Assembly

Abstract

An assembly for handling biological material is described, comprising a planar interface having at least one port, and a component-holding element spaced from the planar interface and configured to hold a component for handling the biological material, wherein at least one of the planar interface and the component-holding element is movable to bring the port and the component-holding element into alignment with one another. Thus, when in use, a fluid communication path can be provided between a component held by the component-holding element and a container associated with the planar interface through the port.

Description

[Technical Field]

[0001] The present invention relates to assemblies for handling biological material. The invention also relates to methods for introducing or removing materials from components of such assemblies. More specifically, the invention relates to assemblies and methods of operation of the assemblies for use in one or more unit operations in cell processing methods, for example in cell and / or gene therapy manufacturing processes. [Background technology]

[0002] Biological handling processes, such as cell and gene therapy (CGT) manufacturing processes, are often complex and involve manual steps across several devices. Equipment systems used in various steps, or unit operations, of cell-based therapeutic product (CTP) manufacturing may include devices for various unit operations. Unit operations may include, for example, cell harvesting, cell separation, selection, cell expansion, cell washing, volume reduction, cell storage, or transport. Unit operations can vary significantly based on the manufacturing model (i.e., autologous vs. allogeneic), cell type, and intended purpose, among other factors. Additionally, cells are "living" entities that are sensitive to even the simplest manipulations (e.g., differences in cell transfer procedures). The role of cell manufacturing equipment in ensuring scalability and reproducibility is a critical factor for cell and gene therapy manufacturing.

[0003] Additionally, cell-based therapeutic products (CTPs) are experiencing significant momentum, and as such, there is a need for improved cell manufacturing equipment for various cell manufacturing procedures, such as, but not limited to, stem cell enrichment, chimeric antigen receptor (CAR) T-cell generation, and various cell manufacturing processes such as harvesting, purification, genetic modification, culture / harvesting, washing, patient infusion, 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, when culturing the cells. Known devices include shaker flasks, roller bottles, T-flasks, and bags. While such bottles or flasks are widely used, they have several drawbacks. Foremost among these is the requirement for the transfer of cells, medium, or other materials without contamination when passaging or processing.

[0005] A current problem in the production of cell or gene therapies for use in medicine 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 to the incubator, removing cells, or removing liquid samples. Furthermore, current operating systems are largely manual and therefore expensive to operate. Multiple pieces of equipment are typically required to cover all of the non-cell culture steps, which involves many transfers, each of which presents an opportunity for operator error and contamination.

[0006] Furthermore, with increased manual actions comes an increased risk of manual error, so current labor-intensive processes may lack the robustness required for the production of clinical-grade therapeutics.

[0007] Therefore, there is a need for an assembly for handling biological material or cell processing equipment, such as multi-stage biological material, that allows such processing in an automated manner, or at least semi-automated manner, i.e., with minimal user intervention and / or action, while maintaining sterility throughout the system. Summary of the Invention [Problem to be solved by the invention]

[0008] It is therefore an object of the present invention to provide an improved assembly for handling biological material, particularly for use in cell and / or gene therapy processing, and more particularly to provide an apparatus that allows for the introduction and removal of material from containers in a sterile, automated or semi-automated manner.

[0009] It is also an object of the present invention to provide an apparatus that combines the advantages of cell culture vessels, which avoid the need for pumps and the requirement for periodic passaging of cells to new culture devices that reserve vessels, tubing, etc., with the advantages offered by having individually configurable cell and / or gene therapy treatment devices.

[0010] It is a further object of the present invention to provide an apparatus that allows various biological processes, such as one or more unit operations in cell processing, to be performed in a single device or apparatus that has a smaller footprint and is less complex than existing equipment. Additionally, the apparatus described herein allows for greater compatibility with automated systems. Other advantages will be apparent from the drawings and description below. [Means for solving the problem]

[0011] According to one aspect of the present invention, there is provided an assembly for handling biological material, comprising: a substantially planar interface having at least one port; a component holding element spaced from the substantially planar interface and configured to hold a component for handling biological material; Equipped with An assembly is provided in which, when in use, at least one of the substantially planar interface and the component holding element is movable to align the at least one port with the component holding element so as to establish a fluid communication path between the component held by the component holding element and a container associated with the substantially planar interface and the at least one port.

[0012] Thus, a substantially planar junction is provided that includes a port, which may be a single port or multiple ports formed within the substantially planar junction. The substantially planar junction can be formed in a substantially plane and can be of any suitable size, shape, or the like. The substantially planar junction is associated with a container when in use. That is, the substantially planar junction can include a container coupled to the junction when in use. The container may be suitable for handling biological materials, such as a bioreactor. Specifically, the container can include a compressible container, such as a container with compressible or flexible sidewalls.

[0013] Accordingly, there is also provided a component retention element that is suitable and arranged to hold, receive, connect or retain a component when in use, where the component retention element is spaced apart from or not formed integrally with the substantially planar joint.

[0014] Thus, during use, the substantially planar interface, the component-retaining element, or both the substantially planar interface and the component-retaining element are movable, such as to bring the or each port of the substantially planar interface and the component-retaining element into alignment with one another or lined up with one another. Thus, by aligning such features, the assembly can provide a fluid communication path between a component retained by the component-retaining element and a container associated or coupled with the substantially planar interface during use, thereby enabling the transfer of fluids and, in turn, the handling of biological material between the respective components.

[0015] This offers the advantage that an assembly for handling biological material is provided that allows for the introduction and removal of materials in a sterile, automated or semi-automated manner. Furthermore, such an assembly has a smaller footprint and is less complex than existing equipment.

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

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

[0018] Thus, during use, the substantially planar interface is rotated to align the port of a component with the subsequent port of the substantially planar interface, which provides the advantage that, during use, sequential introduction or removal of substances can be provided in an automated or semi-automated manner.

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

[0020] Thus, in certain embodiments, the component-holding element is movable along a longitudinal axis, either along a central longitudinal axis of the component-holding element or along a portion of the component-holding element, such as a component-holding head.

[0021] This provides the advantage that the component-retaining element engages the component and port of the interface in a substantially planar manner during use, thereby making it more suitable for automated or semi-automated processing.

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

[0023] Thus, in certain embodiments, the component-retaining element is movable along the longitudinal axis to engage the component with the at least one port. Thus, the longitudinal axis can be substantially coaxially aligned with the longitudinal axis of the at least one port. The engagement between the component and the port can include face-to-face engagement between the port of the component and the port of the substantially planar interface.

[0024] This provides the advantage that a sterile, preferably fluid-tight or hermetic, seal is provided between the component and the port of the substantially planar interface, thus ensuring a sterile biohandling device.

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

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

[0027] This provides the advantage that fewer moving parts are involved in the device, thus providing easier and cheaper manufacture of such a device.

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

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

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

[0031] Thus, 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 can be coupled to an interior, such as an enclosure or stand. The proximal end of the arm can be coupled to a component-holding head. The component-holding head can be configured to hold a component during use.

[0032] In certain embodiments, the component retention head may include one or more coupling elements arranged to cooperate with the component during use to hold, receive, couple, or retain the component during use. For example, the one or more coupling elements may be rails arranged to cooperate with a protrusion on the component. For example, the one or more coupling elements may be fasteners, such as clips, bolt and nut arrangements, or screws, arranged to cooperate with a fastener receiving portion on the component. In one specific example, the component retention head includes a base and an upwardly extending sidewall, where the sidewall and base provide a volume for receiving the component. The base may include an opening or aperture through which a portion of the component, such as a port, may protrude or expose.

[0033] In certain embodiments, the apparatus further comprises an enclosure, the component retention element being formed as part of the enclosure, the enclosure being configured to operably receive the substantially planar interface.

[0034] Thus, in certain embodiments, there are enclosures in which the component-retaining elements are formed as part of such enclosure. In some instances, the component-retaining elements comprise arms that extend from an interior wall of the enclosure and terminate in a component-retaining head, whereby the component-retaining elements may be formed as an integral part of the enclosure. In other instances, the component-retaining elements comprise arms that extend from a stand or structure formed within the enclosure and terminate in the component-retaining head.

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

[0036] Thus, in certain embodiments, a substantially planar junction comprises more than one port, or two or more ports. In certain instances, a substantially planar junction comprises more than 5, 10, 15, 20, 25, or 30 ports. In specific instances, a substantially planar junction comprises 22 ports.

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

[0038] Thus, in certain embodiments, the substantially planar interface includes a central longitudinal axis and each port is disposed radially outward from such axis, specifically, each port is disposed along a radius formed between the central longitudinal axis and an outer edge of the substantially planar interface.

[0039] In certain embodiments, multiple ports are provided in a circular arrangement, a semicircular arrangement, an arcuate arrangement, or the like.

[0040] This provides the advantage that the substantially planar joint can be rotated to align the component with a subsequent port on the substantially planar joint, thus providing an apparatus that is more suited to automated or semi-automated processing.

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

[0042] Thus, in certain embodiments, the or each port is resealable so as to return to a sealed configuration after a fluid passage has been formed therethrough. For example, a resealable port may comprise a hinged door, a valve, or the like, that returns to a closed position after a fluid passage has been formed therethrough, such as in an open position. Furthermore, in other examples, a resealable port may be a self-sealing port, such as a septum seal, that self-seals when puncture ceases.

[0043] This provides the advantage that multiple fluid communication paths can be provided without compromising the sterility of the device.

[0044] In certain embodiments, the resealable port comprises a septum seal.

[0045] In a specific embodiment, the septum seal may comprise a silicone material or a thermoplastic elastomer material.

[0046] In a specific embodiment, the outer surface of the septum seal can be substantially flush with the upper surface of the substantially planar joint.

[0047] Thus, in some embodiments, the septum seal and the substantially planar joint are substantially continuous in shape or flush with one another.

[0048] This provides the advantage that the septum seals can contact adjacent septum seals in a face-to-face manner, thus ensuring sterility of the device during use.

[0049] In a specific embodiment, the septum seal may comprise an annular protruding wall surrounding a substantially flat portion.

[0050] Thus, in certain embodiments, the septum seal, particularly the annular protruding wall, can protrude above the upper surface of the substantially planar joint, and a substantially flat portion of the septum seal can be flush with the upper surface of the substantially planar joint.

[0051] This provides the advantage that the septum seals can receive the protruding portion of an adjacent septum seal, thereby aiding in the location of each septum seal during automated or manual processing.

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

[0053] This provides the advantage of providing increased withdrawal force of the septum seal relative to the substantially planar joint, which is particularly advantageous during retraction of the needle from the septum seal, which may otherwise pull the septum seal away from the substantially planar joint, thus avoiding damage to the substantially planar joint and potentially compromising sterility.

