Apparatus for treating cells and method for treating cells

Abstract

An apparatus for use in cell processing is provided, comprising: a retaining element arranged to receive an upper portion of a container in a first plane; a movable plate spaced from the retaining element and arranged to operably engage a base portion of the container, the movable plate defining a second plane substantially parallel to the first plane; and an actuation mechanism operably coupled to the movable plate and arranged to rotate the movable plate about at least one axis in the second plane, thereby reducing the distance between at least a portion of the second plane and the first plane. Methods of processing cells are also provided.

Description

[Technical Field]

[0001] The present invention relates to an apparatus for use in performing one or more unit operations in cell processing. The present invention also relates to a method of processing cells. [Background technology]

[0002] Within a cell processing method, there can be any number of unit operations. These unit operations vary based on the cells and media, among other variables. A cell processing method can include cell and / or gene therapy manufacturing, biofuel production, small molecule production, screening, and process development, among others.

[0003] For example, there may be a need for an algae bioreactor for producing biofuels, an apparatus for performing one or more tasks in cell and / or gene therapy manufacturing, an apparatus for fabricating small molecules from E. coli, an apparatus for extracting primary cells from solid biopsies and single organoid cultures, and an apparatus for use in screening and processing.

[0004] In one specific, non-limiting example, there may be a need for an apparatus for use in performing one or more unit operations in cell therapy manufacturing and / or gene therapy manufacturing. In such an example, cell therapy and gene therapy manufacturing processes are often complex and involve manual or semi-automated steps across several devices. The equipment systems used in various steps of cell-based therapeutic product (CTP) manufacturing in several unit operations may include devices for cell harvesting, cell separation, cell selection, cell expansion, cell washing and volume reduction, cell storage, and cell transport. Unit operations can vary significantly based on the manufacturing model, e.g., autologous versus allogeneic, cell type, and intended purpose, among other factors. Additionally, cells are "living" entities that are sensitive to even the simplest manipulations, such as different environments in cell transfer procedures. The role of cell manufacturing equipment in ensuring scalability and reproducibility is a critical factor for cell therapy manufacturing and / or gene therapy manufacturing.

[0005] Furthermore, cell-based therapeutic products are gaining considerable momentum, which is increasing the demand for improved cell manufacturing equipment for various cell manufacturing procedures, such as, but not limited to, cell enrichment, generation of chimeric antigen-receptive (CAR) T cells, and various cell manufacturing processes such as harvesting, purification, genetic modification, culture, recovery, washing, patient infusion, and freezing.

[0006] The cultivation of cell treatments typically requires the use of a device to hold the cells, e.g., in a suitable culture medium, as they are cultured. Known devices include shaker flasks, roller bottles, T-flasks, and bags. One example of a known device 10 having a bag 14 is shown in FIGS. 1(a) and 1(b). This known device 10 includes a platform 12 on which a bag 14, e.g., a flexible bag, is placed, providing a disposable chamber for culturing the cells. The flexible bag 14 typically includes a series of inlets and outlets in the form of tubes to allow the passage of medium 16 into the bag 14. The platform 12 is mounted on a base plate 20, which has a pivot point 18 about which the platform 12, and thus the flexible bag 14, can rotate or swing.

[0007] Platform 12 can be oscillated around pivot point 18 through suitable angles thanks to an actuator (not shown). Oscillating platform 12 provides a system of wave-like agitation and bubble-free aeration within bag 14. Thus, the use of mechanical mixing devices that impart large shear forces to media 16 is avoided.

[0008] Foremost among the problems with such known devices is the requirement for contamination-free transfer of cells during passage or subsequent processing, and the requirement for aseptic addition of supplements, factors, media, etc. Additionally, such known devices require a significant amount of manual intervention, particularly when adding or removing media from the bag, making them labor-intensive and prone to human error during handling, and also increasing operating costs. Furthermore, multiple pieces of equipment are typically required to provide all of the functionality necessary to perform cell therapy and / or gene therapy manufacturing processes.

[0009] Therefore, there is a need for a cell processing device, e.g., a multi-stage cell processing device, that allows for such processing and avoids the prerequisite of repeated transfer of cells between different devices. It would also be advantageous if expansion of cells in culture could be achieved without transferring cells to larger or other devices. Furthermore, a single, simple device with lower operating costs while retaining the advantages associated with our device would be beneficial.

[0010] The Applicant has overcome these shortcomings by providing cell culture vessels and devices as described in the Applicant's previous applications (PCT / GB2016 / 051451, PCT / GB2017 / 053389, and PCT / GB2020 / 050007).

[0011] Figures 2(a) and 2(b) show the applicant's previous apparatus 50, as described in PCT / GB2020 / 050007. However, the applicant has identified a number of areas for subsequent improvement of such devices, which are described herein.

[0012] First, applicants have determined that when using larger volumes of culture media, and therefore larger vessels, the actuators 52 of the device 50 tend to bend during use. As a result, the base unit 50 requires periodic maintenance, which can be costly. In some instances, supports 56 may be provided, but this increases the weight and manufacturing costs of such devices 50. Additionally, if the actuators 52 begin to bend during use, the compression of the cell culture vessels may be compromised, potentially reducing the efficiency of the cell therapy and / or gene therapy manufacturing process.

[0013] Second, actuator 52 of device 50 is not suitable for mixing the medium in the vessel on which it acts. Specifically, actuator 52 moves slowly to provide compression of the vessel so that the medium can be removed, sampled, etc. That is, actuator 52 cannot move fast enough to mix the medium in a vessel that is being held. Actuator 52 also does not provide other types of mixing, such as rocking and / or swirling mixing, which are particularly needed when the medium and / or cells do not contact the entire fold of the vessel (see Figures 2(c) and 2(d) for such vessels).

[0014] Third, as shown in Figures 2(c) and 2(d), Applicant's previous devices can improperly mix the cell treatment medium in such an arrangement. Figure 2(c) shows the medium 62 in the cell culture vessel 60 with a portion 64 of the medium submerged in the base of the cell culture vessel 60. While the base unit 50 provides a rotation mechanism 54 for rotating the cell culture vessel 60 about its central axis during use, such rotation must be precise and therefore slow because the auxiliary vessel positioned above the cell culture vessel 60 is positioned so that it can dispense the medium 62 into the cell culture vessel 60. Thus, as shown in Figure 2(d), after rotation of the cell culture vessel 60, a portion 64 of the medium may remain submerged in the base of the cell culture vessel 60. This is due to the fact that the cell culture vessel 60 is centered below the auxiliary vessel, coaxial with the central longitudinal axis of rotation. Therefore, even at high rotational speeds, the cell culture vessel 60 experiences only a minimally agitated environment that is insufficient to ensure homogeneity within the vessel 60, as shown in Figure 2(d). Thus, the prior art rotation mechanism 54 is inadequate to adequately agitate the reaction medium 62 within the cell culture vessel 60. [Prior art documents] [Patent documents]

[0015] [Patent Document 1] International Publication No. 2016 / 185221 Brochure Summary of the Invention [Problem to be solved by the invention]

[0016] Therefore, there is a need for an apparatus that can operate several processes in cell therapy manufacturing and / or gene therapy manufacturing and that can adequately agitate vessels to ensure homogeneity therein.

[0017] More specifically, there is a need for an apparatus such as that discussed in Figures 2(a) and 2(b) that can also impart mixing, such as compressive, oscillating, and / or gyratory mixing, to a medium in a container received in part by the apparatus.

[0018] SUMMARY OF THE INVENTION Accordingly, the present invention aims to obviate or mitigate at least one of the above problems. [Means for solving the problem]

[0019] Apparatus, systems, and methods of use thereof In one embodiment of the invention there is provided an apparatus for use in performing one or more unit operations in cell processing, comprising: a holding element arranged to receive an upper portion of the container in the first plane; a movable plate spaced from the retaining element and positioned to operatively engage a base portion of the container, the movable plate defining a second plane substantially parallel to the first plane; an actuation mechanism operatively coupled to the movable plate for rotating the movable plate about at least one axis in the second plane to thereby reduce the distance between at least a portion of the second plane and the first plane; An apparatus is provided comprising:

[0020] The retaining element may be any suitable element or mechanism configured and / or arranged to receive a portion, some, or all of the top portion of the container during use. The retaining element receives and holds the received top portion of the container in a first plane. The first plane may extend substantially horizontally or perpendicular to the vertical.

[0021] The movable plate may be any suitable element or mechanism configured and / or arranged to engage a portion, some, or all of the base portion of the container during use. The movable plate may act on the base portion of the received container. The movable plate generally defines a second plane. The second plane is generally parallel to the first plane, particularly prior to actuation of the actuation mechanism. The second plane may extend substantially horizontally or perpendicular to the vertical.

