An interface for coupling to a cell processing container

Abstract

There is provided an interface for coupling to a cell processing container having an internal volume for holding a cell suspension, the interface enabling sampling of material within he cell processing container. In particular, the interface includes a port configured to allow egress of a sample, and a conduit extending from said port so as to be located within the internal volume of the cell processing container and able to take a sample therefrom during use. The conduit has an internal bore and / or an inlet configured to minimise or mitigate agglomeration of cells during the sampling process.

Description

AN INTERFACE FOR COUPLING TO A CELL PROCESSING CONTAINER

[0001] The invention relates to an interface, a kit of parts, a conduit, a cell processing container and a method. In particular, but not exclusively, the invention relates to a conduit enabling removal of cellular material whilst minimising, or mitigating, agglomeration of cellular material within such conduits.BACKGROUND

[0002] Cell and gene therapy manufacturing processes are often complex and include manual or semi-automated 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 functions. These various functions may be, for example, cell collection, cell isolation, cell 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, for example, 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.

[0003] 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. These manufacturing procedures, may include, for example, 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 a patient, or freezing.

[0004] The culture or processing of cells typically requires the step of sampling of the culture for further analysis, for example, to assess whether the cells being cultured or processed remain viable and / or the number thereof. An operator may also wish to take samples to assess the efficiency of certain unit operations, such as genetic modification (e.g. transduction efficiency). Sampling devices are generally known, and include pipettes and tubing.

[0005] However, cells are particularly sensitive to shear stress and other forces imparted during culture and processing. Typically, cells are “agitated” by imparting rocking, swirling or other forces onto a container in which they are housed within a cell processing medium.Notably, it has been found that currently known pipettes and tubing (collective referred herein as “tubing”) impart undesirable forces onto the cells during agitation, resulting in agglomeration of cells, so-called “cell clumping”. In such cases, cells agglomerate within such tubing due to shear forces imparted to the cells by virtue of the aperture, or inlet, diameter and / or the diameter of the internal bore of the tubing during ingress to, and egress from, the tubing. This agglomeration of cells in the tubing forms a ring-shaped agglomeration of cells on an inner wall of the internal bore of the tubing. The agglomerated cells may accumulate further within the tubing following further ingress into the tubing and / or may be flushed back out into the bulk material where the detached ring-shaped agglomeration of cells is visible to the naked eye as an elongate agglomeration of cells.

[0006] Agglomeration of cells is highly undesirable within the cell culture process, as it inhibits cell growth, causes cells to die and release debris into the remaining culture, and may also provide an unrepresentative sample during the sampling operation.

[0007] Therefore, it is an object of the present invention to mitigate, or at least reduce, undesirable agglomeration of cells during cell culturing and / or processing, including during sampling.BRIEF SUMMARY OF THE DISCLOSURE

[0008] In accordance with one aspect of the present disclosure, there is provided an interface for coupling to a cell processing container having an internal volume for holding a cell suspension. The interface comprises a port configured to allow egress of at least a portion of the cell suspension from the cell processing container. The interface further comprises a conduit extending from the port so as to be located within the internal volume of the cell processing container during use. The conduit extends between an inlet and an outlet and comprises an internal bore. The inlet is configured to allow ingress of the portion of the cell suspension, and the outlet is in fluid communication with the port.

[0009] At least one of the internal bore and the inlet is configured to minimise or mitigate agglomeration of cells as the portion of the cell suspension ingresses into the conduit.

[0010] In examples, a diameter of the internal bore varies along the length of the conduit. For example, the diameter of the internal bore may reduce (e.g. taper or step inwardly) from the inlet of the conduit towards the outlet of the conduit, or increase (e.g. taper or step outwardly) from the inlet of the conduit towards the outlet of the conduit. The diameter of the internal bore may vary so as to provide a shape that is configured to minimise or mitigateagglomeration of cells as the portion of the cell suspension ingresses into the conduit. In examples, at least a portion of a surface of the internal bore is textured so as to minimise or mitigate agglomeration of cells as the portion of the cell suspension ingresses into the conduit. In examples, the inlet of the conduit is shaped or oriented to minimise or mitigate agglomeration of cells as the portion of the cell suspension ingresses into the conduit.

[0011] In this way, the size, shape, and / or texture of the inlet and / or the internal bore of the conduit can be selected so as to minimise shear force on the cells in the portion of the cell suspension that ingresses into the conduit so as to minimise or mitigate agglomeration of cells.

[0012] Herein, the conduit may be referred to as a dip tube or a sampling tube. Herein, the interface may be referred to as an interface plate. Herein, a cell processing container may be referred to as a bioreactor. Herein, agglomeration of cells may be referred to as clumping of cells.

[0013] In examples, the internal bore is sized and / or shaped to minimise or mitigate agglomeration of cells as the portion of the cell suspension ingresses the conduit. That is, the internal bore may have a size (such as a diameter and / or length) and / or a shape (such as a taper) that minimises or mitigates agglomeration of cells as the portion of the cell suspension ingresses the conduit.

[0014] In some examples, the internal bore is sized and / or shaped to minimise agglomeration of cells as the portion of the cell suspension ingresses the conduit. Herein, the minimisation of the agglomeration of cells means that the agglomeration of cells is below a predetermined threshold. In some examples, the predetermined threshold may be that there is no agglomeration of cells on the internal bore that is visible to the naked eye. In other examples, the predetermined threshold may be that there is no elongate agglomeration of cells visible to the naked eye in a portion of the cell suspension that is extracted through the port. In other words, no agglomeration of cells that was formed as a ring-shape in the internal bore of the conduit is visible in a sample of the cell suspension. In other examples, the predetermined threshold may be that there is no elongate agglomeration of cells visible to the naked eye in the cell suspension in the cell processing container. In other words, no agglomeration of cells that was formed as a ring-shape in internal bore of the conduit will be visible in the harvested cell suspension. In some examples, the predetermined threshold may be that the agglomeration of cells visible to the naked eye in a portion of the cell suspension that is extracted through the port and / or in the cell suspension in the cell processingcontainer does not exceed the agglomeration of cells that would be present in a control where no conduit located within the internal volume of the cell processing container is present.

[0015] In examples, the internal bore has a diameter of approximately 2.0mm to approximately 8.0mm. In examples, the internal bore has a diameter of approximately 2.0mm to approximately 6.0mm. In examples, the internal bore has a diameter of approximately 2.5mm to approximately 5.5mm. In examples, the internal bore has a diameter of approximately 3mm to approximately 5mm. In examples, the internal bore has a diameter of approximately 3.5mm to approximately 4.5mm. In examples, the internal bore has a diameter of approximately 4mm to approximately 5mm.

[0016] In this way, the diameter of the internal bore can be selected to provide a conduit with a bore that is sufficiently large to reduce the shearing force on cells that ingress into the conduit, and avoid rubbing against the walls of the cell processing container, in particular the walls of a compressible cell processing container.

[0017] The internal bore may have a diameter of at least approximately 2.0mm, 2.25mm, 2.5mm, 2.75mm, 3.0mm, 3.25mm, 3.5mm, 3.75mm, 4.0mm, 4.25mm, 4.5mm, 4.75mm, 5.0mm, 5.25mm, 5.5mm, 6mm, 6.25mm, or 6.5mm. The internal bore may have a diameter of at least 2.5mm.

[0018] The internal bore may have a diameter of approximately 2.0mm, 2.25mm, 2.5mm, 2.75mm, 3.0mm, 3.25mm, 3.5mm, 3.75mm, 4.0mm, 4.25mm, 4.5mm, 4.75mm, 5.0mm, 5.25mm, 5.5mm, 6mm, 6.25mm, 6.5mm, 6.75mm, or 7.0mm.