[0054] In a specific embodiment, the substantially planar interface further comprises a removable sterility barrier disposed across the at least one port.

[0055] Thus, in certain embodiments, the substantially planar interface includes a removable barrier that ensures sterility of the or each port. Specifically, the or each port is provided as a sterile port, such as through gamma irradiation or ethanol swabbing. A removable barrier is provided across the or each sterile port.

[0056] This provides the advantage that the sterility of the or each 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 be provided with a handle at one end. The removable sterile barrier may be provided with a fold that defines 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 to be positioned across the or each port. Any number of folds may be provided.

[0058] In certain embodiments, the removable sterility barrier comprises a fastener portion operably coupled to a sterile outer shell, the sterile outer shell being removably positioned over the at least one port. The fastener portion may be coupled to the sterile outer shell in any suitable manner, such as by a protrusion on the fastener portion mechanically coupled to an opening in the sterile outer shell, such as through adhesive or heat welding.

[0059] In certain embodiments, a fastener portion is arranged to connect to an additional fastener portion of an adjacent removable sterility barrier. A fastener portion may include one or more connecting elements arranged to connect to one or more corresponding connecting elements of an adjacent fastener portion.

[0060] This provides the advantage that adjacent removable sterile barriers can be simultaneously engaged and disengaged by the device, thus providing a device that is more adapted for automated or semi-automated processing. Additionally, tactile and / or visual feedback can be provided to the user during the manual disengagement process.

[0061] In certain embodiments, the sterile skin is positioned at one portion over the or each port and at another portion over the or each port to connect to a further sterile skin of an adjacent removable sterile barrier. In some instances, the sterile skin may be provided with a fold that defines a first portion of the sterile skin and a second portion of the sterile skin. The first portion of the sterile skin may be positioned to contact the other sterile skin, and the second portion of the sterile skin may be positioned to span the or each port.

[0062] This provides the advantage that the sterility of each port is ensured before and during use.

[0063] Thus, during use, a removable sterile barrier may be arranged to couple to an adjacent removable sterile barrier. For example, a removable sterile barrier disposed across the or each port of a substantially planar junction may be arranged to couple to a removable sterile barrier of a component such as a connector. Thereafter, upon coupling of the removable sterile barrier, such coupled sterile barrier may be removed before a fluid communication path is provided.

[0064] It is noted that the connection of each removable sterile barrier, such as a sterile outer skin, may be through any suitable means, such as mechanical connection, adhesive, or heat welding.

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

[0066] Thus, in certain embodiments, the substantially planar interface is provided with a slot adjacent the or each port. The slot slidably receives a fastener portion of the removable sterile barrier. The fastener portion is movable, specifically slidable, within the slot between a first configuration and a second configuration. Upon movement of the fastener portion from the first configuration to the second configuration, the sterile envelope is disengaged, i.e., removed, from the or each port.

[0067] This provides the advantage that the device allows the sterility barrier to be easily removed from each port between uses, making it more amenable to automated or semi-automated processes for achieving such removal.

[0068] In certain embodiments, the substantially planar junction comprises one port and one slot adjacent to the port, hi certain embodiments, the substantially planar junction comprises multiple ports and multiple slots, each adjacent to a respective port.

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

[0070] Thus, in certain embodiments, a sterile barrier removal system is provided. The sterile barrier removal system may include a portion configured to couple to or engage a portion of the removable sterile barrier, such as a fastener portion. In a specific example, the sterile barrier removal system includes a protruding tab that is engageable with an opening in the fastener portion of the removable sterile barrier. In such an example, the protruding tab may be movable between a first configuration in which the protruding tab engages the fastener portion and a second configuration in which the sterile envelope is removed from the port of the substantially planar interface.

[0071] This provides the advantage that the sterility barrier can be removed in an automated manner, thus ensuring the sterility of the device between uses.

[0072] In certain embodiments, the substantially planar interface comprises a coupling element configured to operably couple to a corresponding coupling element of the container.

[0073] Thus, in certain embodiments, the substantially planar interface comprises one or more elements arranged to couple to corresponding elements of the container.

[0074] In particular embodiments, the coupling element comprises threads arranged to couple to threads on the container, or a clip portion arranged to couple to a corresponding clip portion on the container, or the like.

[0075] In specific embodiments, the connecting elements of the substantially planar interface and the connecting elements of the container cooperate to provide a sterile, fluid-tight, and / or hermetic engagement between the substantially planar interface 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] Thus, in certain embodiments, the substantially planar joint comprises one or more features that are arranged to be driven by a drive mechanism, for example a drive mechanism of the enclosure.

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

[0079] In certain embodiments, the device or an 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 positioned to mate with a plurality of grooves formed in the periphery of the substantially planar joint.

[0081] In certain embodiments, a controller is provided for controlling the drive mechanism. The controller may include a user interface for accepting user input. For example, a user may provide user input to the user interface regarding positioning of the substantially planar interface, such as positioning one or more ports relative to the component-holding element. In certain examples, the controller is configured to control the drive mechanism based on the user input.

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

[0083] Thus, in certain embodiments, the component-holding element comprises an actuator or movement or actuation system arranged to actuate a portion of the component when in use.

[0084] In certain embodiments, the actuator is configured to actuate a connector portion of the component when in use. Additionally or alternatively, the actuator is configured to actuate a receiving portion of the component when in use to cause fluid dispensing. Additionally or alternatively, the actuator is configured to actuate a receiving portion of the component when in use to cause fluid withdrawal from a container associated with the substantially planar interface to the receiving portion.

[0085] Thus, the actuator may be provided as one or more of a connector actuator, a fluid dispensing actuator, or a fluid withdrawal actuator.

[0086] In certain embodiments, a controller is provided for controlling the actuator. The controller may include a user interface for accepting user input. For example, a user may provide user input to the user interface regarding timing of actuation of the component. In some examples, the controller is configured to control the actuator based on the user input.

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

[0088] Thus, in certain embodiments, the device further comprises a container fluidly connected to the or each port of the substantially planar junction. Thus, a fluid communication path may be provided between the or each port of the substantially planar junction and the volume of the container. In particular, a hermetically sealed and / or sterile sealed fluid communication path may be provided.

[0089] In certain embodiments, the container includes a flexible or compressible sidewall. In such instances, the sidewall may be flexible such that the container, particularly the base against the top, is compressible along a longitudinal axis parallel to the sidewall. To that end, in certain instances, the sidewall may include multiple convolutions, thereby forming a bellows-shaped sidewall. The container may be made 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 a thermoplastic elastomer.

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

[0091] Thus, in certain embodiments, the device further comprises a receiver, such as an expandable receiver, coupled to the substantially planar joint. The expandable receiver may be provided in fluid communication with the container, for example, through a fluid passageway through the substantially planar joint. In certain examples, the fluid passageway 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, so that the pressure within the received container remains substantially the same throughout use, for example through stirring or mixing.

[0093] In certain embodiments, the fluid passage through the substantially planar junction comprises a tortuous fluid passage, i.e., in certain embodiments, the fluid passage comprises a barrier, wall, ledge, flange, or the like that blocks at least a portion of the fluid passage. A tortuous fluid passage can be non-linear.

[0094] This provides the advantage that gases such as air can easily pass through the passageway, but liquids or suspensions such as media containing biological material are substantially prevented from passing through the passageway.

[0095] In certain embodiments, the substantially planar interface includes a central hub that includes a fluid passageway, i.e., the fluid passageway can extend through the central hub of the substantially planar interface from its lower surface to its upper surface.

[0096] In certain embodiments, the central hub may include an inner circular wall surrounded by or concentrically disposed relative to an outer circular wall. A fluid passageway may be formed between the inner and outer circular walls. A flange may be provided extending radially outward from the inner circular wall toward the outer circular wall. A ledge may be provided extending radially inward from the outer circular wall, e.g., at its base, toward the inner circular wall. The flange and / or ledge may define a serpentine fluid passageway.

[0097] In certain embodiments, the flange may be angled relative to the horizontal. In specific embodiments, the flange may be angled toward the underside of the substantially planar joint. In more specific embodiments, the flange may be angled toward a ledge extending radially inward from the base of the outer circular wall.

[0098] This provides the advantage that liquid such as media containing biological material or condensate may be returned to the container between uses, thereby minimizing loss of liquid from the container.

[0099] In certain embodiments, a plurality of radially extending ribs are provided, each extending between the outer circular wall and the flange and connected to the outer circular wall and the flange. Each rib, if provided, may be connected to a ledge in the outer circular wall. In this manner, a plurality of fluid passageways, such as serpentine fluid passageways, are provided.

[0100] In certain embodiments, the expandable receiver comprises a flexible bag.

[0101] In certain embodiments, the expandable receiving portion comprises a receiving portion having a flexible or expandable sidewall. In specific embodiments, the receiving portion may comprise a base wall, a top wall, and an expandable sidewall between the base wall and the top wall. The expandable sidewall may comprise a plurality of convolutions, thereby forming a bellows sidewall.

[0102] In certain embodiments, the device further comprises a component for handling biological material held by said component-holding element.

[0103] In certain embodiments, the component comprises a receiving portion.

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

[0105] In certain embodiments, the component comprises a connector that is fluidly connected to the receptacle.

[0106] In certain embodiments, the apparatus further comprises an enclosure for housing the component-holding element and the substantially planar interface.

[0107] In a specific embodiment, the enclosure includes a slidable drawer configured to operably receive the substantially planar joint. For example, the slidable drawer may include a locating plate positioned to operably receive the substantially planar joint. The slidable drawer may be movable between a first configuration in which the slidable drawer is external to the enclosure and a second configuration in which the slidable drawer is internal to the enclosure.

[0108] In specific embodiments, the enclosure includes an actuator, a drive mechanism, a homing sensor, a localization sensor, etc., depending on the embodiment described herein. Generally, during use, one or more of the features of the assembly, specifically one or more of the features of the component-retaining element and / or the substantially planar interface, may be housed within the enclosure.

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

[0110] According to another aspect of the invention, there is provided a method for introducing or removing a substance into or from a component of an assembly for handling biological material, the method comprising the steps of: Providing an assembly as described herein; holding a component suitable for handling biological material and having at least one port in the component holding element; moving at least one of the substantially planar interface and the component-retaining element to align the at least one port of the component with the at least one port of the substantially planar interface; providing a fluid communication path through the at least one port of the substantially planar interface and the at least one port of the component; introducing or removing a substance into or from the component through the fluid communication path; A method is provided that includes:

[0111] In certain embodiments, the assembly further comprises a container fluidly connected to the at least one port, and the step of introducing or removing a substance from the component comprises: introducing a substance from the component through the fluid communication path into the container; and / or Removing a substance from the container through the fluid communication path to the component.