[0022] The actuation mechanism can be operably coupled to the movable plate to act on a base portion of a received container during use. The actuation mechanism can rotate, tilt, pivot, or move the movable plate, which defines a second plane, around one or more axes within the second plane during use. Thus, the distance between a portion, some, most, or all of the second plane and a portion, some, most, or all of the first plane can be reduced. In other words, a portion, some, most, or all of the second plane can be moved toward the first plane. The first plane can remain stationary during use. The actuation mechanism can act on a portion, some, most, or all of the movable plate to move any portion, some, most, or all of the movable plate relative to the first plane. For example, the actuation mechanism can act on discrete portions of the movable plate. For example, the actuation mechanism can act to move the entire movable plate.

[0023] The movable plate can be movable, rotatable, or tiltable about any axis in a second plane, which is the plane of the movable plate. Thus, the movable plate can be rotatable about a single axis, two axes, three axes, multiple axes, or an infinite number of axes in the second plane. The movable plate can be arranged to rotate about a first axis in a first configuration and then rotate about a second axis in a second configuration. The first and second axes can be perpendicular or parallel to each other. The movable plate can be arranged to rotate about a single axis to impart a wave motion or a rocking motion to a fluid in a received vessel with which the movable plate is operably engaged. The movable plate can be arranged to rotate about two or more axes, for example, two orthogonal axes, to impart a pivoting motion to a fluid in a received vessel with which the movable plate is operably engaged. The movable plate may be generally movable to compress a received container between the movable plate, ie, the second plane, and the first plane, ie, the holding element.

[0024] This provides the advantage that multiple unit operations in cell processing can be performed in a single device. That is, the device can be a multi-step processing device for cell processing. For example, the device can advantageously allow both static and dynamic cell culturing or processing without the need to transfer materials between devices or systems. For example, the device can advantageously allow mixing and / or pumping of materials in received containers, thus negating the need for stirring and / or pumping equipment, or piping equipment. This can reduce the footprint of the device, allowing for compact devices and stackable multiplexing of devices.

[0025] Furthermore, this provides the advantage of being able to agitate the cell treatment medium in situ. Specifically, the present apparatus allows for agitation of the cell treatment medium without transferring the cell treatment medium between devices. Thus, homogeneity can be ensured within a single container so that any subsequent operations, such as sampling, can be performed in situ. Furthermore, the apparatus provided herein allows for agitation in any number of directions, including rotation around an axis to provide wave or gyration agitation, and compression along an axis. Thus, the apparatus can provide improved mixing of the cell treatment medium in situ.

[0026] In certain embodiments, the actuation mechanism is arranged to rotate the movable plate about an axis in the second plane.

[0027] That is, in certain embodiments, the actuation mechanism is arranged to rotate the movable plate about a single axis, i.e., one axis, in the second plane. The single axis may be centrally arranged in the second plane so that the movable plate is rotatable about a central axis in the second plane. The single axis may be off-centered in the second plane so that the movable plate is rotatable about an axis other than the central axis extending perpendicular to the second plane. The single axis may be arranged at a point where the base portion of the container is adjacent to a wall element of the container. The single axis may be arranged at an edge of the movable plate. Thus, the entire base portion may be tilted in one direction.

[0028] This provides the advantage that a wave motion can be imparted to a fluid in a container received in the device, which can thoroughly mix the fluid in the container and provide aeration of the fluid.

[0029] In certain embodiments, the actuation mechanism is arranged to rotate the movable plate about multiple axes in the second plane.

[0030] This provides the advantage that multiple wave motions along multiple different axes are imparted to a fluid in a container received in the device. The multiple wave motions can ensure thorough mixing of the fluid in the container and provide aeration of the fluid. Furthermore, such a device ensures that any volume of fluid in the received container can be adequately mixed.

[0031] In certain embodiments, the actuation mechanism is arranged to rotate the movable plate between 0 and 90 degrees about the or each axis in the second plane.

[0032] It is believed to be preferable for the movable plate to be rotatable through an angle of approximately 1 to 5 degrees, most preferably approximately 3.5 degrees.

[0033] The movable plate may be rotatable at any speed depending on the cell processing task to be performed. For example, the movable plate may be rotatable at 1 to 1,000 oscillations per minute. For example, the movable plate may be rotatable at 1 to 100 oscillations per minute. It may be preferable for the movable plate to be rotatable at a speed of between 5 and 60 oscillations per minute, for example, between 20 and 60 oscillations per minute, preferably between about 10 and 15 oscillations per minute. Oscillations may be defined as a rotation about an axis in one direction, followed by a subsequent rotation about an axis in the opposite direction.

[0034] In certain embodiments, a longitudinal axis extending perpendicular to the first and second planes intersects the second plane at an origin, and the actuation mechanism is arranged to pivot the movable plate about the origin.

[0035] This provides the advantage that a swirling motion is imparted to the fluid in the container received in the device. The swirling motion can be useful for mixing small volumes of fluids or liquids, i.e., volumes of less than 100 ml. The swirling motion can adequately mix the fluid and provide aeration to the fluid.

[0036] In certain embodiments, the origin is centered within the second plane.

[0037] That is, in certain embodiments, the origin is centered within the second plane, or in other words, the longitudinal axis is a central longitudinal axis that intersects the second plane at the central origin.

[0038] In certain embodiments, the actuation mechanism is arranged to move the movable plate about a first axis in the second plane and simultaneously move the movable plate about a second axis in the second plane, hi some instances, the first axis and the second axis are orthogonal.

[0039] In certain embodiments, the actuation mechanism is arranged to rotate the movable plate about an axis in the second plane between a first configuration in which the second plane is substantially parallel to the first plane and a second configuration in which the second plane forms a predetermined angle with respect to the first plane.

[0040] In certain embodiments, the actuation mechanism is further arranged to rotate the movable plate, in the second configuration, about a longitudinal axis that is perpendicular to the first plane and intersects the second plane at the origin.

[0041] In certain embodiments, the origin is centrally located within the second plane. That is, in certain embodiments, the origin is centrally located within the second plane. In other words, the longitudinal axis is a central longitudinal axis that intersects the second plane at the central origin.

[0042] In certain embodiments, the actuation mechanism is arranged to rotate the movable plate about the longitudinal axis through a predetermined angle. In some examples, the predetermined angle is a constant angle. The predetermined angle can be between 0 and 180 degrees, excluding 90 degrees. The predetermined angle generally excludes 0 and 180 degrees.

[0043] In certain embodiments, the actuation mechanism is arranged to rotate the movable plate at a variable angle about the longitudinal axis, i.e., in certain embodiments, when the actuation mechanism rotates the movable plate about the longitudinal axis, the movable plate is also rotated about an axis or an axis in a second plane.

[0044] In certain embodiments, the movable plate is pivotable about an origin such that each point in the second plane, excluding the origin, forms an angle between 0 and 180 degrees, excluding 90 degrees, with the longitudinal axis.

[0045] It is believed that it is preferable that the movable angle is approximately 1 to 5 degrees and / or approximately 91 to 95 degrees, and most preferably approximately 3.5 degrees and / or 93.5 degrees.

[0046] The movable plate may be rotatable at any speed depending on the cell processing task to be performed. The rotation speed of the movable plate may depend on the cells and / or medium used. For example, the movable plate may be rotatable at 1 to 1,000 rocks per minute (rpm). For example, the movable plate may be rotatable at 1 to 100 rocks per minute. It may be preferable for the movable plate to be rotatable at a speed of between 5 and 60 rocks per minute, for example, between 20 and 60 rocks per minute, preferably between about 10 and 15 rocks per minute. Rocking may be defined as a rotation around an axis in one direction, followed by a subsequent rotation around an axis in the opposite direction.

[0047] In specific embodiments, the movable platen may be rotatable from 1, 5, 10, 15, 20, 25, 30, 35, 40, 45, or 50 oscillations per minute to 55, 60, 65, 70, 75, 80, 85, 90, 95, or 100 oscillations per minute. Any combination of a lower lower limit and a higher upper limit is contemplated herein.

[0048] In a specific embodiment, the actuation mechanism is arranged to rotate the movable plate at any of the speeds discussed above.

