Patent Application
20230123559
The disclosure relates to an assembly for handling biological material. The disclosure also relates to a method of introducing material into, or removing material from, a component of such an assembly. More specifically, the disclosure relates to an assembly, and a method of operation thereof, for use in one or more one or more unit operations in a cell processing method, for example, in cell and/or gene therapy manufacturing processing.
Biological handling processes, such as cell and gene therapy (CGT) manufacturing processes, are often complex and include manual steps across several devices. Equipment systems used in various steps or unit operations, of cell-based therapeutic products (CTP) manufacturing may include devices for various unit operations. The unit operations may include, for example, cell collection, cell isolation, selection, cell expansion, cell washing, volume reduction, cell storage or transportation. The unit operations can vary immensely based on the manufacturing model (i.e., autologous versus allogenic), cell type, intended purpose, among other factors. In addition, cells are “living” entities sensitive to even the simplest manipulations (such as differences in a cell transferring procedure). The role of cell manufacturing equipment in ensuring scalability and reproducibility is an important factor for cell and gene therapy manufacturing.
In addition, cell-based therapeutic products (CTP) have gained significant momentum thus there is a need for improved cell manufacturing equipment for various cell manufacturing procedures, for example, but not limited to stem cell enrichment, generation of chimeric antigen receptor (CAR) T cells, and various cell manufacturing processes such as collection, purification, gene modification, incubation/recovery, washing, infusion into patient and/or freezing.
The culture or processing of cells typically requires the use of a device to hold the cells, for example, in an appropriate culture medium when culturing the cells. The known devices include shaker flasks, roller bottles, T-flasks and bags. Such bottles or flasks are widely used but suffer from several drawbacks. Chief among the problems are the requirement for transfer of cells, media or other material without contamination when passaging or processing.
A current problem in the production of cells or gene therapies for use in medicine is the absence of compact, automated closed systems for performing unit operations without contamination. For example, during cell culture, upstream or subsequent processing of cells, there is a risk of contamination when making additions to the culture vessel, or when removing cells or removing liquid samples. Moreover, the current operating systems are largely manual and hence 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 is an opportunity for operator errors and contamination to occur.
Furthermore, with increasing manual operations comes increasing risk of manual errors and therefore the current labor-intensive processes may lack the robustness required for the manufacture of clinical-grade therapeutics.
Therefore, there is a need for assemblies for handling biological material, such as multistep biological material, or cell, processors, that permit such processing in an automated or, at least, in a semi-automated manner, i.e., with minimal user intervention and/or operation, while maintaining sterility of the overall system.
Therefore, it is an object of the present disclosure to provide improved assemblies for handling biological material, particularly those for use in cell and/or gene therapy processing, and more specifically an apparatus that allows for the introduction and removal of material to or from a container in a sterile and automated or semi-automated manner.
It is also an object of the present disclosure to provide an apparatus that combines the advantages of the cell culture containers that avoid the need for pumps and the requirement for constant passaging of cells into fresh culture devices, holding vessels, tubes etc., with the advantages conferred by having individually configurable cell and/or gene therapy processing devices.
It is a further object of the present disclosure to provide an apparatus that permits a variety of biological processes, such as one or more unit operations in cell processing, to be performed within a single device or apparatus having a smaller footprint and being less complex than existing equipment. Furthermore, the apparatus described herein allows for greater compatibility with automated systems. Other advantages will be apparent from the drawings and the description below.
In accordance with one aspect of the present disclosure, there is provided an assembly for handling biological material, comprising:
Thus, there is provided a substantially planar interface including a port, that is a single port or a plurality of ports, formed within the substantially planar interface. The substantially planar interface may be formed substantially within a plane, and may assume any appropriate size, shape or the like. The substantially planar interface, when in use, is associated with a container. That is, the substantially planar interface, when in use, may include a container coupled thereto. The container may be suitable for handling biological material, such as a bioreactor. In particular, the container may comprise a compressible container, such as a container having a compressible, flexible or the like side wall.
Thus, there is also provided a component retaining element, suitable and arranged for retaining, receiving, coupling or otherwise holding a component, when in use. The component retaining element is spaced apart, or otherwise not integrally formed with, the substantially planar interface.
Thus, in use, either the substantially planar interface, the component retaining element or both the substantially planar interface and the component retaining element are moveable so as to bring the, or each, port of the substantially planar interface and the component retaining element into registration, or aligned or the like, with one another. Thus, by bringing such features into registration, the assembly can provide for a fluid communication pathway between a component, retained by the component retaining element, and a container, associated, or coupled to during use, with the substantially planar interface, thereby allowing fluid transfer, and thus handling of biological material, between respective components.
This provides the advantage that an assembly for handling biological material is provided, which allows for introduction or removal of material in a sterile and automated, or semi-automated, manner. Further, such an assembly has a smaller footprint and is less complex than existing equipment.
In certain embodiments, the substantially planar interface is rotatable about an axis of rotation substantially perpendicular to the plane of the substantially planar interface.
In certain embodiments, the substantially planar interface is rotatable about a central axis of the substantially planar interface. In some embodiments, the substantially planar interface may also be arranged to move laterally within the plane of the substantially planar interface.
Thus, during use, the substantially planar interface may be caused to rotate so as to bring into registration a port of the component with subsequent ports of the substantially planar interface. This provides the advantage that, during use, sequential introduction or removal of material may be provided in an automated, or semi-automated, manner.