[0112] According to yet another aspect of the present invention, there is provided a kit of parts comprising a substantially planar interface 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 a component as described herein.

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

[0114] According to yet another aspect of the present invention, there is provided an assembly for handling biological material, comprising: a first biological treatment element comprising a first volume having a first port; a second biological handling element comprising a second volume having a second port; a sterile connection element configured to sterilely fluidly connect the first port and the second port to provide sterile fluid communication between the first volume and the second volume; a sterile disconnect element configured to sterilely fluidly disconnect the first port and the second port to prevent sterile fluid communication between the first volume and the second volume; 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 to align the first port and the second port with one another to cause the sterile connecting element to sterilely fluidly connect the first port and the second port when in use, and to cause the sterile disconnecting element to sterilely fluidly disconnect the first port and the second port when in use.

[0115] This offers the advantage that biological material can be handled in a "just-in-time" manner, i.e., material transfer between volumes is provided when the transfer is needed, rather than having several pre-connected components. This ensures that biological material can be handled in an efficient, sterile, automated or semi-automated manner.

[0116] In some embodiments, the first biological treatment element comprises a substantially planar junction as described herein.

[0117] In some embodiments, the first biological treatment element comprises a first holding element that holds a first container having a first volume and a first port.

[0118] In a specific embodiment, the substantially planar junction includes at least one port fluidly connected to a vessel, such as a bioreactor, the vessel including a first volume. The substantially planar junction may include a plurality of ports. Each port of the plurality of ports may be fluidly connected to the vessel. The vessel may include a top portion, a base portion, and a flexible or compressible wall element between the top portion and the base portion. The wall element may include a plurality of grooves or convolutions, or a bellows wall element.

[0119] In some embodiments, the second biological handling element comprises a component holding element as described herein, the component holding element as described herein being capable of holding a container having a second volume and a second port.

[0120] In some embodiments, the second biological treatment element comprises a second holding element that holds a second container having a second volume and a second port.

[0121] In specific embodiments, the component-retaining element is configured to hold or retains a component. The component may comprise a container having a second volume and including a second port. The container may comprise a top portion, a base portion, and a flexible or compressible wall element between the top portion and the base portion. The wall element may comprise a plurality of grooves or a bellows wall element. The container may be a bag, a flexible bag, or a container including a plunger.

[0122] The first port and / or the second port may comprise an open-ended tube, a closed-ended tube, or a tube with a removable sterile membrane disposed over the end. The tube may be flexible. Alternatively, or in combination, the first port and / or the second port may comprise a hermetic seal, a septum seal, or a Luer lock port.

[0123] The sterile connection element may be integral with the sterile disconnection element. That is, an integral sterile connection and disconnection element may be provided. The integral sterile connection and disconnection element may comprise a connector, such as a sterile or aseptic connector as described herein. Specifically, the connector may comprise a needle. The needle may be operable to engage or pierce a first port and a second port, such as a first septum seal and a second septum seal, during use.

[0124] The sterile connecting element may be a separate component relative to the sterile disconnecting element.

[0125] The sterile connection element may comprise a sterile welding element. Specifically, the sterile connection element may comprise a sterile tubing welder configured and / or arranged to aseptically weld a first tube, such as a first port, to a second tube, such as a second port. The sterile connection element may comprise a robotic arm terminating in the sterile welding element. The sterile welding element may be configured to apply heat and optionally pressure to the respective ports to heat-weld the respective ports. The sterile welding element may be configured to apply heat such that a sterile membrane covering a closed end or end of the tube is melted, thereby allowing fluid passage through the respective tube.

[0126] The sterile disconnect element may comprise a sterile sealing element. Specifically, the sterile disconnect element may comprise a sterile tube sealing machine configured and / or arranged to aseptically seal a first portion of tubing, such as a first tube or a first port, to a second portion of tubing, such as a second tube or a second port. The sterile disconnect element may comprise a robotic arm terminating in the sterile sealing element. The sterile sealing element may be configured to apply heat and optionally pressure to a portion of a connected port to heat seal the portion, thereby providing a first portion of the connected port heat-sealed from a second portion of the connected port. The sterile sealing element may further be configured to cut or separate the sealed region between the first and second portions of the connected port, thereby enabling release of the respective components.

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

[0128] The apparatus may include one or more robotic arms. The one or more robotic arms may be configured to move the first biological handling element and / or the second biological handling element to align the first port and the second port with one another. The one or more robotic arms may include a holding portion configured to hold the first biological handling element and / or the second biological handling element. The one or more robotic arms may include an actuation portion configured to actuate a portion of the first biological handling element and / or the second biological handling element to cause the distribution of biological material from the first volume and / or the second volume. The one or more robotic arms, holding portion, and / or actuation portion may be controlled by a controller. The controller may include a user interface. The controller may be configured to control the one or more robotic arms, holding portion, and / or actuation portion in response to user input to the user interface.

[0129] The device may be an automated device, i.e., the device does not require manual or user intervention. The device may be a semi-automated device, i.e., the device may require minimal manual or user intervention, such as loading biological handling elements onto the device.

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

[0131] According to yet another aspect of the present invention, there is provided a method of handling biological material, comprising the steps of: moving at least one of a first biological treatment element comprising a first volume having a first port and a second biological treatment element comprising a second volume having a second port so that the first port and the second port are aligned with each other; sterilely fluidly connecting the first port and the second port, thereby providing fluid communication between the first volume and the second volume; transferring the biological material from the first volume to the second volume or from the second volume to the first volume; aseptically fluidly disconnecting the first port and the second port that are sterilely fluidly connected, thereby preventing fluid communication between the first volume and the second volume; A method is provided that includes:

[0132] This offers the advantage that biological material can be handled in a "just-in-time" manner, i.e., material transfer between volumes is provided when the transfer is needed, rather than having several pre-connected components. This ensures that biological material can be handled in an efficient, sterile, automated or semi-automated manner.

[0133] In certain embodiments, the step of sterilely fluidly connecting the first port and the second port includes sterile welding the first port to the second port. In specific embodiments, the step of sterile welding can be performed by a sterile tubing welder.

[0134] In certain embodiments, the step of aseptically fluidly disconnecting the first port and the second port includes aseptically sealing the connected first port and second port to provide a sterile sealed first port and a sterile sealed second port. In specific embodiments, the step of aseptically sealing can be performed by a sterile tube sealing machine.

[0135] It will be understood by one of ordinary skill in the art that the method may include one or more components of an apparatus as described above or elsewhere herein, such as a substantially planar joint, a component retaining element, a sterile tube welder, or a sterile tube sealing machine.

[0136] Example embodiments of the present invention will now be described, by way of example only, with reference to the accompanying drawings, in which: [Brief explanation of the drawings]

[0137] [Figure 1] 1 is a perspective view of an overall system including an assembly, an enclosure, and a component according to the present invention; [Figure 2] FIG. 2 is a perspective view of the assembly, enclosure, and components of FIG. 1 during use. [Figure 3] FIG. 1 is a perspective view of a planar joint including an attached container. [Figure 4] 4 is a cross-sectional side view of the assembly of FIG. 3 with an expandable receiver and a cover attached to the planar joint. [Figure 5] FIG. 10 is a perspective view of another planar joint including an attached container. [Figure 6(a)] FIG. 10 is a perspective view of another planar joint including an attached container. [Figure 6(b)] FIG. 7 is a cross-sectional view of the planar joint of FIG. 6(a). [Figure 6(c)] FIG. 7 is an enlarged cross-sectional view of the planar joint portion of FIG. 6(a). [Figure 6(d)] FIG. 7 is another cross-sectional view of the planar joint of FIG. 6(a). [Figure 7] FIG. 6 is a perspective view of the assembly of FIG. 5, further including a component retention element for the assembly. [Figure 8(a)] FIG. 6 is a perspective view of the planar joint of FIG. 5 being mounted into a drawer of an enclosure. [Figure 8(b)] FIG. 1 is a perspective view of a planar joint mounted to a drawer shown in an open position. [Figure 8(c)] FIG. 1 is a perspective view of the enclosure with the drawer in the closed position. [Figure 9(a)] FIG. 8(b) is an enlarged perspective view of FIG. [Figure 9(b)] FIG. 8(c) is a partially cut-away perspective view of FIG. [Figure 9(c)] FIG. 8(b) is an enlarged perspective view of the drive mechanism. [Figure 10(a)] FIG. 10 is a perspective view of another enclosure showing another planar joint locating feature and enclosure drawer. [Figure 10(b)] FIG. 10(b) is a perspective view of FIG. 10(a) showing a planar joint mounted on a drawer. [Figure 11] 8(c) is a partially cut-away front view of the enclosure of FIG. 8(c) including a component retention element formed as part of the enclosure. [Figure 12(a)] FIG. 2 is a cross-sectional side view of the component. [Figure 12(b)] FIG. 12(b) is a perspective view of a cross section of a connector of the component of FIG. 12(a). [Figure 13(a)] FIG. 8(c) is a partially cut-away perspective view of FIG. 8(c) with the component holding element omitted. [Figure 13(b)] FIG. 13(b) is a perspective view of the cross section of FIG. [Figure 13(c)] FIG. 13(b) is another perspective view of FIG. 13(a) showing the stirring mechanism and its stirring mode. [Figure 13(d)] 13(a) showing another stirring mode of the stirring mechanism shown in FIG. 13(c). FIG. [Figure 14(a)] FIG. 10 is a perspective view of another enclosure. [Figure 14(b)] 14(b) is a perspective view of the mounting of the planar joint of FIG. 5 onto the enclosure of FIG. 14(a). [Figure 14(c)] FIG. 14(b) is an enlarged view of FIG. [Figure 15(a)] FIG. 14(b) is a perspective view of the enclosure of FIG. 14(a) with the upper access door in a closed position. [Figure 15(b)] FIG. 14(b) is a perspective view of the enclosure of FIG. 14(a) with the access door in an open position. [Figure 16(a)] FIG. 14(b) is a perspective view of the components and enclosure of FIG. 14(a) prior to installation. [Figure 16(b)] FIG. 15(b) is an enlarged perspective view of FIG. 15(b) showing the components mounted on the component-holding elements of the assembly. [Figure 16(c)] FIG. 15(b) is an enlarged perspective view of FIG. 15(b) showing the components mounted on the component-holding elements of the assembly. [Figure 17(a)]FIG. 16(c) is a perspective view of a component held by a component holding element such as that shown in FIG. 16(c). [Figure 17(b)] FIG. 10 is a perspective view of the initial actuation of the component by the component-holding element. [Figure 17(c)] 10 is a perspective view of further actuation of the component by the component retaining element to engage the component with the planar joint. FIG. [Figure 18(a)] FIG. 16(c) is a schematic side view of a component held by a component holding element such as that shown in FIG. 16(c). [Figure 18(b)] 1 is a schematic side view of the engagement of components into a planar joint such that they are aligned with one another. FIG. [Figure 18(c)] 10A-10C are schematic side views of the components and removal of the sterility barrier of the planar joint to engage the respective ports with each other. [Figure 19(a)] FIG. 1 is a perspective view of the sterile barrier removal system, and specifically, the first step in operating the sterile barrier removal system. [Figure 19(b)] FIG. 10 is a perspective view of the sterile barrier removal system, and specifically, a second step in operating the sterile barrier removal system. [Figure 19(c)] FIG. 10 is a perspective view of the sterile barrier removal system, and specifically, a third step in operating the sterile barrier removal system. [Figure 20(a)] FIG. 17(c) is a perspective view of a component including a connector held by a component holding element as shown in FIG. 17(c) prior to actuation of the connector. [Figure 20(b)] 17(c) is a perspective view of a component including a connector held by a component holding element as shown in FIG. 17(c) after actuation of the connector. [Figure 21(a)] 21A-21C are cross-sectional side views of the connector of FIG. 20 prior to actuation of the connector and during various steps of actuation of the connector. [Figure 21(b)]21A-21C are cross-sectional side views of the connector of FIG. 20 during various steps of actuation of the connector after initial actuation of the connector. [Figure 21(c)] 21A-21C are cross-sectional side views of the connector of FIG. 20 during various steps of actuation of the connector, after further actuation of the connector. [Figure 21(d)] 21A-21C are cross-sectional side views of the connector of FIG. 20 during various steps of actuation of the connector, at the deactivation of the connector. [Figure 22(a)] FIG. 17(c) is a perspective view of a component held by a component holding element as shown in FIG. 17(c), further including a dispensing actuator, prior to dispensing. [Figure 22(b)] FIG. 17(c) is a perspective view of a component held by a component holding element as shown in FIG. 17(c), further including a dispensing actuator, after dispensing. [Figure 23] 17(c) is a schematic side view of a component held by a component holding element as shown in FIG. 17(c) removed from a planar joint. [Figure 24(a)] 10A-10C illustrate a method for aseptically connecting and disconnecting biomedical handling components according to an example. [Figure 24(b)] 10A-10C illustrate a method for aseptically connecting and disconnecting biomedical handling components according to an example. [Figure 24(c)] 10A-10C illustrate a method for aseptically connecting and disconnecting biomedical handling components according to an example. [Figure 24(d)] 10A-10C illustrate a method for aseptically connecting and disconnecting biomedical handling components according to an example. DETAILED DESCRIPTION OF THE INVENTION