[0049] In specific embodiments, the angle can be between 1 and 179 degrees, between 10 and 170 degrees, between 20 and 160 degrees, between 30 and 150 degrees, between 40 and 140 degrees, between 50 and 130 degrees, between 60 and 120 degrees, between 70 and 110 degrees, or between 80 and 100 degrees, excluding 90 degrees. The lower limit of the angle can be 0, 1, 10, 20, 30, 40, 50, 60, 70, 80, 100, 110, 120, 130, 140, 150, 160, 170, 179 degrees, or any integer number of degrees therebetween, excluding 90 degrees. The upper angle limit can be 1 degree, 10 degrees, 20 degrees, 30 degrees, 40 degrees, 50 degrees, 60 degrees, 70 degrees, 80 degrees, 100 degrees, 110 degrees, 120 degrees, 130 degrees, 140 degrees, 150 degrees, 160 degrees, 170 degrees, 179 degrees, 180 degrees, or any integer number of degrees therebetween. Any combination of smaller lower limits and larger upper limits is contemplated herein.

[0050] In certain embodiments, the actuation mechanism is further arranged to move the movable plate along the longitudinal axis substantially perpendicular to the first plane and the second plane, thereby reducing the distance between the second plane and the first plane.

[0051] That is, in some embodiments, the actuation mechanism is arranged to reduce the distance between the second plane, or all or part of the second plane, and the first plane. That is, the distance between each and every point on the second plane and each and every corresponding point on the first plane can be reduced. This can be interpreted as a translation or movement of the longitudinal axis. This can also be interpreted as a compressive movement along the longitudinal axis. This can also be interpreted as a linear compressive movement.

[0052] This provides the advantage that compressive agitation can be imparted to the cell treatment medium in the container. Compressive agitation can be useful for mixing large volumes of cell treatment medium, i.e., 100 ml or more of cell treatment medium. Compressive agitation can also adequately mix the cell treatment medium and provide aeration to the cell treatment medium.

[0053] Furthermore, in addition to the above benefits, the compressive motion along the longitudinal axis allows for in situ control of the headspace, i.e., the space above the cell treatment medium. For example, the compressive motion allows for in situ removal of material from the container, in situ aeration of the cell treatment medium, in situ removal of gas from the container, and breathing between the container and a secondary container or filter (i.e., allowing fluid to be transferred from one container to another container or filter to relieve pressure in the or each container). Thus, the compressive motion not only agitates the cell treatment medium, but can also provide one or more of the other benefits discussed herein.

[0054] In certain embodiments, the actuation mechanism is configured to provide any number of cycles per minute (cpm). One cycle is defined as a compression of the received container followed by a decompression. Alternatively, one cycle is defined as a translation of the longitudinal axis of the second plane relative to the first plane in a first direction, followed by a translation of the longitudinal axis of the second plane relative to the first plane in a second direction opposite the first direction. The distance of translation of each longitudinal axis in each direction may be substantially equal.

[0055] That is, during use, the received container is moved from a first, original, or initial configuration to a second configuration following compression, and then moved back to the first, original, or initial configuration following decompression. The actuation mechanism is arranged to provide any degree of compression. For example, the distance between the first plane and the second plane can be partially, mostly, or completely reduced. Alternatively, the distance between the first plane and the second plane can be increased.

[0056] The movable plate may be movable along the vertical axis at any speed (i.e., any number of cycles per minute) depending on the cell processing task to be performed. The speed may depend on the cells and / or medium used. For example, the movable plate may be moved at 1 to 100 cycles per minute. In one example, the movable plate may be moved at a speed of 5 to 80 cycles per minute, preferably 20 to 80 cycles per minute, and most preferably 20 to 60 cycles per minute.

[0057] In specific embodiments, the movable platen may be movable at a rate of from 1, 5, 10, 15, 20, 25, 30, 35, 40, 45, or 50 cycles per minute to 55, 60, 65, 70, 75, 80, 85, 90, 95, or 100 cycles per minute. Any combination of a lower lower limit and a higher upper limit is contemplated herein.

[0058] In a specific embodiment, the movable plate can be movable along the vertical axis at a first speed to impart turbulence to the contents of the received container during use, and can be movable along the vertical axis at a second speed to allow breathing during use (i.e., to allow transfer of fluid, gas, or liquid from the received container to a secondary container or filter). The first speed can be greater than the second speed. The first speed and second speed can be measured in cycles per minute, as discussed above.

[0059] In specific embodiments, the actuation mechanism is arranged to move or translate the movable plate at any rate as previously discussed, and thus the actuation mechanism can be arranged to impart compression and decompression of the received container at any rate as previously discussed.

[0060] In specific embodiments, the actuation mechanism is configured to provide any suitable magnitude of movement to the received container. For example, the magnitude of longitudinal translation may be measured as the displacement between a first configuration in which the container base is not compressed relative to the container top or the second planar surface is not longitudinally translated relative to the first planar surface, and a second configuration in which the container base is at least partially compressed relative to the container top or the second planar surface is at least partially translated, such as by longitudinal translation, relative to the first planar surface. Stated differently, the magnitude of longitudinal translation may be measured as the displacement or displacement amplitude following compression or longitudinal translation of the second planar surface relative to the device's first planar surface. The displacement may be dependent on the cell processing task being performed. The displacement may depend on the cells and / or media used. For example, the displacement may be from 1 mm to 100 mm. In some instances, the displacement may be from 5 mm to 50 mm, preferably from 10 mm to 30 mm, and most preferably approximately 20 mm. The displacement may be between a portion or part of the second plane and the first plane (i.e., for rotation of the movable plate about an axis in the second plane). The displacement may be between the entire second plane and the first plane (i.e., for longitudinal movement along the longitudinal axis, such as compression of the received container).

[0061] In specific embodiments, the displacement can be from 1 mm, 5 mm, 10 mm, 15 mm, 20 mm, 25 mm, 30 mm, 35 mm, 40 mm, 45 mm, or 50 mm, to 55 mm, 60 mm, 65 mm, 70 mm, 75 mm, 80 mm, 85 mm, 90 mm, 95 mm, or 100 mm. Any combination of a smaller lower limit and a larger upper limit is contemplated herein.

[0062] In certain embodiments, the retaining element comprises a platform operably engageable with the upper portion of the container, a clamping mechanism operably engageable with the upper portion of the container, or a sealing plate operably engageable with the upper portion of the container, although the retaining element may also include combinations thereof.

[0063] In certain embodiments, the holding element comprises a platform, e.g., a cell processing platform. In certain instances, the cell processing platform comprises at least one inlet fluidly connected to at least one outlet, the outlet, some of the outlets, or each outlet being configured for fluid communication with the lumen of the container. In certain instances, the cell processing platform is arranged to receive one or more auxiliary containers in fluid communication with the or each inlet.

[0064] This provides the advantage that multiple unit operations in cell therapy and / or gene therapy manufacturing can be performed in a single device.

[0065] In certain embodiments, the retaining element includes a clamping mechanism. The clamping mechanism may be arranged to clamp the top portion of the container in the first plane. The clamping mechanism may be arranged to be operably coupled to a housing, a unit, or the like. For example, the clamping mechanism may include a flange arranged to be received in a recess of the housing. For example, the clamping mechanism may include a clip for coupling the top portion of the container to another member, such as a platform or a housing.

[0066] In certain embodiments, the retaining element comprises a sealing plate, which may comprise or form the lid of the container.

[0067] This provides the advantage that media in the containers can be easily mixed regardless of their use, which in turn provides the advantage that the device can be used in a broader sense than just cell and / or gene therapy manufacturing.

[0068] In certain embodiments, the actuation mechanism comprises a base plate spaced apart from and substantially parallel to the movable plate, the base plate operably coupled to the movable plate.

[0069] That is, in some embodiments, the actuation mechanism comprises a base plate. The base plate can be a mounting plate. The base plate can be spaced apart from the movable plate along an axis. The base plate can be substantially parallel to the movable plate. The base plate can be substantially parallel to the first plane. The base plate can be operably coupled to the movable plate by any suitable mechanism, such as, for example, a linkage.

[0070] This provides the advantage that the base plate, and therefore the actuation mechanism, can be fixed to a surface, for example a table, incubator or housing unit.

[0071] In certain embodiments, the base plate comprises at least one actuator, and the or each actuator is operably coupled to or operably engageable with the movable plate.

[0072] That is, in some embodiments, the actuation mechanism comprises at least one actuator formed in or as part of the base plate. The or each actuator may be operably coupled to the moveable plate. That is, the or each actuator may be operably coupled to the base plate at one end and to the moveable plate at the other end. In some examples, the or each actuator may be operably engageable with the moveable plate. That is, the or each actuator may be connectable to the base plate at one end and have a free end operable to engage the moveable plate.

[0073] This provides the advantage that the actuation mechanism is easier to manufacture.