In certain embodiments, the component retaining element is longitudinally moveable along an axis substantially perpendicular to the plane of the substantially planar interface.
Thus, in certain embodiments, the component retaining element is moveable along a longitudinal axis. The component retaining element may be moveable along a central longitudinal axis of the component retaining element or a portion thereof, such as the component retaining head thereof
This provides the advantage that the component retaining element can engage the component and the port of the substantially planar interface, during use, thereby being more suited to an automated, or semi-automated, process.
In certain embodiments, the component retaining element is longitudinally moveable to urge, when in use, a component retained by the component retaining element into engagement with the at least one port.
Thus, in certain embodiments, the component retaining element is moveable along a longitudinal axis so as to bring a component into engagement with the at least one port. Thus, the longitudinal axis may be substantially coaxially aligned with a longitudinal axis of the at least one port. The engagement between a component and the port may include a face-to-face engagement between a port of the component and the port of the substantially planar interface.
This provides the advantage that an aseptic, preferably fluid-tight or hermetic, seal is provided between the component and the port of the substantially planar interface. Thus, an aseptic biological handling apparatus is ensured.
In certain embodiments, the component retaining element is substantially laterally immoveable within the plane of the component retaining element.
Thus, in certain embodiments, the component retaining element is substantially immoveable, or substantially static, within a plane defined by the component retaining element.
This provides the advantage that less moving parts are included within the apparatus, and thus providing an easier and less expensive manufacture of such apparatuses.
In alternative embodiments, the component retaining element is laterally moveable within the plane of the component retaining element.
Thus, in certain embodiments, the component retaining element is moveable within a plane defined by the component retaining element.
In certain embodiments, the component retaining element comprises an arm terminating in a component retaining head.
Thus, in certain embodiments, the component retaining element includes an arm extending from a distal end to a proximal end. The distal end of the arm may be coupled to, for example, an interior of an enclosure, a stand, or the like. The proximal end of the arm may be coupled to a component retaining head. The component retaining head may be arranged to retain the component during use.
In certain embodiments, the component retaining head may include one or more coupling elements arranged to cooperate with a component, in use, so as to retain, receive, couple, or otherwise hold the component, in use. For example, the one or more coupling elements may be a rail arranged to cooperate with a protrusion of the component. For example, the one or more coupling elements may be a fastener, such as a clip, a bolt and nut arrangement, a screw or the like, arranged to cooperate with a fastener receiver of the component. In some particular examples, the component retaining head comprises a base and an upwardly extending side wall, wherein the side wall and base provide a volume for receipt of a component therein. The base may include an opening, or an aperture, to allow a portion of the component, such as a port thereof, to protrude or be exposed therethrough.
In certain embodiments, the apparatus further comprises an enclosure, the component retaining element being formed as part of the enclosure, and wherein the enclosure is configured to operably receive the substantially planar interface.
Thus, in certain embodiments, there is an enclosure, in which the component retaining element is formed as part of such enclosure. In some examples, the component retaining element includes an arm extending from an interior wall of the enclosure and terminating in a component retaining head. As such, the component retaining element may be formed as an integral part of the enclosure. In other examples, the component retaining element includes an arm extending from a stand or a structure formed within the enclosure, and terminated in a component retaining head.
In certain embodiments, the substantially planar interface comprises a plurality of ports.
Thus, in certain embodiments, the substantially planar interface includes more than one port, or two or more ports. It some examples, the substantially planar interface includes more than 5, 10, 15, 20, 25 or 30 ports. In particular examples, the substantially planar interface includes 22 ports.
In certain embodiments, each port is arranged radially outwardly of a central longitudinal axis of the substantially planar interface.
Thus, in certain embodiments, the substantially planar interface incudes a central longitudinal axis, and each port is arranged radially outwardly from such axis. In particular, each port is arranged along a radius formed between the central longitudinal axis and the outer edge of the substantially planar interface.
In certain embodiments, the plurality of ports are provided in a circular arrangement, a semi-circular arrangement, an arcuate arrangement, or the like.
This provides the advantage that the substantially planar interface can be rotated so as to bring into register the component and subsequent ports of the substantially planar interface. Thus, an apparatus more suited to an automated, or semi-automated, process is provided.
In certain embodiments, the at least one port of the planar interface is a resealable port.
Thus, in certain embodiments, the or each port is resealable so as to revert to its sealed configuration following a fluid passageway being formed therethrough. For example, the resealable port may include a hinged door, valve or the like, which reverts to a closed position following a fluid passageway being formed therethrough, such as in an open position. Further, in another example, the resealable port may be a self-sealing port, such as a septum seal, which self-seals upon cessation of piercing thereof.
This provides the advantage that a plurality of fluid communication pathways can be provided without compromising the sterility of the apparatus.
In certain embodiments, the resealable port comprises a septum seal.
In particular embodiments, the septum seal may comprise silicone material or a thermoplastic elastomer material.
In particular embodiments, an outer surface of the septum seal may be substantially coplanar with an upper surface of the substantially planar interface.
Thus, in some embodiments, the septum seal and substantially planar interface are substantially continuous in profile, or are flush with one another.
This provides the advantage that the septum seal is able to contact an adjacent septum seal in a face-to-face manner. Thus, sterility of the apparatus is ensured during use.
In particular embodiments, the septum seal may include an annular protruding wall enclosing a substantially flat portion.
Thus, in some embodiments, the septum seal, particularly the annular protruding wall, may protrude above an upper surface of the substantially planar interface. The substantially flat portion of the septum seal may be coplanar with the upper surface of the substantially planar interface.