[0019] The diameter of the internal bore may be substantially uniform between the inlet and the outlet. That is, the internal bore may be substantially straight (such as cylindrical) between the inlet and the outlet. In examples, a diameter of at least a portion of the internal bore (i.e. an internal diameter) is uniform. In other words, the diameter of the internal bore is constant along at least a portion of the length of the conduit. In one example, the diameter of a portion of the internal bore adjacent to the outlet of conduit is uniform. In another example, the diameter of the internal bore is uniform along the entire length of the internal bore. The diameter of the internal bore may be at least 2.5mm. The diameter of the internal bore be any of the diameters mentioned above.

[0020] In examples, the internal bore has a cross-section comprising a substantially circular, cruciform, oval, ortriangular shape. In such cases, the internal bore diameters mentioned above are measured at the widest points of such cross-sections.

[0021] In examples, at least a portion of a surface of the internal bore is textured. In examples, at least a portion of a surface of the internal bore proximate to the inlet of the conduit is textured. In examples, the surface of the internal bore is textured. Herein, textured refers to any texture (e.g. undulations), roughness or other means for interrupting the surface (e.g. projections and / or ribs).

[0022] In some examples, the internal bore comprises one or more undulations.

[0023] In some examples, the inlet and / or at least a portion of the internal bore comprises one or more projections. The one or more projections may be one or more ribs. The one or more projections may project inwardly towards a centre of the internal bore. The internal bore may comprise any number of projections such as one, two, three, four or five or more projections. The projections may extend along a length of the internal bore from the inlet towards the outlet.

[0024] In this way, the undulations and / or projections disrupt the circular cross-section of the surface of the internal bore. This disrupts cells from agglomerating (or clumping) in a ringshape in the internal bore, preventing accumulation of agglomerated cells in the conduit.

[0025] In some examples, the internal bore comprises at least a partially roughened surface. The partially roughened surface may be provided at the inlet, or may be provided along substantially the entire length of the internal bore.

[0026] In this way, the roughened surface of the internal bore reduces the wetting coefficient of the surface of the internal bore. This minimises the formation of a meniscus on the internal bore, reducing the shearing force on cells that ingress into the conduit, and minimising or mitigating agglomeration of cells.

[0027] In examples, at least a portion of the internal bore increases in diameter from the inlet towards the outlet. In other words, a diameter of the internal bore proximate to the inlet (i.e. an inlet diameter) may be less than a diameter of the internal bore proximate to the outlet (i.e. an outlet diameter).

[0028] In examples, at least a portion of the internal bore tapers in diameter between the inlet to the outlet. For example, at least a portion of the internal bore may taper radially outwardly from the inlet towards the outlet. In some examples, the diameter of the internalbore may vary linearly with a distance from the inlet. In other examples the diameter of the internal bore may vary non-linearly with the distance from the inlet. For example, a portion of the internal bore proximate to the inlet may be have a hemispherical or parabolic shape. In other words, a cross-section of at least a portion of the internal bore may have a hemispherical or parabolic shape.

[0029] In examples, the internal bore tapers in diameter between the inlet and the outlet along substantially the entire length of the conduit. In other examples, the majority (e.g. more than 50%, more than 60%, more than 70% or more than 80%) of the internal bore tapers outwardly between the inlet and the outlet. In other words, the internal bore tapers outwardly across the majority length of the conduit between the inlet and the outlet.

[0030] In examples, the internal bore comprises a first section and a second section. The first section may be proximal the outlet. The second section may be proximal the inlet. The first section may comprise a first taper angle and the second section may comprise a second taper angle. The first taper angle may be less than the second taper angle.

[0031] In examples, the internal bore may comprise a stepped profile. The diameter of the internal bore may increase at intervals along a length of the sample tube from the inlet towards the outlet. In other words, the internal bore may have at least a first portion proximate to the inlet having a first diameter, and a second portion proximate to the outlet having a second diameter, the first diameter being less than the second diameter.

[0032] In examples, at least a portion of the internal bore reduces in diameter from the inlet towards the outlet. For example, at least a portion of the internal bore may reduce in diameter from the inlet towards the outlet. In other words, a diameter of the internal bore proximate to the inlet (i.e. an inlet diameter) may be greater than a diameter of the internal bore proximate to the outlet (i.e. an outlet diameter).

[0033] In examples, at least a portion of the internal bore tapers in diameter between the inlet to the outlet. For example, at least a portion of the internal bore tapers radially inwardly from the inlet towards the outlet. In other words, in some examples, the internal bore tapers radially outwardly from the outlet to the inlet. Herein, this may be referred to as an “inverse taper”. In some examples, the diameter of the internal bore may vary linearly with a distance from the inlet. In other examples the diameter of the internal bore may vary non-linearly with the distance from the inlet. For example, a portion of the internal bore proximate to the inlet may be have a hemispherical or parabolic shape. In other words, a cross-section of at least a portion of the internal bore may have a hemispherical or parabolic shape.

[0034] In examples, the internal bore tapers in diameter between the inlet and the outlet along substantially the entire length of the conduit. In other examples, the majority (e.g. more than 50%, more than 60%, more than 70% or more than 80%) of the internal bore tapers inwardly between the inlet and the outlet. In other words, the internal bore tapers inwardly across the majority length of the conduit between the inlet and the outlet.

[0035] In examples, the internal bore comprises a first section and a second section. The first section may be proximal the outlet. The second section may be proximal the inlet. The first section may comprise a first taper angle and the second section may comprise a second taper angle. The first taper angle may be less than the second taper angle.

[0036] In examples, the internal bore may comprise a stepped profile. The diameter of the internal bore may decrease at intervals along a length of the sample tube from the inlet towards the outlet. In other words, the internal bore may have at least a first portion proximate to the inlet having a first diameter, and a second portion proximate to the outlet having a second diameter, the first diameter being greater than the second diameter.

[0037] In examples, the internal bore may comprise a combination of a radially inward taper and a radially outward taper.

[0038] In examples, the internal bore may have a maximum diameter (i.e. at its widest point) of at least approximately 2.25mm, 2.5mm, 2.75mm, 3.0mm, 3.25mm, 3.5mm, 3.75mm, 4.0mm, 4.25mm, 4.5mm, 4.75mm, 5.0mm, 5.25mm, 5.5mm, 6mm, 6.25mm, or 6.5mm. The internal bore may have a maximum diameter of approximately 2.0mm, 2.25mm, 2.5mm, 2.75mm, 3.0mm, 3.25mm, 3.5mm, 3.75mm, 4.0mm, 4.25mm, 4.5mm, 4.75mm, 5.0mm, 5.25mm, 5.5mm, 6mm, 6.25mm, 6.5mm, 6.75mm, or 7.0mm. In some examples, the maximum diameter may be at the inlet of the of the conduit. In other examples, the maximum diameter may be at the outlet of the conduit. In yet other examples, the maximum diameter may be between the inlet and the outlet of the conduit.

[0039] In examples, the internal bore may have a minimum diameter (i.e. at its narrowest point) of at least approximately 1 ,5mm, 1 ,75mm, 2.0mm, 2.25mm, 2.5mm, 2.75mm, 3.0mm, 3.25mm, 3.5mm, 3.75mm, 4.0mm, 4.5mm, 4.75mm, 5.0mm. The internal bore may have a minimum diameter of approximately 1 ,5mm, 1 ,75mm, 2.0mm, 2.25mm, 2.5mm, 2.75mm, 3.0mm, 3.25mm, 3.5mm, 3.75mm, 4.0mm, 4.5mm, 4.75mm, 5.0mm. In some examples, the minimum diameter may be at the outlet of the conduit. In yet other examples, the minimum diameter may be between the inlet and the outlet of the conduit.