[0138] The example embodiments described relate to assemblies for handling biological material. Specifically, certain embodiments relate to assemblies that are aseptic or sterile. It is noted that the terms "aseptic" and "sterile" 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 materials. As will be understood by those skilled in the art, the fluids described herein are merely examples of materials suitable for use with the assemblies as described. Similarly, while references to containers, receptacles, etc. may be made, 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, receptacles, etc. are described herein merely as examples.

[0139] Certain terminology is used in the following description for convenience only, and not as a limitation. The words "upper" and "lower" designate directions in the drawings to which reference is made and relate to the described components when assembled and mounted. The words "inner," "inward," "outer," and "outward" refer to directions toward and away from, respectively, a designated centerline or geometric center (e.g., central axis) of the described element, with the specific meaning being readily apparent from the context of the description. Additionally, the terms "proximal" (i.e., closer to) and "distal" (i.e., away from) designate positions relative to an axis or point of attachment.

[0140] Furthermore, as used herein, terms such as "connect," "attach," and "couple" are intended to include a direct connection between two members, with no other intervening material between them, as well as an indirect connection between two members, where one or more other members are interposed between them. The terms include the words expressly mentioned above, derivatives thereof, and words of similar import.

[0141] Further, unless otherwise expressly stated, the use of ordinal adjectives such as "first," "second," "third," etc. is not intended to imply that different instances of similar objects are being referenced and that the objects so described must be in the given order in time, space, sequence, or in any other manner. Like reference numerals are used throughout to depict like features.

[0142] As shown in FIG. 1 , a biological material handling system 1 including an assembly 10 for handling biological material according to the present invention is shown. Specifically, system 1 includes an enclosure 12, a component retention element 14, a planar interface 16, a container 18, and a component 20. In this specific example, component 20 is a connector 22 including a fluidly attached receptacle 24. Component 20 may be other components, such as one of a cell input component 20a for inputting cells into container 18, a bead input component 20b for inputting beads, such as magnetic beads, into container 18, a virus input component 20c for inputting viruses into container 18, or a medium input component 20d for inputting a medium, such as a biological medium suitable for cell retention, into container 18. Additionally, component 20 may be a removal component, such as one of a cell removal component 20e for removing cells from vessel 18 to an appropriate vessel, a sample component 20f for drawing a sample of the contents of vessel 18, or a media removal component 20g for removing some, most, or all of the media or contents of vessel 18. Generally, in the described embodiment, component 20 comprises a connector 22 and a receptacle 24, with receptacle 24 positioned for appropriate use as an additional or removal component 20a-20g.

[0143] With further reference to FIG. 2 , the enclosure 12 defines an interior volume for housing the component-holding element 14, the planar interface 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, i.e., the component-holding element 14 is formed as part of the enclosure 12 at an interior portion and is arranged to retain, receive, or hold the component 20 during use. Furthermore, as shown in FIG. 1 , the planar interface 16 is coupled to a container 18, such as a bioreactor, which may have flexible walls or may be collapsible, for a fluidly sterile connection. During use, the planar interface 16 and the container 18 are housed within the enclosure 12, as shown in FIGS. 1 and 2 .

[0144] FIG. 3 illustrates a portion of an assembly of the present invention. Specifically, FIG. 3 illustrates a planar interface 116 having a vessel 118, such as a bioreactor, attached thereto. Specifically, the planar interface 116 includes threads, as discussed below in connection with FIG. 4, for connection to complementary threads on the vessel 118. Thus, a sterile, fluid-tight or hermetic seal is formed between the planar interface 116 and the vessel 118. The planar interface 116 includes a plurality of ports 150, formed in this example as 22 septum seals, which are pierceable by needles to thereby allow for the handling of biological materials or fluids. Any number of septum seals may be used. Such use may include, for example, sampling the contents of the vessel 118 during use, adding to the vessel 118 during use, and / or removing or discarding contents from the vessel 118 during use. Generally, each port 150 is positioned to provide a fluid passageway, during use, through the planar junction 116 and into the container 118, as described below. Those skilled in the art will recognize that other ports having openings, doors, valves, etc. to allow selected fluid communication may also be used.

[0145] As shown in this example, each individual port 150 has a sterility barrier 152 disposed thereover. The sterility barrier 152 is generally removably attached to the port 150 at a surface of each port 150. The sterility barrier 152 ensures the sterility of each port 150 prior to use and is generally removed before making a connection to each port 150. The sterility barrier 152 generally takes the form of a sterile envelope, in this example made of paper or polymer material. As described further below, each sterility barrier 152 is arranged to be removed by a portion of the enclosure 12 (see enclosure in FIG. 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 upstanding from the upper surface of the planar joint 116 and including a plurality of connecting elements 156, formed as clips in this embodiment, which are arranged to receive and connect to the expandable receivers as described in connection with FIG. 4.

[0147] Furthermore, the vessel 118 in this example, formed as a bioreactor having an internal chamber, a base wall, and compressible side walls, has a maximum volume of 1.5 L. Generally, the base, or cell growth area, of the vessel 118 may be 150 square cm. Also, in an embodiment not shown, the vessel 118 may contain a 0.2 micron filter, which in some embodiments may be formed as part of the base or side wall of the vessel 118, or alternatively, may be formed as part of the planar joint 116. The filter may provide for gas exchange between the surrounding environment, such as an enclosure, and the internal chamber of the vessel 118. The vessel 118 may generally be manufactured using a blow molding method, such as extrusion or injection blow molding, which provides simplified manufacturing of the vessel 118, having a single-piece vessel, i.e., no joints and therefore no leak paths, a flatter base, and also reduces the amount of plastic entering the medical waste stream. 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] FIG. 4 illustrates a portion of the assembly of FIG. 3 , including the planar joint 116 and the container 118. As shown, the planar joint 116 couples to the container 118 by virtue of a threaded portion 160 of the planar joint 116 that is complementary to a threaded portion 162 of the container 118. Additionally, in this example, a cover 164 is provided disposed over the top surface of the planar joint 116 and coupled thereto, e.g., by clipping, and can be removed prior to use or retained during use. The central hub 154 of the planar joint 116 is shown coupled to an expandable receiver 166, which is shown in a compressed configuration in FIG. 4 . The expandable receiver 166 includes a coupling element, such as a clip, that is complementary to and couples to the coupling portion 156 of the central hub 154. In one specific example, the expandable receiver 166 includes threads that are complementary to the threads formed on the central hub 154. The expandable receiver 166 is fluidly connected to the container 118 by virtue of a fluid passageway 168, indicated by a dotted line. The fluid passageway 168 may be formed by a port (not shown) in the planar joint 116 or an opening (not shown) in the planar joint 116 that communicates with a respective port or opening (not shown) in the expandable receiver 166. In this manner, a breathing mechanism is provided in which fluid, such as air, from the container 118 can enter the expandable receiver 166 upon compression of the container 118, thereby causing expansion of the expandable receiver 166 to the expanded configuration. Similarly, during use, fluid, such as air, from the expandable receiver 166 can be drawn into the container 118 upon expansion of the container 118, thereby causing compression of the expandable receiver 166 to the compressed configuration. Thus, the pressure within the container 118 is maintained at a substantially constant height during compression and decompression of the container 118. In other embodiments not shown, the expandable receptacle 166 can be replaced by a filter, which, if desired, allows fluids such as air to escape or be drawn into the container 118, thereby providing a breathing mechanism. Such a filter can be gas permeable, or oxygen and / or carbon dioxide permeable, but liquid impermeable.

[0149] FIG. 5 illustrates another planar interface 216 for use in the present invention, as described further below. The planar interface 216 is substantially similar to the planar interface 116 of FIGS. 3 and 4 in that it includes several ports (not shown) having a sterility barrier 152 removably attached thereto. The planar interface 216 further includes a periphery 250, in this example formed as a series of grooves, having several drive elements 252 arranged to cooperate with a drive mechanism of the enclosure, as described further below. The planar interface 216 also includes a central hub 254 upstanding from the top surface of the planar interface 216; the central hub 254 is shown not coupled to an expandable receiver, but may include features that allow for connection to an expandable receiver or filter, such as those described in connection with FIGS. 3 and 4.