This provides the advantage that the septum seal may receive a protruding portion of an adjacent septum seal, thereby aiding location of the respective septum seals during an automated or manual process.
In certain embodiments, the substantially planar interface and the septum seal are co-molded.
This provides the advantage that an increased pull-out force of the septum seal, with respect to the substantially planar interface, is provided. This is particularly advantageous upon withdrawal of a needle from the septum seal, which may otherwise pull the septum seal out of the substantially planar interface upon withdrawal. Thus, damage to the substantially planar interface and potential compromised sterility is avoided.
In particular embodiments, the substantially planar interface further comprises a removable aseptic barrier disposed over the at least one port.
Thus, in certain embodiments, the substantially planar interface includes a removable barrier, which ensures sterility of the or each port. In particular, the or each port is provided as a sterile port through gamma-irradiation, ethanol wiping or the like of the same. The removable barrier is provided over the or each sterile port.
This provides the advantage that the sterility of the or each port is ensured prior to, and during, use.
In certain embodiments, the removable aseptic barrier comprises a paper material or a polymeric material. The removable aseptic barrier may be provided with a handle at one end thereof. The removable aseptic barrier may be provided with a fold delimiting a first portion of the barrier and a second portion of the barrier. The first portion of the barrier may be arranged to contact another aseptic barrier, and the second portion of the barrier may be arranged to be disposed over the or each port. Any number of folds may be provided.
In certain embodiments, the removable aseptic barrier comprises a fastener portion operably coupled to an aseptic skin, the aseptic skin being removably disposed over the at least one port. The fastener portion may be coupled to the aseptic skin in any appropriate manner, such as a protrusion of the fastener portion mechanically coupled an aperture of the aseptic skin, through adhesion, through heat welding, or the like.
In certain embodiments, the fastener portion is arranged to couple to a further fastener portion of an adjacent removable aseptic barrier. The fastener portion may comprise one or more coupling elements arranged to couple to one or more corresponding coupling elements of an adjacent fastener portion.
This provides the advantage that adjacent removable aseptic barriers can be coupled and removed simultaneously by the apparatus. Thus, an apparatus more suited to an automated, or semi-automated, process is provided. Furthermore, tactile and/or visual feedback may be provided to a user during a manual removal process.
In certain embodiments, the aseptic skin is disposed on the or each port at one portion thereof, and is arranged to couple to a further aseptic skin of an adjacent removable aseptic barrier at another portion thereof. In some examples, the aseptic skin may be provided with a fold delimiting a first portion of the aseptic skin and a second portion of the aseptic skin. The first portion of the aseptic skin may be arranged to contact another aseptic skin, and the second portion of the aseptic skin may be arranged to be disposed over the or each port.
This provides the advantage that the sterility of each port is ensured prior to, and during, use.
Thus, in use, the removable aseptic barrier may be arranged to couple to an adjacent removable aseptic barrier. For example, the removable aseptic barrier disposed over the or each port of the substantially planar interface may be arranged to couple to a removable aseptic barrier of a component, such as a connector. Thereafter, upon coupling of removable aseptic barriers, such coupled aseptic barriers may be removed prior to a fluid communication pathway being provided.
It is noted that the coupling of the respective removable aseptic barriers, such as the aseptic skins, may be through any appropriate means, such as mechanical coupling, adhesion, heat welding or the like.
In certain embodiments, the fastener portion is slidably received within a slot formed in the substantially planar interface, the fastener portion being moveable within the slot between a first configuration, in which the aseptic skin is disposed over the at least one port, and a second configuration, in which the aseptic skin is removed from the at least one port.
Thus, in certain embodiments, the substantially planar interface is provided with a slot adjacent to the or each port. The slot slidably receives the fastener portion of a removable aseptic barrier therein. The fastener portion is moveable, specifically slidable, within the slot between the first configuration and the second configuration. Upon movement of the fastener portion from the first configuration to the second configuration, the aseptic skin is caused to disengage, i.e., become removed, from the or each port.
This provides the advantage that the apparatus can easily remove the aseptic barrier from each port during use, and is more suited to an automated, or semi-automated, process for achieving such removal.
In certain embodiments, the substantially planar interface includes one port and one slot adjacent to the port. In certain embodiments, the substantially planar interface includes a plurality of ports and a plurality of slots, each slot being adjacent to each port.
In certain embodiments, the apparatus further comprises an aseptic barrier removal system, the aseptic barrier removal system configured to operably engage a portion of the removable aseptic barrier and to remove the removable aseptic barrier from the at least one port, in use.
Thus, in certain embodiments, an aseptic barrier removal system is provided. The aseptic barrier removal system may include a portion configured to couple to, or engage with, a portion of the removable aseptic barrier, such as the fastener portion. In particular examples, the aseptic barrier removal system includes a protruding lug engageable with an aperture of a fastener portion of the removable aseptic barrier. In such examples, the protruding lug may be moveable between a first configuration, in which the protruding lug engages the fastener portion, and a second configuration, in which the aseptic skin is removed from the port of the substantially planar interface.
This provides the advantage that aseptic barriers can be removed in an automated manner. Thus, sterility of the apparatus is ensured during use.
In certain embodiments, the substantially planar interface comprises a coupling element configured to operably couple to a corresponding coupling element of a container.
Thus, in certain embodiments, the substantially planar interface includes one or more elements arranged to couple to a corresponding element of a container.