[0040] In examples, a volume of the internal bore between the inlet and the outlet of the conduit is approximately 2mL or less. In some examples, the volume of the internal bore is approximately 1 ,5mL or less. In examples, the volume of the internal bore is approximately 1 mL or less. In some examples, the volume of the internal bore is approximately 0.5mL or less.

[0041] In examples, a terminal portion of the conduit adjacent to the inlet is bent with respect to an upper portion of the internal bore. In other words, a portion of the conduit adjacent to the inlet extends along a central axis that is angled with respect to a central axis of the remainder of the conduit. For example, a central axis of the internal bore may be substantially longitudinal (i.e. parallel to a direction of immersion in the cell suspension and / or perpendicular to plane of the interface plate) in the upper portion and substantially lateral (i.e. perpendicular to a direction of immersion in the cell suspension and / or substantially parallel to a plane of the interface plate) in the terminal portion.

[0042] In examples, the inlet is sized and / or shaped to minimise or mitigate agglomeration of cells as the portion of the cell suspension ingresses the conduit.

[0043] In examples, the inlet comprises a rounded edge or a chamfered edge.

[0044] In examples, the inlet comprises an outwardly flared portion. In some examples, the inlet comprises a radially outwardly flared portion. In some examples, the inlet comprises a trumpet-shape.

[0045] In examples, the inlet comprises a lead-in edge.

[0046] In examples, the lead-in edge has a rounded edge or a rounded shape. In other examples, the lead-in edge flares radially outwardly. In other examples, the lead-in edge is radially inwardly or outwardly angled. In other examples, the lead-in edge comprises a spout.

[0047] In examples, the inlet comprises a plug. The plug may comprise a flow restrictor configured to allow ingress of a portion of cell suspension through the plug and into the inlet. The plug may comprise apertures or slots to enable such functionality.

[0048] In examples, the inlet has a diameter of approximately 2.0mm to approximately 8.0mm. In examples, the inlet has a diameter of approximately 2.0mm to approximately 6.0mm. In examples, the inlet has a diameter of approximately 2.5mm to approximately 5.5mm. In examples, the inlet has a diameter of approximately 3mm to approximately 5.0mm. In examples, the inlet has a diameter of approximately 3.5mm to approximately5.0mm. In examples, the inlet has a diameter of approximately 3.5mm to approximately 4.5mm. In examples, the inlet has a diameter of approximately 4mm to approximately 5mm.

[0049] The inlet may have a diameter of at least approximately 2.0mm, 2.25mm, 2.5mm, 2.75mm, 3.0mm, 3.25mm, 3.5mm, 3.75mm 4.0mm, 4.25mm, 4.5mm, 4.75mm, 5.0mm, 5.25mm, 5.5mm, 6mm, 6.25mm, or 6.5mm. The inlet may have a diameter of at least 2.5mm..

[0050] The inlet may have a diameter of approximately 2.0mm, 2.25mm, 2.5mm, 2.75mm, 3.0mm, 3.25mm, 3.5mm, 3.75mm, 4.0mm, 4.25mm, 4.5mm, 4.75mm, 5.0mm, 5.25mm, 5.5mm, 6mm, 6.25mm, 6.5mm, 6.75mm, or 7.0mm.

[0051] In some examples, the thickness of a wall of the conduit is uniform along the length of the conduit. In other examples, the thickness of the wall may vary along the length of the conduit. In some examples the thickness of the wall may vary to provide the tapered shape of the internal bore. In other examples, the thickness of the wall may taper in an opposing direction to the taper of the internal bore. For example, the thickness of the wall may increase from the inlet towards the outlet while the diameter of the internal bore decreases from the inlet towards the outlet. In another example, the thickness of the wall may decrease from the inlet towards the outlet while the diameter of the internal bore increases from the inlet towards the outlet.

[0052] In some examples, a diameter of an outer surface of the conduit is constant between the inlet and the outlet. In other words, the outer surface of the conduit has a substantially cylindrical shape. In other examples, the outer surface of the conduit may be tapered to narrow from the inlet towards the outlet (e.g., the outer diameter of the conduit may be greater at the inlet than at the outlet). In other examples, the outer surface of the conduit may be tapered to widen from the inlet towards the outlet (e.g., the outer diameter of the sample tube may be less at the inlet than at the outlet).

[0053] In examples, the conduit is integrally formed with the interface.

[0054] In examples, the conduit comprises a coupling element configured to couple to a corresponding receiving element of the interface.

[0055] In examples, the coupling element comprises a clip and the corresponding receiving element comprises an aperture.

[0056] In examples, the coupling element comprises a gasket, such as a resiliently deformable gasket.

[0057] In examples, the port comprises a pierceable seal, such as a septum seal. The septum seal may be self-sealing and / or self-healing. The septum seal may comprise silicone or a thermoplastic elastomer. The septum seal may be configured to be pierced by a needle, for example, of a connector.

[0058] In examples, the conduit is integrally formed with the port. In specific examples, the conduit, the port and the interface are integrally formed.

[0059] In examples, the interface comprises a plurality of ports. In examples, substantially all of the ports are provided with a conduit. In examples, at least half of the ports are provided with a conduit. In examples, at least one of the ports is provided with a conduit.

[0060] In examples, there are a plurality of conduits. In this way, a user may aseptically sample on numerous occasions throughout a cell processing methodology.

[0061] In some examples, the plurality of conduits have differing lengths. In this way, the conduits are operable to sample material at different depths and / or volumes within the cell processing container.

[0062] In other examples, the plurality of conduits have substantially identical lengths.

[0063] In examples, the interface further comprises an auxiliary container fluidly connected to the conduit via the port. In some examples, the auxiliary container comprises a connector configured to provide a fluid connection through the port. The connector may be connectable, or connected to, the auxiliary container at a first end and connectable, or connected to, the port at a second end. The connector may be a needle-based connector configured to pierce the port and provide a fluid connection. For example, the connector may comprise a double- ended hollow needle disposed between two septum seals and including an actuating mechanism configured to cause piercing of the double-ended hollow needle through each septum seal, during use. The fluid connection may be a sterile, or aseptic, fluid connection. The auxiliary container may comprise a syringe. The auxiliary container may comprise a compressible (and / or expandable) container.

[0064] In examples, the interface further comprises a first set of conduits extending from a first portion of the plurality of ports, the first set of conduits having a first length, and a second set of conduits extending from a second portion of the plurality of ports, the second set of conduits having a second length, the first length being greater than the second length.

[0065] That is, a first set of conduits may have a different length to the second set of conduits. This enables sampling at various depths and / orvolumes within the cell processing container.

[0066] In examples, the interface further comprises a third set of conduits extending from a third portion of the plurality of ports, the third set of conduits having a third length, wherein the second length is greater than the third length.

[0067] That is, three sets of conduits of differing length may be provided. This enables sampling at various depths and / orvolumes within the cell processing container.

[0068] In accordance with another aspect, there is provided a kit of parts, comprising an interface for coupling to a cell processing container having an internal volume for holding a cell suspension, the interface comprising a port configured to allow egress of at least a portion of the cell suspension; and a conduit attachable to the interface such that the conduit extends from the port so as to be located within the internal volume of the cell processing container during use, the conduit comprising an internal bore extending between an inlet and an outlet, wherein the inlet is configured to allow ingress of the portion of the cell suspension, and wherein the outlet is configured to be in fluid communication with the port, wherein at least one of the internal bore and the inlet is configured to minimise or mitigate agglomeration of cells as the portion of the cell suspension ingresses the conduit.

[0069] The conduit or interface of the kit of parts may have any combination of features discussed in relation to the conduit or interface of any other aspect described herein.

[0070] In accordance with another aspect, there is provided a conduit as described herein for use with an interface, such as the interface as described herein.