[0074] In certain embodiments, the base plate includes at least one rail, the or each rail upstanding therefrom substantially perpendicular to the base plate, the movable plate is slidably coupled to the or each rail, and at least one actuator is arranged to slide at least a portion of the movable plate along the or each rail.

[0075] That is, in some embodiments, the base plate includes one or more rails extending upward from the surface of the base plate, perpendicular to that surface, toward the movable plate. The movable plate may be connected to the or each rail in a sliding manner. That is, the movable plate may be slidable along the rail relative to the base plate. One or more actuators may be arranged to slide the movable plate along the or each rail. In some examples, there may be multiple rails. In some examples, one or more actuators may be arranged to slide a portion of the movable plate along each rail. In some examples, one or more actuators may be arranged to slide each portion of the movable plate along each rail simultaneously. In some examples, one or more actuators may be arranged to slide each portion of the movable plate non-simultaneously along each rail.

[0076] This provides the advantage that the movable plate, which is operably engageable with the base portion of the container, can engage the entire base portion of the container during use, In this way, forces applied to the container are distributed over the base portion of the container, thereby avoiding damage to the container or the device during use.

[0077] In certain embodiments, the base plate is operably coupled to the movable plate by at least one biasing element, the or each biasing element being arranged to bias the movable plate towards the base plate so that the second plane is substantially parallel to the first plane.

[0078] That is, in some embodiments, the base plate may include at least one biasing element, the or each biasing element coupled at one end to the base plate and operably coupled at the other end to the movable plate, and the or each biasing element may be arranged to bias the movable plate into a configuration in which the second plane is substantially parallel to the first plane.

[0079] In certain embodiments, the or each biasing element comprises a spring, preferably a tension spring.

[0080] That is, the or each biasing element can be a spring. The spring can be a tension spring. The spring can be a compression spring. The spring can bias the movable plate into a configuration in which the second plane is substantially parallel to the first plane.

[0081] In some embodiments, the or each biasing element comprises a resiliently deformable portion of the movable plate, the base plate, or both the movable plate and the base plate.

[0082] In certain embodiments, the base plate further comprises a rotatable support plate arranged to rotate about a longitudinal axis, the longitudinal axis being substantially perpendicular to the support plate. Further, in such embodiments, the support plate may comprise the or each actuator.

[0083] That is, in some embodiments, the actuation mechanism further comprises a support plate. The support plate may be rotatable about an axis. The axis may be a longitudinal axis that is substantially perpendicular to the support plate. The axis may be perpendicular to the first plane, the second plane, or both the first and second planes. The support plate may be formed as part of the base plate or as a separate element. The support plate may comprise one or more actuators.

[0084] In some embodiments, the support plate includes an actuator fixed to one end of the support plate. When the support plate rotates, the actuator can be actuated to rotate the movable plate about an axis in the second plane. The actuator can be actuated constantly while the support plate rotates to achieve a pivoting movement. The actuator can be actuated at set intervals or manually to move a portion of the movable plate during use.

[0085] This provides the advantage that the angle of rotation and speed at which the movable plate is moved can be easily adjusted.

[0086] In certain embodiments, the or each actuator comprises a linear actuator.

[0087] That is, in some embodiments, the or each actuator is actuable in a linear direction. The linear direction may be perpendicular to the first plane, the second plane, or both the first and second planes. The linear direction may be coaxial with or parallel to a longitudinal axis that is substantially perpendicular to the first and second planes. The linear direction may be toward the first plane, the second plane, or the movable plate.

[0088] In certain embodiments, the movable plate comprises at least one permanent magnet and the base plate comprises at least one corresponding electromagnet.

[0089] That is, in some embodiments, the movable plate comprises at least one permanent magnet. The movable plate may comprise multiple permanent magnets. The base plate may comprise at least one corresponding electromagnet. The base plate may comprise multiple corresponding electromagnets. In this context, corresponding is used to define that the respective magnets are positioned such that their magnetic fields can interact.

[0090] In another example, the movable plate includes at least one permanent magnet and the base plate includes at least one corresponding electromagnet.

[0091] That is, in some embodiments, the movable plate comprises at least one electromagnet. The movable plate may comprise multiple electromagnets. The base plate may comprise at least one corresponding permanent magnet. The base plate may comprise multiple corresponding permanent magnets. In this context, corresponding is used to define that the respective magnets are positioned such that their magnetic fields interact.

[0092] This provides the advantage that the actuation mechanism has no moving parts.

[0093] The or each electromagnet may be controlled by a controller.

[0094] In certain embodiments, the or each permanent magnet is distal from the center of the movable plate and the or each electromagnet is distal from the center of the base plate.

[0095] That is, in certain embodiments, the or each permanent magnet is distal to, or away from, the center of the moveable plate; the or each permanent magnet may be positioned off-center on the moveable plate; the or each electromagnet is distal to, or away from, the center of the base plate; the or each electromagnet may be positioned off-center on the base plate.

[0096] In another example, the or each permanent magnet is distal from the center of the movable plate and the or each electromagnet is distal from the center of the base plate.

[0097] That is, in certain embodiments, the or each electromagnet is distal or away from the center of the moveable plate; the or each electromagnet may be disposed off-center on the moveable plate; the or each permanent magnet is distal or away from the center of the base plate; the or each permanent magnet may be disposed off-center on the base plate.

[0098] In certain embodiments, the base plate includes at least one cam member, the or each cam member operably engageable with the movable plate, and the or each cam member driven by a motor.

[0099] That is, in some embodiments, the actuation mechanism comprises at least one cam member formed in or as part of the base plate. The or each cam member may be operably engageable with the movable plate, i.e., a cam surface may be engageable with a portion of the movable plate. In some examples, the or each cam member is driven by a motor. Each cam member may be driven by an independent motor.

[0100] This provides the advantage of increased ease of manufacturing the actuation mechanism.

[0101] In certain embodiments, the base plate comprises a central hub coaxial with and rotatable about a longitudinal axis perpendicular to the base plate, the central hub comprising connecting rods extending radially outward from the central hub and terminating in wheels, the wheels being operably engageable with the movable plate.

[0102] That is, in some embodiments, there may be a hub centrally disposed in or centrally formed as part of the base plate. The hub may be coaxial with a longitudinal axis extending perpendicular to the base plate or the first plane, the second plane, or the movable plate, and may be arranged to rotate about that longitudinal axis. There may also be a connecting rod extending radially from the hub toward the wheel. The wheel may be arranged to engage a portion of the movable plate. In this manner, when the central hub rotates, the wheel rotates about a circumference defined by the connecting rod, such that a pivoting movement is imparted to the movable plate.

[0103] This provides the advantage that a symmetrical gyrating motion can be achieved. The gyrating motion can be used to apply centrifugal force to the medium in the container on the movable plate, thereby separating materials in the medium based on density. That is, classification processing can be achieved through the gyrating motion. For example, blood can be processed to separate materials therein. Furthermore, this provides the advantage that the rotations per minute of the gyrating motion can be easily adjusted.

[0104] In certain embodiments, the central hub is rotated about a longitudinal axis by a motor.

[0105] That is, in some instances, the central hub may be driven by a motor.

[0106] This offers the advantage that, due to the construction of the base plate, only one motor is required, thereby improving energy efficiency.

[0107] In certain embodiments, the base plate includes a first linkage operably coupled to the movable plate, the first linkage being driven by a first motor.

[0108] That is, in one example, the actuation mechanism further includes a link mechanism, a first link mechanism of the link mechanisms, or a first portion of the link mechanism. The first link mechanism extends from the surface of the base plate toward the movable plate. The first link mechanism provides for movement of the movable plate about at least one axis in the second plane. The first link mechanism can be driven by a motor, such as a first motor.

[0109] In certain embodiments, the base plate further comprises a second linkage operably coupled to the movable plate, the second linkage being driven by a second motor.

[0110] That is, in some examples, the actuation mechanism further includes an additional link mechanism, a second one of the link mechanisms, or a second portion of the link mechanism. The second link mechanism extends from the surface of the base plate toward the movable plate. The second link mechanism serves to move the movable plate about at least one axis in a second plane. The second link mechanism can rotate the movable plate about multiple axes in the second plane. The second link mechanism can be driven by a motor, such as the first motor or the second motor.

[0111] In certain embodiments, the first linkage and the second linkage are operatively coupled at opposite edges of the movable plate.

[0112] That is, in one embodiment, the movable plate has opposite edges, the first linkage is operably connected to the movable plate at one edge or the first edge, and the second linkage is operably connected to the movable plate at the other edge or the second opposite edge.

[0113] In some examples, the first motor and the second motor can be positioned toward opposite edges of the base plate, the first motor can be adjacent to the first linkage, and the second motor can be adjacent to the second linkage.