In particular embodiments, the coupling element comprises a screw thread, arranged to couple to a screw thread of a container, a clip portion, arranged to couple to a corresponding clip portion of a container, or the like.
In particular embodiments, the coupling element of the substantially planar interface and the coupling element of the container cooperate to provide an aseptic, a fluid-tight and/or a hermetic engagement between the substantially planar interface and the container, when in use.
In certain embodiments, the substantially planar interface comprises one or more drive elements arranged to cooperate with a drive mechanism.
Thus, in certain embodiments, the substantially planar interface includes one or more features arranged to be driven by a drive mechanism, for example, a drive mechanism of an enclosure.
This provides the advantage that the drive mechanism may control the location of the substantially planar interface, with respect to the component retaining element, thereby providing an automated, or semi-automated, apparatus.
In certain embodiments, the apparatus, or an enclosure housing the apparatus, comprises a drive mechanism. For example, a drive mechanism to drive the substantially planar interface.
In certain embodiments, the drive mechanism comprises a drive wheel arranged to mesh with a plurality of grooves formed on a circumferential rim of the substantially planar interface.
In certain embodiments, a controller is provided to control the drive mechanism. The controller may include a user interface to receive user input. For example, the user may provide user input to the user interface in relation to the positioning of the substantially planar interface, such as the positioning of one or more ports with respect to the component retaining element. In some examples, the controller is arranged to control the drive mechanism based upon a user input.
In certain embodiments, the component retaining element comprises an actuator configured to actuate, when in use, at least a portion of a component retained by the component retaining element.
Thus, in certain embodiments, the component retaining element comprises an actuator, or actuating or actuation system, arranged to actuate a portion of a component when in use.
In certain embodiments, the actuator is configured to actuate, when in use, a connector portion of a component. Additionally, or alternatively, the actuator is configured to actuate, when in use, a receptacle of a component so as to cause dispensation of a fluid therefrom. Additionally, or alternatively, the actuator is configured to actuate, when in use, a receptacle of a component so as to cause removal of a fluid from a container associated with the substantially planar interface and into the receptacle.
Thus, the actuator may be provided as one or more of a connector actuator, a fluid dispensation actuator, or a fluid removal actuator.
In certain embodiments, a controller is provided to control the actuator. The controller may include a user interface to receive user input. For example, the user may provide user input to the user interface in relation to the timing of the actuation of the component. In some examples, the controller is arranged to control the actuator based upon a user input.
In certain embodiments, the apparatus further comprises a container fluidly coupled to the at least one port of the substantially planar interface.
Thus, in certain embodiments, the apparatus further includes a container fluidly connected to the or each port of the substantially planar interface. Thus, a fluid communication pathway may be provided between the or each port of the substantially planar interface and a volume of the container. Particularly, a hermetically sealed fluid communication pathway, and/or an aseptically sealed fluid communication pathway, may be provided.
In certain embodiments, the container comprises a flexible or compressible side wall. In such examples, the side wall may be flexible such that the container, particularly the base with respect to the top, is compressible along a longitudinal axis, parallel to the side wall. For this reason, in particular examples, the side wall may comprise a plurality of convolutes thereby forming a bellows side wall. The container, in embodiments, comprises any suitable material, such as gas-permeable material or substantially gas-impermeable material, for example, low density polyethylene, high density polyethylene, silicone, a thermoplastic elastomer, or the like.
In certain embodiments, the apparatus further comprises an expandable receptacle operably coupled to the substantially planar interface and configured to fluidly communicate with the receptacle through the substantially planar interface.
Thus, in certain embodiment, the apparatus further includes a receptacle that is expandable, or the like, coupled to the substantially planar interface. The expandable receptacle may be provided in fluidly communication with a container through, for example, a fluid passageway through the substantially planar interface. In some examples, the fluid passageway may be provided as an aperture within the substantially planar interface, or as a port within the substantially planar interface.
This provides a breathing mechanism for the apparatus, thus allowing the pressure within a received container to remain substantially the same throughout use, for example, throughout agitation, mixing or the like.
In certain embodiments, the fluid passageway through the substantially planar interface comprises a tortuous fluid passageway. That is, in certain embodiments, the fluid passageway comprises a baffle, a wall, a ledge, a flange or the like interrupting at least a portion of the fluid passageway. The tortuous fluid passageway may be non-linear.
This provides the advantage that gases, such as air, can pass easily through the passageway, while liquids or suspensions, such as media containing biological material, are substantially prevented from passing through the passageway.
In certain embodiments, the substantially planar interface comprises a central hub comprising the fluid passageway. That is, the fluid passageway may extend through the central hub of the substantially planar interface, from a lower surface thereof to an upper surface thereof
In certain embodiments, the central hub may comprise an inner circular wall surrounded by, or concentrically arranged with respect to, an outer circular wall. The fluid passageway may be formed between the inner circular wall and the outer circular wall. There may be a flange provided extending radially outwardly from the inner circular wall toward the outer circular wall. There may be a ledge provided extending radially inwardly from the outer circular wall, for example, a base thereof, toward the inner circular wall. The flange and/or the ledge may define the tortuous fluid passageway.
In certain embodiments, the flange may form an angle with respect to the horizontal. In particular embodiments, the flange may be angled toward the lower surface of the substantially planar interface. In more particular embodiments, the flange may be angled toward a ledge extending radially inwardly from a base of the outer circular wall.
This provides the advantage that liquid, such as media containing biological material, or condensate is provided back into the container, during use, thereby minimizing liquid losses from the container.