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

[0151] The planar joint 216a includes a central hub 254a having an inner circular wall 254b and a concentrically disposed outer circular wall 254c. The outer circular wall 254c is positioned to allow connection of the expandable receiving portion 166 during use, as shown in FIG. 6(b). For example, the outermost surface of the outer circular wall 254c may include threads, a clip portion, or the like to allow connection of the expandable receiving portion 166.

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

[0153] The outer circular wall 254c includes a ledge 259 extending radially inward from a base 259a toward the inner circular wall 254b. Generally, the ledge 259 and the flange 255 define a fluid passageway 168 therebetween, and specifically, as best shown in Figures 6(b) and 6(c), between the underside of the planar joint 216a to which the container 118 is attached and the upper side of the planar joint 216a, specifically, the upper side of the central hub 254a to which the expandable receiver 166 is attached. In this manner, the central hub 254a defines a fluid passageway 168 from the attached container 118 to the attached expandable receiver 166 to allow for breathing, or air pressure compensation, between the respective containers 118, 166. More specifically, the ledges 259 and flanges 255 define a tortuous or non-linear fluid passageway 168 such that air or gas can pass through the passageway 168 while preventing fluids, such as media containing biological material, from passing through such passageway 168 to the expandable receiver 166.

[0154] A series of radially extending ribs 261 are further provided connecting the flanges 255 to the inner surface of the outer circular wall 254c, with each rib 261 being spaced apart from the others. Each adjacent pair of ribs 261 defines an individual fluid passageway 168 therebetween. Furthermore, as best shown in FIG. 6(c), the flanges 255 are angled relative to the horizontal, i.e., the horizontal plane in which the flanges 255 are positioned, so that they are oriented or angled downward, or toward a ledge 259 of the outer circular wall 254c. In this manner, liquid or condensate originating from the container 118 is directed back toward the container 118 so that the substance is not lost from the container 118 to the expandable receptacle 166 during use.

[0155] Additionally, planar joint 216a has several ports 150 (see FIG. 6(b)), each having a removable sterile barrier 152 removably attached and positioned across the port 150 to provide a sterile seal. Specifically, removable sterile barrier 152 includes a fastener portion 152a connected to a sterile outer shell 152b, which is aseptically coupled to each port 150 (see FIG. 6(b)). Fastener portion 152a is positioned within a space 263 formed between each guide wall 265 and is held in place using clips 267 attached to adjacent guide walls 265. Fastener portion 152a is therefore slidable within space 263 so that sterile outer shell 152b can be removed from port 150 during use, as described in more detail below.

[0156] 6(d), the planar joint 216a further includes a lower volume sampling element 150a extending from a lower surface of the planar joint 216a. More specifically, the lower volume sampling element 150a is integrally formed with one or more of the ports of the planar joint 216a. The lower volume sampling element 150a is formed as a hollow tubular member 150b including a resilient material such as a thermoplastic elastomer or silicone, with through-holes extending from the distal end to the proximal end in communication with the respective ports 150. Specifically, the hollow tubular member 150b is coupled to the lower surface of the planar joint 216a adjacent to the ports 150 using a screw cap 150c having threads that mate with corresponding threads on the hollow tubular member 150b. The screw cap 150c may be coupled to the lower surface of the planar joint 216a by suitable means, such as an adhesive or a clip.

[0157] During use, the container 118 and / or the planar joint 216a can move such that the hollow tubular member 150b extends into the liquid held within the container 118 to allow sampling of the container 118. Additionally, due to the elastic nature of the hollow tubular member 150b, the hollow tubular member 150b can be positioned to contact the base of the container 118 without damaging the base. Specifically, the hollow tubular member 150b, being an elastic material, is positioned to bend into or toward a corner of the container 118, specifically a corner that causes the base of the container 118 to abut a sidewall of the container 118. This allows a sample, even a small amount, to be taken from the container 118 without risking damage to the container 118. More specifically, in this particular example, the connector needle is inserted through port 150, as discussed below, such that the throughbore of port 150 is in fluid communication with the throughbore of hollow tubular member 150b. A component coupled to the other end of the connector needle can then be actuated to draw fluid from container 118, through hollow tubular member 150b, through the connector needle, and into or toward the component. A sample can thereby be taken from container 118.

[0158] 6(b) and 6(d), the container 118 in this example is coupled to the planar interface 216a using a fastening ring 269. The fastening ring 269 includes a protrusion 269a that frictionally engages the outer surface of the container 118, fastening the container 118 between the protrusion 269a of the fastening ring 269 and a coupling wall 271 that extends distally from the underside of the planar interface 216a. The fastening ring 269 is coupled to the planar interface 216a using a plurality of fasteners 269b, such as screws or bolts. Alternatively, the container 118 may include threads that engage with the threads of the planar interface 216a, thereby eliminating the need for the fastening ring 269.

[0159] Further, as shown in FIGS. 6(b) and 6(d), an expandable receiver 166 is provided, coupled to the central hub 254a. The expandable receiver 166 includes 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 convolutions, thereby allowing the receiver 166 to expand and compress. The upper portion 166a of the expandable receiver 166 includes an air filter 273 in communication with the interior volume of the expandable receiver 166 and the external environment. The air filter 273 is positioned to allow air to pass into or out of the expandable receiver 166 without allowing liquids 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, capable of filtering bacteria, viruses, or other substances, thereby providing a sterile environment within the container 118 and / or the expandable receiver 166. The base portion 166b of the expandable receiver 166 is open-ended and includes a circular base wall 166d that is positioned to couple to the central hub 254a of the planar joint 216a. Specifically, the circular base wall 166d is coupled to the outer circular wall 254c of the central hub 254a using a spring clamp or spring clip (not shown). Alternatively, the circular base wall 166d may include external threads configured to engage with threads in the outer circular wall 254c of the central hub 254a.

[0160] FIG. 7 illustrates an assembly 100 including the planar joint 216 of FIG. 5 and a container 118. Alternatively, the planar joint 116 of FIG. 3, FIG. 4, or FIG. 6(a) may be used. The assembly includes a component receiving element 114, such as the component receiving element 14 formed as part of the enclosure 12 of FIGS. 1 and 2, for retaining a component 120, such as the component 20 of FIGS. 1 and 2. Specifically, the component receiving element 114 is formed by an arm 114a extending from the interior of the enclosure (not shown) and terminating in a component retaining head 114b. The component retaining head 114b includes a retaining element for retaining, receiving, or retaining the component 120 during use. For example, the component retaining head 114b may include a rail for receiving a portion of the component 120 so that the component 120 can slide within the component retaining head 114b as needed. In other examples, the component retaining head 114b retains the component 120 due 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 into which the component 120 is received, and in particular, against which the component 120 bears or rests during use. As will be recognized by one of ordinary skill in the art, suitable mechanisms for retention of the component 120 in the component-retaining element 114 are contemplated.

[0161] Generally, the component-holding element 114 and / or the planar joint 216 are movable to line up or align a port of the component 120 with one of the ports of the planar joint 216. In this specific example, the planar joint 216 is rotatable about a central longitudinal axis L of the planar joint 216, as shown by arrow A. Also, the component-holding element 114 is substantially immovable laterally, i.e., within the plane formed by the component-holding element 114, but is movable longitudinally, such as in the direction indicated by arrow B, along the longitudinal axis L1 of the component-holding element 114, specifically the component-holding head 114b. Thus, during use, as described further below, the planar interface 216 is rotated about the central longitudinal axis L such that the ports of the component 120 held by the component retaining head 114b of the component retaining element 114 are aligned with the ports of the planar interface 216, and then the component retaining head 114b, or alternatively the entire component retaining element 114, is moved along axis L1 in direction B to engage the ports of the component 120 with the ports of the planar interface 216, specifically, in the first example, the sterility barrier 152. Thereafter, the component retaining head 114b, or the component retaining element 114 in its entirety, is moved along axis L1 in a direction opposite direction B to disengage the respective ports. The planar interface 216 is then rotated about the central longitudinal axis L to align the next port of the planar interface 216 with the port of the component 120 in a consecutive manner. The process can then be repeated any number of times. Detailed operation of assembly 100 is described below. Generally, the described assembly 100 provides an assembly that is more amenable to automation and requires less manual intervention or manipulation. As will be appreciated by those skilled in the art, this is an example of the invention, and thus, in other examples, the arms may be rotatable and movable to align the respective ports, and the planar joints may be substantially immovable.A further example may include both a movable arm and a movable planar joint.

[0162] 8(a)-8(c) illustrate a method for mounting the planar joint 216 and container 118 of FIG. 7 to the enclosure 112. As shown in FIG. 8(a), the enclosure 112 includes a sliding drawer 180 having a mounting plate 182 that is slidable on telescoping rails between an open configuration (see FIGS. 8(a) and 8(b)) in which the planar joint 216 can be mounted to the drawer 180, and a closed configuration (see FIG. 8(c)) in which the drawer 180 is positioned and housed within the enclosure 112. Generally, during use, a user slides the drawer 180 open in a direction perpendicular to the central longitudinal axis of the planar joint 216 to the open configuration, mounting the planar joint 216 to the mounting plate 182 and thereby mounting the drawer 180 (FIG. 8(a)). Once loaded, the user slides the drawer 180, and thus the planar interface 216, closed in the indicated direction C to the closed configuration (FIG. 8(b)). In the closed configuration, the planar interface 216 and receiver 118 are loaded into the enclosure 112 and housed within the enclosure 112, specifically within the interior volume of the enclosure 112 (FIG. 8(c)), and use of the system can begin.

[0163] FIGS. 9(a)-9(c) show more detailed views of the enclosure 112, the planar joint 216, and the drive mechanism 184 of the enclosure 112. As shown in FIGS. 9(a) and 9(b), the planar joint 216 is loaded into the drawer 180 of the enclosure 112 as previously described. Once loaded, as shown in FIG. 9(c), the drive mechanism 184, specifically the grooved drive wheel 186, engages with a rim 250 having a plurality of drive elements 252. The grooved drive wheel 186 and the drive elements 252 of the rim 250 mesh during use to act as a gear arrangement, thereby providing rotation of the planar joint 216 about its central longitudinal axis during use. Specifically, the drive wheel 186 can be driven by a motor in a clockwise direction, as indicated by arrow D, thereby driving the planar joint 216 in a counterclockwise manner about its central longitudinal axis.