[0114] This offers the advantage that wave agitation can be easily achieved in addition to compression movement.

[0115] In certain embodiments, the base plate further comprises a third linkage operably coupled to the movable plate, the third linkage being driven by a third motor.

[0116] That is, in some embodiments, the base plate may further include an additional linkage, a third linkage among the linkages, or a third portion of the linkage. The third linkage extends from the surface of the base plate toward the movable plate. The third linkage serves to move the movable plate about at least one axis in the second plane. The third linkage may move the movable plate about multiple axes in the second plane. The third linkage may be driven by a motor, such as the first motor, the second motor, or the third motor.

[0117] This provides the advantage that an agitation movement can be realized in combination with a compression movement, and further provides the advantage that the agitation movement can be customized by the user.

[0118] In certain embodiments, a linkage having several portions may be provided. For example, there may be a linkage having a first portion, a second portion, and optionally a third portion. The various portions may be arranged to provide rotation about one axis, two axes, three axes, or an infinite number of axes in a second plane.

[0119] In certain embodiments, the first linkage, the second linkage, and the third linkage are operably coupled to the movable plate in a triangular arrangement.

[0120] That is, in some embodiments, the attachment points of each linkage form a triangular arrangement, i.e., there can be three attachment points spaced apart in a triangular arrangement.

[0121] This provides the advantage that additional support is provided to the movable plate.

[0122] In certain embodiments, the actuation mechanism comprises a first motor operably coupled to the movable plate and configured to rotate the movable plate about at least one axis in the second plane.

[0123] In some examples, the first motor is a reciprocating motor, a brushless motor, a brush motor, etc. In some examples, the first motor is positioned to impart a rocking or undulating motion to the movable plate and, in turn, to the received container.

[0124] This provides the advantage that motors can be designated for only rocking, swinging, or undulating motion. Thus, the rocking, swinging, or undulating motion can be more carefully controlled. Furthermore, by having designated rocking or undulating motors, the motors of the device do not need to be synchronized.

[0125] In certain embodiments, the actuation mechanism further includes a second motor operably coupled to the movable plate and configured to move the movable plate along a longitudinal axis substantially perpendicular to the first plane and / or the second plane, thereby reducing the distance between at least a portion of the second plane and the first plane. The first and second planes can be substantially parallel throughout the movement. The longitudinal axis can be substantially perpendicular to the first and second planes prior to actuation of the actuation mechanism.

[0126] This provides the advantage that a motor can be designated solely for longitudinal translation of the movable plate, and thus solely for compression / decompression of the received container. Specifically, a second motor can be designated solely for linear compression mixing of the contents of the received container within the device. Furthermore, by having a designated compression motor, the device motors do not need to be synchronized.

[0127] In certain embodiments, the actuation mechanism includes a third motor operably coupled to the movable plate and configured to move the movable plate along the longitudinal axis, thereby reducing the distance between a portion of the second plane and the first plane.

[0128] This provides the advantage that the other motor can be designated solely for longitudinal translation of the movable plate, and thus solely for compression / decompression of the received container. Thus, the third motor can operate independently of or in harmony with the second motor to achieve the desired compression / decompression. Specifically, the third motor may be designated solely for respiration or perfusion movements, i.e., for long, slow compressions or decompressions of the received container.

[0129] In a specific embodiment, the linkage comprises a first linkage portion positioned to operably connect the second motor to the movable plate.

[0130] In a specific embodiment, a linkage, such as a first linkage portion, includes a crank housing with a rotatable crank slidable along a first longitudinal rail and extending substantially parallel to the longitudinal axis. The first longitudinal rail can be a single rail or a pair of parallel rails. The crank housing can be operably coupled to the first longitudinal rail so as to be slidable along the first longitudinal rail or slidably connected to the first longitudinal rail.

[0131] Thus, in some embodiments, the crank can be driven by a second motor to convert rotational motion of the motor into axial translation of the movable plate. With each revolution of the crank, i.e., through 360 degrees of rotation, the crank can move the movable plate axially along the longitudinal axis in a first direction toward the retaining element and then axially along the longitudinal axis in a second direction opposite the first direction away from the retaining element. Thus, each revolution of the crank can result in a complete compression and decompression cycle.

[0132] In a specific embodiment, the linkage includes a second linkage portion positioned to operably connect the third motor to the movable plate.

[0133] In a specific embodiment, a linkage, such as a second linkage portion, is operably coupled to the movable plate and includes a slider portion slidable along a second longitudinal rail. The second longitudinal rail may extend substantially parallel to the first longitudinal rail. The second longitudinal rail may be a single rail or a pair of parallel rails. The slider portion may be operably coupled to the rotatable crank by a connecting rod. The slider portion may be operably coupled to the second longitudinal rail so as to be slidable along the second longitudinal rail or slidably connected to the second longitudinal rail.

[0134] In a specific embodiment, a second motor is operably coupled to the rotatable crank to rotate the rotatable crank and move the slider portion along the second longitudinal rail. Further, in a specific embodiment, a third motor is operably connected to the crank housing to move the crank housing along the first longitudinal rail.

[0135] This arrangement provides the advantage that the second motor can be of unidirectional motion, thereby improving the force output while also reducing the noise or heat output. Additionally, a rapid compressive mixing motion can be imparted to the received container through a single motor.

[0136] In certain embodiments, the third motor comprises a ball screw motor or a lead screw motor. The ball screw motor or the lead screw motor may be operably coupled to a corresponding threaded portion of the crank housing. The threaded portion of the crank housing or the crank housing may be movable along the first longitudinal rail. The threaded portion of the crank housing or the crank housing may be slidably connected to the first longitudinal rail.

[0137] Thus, in some embodiments, the ball screw or lead screw motor can move the movable plate axially along the longitudinal axis in a first direction toward the holding element. Furthermore, the ball screw or lead screw motor can move the movable plate axially along the longitudinal axis in a second direction opposite the first direction away from the holding element. Thus, the ball screw or lead screw motor can cause compression and / or decompression of the received container. The ball screw or lead screw motor can cause a complete compression and decompression cycle. The ball screw or lead screw motor can cause compression and decompression at a slower rate than the second motor. That is, the second motor can have a first compression and decompression cycle speed, and the third motor can have a second compression and decompression cycle speed, the first speed being greater than the second speed.

[0138] This offers the advantage of providing slow longitudinal translation of the movable plate, which is desirable for many unit operations in cell processing, such as respiration, gas exchange, harvesting, or removal of vessel contents, etc. This is particularly advantageous in freestanding vessel cell processing systems.

[0139] Overall, in embodiments utilizing the above-described first, second, and / or third motors, optionally in combination with the described linkage, the following advantages are realized: · The required motion can be achieved by a single device, thus a single device can provide compression, wave, rocking and / or gyration motion to the received container. Increased power output. · Reduced noise output. Reduced heat output and therefore less need for cooling equipment. Reduced wear on the components, especially on the linkages connected to the corresponding motors. There is no need to synchronize the motor inside the device before use. Complex mixing movements as a combination of compression, wave, rocking, and / or swirling movements can be achieved in a single device. Each movement can be tailored to the user's needs through control of each motor. The motor is positioned behind the received container rather than directly below it, thereby reducing the height of the device, an important consideration as space is limited in such lab and / or high throughput settings.

[0140] Thus, an improved apparatus for imparting agitation and / or mixing to a received container is provided, particularly for apparatus for use in one or more unit operations of cell processing.

[0141] In certain embodiments, the or each motor comprises a stepper motor.

[0142] In certain embodiments, the or each motor is operably connected to one or more gearboxes.

[0143] That is, in some embodiments, one, more than one, or several, or most or all of the motors may be connected to one or more gearboxes, each of which may have its own independent gearbox.

[0144] In certain embodiments, the device further comprises a controller communicatively coupled to the actuation mechanism.

[0145] That is, in some embodiments, the device may further include a controller. The controller may be configured to control the actuation mechanism or a portion thereof. The controller may be communicatively coupled, e.g., electrically or mechanically coupled, to the actuation mechanism or a portion thereof. For example, the controller may be communicatively coupled to one or more motors, one or more linkages, or one or more actuators, etc. The controller may take the form of a personal computer, tablet, smartphone, etc. The controller may include a series of pre-programmed programs for executing pre-programmed movements of the movable plate.

[0146] This provides the advantage that the user can customize the stirring action, and also allows the user to easily select pre-set stirring actions, thereby providing a more user-friendly device.

[0147] Still further, the control device may allow monitoring of media and / or cells, etc., in vessels disposed on the movable plate during use so that stirring control motion can be adjusted on the fly.