In certain embodiments, there is provided a plurality of radially extending ribs, each rib extending between, and connected to, the outer circular wall and the flange. Each rib may be connected to the ledge of the outer circular wall, where provided. In this way, a plurality of fluid passageways, such as tortuous fluid passageways, are provided.
In certain embodiments, the expandable receptacle comprises a flexible bag.
In certain embodiments, the expandable receptacle comprises a receptacle comprising a flexible, or an expandable, side wall. In particular embodiments, the receptacle may include a base wall, a top wall and an expandable side wall therebetween. The expandable side wall may comprise a plurality of convolutes, thereby forming a bellows side wall.
In certain embodiments, the apparatus further comprises a component for handing biological material retained by the component retaining element.
In certain embodiments, the component comprises a receptacle.
In certain embodiments, the component comprises a connector.
In certain embodiments, the component comprises a connected fluidly coupled to a receptacle.
In certain embodiments, the apparatus further comprises an enclosure for housing the component retaining element and the substantially planar interface therein.
In specific embodiments, the enclosure comprises a slidable drawer configured to operably receive the substantially planar interface. For example, the slidable drawer may include a locating plate arranged to operably receive the substantially planar interface. The slidable drawer may be moveable 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.
In specific embodiments, the enclosure includes actuators, drive mechanisms, homing sensors, locating sensors and the like in accordance with the embodiments described herein. Generally, in use, any one or more of the features of the assembly, specifically of the component retaining element and/or the substantially planar interface, may be housed within the enclosure.
In specific embodiments, the enclosure is provided as an incubator unit. The incubator unit may include a temperature controller and/or a gaseous supply controller, such as an oxygen and/or carbon dioxide controller for controlling the supply thereof
In accordance with another aspect of the present disclosure, there is provided method of introducing material into, or removing material from, a component of an assembly for handling biological material, comprising:
In certain embodiments, the assembly further comprises a container fluidly coupled to the at least one port, and the step of introducing material into, or removing material from, the component comprises:
In accordance with yet another aspect of the present disclosure, 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 includes a container, an expandable receptacle, and/or a component as described herein.
In accordance with yet another aspect of the present disclosure, there is provided a system for handling biological material, comprising an enclosure and an assembly as described herein.
In accordance with yet another aspect of the present disclosure, there is provided an assembly for handling biological material, comprising:
This provides the advantage that biological material may be handled in a “just-in-time” process. That is, transfer of material between volumes is provided for at the time at which transfer is required, rather than having several pre-connected components. This ensures that biological material can be handled efficiently, aseptically and in an automated, or semi-automated, manner.
In some embodiments, the first biological handling element comprises a substantially planar interface as described herein.
In some embodiments, the first biological handling element comprises a first retaining element retaining a first container having a first volume and a first port.
In particular embodiments, the substantially planar interface includes at least one port therein fluidly coupled to a container, such as a bioreactor, the container including the first volume. The substantially planar interface may include a plurality of ports. Each port of the plurality of ports may be fluidly coupled to the container. The container may comprise a top section, a base section, and a flexible or compressible wall element between the top section and the base section. The wall element may comprise a plurality of flutes or convolutes, or a bellows wall element.
In some embodiments, the second biological handling element comprises a component retaining element as described herein. The component retaining element as described herein may retain a container having the second volume and the second port.
In some embodiments, the second biological handling element comprises a second retaining element retaining a second container having a second volume and a second port.
In particular embodiments, the component retaining element is configured to retain, or retains, a component. The component may comprise a container, having the second volume, and comprising the second port. The container may comprise a top section, a base section, and a flexible or compressible wall element between the top section and the base section. The wall element may comprise a plurality of flutes, or a bellows wall element. The container may be a bag, a flexible bag, or a container comprising a plunger.
The first port and/or the second port may comprise an open-ended tube, a closed-ended tube, or a tube having a removable aseptic membrane disposed over an end thereof. The tube may be a flexible tube. Alternatively, or in combination, the first port and/or the second port may comprise a hermetic seal, a septum seal, a Luer lock port or the like.
The aseptic connecting element may be unitary with the aseptic disconnecting element. That is, there may be provided a unitary aseptic connecting and disconnecting element. The unitary aseptic connecting and disconnecting element may comprise a connector, such as a sterile or aseptic connector as described herein. In particular, the connector may comprise a needle. The needle may be actuatable to engage or pierce the first port and the second port, such as a first septum seal and a second septum seal, during use.
The aseptic connecting element may be a separate component with respect to the aseptic disconnecting element.
The aseptic connecting element may comprise an aseptic welding element. In particular, the aseptic connecting element may comprise an aseptic tube welder, configured and/or arranged to aseptically weld a first tube, such as the first port, to a second tube, such as the second port. The aseptic connecting element may comprise a robotic arm terminating in an aseptic welding element. The aseptic welding element may be configured to apply heat, and optionally pressure, to the respective ports so as to heat weld the same. The aseptic welding element may also be configured to apply heat so that the closed-end of a tube, or the aseptic membrane covering the end of a tube, is melted thereby enabling a fluid passageway through the respective tube.
The aseptic disconnecting element may comprise an aseptic sealing element. In particular, the aseptic disconnecting element may comprise an aseptic tube sealer, configured and/or arranged to aseptically seal a first portion of a tube, such as the first tube or the first port, with respect to a second port of a tube, such as the second tube or the second port. The aseptic disconnecting element may comprise a robotic arm terminating in an aseptic sealing element. The aseptic sealing element may be configured to apply heat, and optionally pressure, to a portion of the connected ports so as to heat seal the same, thereby providing a first portion of the connected ports heat sealed from a second portion of the connected ports. The aseptic sealing element may be further configured to cut, or otherwise separate, the sealed region between the first portion and the second portion of the connected ports, thereby allowing release of the respective components.