[0071] The conduit may have any combination of features discussed in relation to the conduit of any other aspect described herein (e.g., of the interface or kit or parts).

[0072] In accordance with another aspect, there is provided a cell processing device comprising a cell processing container defining an internal volume for holding a cell suspension, and an interface as described herein. The interface is attached to the cell processing container such that the cell processing container is closed by the interface and the conduit is arranged in the internal volume of the cell processing container.

[0073] In examples, the cell processing container comprises a compressible cell processing container.

[0074] In examples, the cell processing container comprises at least one side wall extending between a top and a base. The top may be open-ended. The top may be coupled to the interface. The at least one side wall may comprise a bellows.

[0075] In examples, the cell processing container further comprises a baffle within the internal volume of the cell processing container to aid in the agitation of material within the cell processing container.

[0076] In accordance with another aspect, there is provided a method of manufacturing a conduit for delivering a cell suspension to a cell processing container.

[0077] In examples, the method may comprise a step of applying a surface treatment to at least a portion of an internal surface of the conduit to increase its surface roughness.

[0078] In examples, the method may comprise moulding the conduit.

[0079] In some examples the method involves: providing an interface for coupling to a cell processing container having an internal volume for holding a cell suspension, the interface comprising a port configured to allow egress of at least a portion of the cell suspension; and attaching the conduit to the interface such that the conduit extends from the port (e.g., so as to be located within the internal volume of the cell processing container during use), wherein an inlet of the conduit is configured to allow ingress of the portion of the cell suspension, and wherein an outlet of the conduit is configured to be in fluid communication with the port.

[0080] In some examples the conduit and the interface plate may be formed as a single integral piece. In some examples the conduit and the interface plate may be moulded as a single integral piece. In some examples, the method may comprise co-mouldingthe conduit with the interface.

[0081] In accordance with another aspect, there is provided a conduit and / or an interface manufactured according to the above method.

[0082] In accordance with another aspect, there is provided a method of extracting at least a portion of a cell suspension from a cell processing device, comprising providing a cell processing device as described herein; providing a cell suspension within the internal volume of the cell processing container; at least partially submerging the conduit in the cell suspension; and generating a pressure differential to move at least a portion of the cell suspension through the conduit and the port to egress the cell processing container.

[0083] In examples, generating a pressure differential to move at least a portion of the cell suspension through the conduit and the port to egress the cell processing container comprises providing positive pressure within the cell processing container.

[0084] In examples, the cell processing container is a compressible cell processing container, and providing positive pressure within the cell processing container comprises compressing the compressible cell processing container.

[0085] In examples, generating a pressure differential to move at least a portion of the cell suspension through the conduit and the port to egress the cell processing container comprises applying negative pressure to the port to draw the cell suspension from the cell processing container.

[0086] In examples, applying negative pressure to the port comprises retracting a syringe or expanding a collapsible container, the syringe or collapsible container being coupled to the port.

[0087] Herein, the conduit may be composed of any appropriate material. The conduit may comprise a biological-compatible material. The conduit may comprise a cell-compatible material. The conduit may comprise silicone or a thermoplastic elastomer.BRIEF DESCRIPTION OF THE DRAWINGS

[0088] Embodiments of the invention are further described hereinafter with reference to the accompanying drawings, in which:FIG. 1 illustrates a cross-section side view of a bioreactor;FIG. 2 illustrates (a) a cross-sectional side view and (b) a bottom view of a sampling tube having a small inlet diameter;FIG. 3 illustrates (a) a cross-sectional side view and (b) a bottom view of a sampling tube having a large inlet diameter;FIG. 4 illustrates (a) a cross-sectional side view and (b) a bottom view of a sampling tube having an inverted tapered bore;FIG. 5 illustrates (a) a cross-sectional side view and (b) a bottom view of a sampling tube having a cruciform-shaped bore;FIG. 6 illustrates (a) a cross-sectional side view and (b) a bottom view of a sampling tube having slots within its wall;FIG. 7 illustrates (a) a cross-sectional side view and (b) a bottom view of a sampling tube having a spout;FIG. 8 illustrates (a) a partial cross-sectional side view and (b) an enlarged crosssection view of a sampling tube having a rounded edge at its inlet;FIG. 9 illustrates a cross-sectional side view of a sampling tube having a substantially uniform bore diameter;FIG. 10 illustrates a cross-sectional side view of a sampling tube having an offset inverted tapered bore;FIG. 11a illustrates a cross-sectional side view of a sampling tube having internal projections; andFIG. 11 b illustrates a cross-sectional view of the sampling tube of FIG 11 a.DETAILED DESCRIPTION

[0089] Throughout the description and claims of this specification, the words “comprise” and “contain” and variations of them mean “including but not limited to”, and they are not intended to (and do not) exclude other components, integers or steps. Throughout the description and claims of this specification, the singular encompasses the plural unless the context otherwise requires. In particular, where the indefinite article is used, the specification is to be understood as contemplating plurality as well as singularity, unless the context requires otherwise.

[0090] Features, integers, characteristics or groups described in conjunction with a particular aspect, embodiment or example of the invention are to be understood to be applicable to any other aspect, embodiment or example described herein unless incompatible therewith. All of the features disclosed in this specification (including any accompanying claims, abstract and drawings), and / or all of the steps of any method or process so disclosed, may be combined in any combination, except combinations where at least some of such features and / or steps are mutually exclusive. The invention is not restricted to the details of any foregoing embodiments. The invention extends to any novel one, or any novel combination, of the features disclosed in this specification (including any accompanying claims, abstract and drawings), or to any novel one, or any novel combination, of the steps of any method or process so disclosed.

[0091] FIG. 1 illustrates a bioreactor 4 comprising a container 12 and an interface plate 13. The interface plate 13 comprises at least one port 21 for connecting to an external component, for example, one or more consumables. The port 21 acts as a connector interface. The one or more consumables may be provided in the form of a container, such as a compressible container, or a syringe coupled to a connector. The connector may be a needle-based connector enabling connection between an auxiliary container (e.g. a consumable) and the container via the interface plate 13. In examples, the port 21 includes a septum seal that maintains a normally sealed environment within the container 12 and also permits a needle of the connector to pass through to create a fluid connection into the container 12.

[0092] The container 12 is a compressible container. In particular, the container 12 has a bottom wall 15 disposed opposite to the interface plate 13, and a compressible wall 23 defining a sidewall of the container 12. Atop part 17 of the compressible wall 23 is attached to the interface plate 13. The top part 17 may include a rigid ring, a screw thread, a bayonet fitting or similar for attaching to a complementary feature of the interface plate 13. The compressible wall 23 is compressible such that the bottom wall 15 can move towards and away from the interface plate 13, changing the internal volume of the container 12.

[0093] The compressible wall 23 may be a bellows wall, having a concertina arrangement that allows the compressible wall 23 to fold onto itself in order to collapse. In particular, the compressible wall 23 may comprise a series of alternately arranged inward folds 16a and outward folds 16b that allow the compressible wall 23 to collapse like a bellows or concertina. The inward folds 16a and outward folds 16b may be formed by thinned sections in the compressible wall 23, with the inward folds 16a comprise a thinned section arranged on the outer surface of the compressible wall 23, and the outward folds 16b comprising a thinned section arranged on the inner surface of the compressible wall 23.

[0094] The container 12 can therefore expand and contract, or be expanded and contracted, according to the material held in the container 12. In particular, the compressible container 12 may expand as the cell culture within the container 12 grows, and / or as additional materials are added. A cell processing housing (not shown) may comprise an actuator adapted to move, for example push and / or pull, the bottom wall 15 of the container 12 and / or the interface plate 13 to change the volume of the container 12.