[0148] In certain embodiments, the apparatus further comprises one or more sensors, the or each sensor configured to monitor, analyze, detect, etc., material in the containers on the movable platen. The or each sensor may be communicatively coupled to the controller. The or each sensor may be any suitable sensor for monitoring, analyzing, detect, etc., material in the containers on the movable platen.

[0149] In certain embodiments, the controller may upload data collated from the or each sensor to a personal computer, smartphone, tablet, storage medium, or internet-based storage system, such as the cloud.

[0150] This provides the advantage that the collated data can be used to improve the application of the device to different media and / or cells.

[0151] In certain embodiments, the control device includes a user interface to allow a user to control, monitor, etc. the device during use.

[0152] In certain embodiments, the device further comprises one or more positioning sensors, the or each positioning sensor being communicatively coupled to a controller, the controller generating a signal to the actuation mechanism based on a signal received from the or each positioning sensor.

[0153] That is, in some embodiments, the device includes one or more sensors. The one or more sensors may be positioned and / or configured to sense the position of the movable plate relative to the first plane. The or each sensor may be communicatively coupled, e.g., electrically or mechanically, to a controller. The or each sensor may optionally be communicatively coupled, e.g., electrically or mechanically, to an actuation mechanism or portion thereof, such as one or more motors, one or more linkages, or one or more actuators. The sensor may be arranged to generate a signal, which may indicate, e.g., the relative positioning of the movable plate or the status of the actuation mechanism or portion thereof, and the sensor may be arranged to send such a signal to the controller. The controller may generate a signal to the actuation mechanism or portion thereof, such as one or more motors, one or more linkages, or one or more actuators, based on the signal received from the or each sensor.

[0154] This provides the advantage that the actuation mechanism precisely performs the desired stirring movement.

[0155] As disclosed herein, any retention mechanism, actuation mechanism, or any other feature can be used in combination with any other actuation mechanism, retention element, or any other feature. Specifically, there may be many actuation mechanisms that can be used in combination. For example, an actuation mechanism may have a magnet-electromagnet arrangement combined with a cam arrangement. In other examples, any suitable linear actuator mechanism, such as a series of linear actuators, may be used in combination with any rotary actuation mechanism, such as one or more linkages driven by a motor. Any other combinations are contemplated herein.

[0156] Alternatively or in addition to any one of the previously discussed embodiments, an apparatus for use in performing one or more unit operations in cell processing is provided, comprising: a retaining element arranged to receive an upper portion of a container in a first plane; a movable plate spaced from the retaining element and arranged to operably engage a base portion of the container, the movable plate defining a second plane substantially parallel to the first plane; and an actuation mechanism operably coupled to the movable plate and arranged to move the movable plate along a longitudinal axis substantially perpendicular to the first and second planes, thereby reducing the distance between the second plane and the first plane. The distance between the entire second plane and the entire first plane may be reduced. Any one of the above-described embodiments, such as the retaining element, actuation mechanism, movable plate, or container, may be used in combination with this specific embodiment of the apparatus. Similarly, the method of use of the above-described specific embodiment, i.e., axial translation of the movable plate in combination with or as an alternative to rotation about an axis in the second plane, is discussed.

[0157] In another embodiment of the invention, there is provided a system for use in performing one or more unit operations in cell processing, comprising: a device as described herein; a container having a base portion, an upper portion parallel to the base portion, and a compressible wall element extending substantially vertically between the base portion and the upper portion; Equipped with A system is provided in which the container is disposed between the retaining element and the movable plate, and the actuation mechanism is arranged to move the movable plate such that at least a portion of the compressible wall element is at least partially compressed along a longitudinal axis perpendicular to the first plane and the second plane.

[0158] In certain embodiments, the base portion of the container is fixedly attached to the movable plate.

[0159] Thus, in certain embodiments, the base portion is fixedly coupled, connected, or otherwise attached to the movable plate, i.e., there is a physical connection, whereby the base portion of the container is moved directly by the device, which can provide more controlled mixing of the contents of the container.

[0160] In certain embodiments, the base portion of the container is fixedly attached to the movable plate, such as by one or more adhesives, fasteners, or the like.

[0161] In certain embodiments, the base portion of the container is engageable with the movable plate.

[0162] Thus, in certain embodiments, the base portion is not directly coupled, connected, or otherwise attached to the movable plate; that is, there is no physical connection. Instead, the base portion can intermittently contact the movable plate. This can achieve a so-called "slapping" effect, whereby the movable plate intermittently contacts or "smacks" with the base portion of the vessel. This can provide improved mixing, and more specifically, improved suspension, of the cells in the medium.

[0163] In another embodiment of the invention, there is provided a system for use in performing one or more unit operations in cell processing, comprising: a container having a base portion, an upper portion parallel to the base portion, and a compressible wall element extending substantially vertically between the base portion and the upper portion; a retaining element operably engaged with the top portion of the container to retain the top portion of the container in the first plane; a movable plate spaced from the retaining element and operably engaged with a base portion of the container, the movable plate defining a second plane substantially parallel to the first plane; an actuation mechanism operatively coupled to the movable plate for moving the movable plate about at least one axis in the second plane to at least partially compress at least a portion of the compressible wall element along a longitudinal axis perpendicular to the first plane and the second plane; A system is provided comprising:

[0164] Thus, a system is also provided that includes an apparatus as described herein and a container.

[0165] In certain embodiments, the base portion of the container is fixedly attached to the movable plate.

[0166] Thus, in certain embodiments, the base portion is fixedly coupled, connected, or otherwise attached to the movable plate, i.e., there is a physical connection, whereby the base portion of the container is moved directly by the device, which can provide more controlled mixing of the contents of the container.

[0167] In certain embodiments, the base portion of the container is fixedly attached to the movable plate, such as by one or more adhesives, fasteners, or the like.

[0168] In certain embodiments, the base portion of the container is engageable with the movable plate.

[0169] Thus, in certain embodiments, the base portion is not directly coupled, connected, or otherwise attached to the movable plate; that is, there is no physical connection. Instead, the base portion can intermittently contact the movable plate. This can achieve a so-called "slapping" effect, whereby the movable plate intermittently contacts or "smacks" with the base portion of the vessel. This can provide improved mixing, and more specifically, improved suspension, of the cells in the medium.

[0170] In certain embodiments, the container may comprise a base portion, an upper portion extending parallel to the base portion, and a compressible wall element extending between the upper portion and the base portion. The compressible wall element may extend substantially perpendicular to the upper portion and the base portion.

[0171] In certain embodiments, the vessel may include a base portion, an upper portion extending parallel to the base portion, and a wall element extending between the upper portion and the base portion. The wall element may be a compressible wall element, a flexible wall element, a deformable wall element, an elastically deformable element, or the like. The wall element may allow compressibility along at least one axis. In certain examples, a portion of the vessel wall element may be compressible, flexible, deformable, elastically deformable, or the like. The vessel may be a cell processing vessel. The vessel may be a cell culture vessel. The vessel may be a bioreactor. The vessel may be bellows, may include bellows, may form bellows, may be concertina-shaped, may include a concertina-shaped, or may form a concertina-shaped. The vessel may be a bellows-based bioreactor. The vessel may include a lumen for receiving a cell processing medium or material therein.

[0172] The device, i.e., the retaining element, may be arranged to receive the top portion of the container. The retaining element may be arranged to hold the top portion of the container in a first plane.

[0173] The device, i.e., the movable plate, can be arranged to operatively engage with a base portion of the container. The movable plate can be coupled to the base portion of the container, i.e., there can be some physical connection between the movable plate and the base portion of the container. The movable plate can be engageable with the base portion of the container, i.e., the movable plate need not be physically connected to the base portion of the container; instead, the movable plate can be configured and arranged to act on the base portion of the container. In some examples, the movable plate is configured for face-to-face engagement with the base portion of the container during use.

[0174] The movable plate is movable around an axis of a second plane defined by the plane of the movable plate. When the movable plate is moved by the actuation mechanism, the base portion of the container is moved. When the upper portion is held in the first plane and the second plane changes so that the base portion of the container changes, this results in compression of at least a portion of the compressible wall element. The compressible wall element may be compressible along a longitudinal axis extending substantially perpendicular to the first plane and the second plane and extending substantially parallel to the compressible wall element. That is, the distance between at least a portion of the second plane and the first plane is reducible during use. As a result, the container, and specifically the compressible wall element, may be compressed.

[0175] In one example, the movable plate may be movable along the longitudinal axis to compress the container, specifically the wall elements of the container, when the entire second plane is moved towards the first plane.

