sense, and that various modifications and changes are possible without departing from the scope of the invention as defined by the appended claims. Various changes to the detailed design described above are possible, for example, variations in shape, size, arrangement, assembly, or sequence. For example, any of the enclosure, planar joint, or component retaining elements may be used in any suitable combination. Furthermore, although the invention is described in relation to automated processing, it will be understood by those skilled in the art that the user may undertake one or more of the above processing steps manually or semi-automatically. [Explanation of symbols]

[0195] 1. Biomaterial Handling System 10 assembly 12 Encircling bodies 14 Component holding elements, component acceptance elements 16 Planar joint 18 Container 20 components 20a Cell loading component 20b Bead loading component 20c Virus Injection Component 20d Media Loading Component 20e Sample Collection Component 20f sample component 20g media extraction component 22 connectors 24 Receiving Department 100 assemblies 112 Encirclement 114 Component acceptance elements, component retention elements 114a Arm 114b Component holding head 116 Planar joint, joint plate 118 Container 120 components 122 connector 123a Upper casing section 123b Lower casing section 124 Receiving section 124a Plunger 124a Diaphragm seal 124b Piston 125a Distal end 125b Proximal end 126 Screw thread portion 127 Screw cap 128a First diaphragm seal 128b Second diaphragm seal 129 Hollow needle 130a First end 130b Second end 131 Sterile barrier 132 ring body 133 Outer cover 133a First spiral spring 133b Second spiral spring 150 ports 150a Lower volume sampling element 150b Hollow, tubular member 150c Screw Cap 152 Sterile barrier 152a Fastener part 152b Sterile envelope 154 Central Hub 156 Connected elements, connected parts 160, 162 Screw thread portion 164 Cover 166 Expandable receiving section 166a Upper part 166b Foundation part 166c wall section 166d Circular foundation wall 168 Fluid passage 170 Actuators 171 Rotatable disk 172 Distribution Actuator 173 Actuator housing 180 sliding drawer 182 Mounting plate 184 Drive mechanism 186 Grooved drive wheels 216, 216a Planar joint 250 Periphery 252 Drive mechanism 254, 254a Central Hub 254b Inner circular wall 254c Outer circular wall 255 Edge 257 Dividing Wall 259 Shelf 259a Basics 261 Rib 263 Space 265 Guide Wall 267 clips 269 ​​Fastening ring 269a Protrusion 269b Fasteners 271 Connecting wall 273 Air filter 280 drawers 282 mounting plate 284 Positioning Features 312 Encirclement 316 Planar joint 350 Periphery, stirring plate 352 Positioning Features Linear actuators 354, 354a, 354b 412 Encirclement 450 hinged door 452 slots 454 Positioning Features 512 Encirclement 550 doors 554 Hinged Door 600 Sterile Barrier Removal System 602 Beam 604 Rail 606 Slidable arm member 608 Actuation protrusion 650 Sterile Barrier 652 Sterile envelope 654a, 654b Fastener part 655 Introduction Edge 657 Opening 660 Waste Chute 1000 assemblies 1002 Component holding element 1004 Container 1006 tube 1008 Robot Arm 1010 Holding part 1012 Gripping arm 1014 A substantially planar joint 1016 Biological reactor 1018 tube 1022 Sterile pipe welding machine 1024 Sterile tube sealing machine 1026 Sterile Fluid Pathway 1027 Thermal sealing L central vertical axis L1 Vertical axis L2 Vertical axis

Claims

1. An assembly for handling biological materials, A first biological handling element having a first volume having a first port, A second biological handling element having a second volume having a second port, A sterile connection element is configured to provide sterile fluid communication between the first volume and the second volume, and to provide sterile fluid connection between the first port and the second port. To prevent sterile fluid communication between the first volume and the second volume, a sterile disconnection element is configured to sterilely disconnect the fluid between the first port and the second port. Equipped with, An assembly wherein at least one of the first biological handling element and the second biological handling element is movable to align the first port and the second port with each other in order to sterilely fluid connect the first port and the second port to the sterile connecting element when in use, and to sterile fluid disconnect the first port and the second port to the sterile disconnection element when in use.

2. The assembly according to claim 1, wherein the first biological handling element comprises a substantially planar joint having the first port, the first port being fluid-coupled to or configured to be fluid-coupled to the first volume.

3. The assembly according to claim 1 or 2, wherein the second biological handling element comprises a component holding element for holding a component having the second volume and the second port.

4. The assembly according to any one of claims 1 to 3, wherein the sterile connection element and the sterile disconnection element are an integrated sterile connection and disconnection element.

5. The assembly according to claim 4, wherein the integrated sterile connection and disconnection element is a sterile connector.

6. The assembly according to claim 5, wherein the sterile connector comprises a needle that is operable to engage with or puncture the first port and the second port during use.

7. The assembly according to claim 5 or 6, wherein the first port is a first diaphragm seal and / or the second port is a first diaphragm seal.

8. The assembly according to any one of claims 1 to 4, wherein the first port comprises a first pipe, the second port comprises a second pipe, and the sterile connecting element comprises a sterile pipe welding machine.

9. The assembly according to any one of claims 1 to 4 or claim 8, wherein the first port comprises a first tube, the second port comprises a second tube, and the sterile connection release element comprises a sterile tube sealing machine.

10. The assembly according to claim 8 or 9, wherein the first tube and / or the second tube comprises an open-end tube, a closed-end tube, or a tube having a removable sterile membrane positioned across its end.

11. The assembly according to any one of claims 8 to 10, wherein the first tube and / or the second tube comprises a flexible tube.

12. The assembly according to any one of claims 8 to 11, further comprising a robotic arm terminating in the sterile tube welding machine and / or the sterile tube sealing machine.

13. The assembly according to any one of claims 1 to 12, comprising one or more robotic arms arranged to move the first biological handling element and / or the second biological handling element in order to align the first port and the second port with respect to each other.

14. The assembly according to claim 13, wherein the one or more robotic arms include an actuation part arranged to actuate the first biological handling element and / or a portion of the second biological handling element to cause the distribution of biological material from the first volume and / or the second volume.

15. The assembly according to any one of claims 12 to 14, wherein the one or more robotic arms are controlled by a control device.

16. The assembly according to claim 15, wherein the control device comprises a user interface, and the control device is arranged to control one or more robot arms in response to user input to the user interface.

17. The assembly is an automated assembly, according to any one of claims 1 to 16.

18. A method for handling biological substances, A step of moving at least one of a first biological handling element having a first volume having a first port and a second biological handling element having a second volume having a second port, such that the first port and the second port are aligned with each other. The steps include: sterilely fluidizing the first port and the second port, thereby providing fluid communication between the first volume and the second volume; A step of transferring a biological substance from the first volume to the second volume, or from the second volume to the first volume, The steps include: sterilely deconnecting the first port and the second port, which are fluidly connected, thereby preventing fluid communication between the first volume and the second volume; A method that includes this.

19. The method according to claim 18, wherein the step of aseptically fluidizing the first port and the second port includes aseptically welding the first port to the second port.

20. The method according to claim 18 or 19, wherein the step of aseptically de-fluidally disconnecting the first port and the second port comprises aseptically sealing the connected first port and the second port in order to provide an aseptically sealed first port and an aseptically sealed second port.

21. The method according to any one of claims 18 to 20, wherein the step of moving at least one of the first biological handling element and the second biological handling element is performed by using one or more robotic arms to move at least one of the first biological handling element and the second biological handling element.

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