The apparatus may comprise a component retaining element as described herein. The component retaining element may be configured to retain the first biological handling element and/or the second biological handling element.
The apparatus may comprise one or more robotic arms. The one or more robotic arms may be arranged to move the first biological handling element and/or the second biological handling element to bring the first port and the second port into registration with one another. The one or more robotic arms may comprise a retaining portion arranged to retain the first biological handling element and/or the second biological handling element. The one or more robotic arms may comprise an actuator portion arranged to actuate a portion of the first biological handling element and/or the second biological handling element to cause dispensation of biological material from the first volume and/or the second volume. The one or more robotic arms, the retaining portion and/or the actuator portion may be controlled by a controller. The controller may comprise a user interface. The controller may be arranged to control the one or more robotic arms, the retaining portion and/or the actuator portion in response to user input to the user interface.
The apparatus may be an automated apparatus. That is, the apparatus does not require manual or user intervention. The apparatus may be a semi-automated apparatus. That is, the apparatus may require minimal manual or user intervention, such as the loading of biological handling elements into the apparatus.
The apparatus may comprise an incubator or a housing enclosing the respective components of the apparatus.
In accordance with yet another aspect of the present disclosure, there is provided a method of handling biological material, comprising:
This provides the advantage that biological material may be handled in a “just-in-time” process. That is, transfer of material between volumes is provided for at the time at which transfer is required, rather than having several pre-connected components. This ensures that biological material can be handled efficiently, aseptically and in an automated, or semi-automated, manner.
In certain embodiments, the step of aseptically fluidly connecting the first port and the second port comprises aseptically welding the first port to the second port. In particular embodiments, the step of aseptically welding may be carried out by an aseptic tube welder.
In certain embodiments, the step of aseptically fluidly disconnecting the first port and the second port comprises aseptically sealing the connected first port the second port to provide an aseptically sealed first port and an aseptically sealed second port. In particular embodiments, the step of aseptically sealing may be carried out by an aseptic tube sealer.
It will be appreciated by those skilled in the art that the method may include one or more components of the apparatus as described above or elsewhere herein, such as the substantially planar interface, the component retaining element, the aseptic tube welder, the aseptic tube sealer, or the like.
Example embodiments of the disclosure are now described, by way of example only, hereinafter with reference to the accompanying drawings, in which:
The described example embodiments relate to an assembly for handling biological material. In particular, some embodiments relate to an assembly that is aseptic, or sterile. It is noted that the terms “aseptic” and “sterile” may be used interchangeably throughout the present disclosure. References to fluids in the detailed description are not intended to limit the scope of protection to such materials. As will be recognized by a person skilled in the art, fluids as described herein are merely an example of a suitable material for use with the assembly as described. Equally, reference may be made to a container, receptacle, or the like, however, such references are not intended to limit the scope of protection to such containers or receptacles. As will be recognized by a person skilled in the art, containers, receptacles or the like are described herein as mere examples.
Certain terminology is used in the following description for convenience only and is not limiting. The words ‘upper’ and ‘lower’ designate directions in the drawings to which reference is made and are with respect to the described component when assembled and mounted. The words ‘inner,’ ‘inwardly’ ‘outer,’ and ‘outwardly’ refer to directions toward and away from, respectively, a designated centerline or a geometric center of an element being described (e.g., a central axis), the particular meaning being readily apparent from the context of the description. Further, the terms ‘proximal’ (i.e., nearer to) and ‘distal’ (i.e., away from) designate positions relative to an axis or a point of attachment.
Further, as used herein, the terms ‘connected,’ ‘affixed,’ ‘coupled’ and the like are intended to include direct connections between two members without any other members interposed therebetween, as well as, indirect connections between members in which one or more other members are interposed therebetween. The terminology includes the words specifically mentioned above, derivatives thereof, and words of similar import.
Further, unless otherwise specified, the use of ordinal adjectives, such as, ‘first,’ ‘second,’ ‘third,’ etc., merely indicate that different instances of like objects are being referred to and are not intended to imply that the objects so described must be in a given sequence, either temporally, spatially, in ranking or in any other manner. Like reference numerals are used to depict like features throughout.
As shown in
Referring further to
As shown in this example, each individual port 150 has an aseptic barrier 152 disposed thereover. The aseptic barrier 152 is generally removable attached to each port 150 at one surface thereof. The aseptic barrier 152 ensures sterility of each port 150 prior to use, and is generally removed prior to making a connection to each port 150. The aseptic barrier 152 generally assumes the form of an aseptic skin, composed from a paper or a polymer material, in the present example. Each aseptic barrier 152 is arranged to be removed by a portion, such as a barrier removal system, of the enclosure 12 (see enclosure of
The planar interface 116 of the present example further includes a central hub 154, upstanding from an upper surface of the planar interface 116, and including a plurality of coupling elements 156, formed as clips in the present embodiment, which are arranged to receive and couple to an expandable receptacle, as described in relation to
Further, the container 118 in the present example, formed as a bioreactor having an internal chamber, a base wall and a compressible side wall, has a maximum volume of 1.5 L. Generally, the base of the container 118, i.e., the cell growing area, may be 150 sq cm. Additionally, in some embodiments not shown, the container 118 may accommodate a 0.2 micron filter, formed as part of the base or the side walls of the container 118 or, alternatively, formed as part of the planar interface 116. The filter may provide gaseous exchange between the surrounding environment, such as the enclosure, and the internal chamber of the container 118. The container 118 may generally be manufactured using a blow molding method, such as extrusion or injection blow molding, which provides a simplified manufacture of a container 118, having a single piece container, i.e., no joints and so no leak paths, a flatter base, and also provides less plastic for entering the clinical waste stream. The container 118 comprises any suitable material, such as low density polyethylene (LDPE), high density polyethylene (HDPE), a thermoplastic elastomer (TPE) or silicon.