[0176] Any of the features discussed in relation to the device may form part of the system.

[0177] In specific embodiments, the system may further include a platform, e.g., a cell processing platform, sealingly engaged with the upper portion of the container. The upper portion of the container may include a passageway for fluid. The platform may form a liquid-tight seal, preferably a fluid-tight seal, at, near, or around the fluid passageway of the container. The platform may include at least one inlet fluidly connected to at least one outlet. In preferred examples, the platform may include at least one inlet, e.g., multiple inlets, fluidly connected or directly fluidly connected to, e.g., only one, outlet. The or each outlet of the platform may be in fluid communication with the passageway of the container.

[0178] In specific embodiments, the platform can include at least one auxiliary container sealingly engaged with the platform. The or each auxiliary container can include a passageway for fluid. The passageway of the or each auxiliary container can be fluidly connected to one or more inlets of the platform or can be fluidly connected directly. Thus, a fluid passageway can be formed from one or more auxiliary containers, for example, from a lumen of the or each auxiliary container, through the platform and into the lumen of the container.

[0179] In some embodiments, the auxiliary vessel may include a base portion, an upper portion extending parallel to the base portion, and a wall element extending between the upper portion and the base portion. The wall element may be a compressible wall element, a flexible wall element, a deformable wall element, an elastically deformable element, or the like. The wall element may allow compressibility along at least one axis, such as, for example, along a longitudinal axis extending perpendicular to the upper portion and the base portion. In some examples, a portion of the vessel wall element may be compressible, flexible, deformable, elastically deformable, or the like. The auxiliary vessel may be a cell processing vessel. The auxiliary vessel may be a cell culture vessel. The auxiliary vessel may be a bioreactor, e.g., an additional or secondary bioreactor. The auxiliary vessel may be a breathing vessel, e.g., a breathing bellows. That is, the auxiliary vessel may compensate for pressure changes in the primary vessel, as discussed herein. The auxiliary container may be, include, form, or be a bellows. The auxiliary container may be, include, or form a concertina. The auxiliary container may be a bellows-based breathing container. The auxiliary container may include a lumen for receiving cell processing media or materials therein.

[0180] In certain embodiments, a platform, e.g., a cell processing platform, may comprise a primary vessel, e.g., a bioreactor, sealingly engaged on a first side thereof, and one or more secondary or auxiliary vessels sealingly engaged on a second side thereof. As previously described, the primary vessel may be in fluid communication with an outlet of the platform, and / or the or each secondary vessel may be in fluid communication with one or more inlets of the platform. The or each secondary vessel may comprise an upper portion, a base portion extending parallel to the upper portion, and a compressible wall element between the upper portion and the base portion. The or each primary vessel, e.g., a bioreactor, cell processing vessel, or cell culture vessel, may comprise an upper portion, a base portion extending parallel to the upper portion, and a compressible wall element between the upper portion and the base portion. During use, the or each primary vessel may be in fluid communication with the or each secondary vessel through or via the platform. Thus, in use, when the primary container is compressed, rotated, pivoted, etc. by the movable plate, the or each secondary container can offset the increase or decrease in pressure in the or each primary container, i.e., the secondary container can act as a breathing container, expelling or drawing fluid into or from the secondary container as pressure shifts in the primary container.

[0181] This provides the advantage that there is no vacuum or pressure buildup in the main vessel, which can be beneficial in, for example, cell culture vessels.

[0182] In another aspect of the invention, there is provided a method of treating cells, comprising the steps of: providing a cell treatment medium to a container, the container having a base portion, an upper portion parallel to the base portion, and a compressible wall element extending substantially vertically between the base portion and the upper portion; holding a top portion of the container in a first plane; engaging a base portion of the container with a movable plate defining a second plane substantially parallel to and spaced apart from the first plane; rotating the base portion of the vessel about at least one axis in a second plane, thereby inducing turbulent flow of the cell treatment medium within the vessel; A method is provided that includes:

[0183] The movable plate may be a movable plate as discussed herein in connection with the device or system.

[0184] That is, rotating the base portion of the container about at least one axis in the second plane can thereby cause agitation, mixing, turbulence, or the like of the cell treatment medium within the container.

[0185] In certain embodiments, the step of rotating the base portion of the container includes rotating the base portion of the container about an axis in the second plane.

[0186] In some instances, this can result in undulating turbulence of the cell treatment medium within the vessel.

[0187] That is, in some embodiments, rotating the base portion of the vessel about an axis in the second plane creates turbulent flow of the cell treatment medium, e.g., wave motion, wave agitation, or wave turbulence, such that the cell treatment medium can be pushed toward one side of the vessel adjacent the wall element and then toward the opposite side of the vessel adjacent the opposing wall element, thereby creating a wave or undulating effect.

[0188] In certain embodiments, a longitudinal axis extending perpendicular to the first plane and the second plane intersects the second plane at an origin, and the step of rotating the base portion of the container includes pivoting the base portion of the container about the origin.

[0189] In some instances, this can result in turbulent swirling of the cell treatment medium within the vessel.

[0190] That is, in certain embodiments, pivoting the base of the vessel about an origin results in turbulent flow of the cell treatment medium, e.g., a whirling motion, whirling agitation, or whirling turbulence, i.e., the cell treatment medium can be rotated about a longitudinal axis, such as the central longitudinal axis of the vessel, i.e., rotated in a whirling manner.

[0191] In certain embodiments, the origin is centered within the second plane.

[0192] In certain embodiments, the method further includes compressing the compressible container along a longitudinal axis that is perpendicular to the first plane and the second plane.

[0193] In some embodiments, the step of holding the top portion of the container includes holding the top portion of the container in the first plane with a holding element.

[0194] The retaining element can be any retaining element as discussed herein in connection with the device or system.

[0195] In some embodiments, the step of rotating the base portion of the container about at least one axis in the second plane includes actuating an actuation mechanism operably coupled to the movable plate.

[0196] In some embodiments, engaging the base portion of the container with the movable plate comprises forming a physical connection between the base portion of the container and the movable plate, while in other embodiments, engaging the base portion of the container with the movable plate comprises forming an intermittent (i.e., non-continuous) connection between the base portion of the container and the movable plate.

[0197] The actuation mechanism can be any actuation mechanism as discussed herein in connection with the device or system.

[0198] The device or system may be used in the context of cell therapy manufacturing and / or gene therapy manufacturing.

[0199] The device or system may be housed within a cell processing unit. Preferably, the cell processing unit comprises an incubator. The incubator may include a supply of gases, such as oxygen and / or carbon dioxide. The incubator may comprise a device described herein, a system described herein, or a controller configured to control the incubator itself, such as controlling the gas supply to the incubator.

[0200] Cell processing method According to a further aspect of the invention there is provided a method of treating cells, comprising the steps of: (a) providing a compressible container comprising a population of cells in a liquid medium; (b) maintaining the population of cells in the liquid medium while applying pressure to at least a portion of the compressible container to compress the container; A method is provided that includes:

[0201] In one embodiment, the liquid medium is retained in the compressible container after compression is applied.

[0202] In one embodiment, the compressible container is comprised in the apparatus of the first aspect of the invention or the system of the second or third aspects of the invention.

[0203] According to a further aspect of the present invention there is provided a method of treating cells using the apparatus of the first aspect of the present invention, wherein the apparatus further comprises a container.

[0204] In one embodiment, the container is as described elsewhere herein. In one embodiment, the container is suitable for containing a population of cells in a liquid medium. In one embodiment, the container is compressible.

[0205] In one embodiment, the method comprises: (a) providing a population of cells in a liquid medium in a container; (b) operating the device to process the population of cells in the liquid medium; Includes.

[0206] According to a further aspect of the invention there is provided a method of treating cells, comprising the steps of: (a) providing an apparatus according to a first aspect of the present invention, the apparatus further comprising a container comprising a population of cells in a liquid medium; (b) operating the device to process the population of cells in the liquid medium; A method is provided, comprising:

[0207] In one embodiment, treating the population of cells comprises maintaining the population of cells in a liquid medium while pressure is applied to at least a portion of the container to compress the container.

[0208] According to a further aspect of the present invention there is provided a method of treating cells using a system according to the second or third aspect of the invention.

[0209] In one embodiment, the container of the system is compressible.

[0210] In one embodiment, the method comprises: (a) providing a population of cells in a liquid medium in a container; (b) operating the system to process a population of cells in a liquid medium; Includes.