[0164] The drive mechanism 184, specifically the drive wheel 186, can be driven by a controller (not shown) of the enclosure 112, which can be coupled to a number of sensors (not shown) for sensing the positioning of the planar joint 216 within the enclosure 112. To that end, the planar joint 216 can include a number of magnets and the enclosure 112 can include Hall-effect sensors, or the enclosure 112 can include a number of magnets and the planar joint 216 can include Hall-effect sensors. The controller can control the positioning of the planar joint 216, specifically relative to the component-holding element during use, to position the respective ports and components of the planar joint during use. Thus, controlled or automated homing and / or rotation of the planar joint 216 is provided within the enclosure 112 without manual intervention or operation. In this manner, the planar interface 216 can be loaded into the enclosure 112 without the user having to precisely align the planar interface 216, i.e., the planar interface 216 can be placed into the enclosure without having to align with a port of a component held by a component-retaining element. The planar interface 216 is then positioned and rotated by a controller that controls the drive wheels 186 to align the planar interface 216 and the respective ports of the component in response to user input, such as selection of a specific port of the planar interface 216 in a user interface of the enclosure 112. The drive wheels 186 can then control subsequent movements of the planar interface 216 to align different ports of the planar interface 216 with ports of the component in a sequential manner as described below, thereby providing an automated system.

[0165] 10(a) and 10(b) illustrate another planar joint 316 and another enclosure 212. The planar joint 316 is substantially similar to the planar joint 216 of FIGS. 5, 6, and 7, except that the planar joint 316 includes several locating features 352 formed on the lower surface, or underside, of the planar joint 316. In this specific example, the locating features 352 are formed as sinusoidally shaped portions, such as cutouts, on the lower surface. Furthermore, the planar joint 316 does not include a perimeter with a grooved outer surface as shown in the planar joint 216 of FIGS. 5, 6, and 7, but instead includes a smooth perimeter 350. In other embodiments, the planar joint 316 may include both locating features 352 on the underside of the planar joint 316 and a grooved perimeter.

[0166] The enclosure 212 similarly includes a drawer 280 as described in connection with FIGS. 8(a)-8(c). However, in this example, the drawer 280 includes a mounting plate 282 with a corresponding locating feature 284 on its upper surface. The locating feature 284, in this specific example, is formed as a sinusoidally shaped portion, such as a cutout portion, on the upper surface. The locating feature 284 is thus complementary to the locating feature 352 of the planar joint 316. In this manner, tactile feedback is provided to the user that the planar joint 316 is seated within the drawer 280. During use, the assembly 212 can effect rotation of the planar joint 316 in the manner described in connection with FIGS. 9(a)-9(c), or alternatively, the drawer 280, and specifically the mounting plate 282, can be rotated by a drive mechanism, as indicated by the arrow in FIG. 10(a). Thus, the positioning features 284, 352 can provide a user with confidence that the planar joint 316 is seated in the drawer 280, while eliminating the need for the user to mount the planar joint 316 in a particular orientation.

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

[0168] 11, the component-retaining element 114 is shown as further comprising an actuator 170 arranged to actuate the component 120, specifically its connector 122 (see FIGS. 12(a) and 12(b)). For example, with reference to FIGS. 11, 12(a), and 12(b), the actuator 170 can provide fluid communication between the second septum seal 128b of the connector 122 and a port of the planar interface 116, as described further below. The planar interface 116 is housed within the enclosure 312, specifically between a stirring plate 350 engageable with a base surface of the vessel 118 attached to the planar interface 116, and a plate 352 that can house or receive the planar interface 116 and / or can include a drive mechanism (not shown) for driving the planar interface 116. The planar joint 116 may be housed in an enclosure 312, for example by virtue of a drawer, according to any one of the examples discussed above.

[0169] 12(a) and 12(b), the component 120 in this example includes a connector 122 to which a receptacle 124, such as a blood collection tube, is attached. Thus, in this specific example of component 120, a sample collection component 20e (see FIG. 1) is provided. As will be apparent to those skilled in the art, this is merely one example of a component that may be used in the assembly herein.

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

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

[0172] In this embodiment, connector 122 includes a first port formed as first septum seal 128a and disposed at distal end 125a of the housing, and a second port formed as second septum seal 128b and disposed at proximal end 125b of the housing. The housing further includes a hollow needle 129 mounted therein and biased in this specific example. Hollow needle 129 is aligned generally coaxially with the longitudinal axis of connector 122. Hollow needle 129 includes a first end 130a facing first septum seal 128a and a second end 130b facing second septum seal 128b. First end 130a is configured to be capable of piercing first septum seal 128a during use, and second end 130b is configured to be capable of piercing second septum seal 128b during use. The first septum seal 128a, the second septum seal 128b, or both the first septum seal 128a and the second septum seal 128b may optionally be provided with a sterility barrier 131 disposed thereover. The sterility barrier 131 is generally configured to mate with a corresponding sterility barrier 152 (see FIG. 3) at the planar joint 116, 216, 216a, 316 (see FIGS. 3-7 and 8). The sterility barrier 131 may be arranged to adhere to or otherwise couple with the corresponding sterility barrier 152 such that both barriers 131, 152 may be simultaneously removed, as described further below.

[0173] Hollow needle 129 is mounted within the housing via an annulus 132, which in this specific example is spring-biased by first and second helical springs 133a and 133b. In other embodiments, hollow needle 129 may be mounted in other suitable manners, for example, hollow needle 129 may be mounted statically, i.e., non-moving, and the housing may be movable relative to hollow needle 129. In a further alternative, hollow needle 129 may be axially movable via annulus 132, and upper housing portion 123a may be axially movable while lower housing portion 123b remains static, i.e., non-moving. To that end, upper housing portion 123a may be provided with actuable tabs and annulus 132 may be provided with actuable tabs, each set of actuable tabs being actuable by an actuation mechanism arranged to move hollow needle 129 and upper housing portion 123a to cause puncture of a respective septum seal 128a, 128b. In this example, the order of puncture of septum seals 128a, 128b is controlled by the respective spring forces of springs 133a, 133b. Specifically, first spring 133a provides a first biasing force to hollow needle 129 via annulus 132 in a direction toward proximal end 125b of the housing, and second spring 133b provides a second biasing force to hollow needle 129 via annulus 132 in a direction toward 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 sequential puncture of the septum seals 128a, 128b. In this example, the first biasing force is greater than the second biasing force due to the larger wire diameter of the first spring 128a compared to the second spring 128b.

[0174] In use, as will be appreciated by those skilled in the art, hollow needle 129 is caused to engage and pierce respective ports 128a, 128b to fluidly couple receiver 124 (see FIG. 12(a)) to a second volume of fluid, such as a container 118, connected to planar joints 116, 216, 216a (see, e.g., FIGS. 3, 5, and 6). To accomplish such piercing, connector 122 is provided with an actuation mechanism, provided in this example as an outer cover 133 that surrounds upper and lower housing portions 123a, 123b. Outer cover 133 is rotatable about a central longitudinal axis of connector 122. Outer cover 133 includes a protrusion (not shown) on its inner surface that engages with a slot (not shown) in the outer surface of upper housing portion 123a. The protrusions and slots provide a camming 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 septum seal 128b is arranged to cooperate with a port, such as a planar joint septum seal, as described below. To that end, a hollow needle 129 can be punctured through both the second septum seal 128b and the planar joint septum seal to provide a fluid communication path through the joint septum seal during puncture. The method of fluid connection is provided in more detail below with reference to Figures 21(a)-21(d).

[0175] FIGS. 13(a)-13(d) show alternative views of the assembly 100 and enclosure 312 of FIG. 11. Specifically, several linear actuators 354 are provided as part of the enclosure 312, positioned to move the agitator plate 350 during use. As shown in FIGS. 13(b) and 13(c), the linear actuators 352 are configured to move the agitator 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 opposite sides of the assembly 100, specifically on opposite sides of the planar joint 116 and the vessel 118. The linear actuators 354a, 354b are positioned and configured to act synchronously. For example, one pair of linear actuators 354a acts in one direction, and the other pair of linear actuators 354b acts in the same direction. In this manner, the linear actuators 354a, 354b are arranged to cause linear compression, or 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 the material within the container 118. Furthermore, as best shown in FIG. 13(d), opposing pairs of linear actuators 354a, 354b are arranged and configured to act asynchronously, e.g., one pair of linear actuators 354a acting in one direction and the other pair of linear actuators 354b acting in the opposite direction, as indicated by arrows E and F in FIG. 13(d), thereby imparting a rocking or undulating motion to the container 118. Such motion may be useful, among other things, for mixing material within the container 118, such as resuspending biological material, such as cells, within a medium.

[0176] Figures 14(a)-14(c) illustrate another enclosure 412 for use with an assembly as described herein. Specifically, Figures 14(a) and 14(b) show the enclosure 412 including a hinged door 450 arranged to rotate about an axis in direction G between a closed configuration (Figure 14(a)) that encloses the contents of the enclosure 412 and an open position (Figure 14(b)) that provides 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 (Figures 14(b) and 14(c)), as shown by arrow H, with the periphery of the planar joint 116 being slidably received in a slot 452 in a plate of the enclosure 412 (see, for example, plate 352 in Figure 13(a)). Additionally, locating features 454 may be provided on the stir plate of the enclosure 412 to aid in mounting the planar interface 116, and specifically the container 118 attached thereto, to the enclosure 412.

[0177] 15(a) and 15(b) illustrate another enclosure 512 for use with an assembly as described herein. Specifically, the enclosure 512 includes a pair of slidable doors 550 that are movable away from each other within their own plane. The slidable doors 550 may thus be movable between a closed position (FIG. 15(a)), in which the contents of the enclosure are enclosed, and an open position (FIG. 15(b)), in which the contents of the enclosure 512 may be accessed. In this specific example, the doors 550 are openable in direction I to allow access to the top surfaces of the component-retaining elements 114, components 120, and / or planar joints 116. In this manner, the components above enclosure 512, i.e., component-retaining element 114, the top surface of planar interface 116, and component 120, are accessible by virtue of door 550, while the components below enclosure 512, i.e., the container (not shown) and the lower portion of planar interface 116, are accessible by virtue of drawer or hinged door 554, as described in the previous example. Thus, the various accessible parts are compartmentalized, so that user access can be limited to certain parts of the system during use.

[0178] The assembly and its components, as well as the use of an exemplary enclosure, will now be described, by way of example only and without limitation, with reference to Figures 16(a) to 23.

[0179] Referring initially to FIG. 16(a), the component 120 held by the component-retaining element is provided as being an enclosure 512, as described in connection with FIGS. 15(a) and 15(b), although such an enclosure may be any of the enclosures described herein. The enclosure 512, specifically its upper slidable door 550, is opened (FIG. 16(b)), thereby revealing the component-retaining element 114 of the assembly 100 within the enclosure 512. The component 120, shown as a connector 122 having a receptacle 124 with a compressible plunger 124a, is placed within the component-retaining element 114, specifically the component-retaining head, as indicated by arrows J and K, and is held by the component-retaining head (FIG. 16(c)). Although the component-holding element 114 can hold the component 120 by any suitable means, as previously described, the component-holding element 114 holds the component 120 in this example by virtue of rails formed in the component-holding head that cooperate with a portion, such as a protrusion, of the component 120. In this specific example, the planar joint 116 and the container (not shown) are pre-loaded into the enclosure 512. As will be appreciated by those skilled in the art, the planar joint 116 and the container (not shown) may be loaded according to any of the previously described examples. A user can close the slidable door 550 to enclose the contents of the enclosure 512 following loading.