[0095] As illustrated, the interface plate 13 also includes an expansion container 14, otherwise called a breathing container. The expansion container 14 allows for the container12 to expand and contract without greatly changing the pressure in the container 12. Alternatively or additionally, the expansion container 14 may be operable, for example by being mechanically or manually compressed or expanded, to expand or retract the compressible wall 16 of the container 12 and thereby change a volume of the container 12. Alternatively or additionally, the expansion container 14 may be operable, for example by being mechanically or manually compressed or expanded, to alter the pressure within the container 12.

[0096] The bioreactor 4 includes a baffle 22. The baffle 22 is mounted to the interface plate13 such that the baffle 22 is suspended within the container 12. The baffle 22 includes a mounting portion 27 that is attachable to the interface plate 13. In examples, the mounting portion 27 is attachable to the interface plate 13 by a threaded connector, or by a clip or clamp. In the illustrated examples the mounting portion 27 is attached to the centre of the interface plate 13 such that the baffle 22 is centrally positioned within the container 12. However, it will be appreciated that the baffle 22 may be positioned off-centre within the container 12. The mounting portion 27 extends from the interface plate 13 towards the base portion 15, and a baffle member 24 is attached to the mounting portion 27 or formed therewith. In this example the baffle member 24 comprises a substantially flat bottom surface 25 facing the base portion 15 of the container 12. The baffle member 24 also has a conical upper surface 26, facing the interface plate 13.

[0097] The bioreactor 4 includes a sampling tube 28 so as to provide a fluid sampling path from the container 12 to the interface plate 13. The sampling tube 28 provides, during use, a fluid sampling path from the internal volume of the container 12 to an auxiliary container (e.g. a consumable) attached to an upper region of the interface plate 13. The fluid sampling path is provided through the interface plate 13, particularly the port 21 , such as a septum seal, via a needle-based connector that is coupled to the port 21 at one end and to the consumable at another end. In this way, a material 29 within the container 12 may be sampled during use.

[0098] The bioreactor 4 may include any number of sampling tubes 28. The sampling tubes 28 may be provided as having equal, or different, lengths. Varying the length of the sampling tubes 28 may be advantageous where the volume of the material 29 varies during the cell processing methodology. For instance, longer sampling tubes 28 may be provided to take samples of the material 29 at lower volumes, whereas shorter sampling tubes 28 may be provided to take samples of the material at larger volumes.

[0099] FIG. 2 to 9 illustrate various examples of the sampling tubes 28 of bioreactor 4 (FIG.1).

[0100] FIG. 2(a) and (b) illustrate a sampling tube 100 that includes a wall 102 and an internal bore 104. The wall 102 and the internal bore 104 generally taper in cross section between an inlet 106 and an outlet 108. The thickness of the wall 102 is uniform along the length of the sampling tube 100. The sampling tube 100 tapers radially outwardly from the inlet 106 to the outlet 108. The outlet 108 is provided with a connecting region 110 for connecting to the interface plate 13 (see FIG. 1 ). The connecting region 110 may include a clip or any other means for coupling the sampling tube 100 to the interface plate 13 (see FIG. 1). The inlet 106 of sampling tube 100 has a diameter of about 1 ,2mm.

[0101] FIG. 2(a) also illustrates the taper angle a formed with respect to a longitudinal axis L. The longitudinal axis L is generally defined by a longitudinal axis extending substantially in parallel to a central longitudinal axis of the bore 104 and being tangential to the inlet 106. The taper angle a may be referred to as the draft angle.

[0102] FIG. 3(a) and (b) illustrate a sampling tube 200 that includes a wall 202 and an internal bore 204. The wall 202 and the internal bore 204 generally taper in cross section between an inlet 206 and an outlet 208. The thickness of the wall 202 is uniform along the length of the sampling tube 200. The sampling tube 200 tapers radially outwardly from the inlet 206 to the outlet 208. The outlet 208 is provided with a connecting region 210 for connecting to the interface plate 13 (see FIG. 1 ). The connecting region 210 may include a clip or any other means for coupling the sampling tube 200 to the interface plate 13 (see FIG. 1). The inlet 206 of sampling tube 200 has a diameter of about 3.0mm, but other diameters are equally possible within the scope of this disclosure and as noted herein.

[0103] FIG. 4(a) and (b) illustrates a sampling tube 300 having a wall 302 that is generally cylindrical and straight in cross section, and includes an internal bore 304 that tapers between an inlet 306 and an outlet 308. As such, the thickness of the wall 302 varies along the length of the sampling tube 300 to provide the tapered shape of the internal bore 304. The bore 304 tapers radially inwardly from the inlet 306 to the outlet 308 (i.e. tapers radially outwardly from the outlet 308 to the inlet 306 - i.e. a “reverse” taper in comparison to the sampling tubes 100, 200). That is, the diameter of the bore 304 varies between the inlet 306 and the outlet 308 such that the diameter of the bore 304 at the inlet 306 is larger than at the outlet 308. The outlet 308 is provided with a connecting region 310 for connecting to the interface plate 13 (see FIG. 1 ). The connecting region 310 may include a clip or any othermeans for coupling the sampling tube 300 to the interface plate 13 (see FIG. 1). The inlet 306 of sampling tube 300 has a diameter of about 5.0mm, but other diameters are equally possible within the scope of this disclosure and as noted herein.

[0104] FIG. 5(a) and (b) illustrate a sampling tube 400 that includes a wall 402 and an internal bore 404 that generally taper in cross section between an inlet 406 and an outlet 408. The sampling tube 400 tapers radially outwardly from the inlet 406 to the outlet 408 . The outlet 408 is provided with a connecting region 410 for connecting to the interface plate 13 (see FIG. 1). The connecting region 410 may include a clip or any other means for coupling the sampling tube 400 to the interface plate 13 (see FIG. 1). The cross-sectional shape of the bore 404 is a cruciform in this particular example, although could be any other appropriate shape.

[0105] FIG. 6(a) and (b) illustrate a sampling tube 500 that includes a wall 502 and bore 504 that generally taper in cross section between an inlet 506 and an outlet 508. The thickness of the wall 502 is uniform along the length of the sampling tube 500. The sampling tube 500 tapers radially outwardly from the inlet 506 to the outlet 508. The outlet 508 is provided with a connecting region 510 for connecting to the interface plate 13 (see FIG. 1). The connecting region 510 may include a clip or any other means for coupling the sampling tube 500 to the interface plate 13 (see FIG. 1 ). The inlet 506 is provided with diametrically opposed slots 512 provided within the wall 502 of the sampling tube 500.

[0106] FIG. 7(a) and (b) illustrate a sampling tube 600 that includes a wall 602 and an internal bore 604 that generally taper in cross section between an inlet 606 and an outlet 608. The sampling tube 600 tapers radially outwardly from the inlet 606 to the outlet 608. The outlet 608 is provided with a connecting region 610 for connecting to the interface plate 13 (see FIG. 1). The connecting region 610 may include a clip or any other means for coupling the sampling tube 600 to the interface plate 13 (see FIG. 1). The inlet 606 includes a spout 612 extending substantially perpendicular to the central axis of the sampling tube 600 and integrally formed with the wall 602.

[0107] FIG. 8(a) illustrates a sampling tube 700 having a wall 702 and an internal bore 704 that generally taper in cross section between an inlet 706 and an outlet 708. The thickness of the wall 702 is uniform along the length of the sampling tube 700, except for the rounded edge as discussed below. The sampling tube 700 tapers radially outwardly from the outlet 708 to the inlet 706- i.e. a “reverse” taper in comparison to sampling tubes 100, 200). That is, the diameter of the bore 704 varies between the inlet 706 and the outlet 708 such that the diameter of the bore 704 at the inlet 706 is larger than at the outlet 708. The outlet 708 isprovided with a connecting region 710 for connecting to the interface plate 13 (see FIG. 1 ). The connecting region 710 includes a plurality of clips 712 and a resiliently deformable gasket 714 which cooperates with complementary features of the interface plate 13 (see FIG. 1 ) to provide a secure and fluid-tight seal.