The planar interface 216a includes a central hub 254a having an inner circular wall 254b and an outer, concentrically arranged, circular wall 254c. The outer circular wall 254c is arrange to allow the coupling of an expandable receptacle 166, as shown in
The inner circular wall 254b includes a radially extending flange 255 extending from the inner circular wall 254b radially outwardly toward the outer circular wall 254c. The flange 255 is illustrated as being C-shaped, although the flange 255 may extend around the entire circumference of the inner circular wall 254b. In this example, the central hub 254a is further provided with a dividing wall 257 that extends from, and connects, a portion of the outer circular wall 254c to a portion of the inner circular wall 254b, for example, the portion of the inner and outer circular walls 254b, 254c, which does not include the C-shaped flange 255. As such, the dividing wall 257 may connect opposing ends of the C-shaped flange 255.
The outer circular wall 254c includes a ledge 259 extending from a base 259a thereof radially inwardly toward the inner circular wall 254b. Generally, the ledge 259 and the flange 255 define a fluid passageway 168 therebetween, particularly a fluid passageway 168 between the lower surface of the planar interface 216a, to which a container 118 is attached, and the upper surface of the planar interface 216a, particularly the central hub 254a, to which an expandable receptacle 166 is attached, as illustrated best in
There is further provided a series of radially extending ribs 261, connecting the flange 255 to the inner surface of the outer circular wall 254c, each rib 261 being spaced apart from one another. Each adjacent pair of ribs 261 defines an individual fluid passageway 168 therebetween. Furthermore, as illustrated best in
Furthermore, the planar interface 216a includes a number of ports 150 (see
With particular reference to
During use, the container 118 and/or the planar interface 216a may be moved so that the hollow tubular member 150b extends into a liquid held within the container 118 to enable sampling of the same. Additionally, due to the resilient nature of the hollow tubular member 150b, the same may be arranged to contact the base of the container 118, without damaging the same. In particular, the hollow tubular member 150b, being of resilient material, is arranged to bend into, or toward, a corner of the container 118, particularly a corner adjoining the base of the container 118 to a side wall of the container 118. As such, samples may be taken from the container 118, even at low volumes, without risking damage to the container 118. More particularly, in this specific example, a needle of a connector, as discussed below, is inserted through the port 150 so that the throughbore thereof is in fluid communication with the throughbore of the hollow tubular member 150b. A component coupled to the other end of the needle of the connector may then be actuated so as to draw fluid from the container 118, through the hollow tubular member 150b, through the needle of the connector and into or toward the component. As such, a sample may be taken from the container 118.
Furthermore, as illustrated in
Furthermore, as shown in
Generally, the component retaining element 114 and/or the planar interface 216 are moveable so as to align, or bring into register, a port of the component 120 with one of the ports of the planar interface 216. In this particular example, as illustrated by arrow A, the planar interface 216 is rotatable about a central longitudinal axis L of the planar interface 216. Additionally, the component retaining element 114 is substantially immovable laterally, i.e., within the plane formed by the component retaining element 114, but longitudinally moveable along a longitudinal axis L1 of the component retaining element 114, specifically the component retaining head 114b, such as in the direction indicated by arrow B. Thus, during use and as described further below, the planar interface 216 is caused to rotate, about central longitudinal axis L, such that a port of the component 120 held by the component retaining head 114b of the component retaining element 114 aligns with a port of the planar interface 216, and then the component retaining head 114b, or alternatively the entirety of the component retaining element 114, is caused to move along the axis L1, in direction B, to bring the port of the component 120 into engagement with the port of the planar interface 216, particularly the aseptic barriers 152 in the first instance. Thereafter, the component retaining head 114b, or the component retaining element 114 in its entirety, is caused to move along the axis L1, in an opposing direction to direction B, to remove the engagement between the respective ports. Thereafter, the planar interface 216 is caused to rotate, about central longitudinal axis L, to align the next port of the planar interface 216 with a port of the component 120 in a sequential manner. The process may then be repeated any number of times. The detailed operation of the assembly 100 is described below.
Generally, the assembly 100 described provides an assembly that is more suitable to automation, and requires less manual intervention or operation. As will be appreciated by the person skilled in the art, this is an example of the disclosure and so, in other examples, the arm may be rotatable and moveable so as to align the respective ports, and the planar interface may be substantially immoveable. Further examples may also include both a moveable arm and a moveable planar interface.