[0180] 17(a)-17(c) illustrate a method for engaging a component held by a component-holding element with a planar joint. As shown in FIG. 17(a), once the component 120 is loaded onto the component-holding element 114, the controller activates the actuator 170. To do so, a user can provide input to the controller's user interface. Specifically, the actuator 170, formed as part of the component-holding element 114, includes a rotatable disk 171 having cutout portions and housed within an actuator housing 173. The housing 173 also has cutout portions. Each cutout portion is arcuate to provide a half-moon-shaped cutout. Thus, with the respective cutout portions aligned, the component 120 can be loaded onto the component-holding head 114b prior to use, as shown in FIG. 17(a). 17(b), in operation, the rotatable disc 171 rotates about the central longitudinal axis of the component-holding head 114b in the indicated direction L to expose an engagement surface of the disc 171 that is positioned to engage the component 120. The engagement surface in this example is provided as a segment of the rotatable disc 171. The rotatable disc 171 is also axially movable, as shown in FIG. 17(c), such that the engagement surface engages an upper surface of the component 120, thereby moving the component 120 axially within the component-holding head 114b due to the cooperative rail configuration of the component-holding head 114b and the component 120. To that end, the component 120 may be slidably received and thus slidable or axially movable within the component-holding head 114b. The component 120 is moved axially in the indicated direction M until the sterile barrier 131 (see FIG. 12(b)) of the connector 122 of the component 120 engages the corresponding sterile barrier 152 of the planar interface 116. Specifically, the sterile barriers 131, 152 are brought into face-to-face engagement.

[0181] 18(a)-18(c), there is shown a schematic of an example of a component retaining element 114, a component 120, and a planar interface 116 housed within an enclosure 512. In this example, an example of a sterile barrier 650 is provided across the port 150 of the planar interface 116. The sterile barrier 650 comprises a sterile outer shell 652 disposed across the port 150 and terminates in a fastener portion 654a. The fastener portion 654a is generally received within a slot (not shown) in the planar interface 116 such that the fastener portion 654a is slidable within the slot between a first configuration in which the sterile outer shell 652 is disposed across the port 150 and a second configuration in which the sterile outer shell 652 is removed from the port 150. The fastener portion 654a is generally comprised of a rigid plastic material, while the sterile outer shell 652 is comprised of a paper or polymer material. The fastener portion 654a is connected to the sterile outer shell 652 in any suitable manner, such as, for example, through mechanical connection of a protrusion to an opening in the sterile outer shell 652 (see Figures 19(a)-19(c)) or through adhesion to the sterile outer shell 652.

[0182] Further, in this specific example, the sterility barrier 131 of the connector 122 (see also FIG. 12(b)), which is disposed across the port 128b of the connector 122, further comprises a sterile outer shell coupled to the fastener portion 654a. However, as will be understood by those skilled in the art, in other examples, the fastener portions 654a, 654b may be provided on only one of the component 120 or the mating plate 116. In this example, the fastener portions 654a, 654b have corresponding features, such as a protrusion and opening configuration, such that they are positioned in a mating relationship to one another during use. With further reference to FIGS. 18(b) and 18(c), as described further below, upon face-to-face engagement with the planar mating portion 116 of the connector 122, the fastener portions 654a, 654b interlock with one another, and their respective sterile outer shells also interlock with one another (see FIG. 18(b)). The sterility barriers 131, 650 are then removed (see FIG. 18(c)) primarily through removal of the coupled fastener portions 654a, 654b from the component 120 and planar joint 116, respectively. In this manner, lateral movement of the fastener portions 654a, 654b connected to their respective sterile outer shells causes the sterile outer shells to remove from their respective ports 150, 128b, thereby causing the ports 150, 128b to engage with one another in face-to-face engagement.

[0183] 19(a)-19(c), there is shown a sterile barrier removal system 600 and its method of operation. The sterile barrier removal system 600 comprises a laterally extending beam 602 having a sidewall with a rail 604. A slidable arm member 606 is also provided that is slidably received within, and is slidable along and within, the rail 604, and that terminates in a longitudinally extending actuation protrusion 608.

[0184] In this example, the sterile barrier 131, 650 of Figures 18(a)-18(c) is provided for use with a sterile barrier removal system 600. In use, the sterile barrier removal system 600 is positioned to remove the sterile barrier 131, 650 of the cooperatively coupled together connector 120 and planar joint 116 (see Figure 18(a)), as previously described. Specifically, in this example, the actuation projection 608 is moved in direction N along the rail 604 to engage with the coupled fastener portions 654a, 654b, as shown in Figure 19(a). More specifically, the fastener portions 654a, 654b may have leading edges 655 (see Figure 19(a)) for guiding the projection 608 into openings 657 (see Figure 19(b)) in the fastener portions 654a, 654b. Upon engagement of the actuation protrusion 608 with the fastening portions 654a, 654b, the actuation protrusion 608 is retracted, i.e., moved in direction O along the rail 604 away from the component 120, to apply a removal force to the fastening portions 654a, 654b. In this manner, the fastening portions 654a, 654b are pulled outwardly away from the component 120 and the planar interface 116, respectively, which in turn causes the respective sterile envelopes to be pulled outwardly and removed from their respective ports 128b, 150 (see FIG. 18(a)). In this manner, the port 150 of the planar interface 116 and the port of the connector 122, i.e., the second septum seal 128b, can be engaged in a face-to-face manner (see FIG. 18(c)). Additionally, when the sterility barrier 131, 650 is removed, it falls into a waste chute 660, as shown by arrow P in Figure 19(c), which may provide a path for removal of the sterility barrier directly or indirectly into a medical waste workstream, such as to a trash can.

[0185] With reference to Figures 20(a) and 20(b), and further with reference to Figures 21(a)-21(d), a method of actuating components to provide fluid communication through a planar junction will be described.

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

[0187] With reference to Figures 21(a)-21(d), various steps in the actuation of the component are described. Figure 21(a) shows the second septum seal 128b of the port, or connector 122, of the component 120 aligned with the port 150 of the planar interface 116. That is, the ports 128b, 150 are coaxial or aligned. Figure 21(b) shows the first step in the actuation of the connector 122, specifically the initial rotation of the outer cover 133 by an actuator of the component retention element (not shown). Following this first step in the actuation of the connector 122, the second end 130b of the hollow needle 129 is pierced through the second septum seal 128b of the connector 122 and through the port 150 of the planar interface 116. This is accomplished through rotation of outer cover 133, which causes upper housing 123a to collapse relative to lower housing 123b, causing hollow needle 129 at its second end 130b to pierce second septum seal 128b and port 150. As shown, first septum seal 128a opposite connector 122 remains unpierced due to the spring bias discussed in connection with FIG.

[0188] FIG. 21(c) illustrates a second step in the actuation of the connector 122, specifically further rotation of the outer cover 133 by an actuator of a component-retaining element (not shown). Following this second step in the actuation of the connector 122, i.e., further rotation of the outer cover 133, causes the first end 130a of the hollow needle 129 to pierce the first septum seal 128a of the connector 122 and into the receiver 124. In this specific example, the receiver 124 also includes a septum seal 124a having a trapezoidal cutout portion, through which the first end 130a of the hollow needle 129 is also pierced. As shown in FIG. 21(c), fluid communication is provided through the bore of the hollow needle 129 between the receiver 124 and the interior volume of the planar interface 116, e.g., the attached receiver. At this point, fluids, such as media or biological materials, can be passed in either direction between the receptacle 124 and the container attached to the planar joint. When fluid communication is desired to be stopped, the outer cover 133 is rotated, by virtue of an actuator of a component retention element (not shown), in a direction opposite to the direction of rotation to cause the hollow needle 129 to pierce each septum seal. Thus, as shown in FIG. 21(d), the puncture of each septum seal 128a, 128b is stopped when the hollow needle 129 returns to its original configuration. Specifically, the order of stopping the puncture of each septum seal 128a, 128b is opposite to the order of puncture. Stated another way, in this particular example, first the first end 130a of hollow needle 129 is caused to stop puncturing first septum seal 128a, and then the second end 130b of hollow needle 129 is caused to stop puncturing second septum seal 128b. As will be appreciated by those skilled in the art, the order of puncturing and stopping puncturing can be varied by controlling the spring bias force and / or by providing alternative actuation mechanisms for connector 122.

[0189] 22(a) and 22(b) illustrate a method for providing fluid dispensing of the receiving portion 124 of the component 120 while fluid communication is established through respective ports of the component 120 and the planar interface 116, such as the fluid communication previously shown in FIG. 21(c). Specifically, fluid communication between the receiving portion 124 of the component 120 through the planar interface 116 is established to a container (not shown) attached to the planar interface 116, as shown in FIGS. 21(c) and 22(a). Once fluid communication is established, a dispensing 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 interface 116. The dispensing actuator 172 is formed as a spatula driven by a motor in this example. In other examples, dispensing actuator 172 may be formed as part of previously discussed actuator 170 (FIGS. 17(a)-17(c)), thereby providing a single actuator for actuating connector 122 and receptacle 124. When piston 124b is biased downward, the contents of receptacle 124 are dispensed from receptacle 124 through a hollow needle of connector 122 (see also FIG. 21(c)), through connector 122 and planar interface 116, and into a container (not shown) attached to planar interface 116. Thus, additional fluid is provided from component 120 to a container (not shown) attached to the planar interface. Those skilled in the art will also recognize that dispensing actuator 172 may be replaced by a removal actuator arranged to act on plunger 124a in a direction opposite to that described above, i.e., to move plunger 124a and piston 124b axially upward, i.e., axially away from connector 122 and planar interface 116. Thus, a negative pressure configuration may be provided such that the contents of a receiver (not shown) attached to planar interface 116 are removed or drawn into receiver 124.Also, as will be appreciated by those skilled in the art, the actuator 172 may be configured and arranged to both dispense fluid from the receptacle 124 and to draw fluid into the receptacle 124 .