[0108] FIG. 8(b) illustrates an enlarged view of the inlet 706 of sampling tube 700. As can be seen, the inlet 706 includes a rounded end 716. Alternatively, in other examples, the inlet 706 may incorporate an outwardly flared end and / or a chamfered end (not shown).

[0109] FIG. 9 illustrates a sampling tube 800 having a substantially straight cylindrical wall 802 and a substantially cylindrical straight bore 804 between an inlet 806 and an outlet 808. That is, the cross-sectional diameter of the bore 804 and the wall 802 are substantially uniform along the length of the sampling tube 800. The thickness of the wall 802 is uniform along the length of the sampling tube 800. The outlet 808 is provided with a connecting region 810 for connecting to the interface plate 13 (see FIG. 1 ). The connecting region 810 includes a plurality of clips 812 and a resiliently deformable gasket 814 which cooperates with complementary features of the interface plate 13 (see FIG. 1 ) to provide a secure and fluid- tight seal. The bore 804 of sampling tube 800 (and thereby the inlet 806) is provided with a diameter of about 3.0mm, but other diameters are equally possible within the scope of this disclosure and as noted herein.

[0110] Whilst the sampling tubes as discussed with reference to FIGS. 2(a), 2(b), 3(a), 3(b), 6(a), 6(b), 7(a), 7(b), 8(a) and 8(b) have a wall having a uniform thickness along the length of the sampling tube, alternatively, the thickness of the wall mayvary. In particular, the thickness of the wall may vary to provide the tapered shape of the sampling tubes 100, 200, 400, 500, 600 and 700 as described above.

[0111] FIG. 10 illustrates a sampling tube 900 having a wall 902. The wall 902 is generally cylindrical. The wall 902 includes an internal bore 904 that tapers between an inlet 906 and an outlet 908. As such, the thickness of the wall 902 varies along the length of the sampling tube 900 to provide the tapered shape of the internal bore 904. The bore 904 tapers radially inwardly from the inlet 906 to the outlet 908 (i.e. tapers radially outwardly from the outlet 908 to the inlet 906 - i.e. a “reverse” taper in comparison to the sampling tubes 100, 200). That is, the diameter of the bore 904 varies between the inlet 906 and the outlet 908 such that the diameter of the bore 904 at the inlet 906 is larger than at the outlet 908.

[0112] In this example, the wall 902 is also tapered to narrow from the outlet 908 to the inlet 906 (i.e., the outer diameter of the sample tube 900 is greater at the outlet 908 than at theinlet 906). This combination of the tapered internal bore 904 and tapered wall 902 may beneficially improve the ease of manufacture. For example, the lower (submersible) portion of the sampling tube 900 may be manufactured using a single mould piece (e.g., by injection moulding).

[0113] The outlet 908 is provided with a connecting region 910 for connecting to the interface plate 13 (see FIG. 1 ). The connecting region 910 may include a clip or any other means for coupling the sampling tube 900 to the interface plate 13 (see FIG. 1). Alternately, the sampling tube(s) 900 and the interface plate 13 may be formed as a single integral piece.

[0114] The tapered configuration of the internal bore 904 adds significant thickness towards a top of the sampling tube 900 near the outlet 908 and connecting region 910. As shown in Fig. 10, the sample tube 900 may be configured such that a central axis 912 of the outlet 910a of the connecting region 910 is offset from a central axis 911 extending between the inlet 906 and the outlet 908 of the internal bore 904. This is illustrated by dashed lines 911 and 912 which indicate the axes of the inlet 906 and the outlet 910a of the connecting region 910 respectively. The central axis 912 of the connecting region and the central axis 911 of the internal bore are parallel.

[0115] Where the sample tube 900 is located away from a central axis of the interface plate 13, the sample tube 900 may be configured such that the inlet 906 of the sample tube 900 lies closer to the central axis than the outlet 910a of the connecting portion 910 of that sample tube 900. Beneficially, this may mitigate or eliminate rubbing between the top of the sample tube(s) 900 and the walls of the cell processing container into which the sample tube 900 extends.

[0116] In this example, the inlet 906 of the sampling tube 900 has a diameter of between 4.0mm to 5.0mm. However, other diameters are equally possible within the scope of this disclosure and as described herein.

[0117] FIG. 11 a and FIG. 11 b illustrate a sampling tube 1000 having a wall 1002. The wall 1002 includes an internal bore 1004 that tapers between an inlet 1006 and an outlet 1008. As such, the thickness of the wall 1002 varies along the length of the sampling tube 1000 to provide the tapered shape of the internal bore 1004. The bore 1004 tapers radially inwardly from the inlet 1006 to the outlet 1008, i.e. tapers radially outwardly from the outlet 1008 to the inlet 1006 ( i.e. a “reverse” taper as in the preceding example). That is, the diameter of the bore 1004 varies between the inlet 1006 and the outlet 1008 such that the diameter of the bore 1004 at the inlet 1006 is larger than at the outlet 1008.

[0118] In this example, the wall 1002 is also tapered to narrow from the outlet 1008 to the inlet 1006 (i.e. the outer diameter of the sample tube 1000 is greater at the outlet 1008 than at the inlet 1006). As explained in relation to FIG. 10, this combination of the tapered internal bore 1004 and tapered wall 1002 may beneficially improve the ease of manufacture.

[0119] In this example, the internal bore 1004 comprises one or more projections 1011 which project inwardly towards a centre of the internal bore 1004. In this example the internal bore 1004 comprises three projections 1011 , but it will be understood that the internal bore 1004 may comprise any number of projections 1011 such as one, two, four or five or more projections 1011 . As shown in FIG.11a, the projections 1011 extend along a length of the internal bore 1004 from the inlet 1006 towards the outlet 1008. In this example, the projections 1011 do not extend along a full length of the sample tube 1000, instead terminating before reaching the outlet 1008. In other examples, the projections 1011 may extend along a full length of the internal bore 1004.

[0120] Compared with a smooth cylindrical wall, the provision of the projections 1011 may disrupt the wetting coefficient inhibiting cells from clinging to the wall 1002. In this way, the projections 1011 may inhibit the agglomeration of cells around an internal perimeter of the wall 1002. Specifically, Fig. 11 b shows a ringlet of cells 1013 on the wall of the internal bore which has been disrupted by the projections 1011.

[0121] The outlet 1008 is provided with a connecting region 1010 for connecting to the interface plate 13 (see FIG. 1 ). The connecting region 1010 may include a clip or any other means for coupling the sampling tube 900 to the interface plate 13 (see FIG. 1). Alternately, the sampling tube(s) 1000 and the interface plate 13 may be formed as a single integral piece.Examples

[0122] In the following examples, viable T cells (CD3+ T cells having CD4+ and CD8+ markers seeded at a density of 106cells / mL) in cell processing medium (including X-VIVO™ 15 (Lonza), 5% Normal human AB serum (Sigma), 12.5nm / mL IL-2 (R&D Systems), and 1% antibiotic-antimycotic 100X (ThermoFisher)) were activated (CTS™ Dynabeads™ (ThermoFisher) in a 3:1 bead:cell ratio on Day 0) and then the cell suspension was allowed to be cultured.