The drive mechanism 184, particularly the drive wheel 186, may be driven by a controller (not shown) of the enclosure 112, which may be coupled to a number of sensors (not shown) for sensing the positioning of the planar interface 216 within the enclosure 112. For this reason, the planar interface 216 may include a number of magnets and the enclosure 112 may include a Hall effect sensor, or vice versa. The controller may control the positioning of the planar interface 216, particularly with respect to the component retaining element during use, so as to position the respective ports of the planar interface and the component during use. Thus, a controlled or automated homing and/or rotation of the planar interface 216 is provided within the enclosure 112 without manual intervention or operation. In this way, the planar interface 216 may be loaded into the enclosure 112 without the user having to correctly align the same, i.e., the planar interface 216 may be placed into the enclosure without aligning to a port of the component held by the component retaining element. The planar interface 216 is then located and rotated by the controller, in accordance with a user input such as the selection of a particular port of the planar interface 216 on a user interface of the enclosure 112, controlling the drive wheel 186 so as to align the respective ports of the planar interface 216 and the component. The drive wheel 186 may, thereafter, control subsequent movement of the planar interface 216 so as to align another port of the planar interface 216 with a port of the component in a sequential manner as described below, thereby providing an automated system.
The enclosure 212 similarly includes a drawer 280, as described in relation to
Referring further to
With further reference to
Referring to
The housing includes a threaded portion 126 at its distal end 125a for connecting to a corresponding threaded portion of a receptacle, such as a threaded screw cap 127 of the receptacle 124 illustrated in
In this embodiment, the connector 122 includes a first port, formed as a first septum seal 128a, disposed at the distal end 125a of the housing, and a second port, formed as a second septum seal 128b, disposed at the proximal end 125b of the housing. The housing further includes a hollow needle 129 that is mounted, biasedly mounted in this particular example, within the housing. The hollow needle 129 is generally coaxially aligned with the longitudinal axis of the connector 122. The hollow needle 129 includes a first end 130a, facing the first septum seal 128a, and a second end 130b, facing the second septum seal 128b. The first end 130a is configured to be able to pierce through the first septum seal 128a, in use, and the second end 130b is configured to be able to pierce through the second septum seal 128b, in use. The first septum seal 128a, the second septum seal 128b, or both the first and second septum seals 128a, 128b, 128b may optionally be provided with an aseptic barrier 131 disposed thereover. The aseptic barrier 131 is generally configured to mate with a corresponding aseptic barrier 152 (see
The hollow needle 129 is mounted within the housing through a collar 132 that is spring-biased in this particular example by a first helical spring 133a and a second helical spring 133b. In other embodiments, the hollow needle 129 may be mounted in another suitable manner, for example, the hollow needle 129 may be statically mounted, i.e., such that it does not move, and the housing may be moveable about the hollow needle 129. Further alternatively, the hollow needle 129 may be axially moveable, via the collar 132, and the upper housing portion 123a may also be axially movable while the lower housing portion 123b remains static, i.e., such that it does not move. For this reason, the upper housing portion 123a may be provided with actuatable lugs, and the collar 132 may be provided with actuatable lugs, each set of actuatable lugs being actuatable by an actuation mechanism arranged to move the hollow needle 129 and upper housing portion 123a to cause piercing of respective septum seals 128a, 128b. In the present example, the order of piercing of the septum seals 128a, 128b is controlled by virtue of the respective spring forces of springs 133a, 133b. In particular, the first spring 133a provides a first biasing force to the hollow needle 129, via the collar 132, in a direction toward the proximal end 125b of the housing, and the second spring 133b provides a second biasing force to the hollow needle 129, via the collar 132, in a direction toward the distal end 125a of the housing. The first biasing force may be greater than, equal to, or less than the second biasing force, so as to control sequential piercing of the septum seals 128a, 128b. In this example, the first biasing force is greater than the second biasing force, by virtue of a larger wire diameter of first spring 133a compared to second spring 133b.
In use, as would be recognized by a person skilled in the art, the hollow needle 129 is caused to engage, and pierce through, respective septum seals 128a, 128b to fluidly couple a receptacle 124 (see
The use of the assembly, and its components thereof, as well as the exemplary enclosures shall now be described by way of one non-limiting example and with reference to
Referring firstly to
Referring to
Referring to
Moreover, in this particular example, an aseptic barrier 131 of the connector 122 (see also
Referring to
In the present example, the aseptic barriers 131, 650 of
Referring to
As shown in
Referring to
As illustrated in
As illustrated in
The assembly 1000 will now be described in use with respect to
Generally, it will be appreciated by persons skilled in the art that the above embodiments have been described by way of an example only and not in any limitative sense, and that various alternations and modifications are possible without departing from the scope of the disclosure as defined by the accompanying claims. Various modifications to the detailed designs as described above are possible, for example, variations may exist in shape, size, arrangement, assembly, sequence or the like. For example, any one of the enclosures, planar interfaces, component retaining elements or the like may be used in any suitable combination. Moreover, while the present disclosure has been described in relation to an automated process, it will be appreciated by persons skilled in the art that a user may manually, or semi-automatedly, undertake one or more of the above process steps.
| Number | Date | Country | Kind |
|---|---|---|---|
| 2003403.9 | Mar 2020 | GB | national |
| 2019859.4 | Dec 2020 | GB | national |
This application is a national phase entry under 35 U.S.C. § 371 of International Patent Application PCT/GB2021/050581, entitled “AN ASSEMBLY,” filed Mar. 9, 2021, designating the United States of America and published as International Patent Publication WO 2021/181081 A1 on Sep. 16, 2021, which claims the benefit under Article 8 of the Patent Cooperation Treaty to Great Britain Patent Application Serial Nos. 2003403.9, filed Mar. 9, 2020, and 2019859.4, filed Dec. 16, 2020.
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/GB2021/050581 | 3/9/2021 | WO |