[0190] FIG. 23 outlines the final step in the use of the assembly and other associated components. Specifically, once fluid dispensing is complete and the component 120 is disconnected from the planar interface 116, the component-holding element 114, specifically its actuator 170 (see FIG. 17(b)), removes the component 120 from the planar interface 116 by axially translating the component 120 in direction S away from the planar interface 116. The component 120 can then be removed from the component-holding element 114, such as by a user or a robotic arm of an enclosure, and replaced with another component. The operation of the assembly and similar features can then be repeated as many times as desired, using subsequent ports on the planar interface 116. Specifically, the planar interface 116 is rotated to align the ports of the new component with the subsequent ports on the planar interface 116, as shown in FIGS. 7 and 9(c).

[0191] As shown in FIGS. 24(a)-24(d), another embodiment of an assembly 1000 for handling biological material is disclosed. As shown in FIG. 24(a), the assembly 1000 includes a component holding element 1002 that holds a container 1004 having a tube 1006. The tube 1006 may include a sterile membrane (not shown) coupled to its distal end. The component holding element 1002 is formed as a robotic arm 1008 that terminates in 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 includes a substantially planar joint 1014, such as those described herein, e.g., with respect to FIGS. 3-7, that is coupled to a bioreactor 1016. However, in this particular embodiment, the substantially planar junction 1014 comprises a plurality of tubes 1018 having sterile membranes (not shown) connected to the ends thereof.

[0192] As shown in Figures 24(b) and 24(c), assembly 1000 also includes a sterile tube welder 1022 and a sterile tube sealing machine 1024. The sterile tube welder 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. Each robotic arm is thereby movable to operate the sterile tube welder 1022 and the sterile tube sealing machine 1024 during use. The robotic arms can also effect operation of the respective sterile tube welder 1022 or sterile tube sealing machine 1024.

[0193] Assembly 1000 will now be described in use in connection with Figures 24(a)-24(d). As shown in Figures 24(a) and 24(b), component-retaining element 1002 is movable to align tube 1006 of container 1004 with tube 1018 of planar joint 1014. Once tubes 1006, 1018 are aligned with one another, as shown in Figure 24(b), sterile tube welder 1022 is actuated to form a sterile weld between each tube 1006, 1018, as shown in Figure 24(c). If coupled, the sterile membrane may be removed during this step as part of the welding process, such as through heat welding or melting, or in a separate removal actuation process operated by sterile tube welder 1022 or another actuation component. Thus, the sterile tube welder 1022 forms a sterile weld between the tubes 1006, 1018, fluidly connecting the lumens of each tube 1006, 1018. In this manner, a sterile fluid pathway 1026 is provided through the connected tubes 1006, 1018 to connect the vessel 1004 and the bioreactor 1016 through the planar joint 1014, as shown in FIG. 24(c). The biological material is then transferred from the vessel 1004 to the bioreactor 1016, for example, in a manner as previously described. Once the biological material has been transferred, as shown in FIG. 24(d), the sterile tube sealer 1024 is actuated to form a sterile seal between the connected tubes 1006, 1018. In this manner, the sterile fluid pathway 1026 is blocked between the vessel 1004 and the bioreactor 1016 by the heat seal 1027. The aseptic tube sealing machine 1024 may also have a cutting element positioned to cut the sealed tubes 1006, 1018 along the heat seal 1027 to release the respective components, or a user may provide the necessary cutting in a manual step. The container 1004 is then removed from the planar joint 1014.The container 1004 may then be discarded, and the component-retaining element 1002 may hold the next container 1004 for the next addition to or removal from the bioreactor 1016 via the planar joint 1014, and the process may be repeated beginning with FIG. 24(a). Generally, those skilled in the art are familiar with sterile tube welding and sealing machines, and therefore they will not be described further here. This example provides an automated, or at least semi-automated, technique for sterilely connecting and disconnecting fluid volumes suitable for "just-in-time" addition or removal of media from a bioreactor.

[0194] In general, those skilled in the art will appreciate that the above-described embodiments have been described by way of example only and not by way of limitation, and that various modifications and variations are possible without departing from the scope of the present invention as defined by the appended claims. Various changes to the detailed designs as described above are possible, such as changes in shape, size, arrangement, assembly, or sequence. For example, any of the enclosures, planar joints, or component-retaining elements may be used in any suitable combination. Furthermore, while the present invention has been described in connection with automated processing, those skilled in the art will appreciate that a user may undertake one or more of the above-described processing steps manually or semi-automatically. [Explanation of symbols]

[0195] 1. Biological material handling system 10 assembly 12 Enclosure 14 Component holding elements, component receiving elements 16 Planar joints 18 Container 20 Components 20a Cell input component 20b Bead Dosing Component 20c Virus injection component 20d Media Input Component 20e Sampling Components 20f Sample Components 20g Media Eject Component 22 Connectors 24 Receiving Department 100 assemblies 112 Enclosure 114 Component receiving element, component holding element 114a Arm 114b Component holding head 116 Planar joints, joint plates 118 Container 120 components 122 Connector 123a Upper housing part 123b Lower housing part 124 Receiving 124a plunger 124a Diaphragm Seal 124b piston 125a distal end 125b proximal end 126 Threaded part 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 members 150c screw cap 152 Sterile Barrier 152a Fastener part 152b Sterile envelope 154 central hub 156 Connected elements, connected parts 160, 162 Threaded part 164 Cover 166 Expandable Receptacle 166a Upper part 166b Foundation part 166c wall section 166d Circular foundation wall 168 Fluid passage 170 Actuator 171 Rotatable disc 172 Distribution Actuator 173 Actuator housing 180 sliding drawer 182 Mounting Plate 184 Drive Mechanism 186 Grooved drive wheel 216, 216a Planar joints 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 Ribs 263 Space 265 Guide Wall 267 clips 269 ​​Fastening Ring 269a Protrusion 269b Fastener 271 Connecting wall 273 Air Filter 280 Drawer 282 Mounting Plate 284 Positioning Features 312 Enclosure 316 Planar joint 350 Periphery, stirring plate 352 Positioning Features 354, 354a, 354b Linear actuators 412 Enclosure 450 hinged door 452 Slots 454 Positioning Features 512 Enclosure 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 657 Opening 660 Waste Chute 1000 assemblies 1002 Component Holding Elements 1004 Container 1006 tube 1008 Robot Arm 1010 Holding part 1012 Grasping arm 1014 Substantially planar joints 1016 Bioreactor 1018 tube 1022 sterile pipe welding machine 1024 Sterile tube sealing machine 1026 Sterile Fluid Pathway 1027 Heat sealing L central vertical axis L1 vertical axis L2 vertical axis

Claims

1. 1. An apparatus for handling biological material, comprising: a component holding element configured to hold a component for handling biological material; and Equipped with the component-holding element is movable to align the component-holding element with at least one port of a substantially planar interface spaced from the component-holding element, allowing, in use, fluid communication between a component held by the component-holding element and a container associated with the substantially planar interface via the at least one port; the device comprising a sterile barrier removal system configured to operably engage a portion of a removable sterile barrier positioned over at least one port of the substantially planar joint and to remove the removable sterile barrier from the at least one port during use.

2. The device of claim 1, further comprising a substantially planar joint having at least one port.

3. The apparatus of claim 2 , wherein the substantially planar joint is rotatable about an axis of rotation that is substantially perpendicular to the plane of the substantially planar joint.

4. 4. The apparatus of claim 2 or 3, wherein the component-holding element is longitudinally movable along an axis substantially perpendicular to the plane of the substantially planar joint.

5. 5. The device of claim 4, wherein, when in use, the component holding element is movable longitudinally along a central longitudinal axis of the component holding element or a portion thereof to engage a component held by the component holding element with the at least one port.

6. 6. The apparatus of claim 1, wherein the component-holding element comprises an arm terminating in a component-holding head.

7. 7. The apparatus of claim 1, further comprising an enclosure, the component retaining element being formed as part of the enclosure, the enclosure being configured to operably receive the substantially planar joint.

8. 8. The apparatus of claim 2, or any one of claims 3 to 7 when relying on claim 2, wherein the substantially planar joint comprises a plurality of ports.

9. 9. The apparatus of claim 8, wherein each port is disposed radially outward of a central longitudinal axis of the substantially planar joint.

10. 10. The device of claim 2 or any one of claims 3 to 9 that cites claim 2, wherein the at least one port in the planar joint is a resealable port.

11. The device of claim 10 , wherein the resealable port comprises a septum seal.

12. 12. The device of claim 11, wherein the substantially planar joint and the diaphragm seal are co-molded.

13. 13. The device of claim 2, or any one of claims 3 to 12 that cites claim 2, wherein the substantially planar joint further comprises a removable sterility barrier positioned across the at least one port.

14. 14. The device of claim 13, wherein the removable sterility barrier comprises a fastener portion operably coupled to a sterile outer shell, the sterile outer shell being removably disposed over the at least one port.

15. 15. The device of claim 14, wherein the fastener portion is slidably received in a slot formed in the substantially planar joint, the fastener portion being movable within the slot between a first configuration in which the sterile outer shell is positioned across the at least one port and a second configuration in which the sterile outer shell is removed from the at least one port.

16. 16. The apparatus of claim 2, or any one of claims 3 to 15 when relying on claim 2, wherein the substantially planar joint comprises a connecting element configured to operably connect to a corresponding connecting element of a container.

17. 17. Apparatus according to claim 2 or any one of claims 3 to 16 which cites claim 2, wherein the substantially planar joint comprises one or more drive elements arranged to cooperate with a drive mechanism.

18. 18. The apparatus of any one of claims 1 to 17, wherein the component-holding element comprises an actuator configured to, when in use, actuate at least a portion of a component held by the component-holding element.

19. 19. The apparatus of claim 2 or any one of claims 3 to 18 that recites claim 2, further comprising a container fluidly connected to the at least one port of the substantially planar junction.

20. 20. The device of claim 19, further comprising an expandable receiver operably coupled to the substantially planar junction and configured to be in fluid communication with the container through the substantially planar junction.

21. 21. The device of claim 20, wherein the expandable receiver comprises a flexible bag or a receiver with an expandable sidewall.

22. 22. The apparatus of claim 1, further comprising a component for handling biological material held by the component-holding element.

23. 23. The device of claim 22, wherein the component comprises a receptacle, a connector, or a receptacle fluidly connected to a connector.

24. 1. A method for introducing or removing a substance into or from a component of an apparatus for handling biological material, the method comprising: Providing an apparatus according to claim 2 or any one of claims 3 to 23 which cites claim 2; holding a component suitable for handling biological material and having at least one port in the component holding element; moving the component-holding element to align the at least one port of the component with the at least one port of the substantially planar interface; engaging a sterile barrier removal system with a portion of a removable sterile barrier disposed over at least one port of the substantially planar interface; providing a fluid communication path through the at least one port of the substantially planar interface and the at least one port of the component; introducing or removing a substance into or from the component through the fluid communication path; A method comprising:

Images