[0123] In the following examples, the cell suspension was either cultured in a rigid, static, cell culture container having a gas permeable base (starting volume of 1000mL) for Days 0 to 5 and then transferred to the bioreactor 4 (transfer volume of 800mL) on Day 5 or Day 6 forcompression mixing (i.e. no rocking mixing provided) as noted below. Alternatively, in other examples, the cell suspension was cultured in bioreactor 4 from Day 0 using the methodology noted below. In either instance, like agglomeration results were obtained as outlined in the examples below.

[0124] Cell culture methodology in bioreactor 4:Day 0 to Day 1 : 100mL of cell processing medium with viable T cells was provided in a static mode (i.e. not agitated)Day 1 to Day 3: No further addition of cell processing medium. A rocking mode was provided during this time. The bottom wall 15 of the bioreactor 4 was rocked at a rate of 10 rocks per minute at a maximum angle of 10 degrees from a horizontal plane of the bottom wall 15.Day 3 to Day 4: Further cell processing medium was added to provide a total volume of 250mL. The bottom wall 15 of the bioreactor 4 was rocked at a rate of 6 rocks per minute at a maximum angle of 10 degrees from a horizontal plane of the bottom wall 15. A “rock” constituted movement of the bottom wall 15 in a first direction (i.e. clockwise) followed by movement of the bottom wall 15 in a second direction (i.e. anticlockwise). The bottom wall 15 was held statically for a period of 6 seconds following each rock.Day 4 to Day 5: Further cell processing medium was added to provide a total volume of 500mL. The bottom wall 15 of the bioreactor 4 was rocked at a rate of 25 rocks per minute at a maximum angle of 10 degrees from a horizontal plane of the bottom wall 15. A “rock” constituted a rotational movement of the bottom wall 15 in a first direction (i.e. clockwise) followed by a rotational movement of the bottom wall 15 in a second direction (i.e. anticlockwise). The bioreactor wall 15 was continuously rocked during this time.Day 5 to Day 6: Further cell processing medium was added to provide a total volume of 750mL. The bottom wall 15 of the bioreactor 4 was translated towards, and away from, the interface plate 13 (i.e. “compression mixing”). The bioreactor 4 was compressed at a rate of 13 compressions per minute. A “compression” constituted a longitudinal translation of the bottom wall 15 in a first direction (i.e. upwardly, so as to compress the container 12), followed by a longitudinal translation of the bottom wall 15 in a second direction (i.e. downwardly, so as to expand the compressed container12). The bottom wall 15 was held statically for a period of 3 seconds following each compression.Day 6 to Day 7: Further cell processing medium was added to provide a total volume of 10OOmL. The bottom wall 15 of the bioreactor 4 was translated towards, and away from, the interface plate 13 (i.e. “compression mixing”). The bioreactor 4 was compressed at a rate of 13 compressions per minute. A “compression” constituted a longitudinal translation of the bottom wall 15 in a first direction (i.e. upwardly, so as to compress the container 12), followed by a longitudinal translation of the bottom wall 15 in a second direction (i.e. downwardly, so as to expand the compressed container 12). The bottom wall 15 was held statically for a period of 3 seconds following each compression.

[0125] Samples were taken by compressing the container 12 so that the respective sampling tubes 28 were immersed in the material 29 within the container 12. A needle-based connector coupled to a syringe at a first end and coupled to the port (septum seal) 21 of the interface plate 13 at a second end was utilised. The connector was actuated so as to provide a fluid pathway between the syringe and the container 12 via the needle that extended through the port 21 . The syringe was actuated, particularly drawn backwards, to create negative pressure and hence remove a sample from the container 12. Thereafter, the syringe ceased actuation, the needle was retracted (and the septum seal 21 self-sealed), and the syringe-connector consumable was removed. The sample in the syringe was then analysed. A sample was taken each day from Day 4 onwards and visually observed each day for any agglomeration of cells.Example 1

[0126] In the following example, a bioreactor4 was tested having various types of sampling tubes 28 (see FIG. 1). In total, twelve sampling tubes 28 were tested as shown in Table 1 below:The “1 ,2mm long” sampling tube is as generally illustrated in FIG. 2(a) and (b) and having an inlet diameter of 1 ,2mm, a taper angle of approximately 1 .56 degrees, and a length from the outlet to the inlet of approximately 61 ,6mm.The “1 ,2mm short” sampling tube is as generally illustrated in FIG. 2(a) and (b) and having an inlet diameter of 1 ,2mm, a taper angle of approximately 1 .74 degrees, and a length from the outlet to the inlet of approximately 38.9mm.The “1 ,3mm” sampling tube is as generally illustrated in FIG. 2(a) and (b) and having an inlet diameter of 1 ,3mm, a taper angle of approximately 1 .74 degrees, and a length of approximately 38.9mm.The “roughened 3mm” sampling tube is as generally illustrated in FIG. 3(a) and (b) and having an inlet diameter of 3.0mm. This sampling tube was created by boring (e.g. drilling) the inlet of a 1 ,2mm short sampling tube to an inlet diameter of 3.0mm. In this way, the roughened 3mm sampling tube incorporated an inner surface of the side wall adjacent the inlet that was roughened (i.e. incorporated undulations or abrasions on the internal surface of the side wall).

[0127] The “inverted 5mm” sampling tube is as generally illustrated in FIG. 4(a) and (b) and having an inlet diameter of 5.0mm, a taper angle of approximately 1 .74 degrees, and a length from the outlet to the inlet of 38.9mm.Table 1 : Results of Example 1

[0128] As can be seen in Table 1 , the provision of an “inverted” sampling tube, and a sampling tube having a wider bore and roughened inner surface, mitigated agglomeration of cells following sampling.Example 2

[0129] In the following example, a bioreactor4 was tested having various types of sampling tubes 28 (see FIG. 1). In total, twelve sampling tubes 28 were tested as shown in Table 2 below:The “roughened 3mm” sampling tube is as generally illustrated in FIG. 3(a) and (b) and having an inlet diameter of 3.0mm. This sampling tube was created by boring the inlet of a 1 ,2mm short sampling tube to an inlet diameter of 3.0mm. In this way, the roughened 3mm sampling tube incorporated an inner surface of the side wall that was roughened (i.e. incorporated undulations or abrasions on the internal surface of the side wall).Table 2: Results from Example 2

[0130] As can be seen in Table 2, the provision of such a sampling tube mitigated agglomeration of cells following sampling.

[0131] The material 29 within the bioreactor 4 was also removed following the experiment, and no agglomeration of cells were found.Example 3

[0132] In the following example, a bioreactor4 was tested having various types of sampling tubes 28 (see FIG. 1). In total, ten sampling tubes 28 were tested as shown in Table 3 below:The “inverted 5mm” sampling tube is as generally illustrated in FIG. 4(a) and (b) and having an inlet diameter of 5.0mm, a taper angle of approximately 1 .74 degrees, and a length from the outlet to the inlet of 38.9mm.Table 3: Results from Example 3

[0133] As can be seen in Table 3, the provision of such a sampling tube mitigated agglomeration of cells following sampling.

[0134] The material 29 within the bioreactor 4 was also removed following the experiment, and no agglomeration of cells were found.Example 4

[0135] In the following example, a bioreactor4 was tested having various types of sampling tubes 28 (see FIG. 1). In total, twelve sampling tubes 28 were tested as shown in Table 3 below:The “inverted rounded long” sampling tube is as generally illustrated in FIG. 8(a) and (b) and having an inlet diameter of 5.0mm, a taper angle of approximately 1 .56 degrees, and a length from the outlet to the inlet of 61 ,6mm. - The “inverted rounded medium” sampling tube is as generally illustrated in FIG. 8(a) and (b) and having an inlet diameter of 5.0mm, a taper angle of approximately 1 .74 degrees, and a length from the outlet to the inlet of 55.1 mm.The “inverted rounded short” sampling tube is as illustrated generally in FIG. 8(a) and (b) and having an inlet diameter of 5.0mm, a taper angle of approximately 1 .74 degrees, and a length from the outlet to the inlet of 38.9mm.Table 4: Results from Example 4

[0136] As can be seen in Table 4, the provision of such a sampling tube mitigated agglomeration of cells following sampling.

[0137] The material 29 within the bioreactor 4 was also removed following the experiment, and no agglomeration of cells were found.Example 5

[0138] In the following example, a bioreactor4 was tested having various types of sampling tubes 28 (see FIG. 1). In total, twelve sampling tubes 28 were tested as shown in Tables 5 and 6 below:The “1 ,2mm” sampling tube is as generally illustrated in FIG. 2(a) and (b) and having an inlet diameter of 1 ,2mm, a taper angle of approximately 1 .74 degrees, and a length of 38.9mm.The “1 ,5mm” sampling tube is as generally illustrated in FIG. 2(a) and (b) and having an inlet diameter of 1 ,5mm, a taper angle of approximately 1 .5 degrees, and a length of 38.9mm.The “1 ,75mm” sampling tube is as generally illustrated in FIG. 2(a) and (b) and having an inlet diameter of 1 ,75mm, a taper angle of approximately 1 .4 degrees, and a length of 38.9mm.The “2.0mm” sampling tube is as generally illustrated in FIG. 3(a) and (b) and having an inlet diameter of 2.0mm, a taper angle of approximately 1 .3 degrees, and a length of 38.9mm.The “2.25mm” sampling tube is as generally illustrated in FIG. 3(a) and (b) and having an inlet diameter of 2.25mm, a taper angle of approximately 1 .2 degrees, and a length of 38.9mm.The “2.5mm” sampling tube is as generally illustrated in FIG. 3(a) and (b) and having an inlet diameter of 2.5mm, a taper angle of approximately 1 .1 degrees, and a length of 38.9mm.The “2.75mm” sampling tube is as generally illustrated in FIG. 3(a) and (b) and having an inlet diameter of 2.75mm, a taper angle of approximately 1 .0 degrees, and a length of 38.9mm.The “Smooth 3.0mm” sampling tube is as generally illustrated in FIG. 3(a) and (b) and having an inlet diameter of 3.0mm, a taper angle of approximately 0.9 degrees, and a length of 38.9mm. This sampling tube is 3D printed and incorporated an inner surface of the wall that was substantially smooth (i.e. substantially not roughened as per the “roughened 3mm” sampling tube noted above)The “Smooth 3.0mm (lo)” sampling tube is as illustrated in FIG. 9 and having a bore diameter (and inlet diameter) of 3.0mm, a taper angle of approximately 0.9 degrees, and a length of 38.9mm. This sampling tube is 3D printed and incorporated an inner surface of the wall that was substantially smooth (i.e. substantially not roughened as per the “roughened 3mm” sampling tube noted above)Table 5: Results from first experiment of Example 5

[0139] As can be seen in Table 5, the provision of smaller inlet diameters for sampling tubes resulted in clumping.Table 6: Results from second experiment of Example 5.

Claims

CLAIMS1 . An interface for coupling to a cell processing container having an internal volume for holding a cell suspension, the interface comprising: a port configured to allow egress of at least a portion of the cell suspension from the cell processing container; and a conduit extending from said port so as to be located within the internal volume of the cell processing container during use, said conduit extending between an inlet and an outlet and comprising an internal bore, wherein said inlet is configured to allow ingress of the portion of the cell suspension, and wherein said outlet is in fluid communication with said port, wherein at least one of said internal bore and said inlet is configured to minimise or mitigate agglomeration of cells as the portion of the cell suspension ingresses said conduit.

2. The interface according to claim 1 , wherein said internal bore is sized and / or shaped to minimise or mitigate agglomeration of cells as the portion of the cell suspension ingresses said conduit.

3. The interface according to claim 2, wherein said internal bore has a diameter of at least approximately 2.5mm.

4. The interface according to claim 2 or claim 3, wherein said internal bore has a crosssection comprising a substantially circular, cruciform, oval, or triangular shape.

5. The interface according to any preceding claim, wherein at least a portion of said internal bore tapers radially inwardly in diameter from said inlet to said outlet.

6. The interface according to claim 5, wherein said internal bore tapers in diameterfrom said inlet to said outlet along substantially the entire length of said conduit.

7. The interface according to any preceding claim, wherein said inlet is sized and / or shaped to minimise or mitigate agglomeration of cells as the portion of the cell suspension ingresses said conduit.

8. The interface according to claim 7, wherein said inlet comprises a rounded edge or a chamfered edge.

9. The interface according to claim 7 or claim 8, wherein said inlet comprises an outwardly flared portion.

10. The interface according to any one of claims 7 to 9, wherein said inlet has a diameter of at least approximately 2.5mm.11 . The interface according to any preceding claim, wherein said conduit is integrally formed with said interface.

12. The interface according to any one of claims 1 to 11 , wherein said conduit comprises a coupling element configured to couple to a corresponding receiving element of said interface.

13. The interface of claim 12, wherein said coupling element comprises a clip and said corresponding receiving element comprises an aperture.

14. The interface of any preceding claim, wherein said port comprises a pierceable seal, such as a septum seal.

15. The interface of any preceding claim, wherein said interface comprises a plurality of ports.

16. The interface of claim 15, wherein said interface further comprises: a first set of conduits extending from a first portion of said plurality of ports, said first set of conduits having a first length; and a second set of conduits extending from a second portion of said plurality of ports, said second set of conduits having a second length, wherein said first length is greater than said second length.

17. The interface according to claim 16, wherein said interface further comprises:a third set of conduits extending from a third portion of said plurality of ports, said third set of conduits having a third length, wherein said second length is greater than said third length.

18. A kit of parts, comprising: an interface for coupling to a cell processing container having an internal volume for holding a cell suspension, the interface comprising a port configured to allow egress of at least a portion of the cell suspension; and a conduit attachable to said interface such that said conduit extends from said port so as to be located within the internal volume of the cell processing container during use, said conduit comprising an internal bore extending between an inlet and an outlet, wherein said inlet is configured to allow ingress of the portion of the cell suspension, and wherein said outlet is configured to be in fluid communication with said port, wherein at least one of said internal bore and said inlet is configured to minimise or mitigate agglomeration of cells as the portion of the cell suspension ingresses said conduit.

19. A conduit for use with the interface according to any one of claims 1 to 17.

20. A cell processing device comprising: a cell processing container defining an internal volume for holding a cell suspension; and an interface according to any one of claims 1 to 17, wherein said interface is attached to said cell processing container such that said cell processing container is closed by said interface and said conduit is arranged in said internal volume of said cell processing container.21 . The cell processing device according to claim 20, wherein said cell processing container comprises a compressible cell processing container.

22. A method of extracting at least a portion of a cell suspension from a cell processing device, comprising: providing a cell processing device according to claim 20 or claim 21 ; providing a cell suspension within said internal volume of said cell processing container;at least partially submerging said conduit in said cell suspension; and generating a pressure differential to move at least a portion of said cell suspension through said conduit and said port to egress said cell processing container.

23. The method of claim 22, wherein generating a pressure differential to move at least a portion of said cell suspension through said conduit and said port to egress said cell processing container comprises providing positive pressure within said cell processing container.

24. The method of claim 22, wherein said cell processing container is a compressible cell processing container, and wherein providing positive pressure within said cell processing container comprises compressing said compressible cell processing container.

25. The method of any one of claims 22 to 24, wherein generating a pressure differential to move at least a portion of said cell suspension through said conduit and said port to egress said cell processing container comprises applying negative pressure to said port to draw said cell suspension from said cell processing container.

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