[0211] According to a further aspect of the invention there is provided a method of treating cells, comprising the steps of: (a) providing a system according to the second or third aspect of the present invention, wherein a container comprises a population of cells in a liquid medium; (b) operating the system to process a population of cells in a liquid medium; A method is provided, comprising:

[0212] In one embodiment, treating the population of cells comprises maintaining the population of cells in a liquid medium while pressure is applied to at least a portion of the container to compress the container.

[0213] Suitably, the container is compressible. Suitably, the compressible container is adapted for storing and / or culturing cells. Suitably, the compressible container is sterile.

[0214] Suitably, the compressible vessel has a volume suitable for cell culture, suitably on an industrial scale. Suitably, the compressible vessel has a volume of between 1 μl and 1000 L. Suitably, the compressible vessel has a volume of at least 50 ml, suitably up to 1 litre. Suitably, this is the volume of the vessel when depressurised.

[0215] Suitably, the compressible vessel is a bioreactor. Suitably, the compressible vessel is operable to expand and contract. Suitably, the compressible vessel comprises a bellows. Suitably, the compressible vessel comprises a bellows bioreactor. In one embodiment, the compressible vessel is a bellows bioreactor as described in U.S. Patent No. 5,649,999.

[0216] Suitably, the compressible container is mounted within a device. Suitably, the device is operable to apply pressure to at least a portion of the compressible container. Suitably, the device is operable to release pressure from the compressible container. Suitably, the device is operable to thereby compress and decompress the compressible container, as described elsewhere herein. In one embodiment, the device is an apparatus according to the first aspect of the invention, or a system according to the second or third aspect of the invention, as described elsewhere herein.

[0217] Suitably, the population of cells comprises one or more cells present in a liquid medium.

[0218] Suitably, the population of cells may comprise any cell type. Suitably, the population of cells may comprise a homogenous cell type. Alternatively, the population of cells may comprise a mixed population of cells.

[0219] Suitably, the population of cells may comprise any human or animal cell type, for example, any type of adult stem or primary cell, T cells, CAR-T cells, monocytes, leukocytes, erythrocytes, NK cells, gamma delta T cells, tumor infiltrating T cells, mesenchymal stem cells, embryonic stem cells, induced pluripotent stem cells, adipose-derived stem cells, Chinese hamster ovary cells, NS0 mouse myeloma cells, HELA cells, fibroblasts, HEK cells, insect cells, organoids, etc. Suitably, the population of cells may comprise T cells.

[0220] Alternatively, the population of cells may include any microbial cell type, such as bacterial, fungal, archaeal, protozoan, or algal cells.

[0221] Suitably, the liquid medium can be any sterile liquid that can support cells. Suitably, the liquid medium can be selected from physiological saline or cell culture medium. Suitably, the liquid medium is a cell culture medium selected from any suitable medium, such as DMEM, XVIVO 15, TexMACS, etc. Suitably, the liquid medium is suitable for the type of cells present in the population. Those skilled in the art will know the suitable medium to use when culturing cells.

[0222] For example, the population of cells includes T cells and the liquid medium includes XVIVO 10.

[0223] Suitably, the liquid medium may further comprise additives such as growth factors, nutrients, buffers, minerals, stimulants, or stabilizers.

[0224] Suitably, the liquid medium comprises a growth factor, such as a cytokine and / or a chemokine. Suitably, the growth factor is appropriate for the type of cells present in the population and the desired treatment to be performed. Suitably, the liquid medium comprises a stimulatory agent, such as an antigen or antibody, which can be loaded onto a support. Suitable stimulatory agents are appropriate for the type of cells present in the population and the desired treatment to be performed. Suitably, when culturing T cells, for example, an antibody is provided as a stimulatory agent in the liquid medium. Suitably, the antibody is incorporated into an inert support, such as beads, for example, Dynabeads.

[0225] Suitably, the additive is present in the liquid medium at an effective concentration, which can be determined by one skilled in the art based on the population of cells and the desired treatment to be performed using teachings and techniques known in the art.

[0226] Suitably, the population of cells is 1x10 4 cfu / ml to 1x10 8 It is seeded in liquid media at concentrations ranging from 0.01 to 0.01 cfu / ml.

[0227] Suitably, the method of the present invention may be a batch, fed-batch, continuous method of processing cells, or a combination thereof.

[0228] Suitably, the liquid medium may be batch fed during processing to reach a desired volume, suitably this may be known as batch fed processing. Suitably, the liquid medium is batch fed into a compressible container. Suitably, the liquid medium may be suitably replaced with fresh medium. Suitably, the liquid medium may be replaced by batch fed medium replacement. Suitably, this may be known as perfusion culture.

[0229] Suitably, the method of the invention may be fed-batch for a period of time followed by fed-batch with medium replacement. Suitably, the method of the invention may be fed-batch for a period of time followed by perfusion for a period of time.

[0230] Suitably, batch-fed medium replacement or perfusion may be achieved by compressing a compressible container to expel medium from the container and adding fresh medium to the container.

[0231] Suitably, the liquid medium may be present in a desired volume at the start of the process and no further medium may be added, suitably this is known as batch processing.

[0232] Suitably, the liquid medium may be continuously added to the vessel throughout the process to maintain the desired volume, suitably this is known as continuous processing.

[0233] Suitably, the desired total volume of medium is calculated based on the treatment and cell type used in the method.

[0234] Suitably, in a fed batch process the medium may be fed in batches of 50ml to 500ml.

[0235] Suitably, the liquid medium is pumped into the compressible vessel at different times during the treatment.

[0236] Suitably, the amount of liquid medium pumped into the compressible container at any given time during processing may vary depending on the step of the processing and the cell processing being performed.

[0237] Suitably, between 0 mL and 200 mL per day is pumped into the compressible container during the step under static conditions.

[0238] Suitably, between 0 mL and 500 mL per day is pumped into the compressible container during the step under dynamic conditions.

[0239] Suitably, between 0 mL and 800 mL per day is pumped into the compressible container during the step under compression.

[0240] Maintaining a population of cells in a suitable liquid medium can involve performing any type of cell treatment.

[0241] Suitably, cell processing may include culturing, mixing, washing, expanding, genetically modifying, stimulating, transforming, transfecting, or engineering a population of cells, arresting cell growth, selecting cells, or freezing or thawing cells.

[0242] Suitably, cell processing may include the derivation / isolation of primary cells from solid biopsies, embryonic and fetal material, blood, and other liquid samples.

[0243] Suitably, cell processing may involve decellularization of solid tissue, suitably for tissue engineering.

[0244] Suitably, cell treatment may include growing organoids, growing cells on microcarriers, or growing cell aggregates.

[0245] Suitably, the method of treating cells may comprise two or more types of cell treatment. Suitably, the method of treating cells may comprise a plurality of different steps of cell treatment. Suitably, the different steps of cell treatment may be selected from any of the types of cell treatment described above.

[0246] For example, the method of treating cells may include growing cell aggregates (e.g., growing embryoid bodies) prior to expanding the cell aggregates.

[0247] Typically, the step of maintaining the population of cells in a liquid medium comprises culturing the population of cells in the liquid medium. Suitably, culturing the population of cells comprises expanding the population of cells in the liquid medium.

[0248] Suitably, the population of cells is maintained in the liquid medium for a period of time sufficient for the desired cell processing to be completed.

[0249] The process of the present invention includes at least the step of maintaining a population of cells in a liquid medium while pressure is applied to at least a portion of a compressible container to compress the container. Suitably, the process of the present invention may further include other cell processing steps, as discussed above.

[0250] Suitably, the or each further processing step of the method may be carried out under any conditions. Suitably, the or each further processing step of the method may be carried out under static or dynamic conditions.

[0251] Suitably, the treatment may further comprise one or more steps of maintaining the population of cells under static or dynamic conditions. Suitably, the treatment may further comprise one or more steps of culturing the population of cells under static or dynamic conditions. Suitably, such additional steps are carried out before the compacting step (b).

[0252] Suitably, the treatment comprises, suitably prior to step (b), at least one step of maintaining the population of cells under static or dynamic conditions.

[0253] Suitably, the treatment comprises, suitably prior to step (b), at least one step of maintaining the population of cells under static conditions and at least one step of maintaining the population of cells under dynamic conditions.

[0254] Suitably, the process may comprise a plurality of static and / or dynamic steps, suitably prior to step (b). Suitably, the process may comprise a first static step and a first dynamic step.

[0255] Suitably, the process may further comprise a second static step and a second dynamic step. Suitably, the static and dynamic steps may alternate.

[0256] For example, the process (a) providing a compressible container comprising a population of cells in a liquid medium; (b) maintaining the population of cells in a liquid medium under static conditions; and / or (c) maintaining the population of cells in a liquid medium under dynamic conditions; (d) maintaining the population of cells in the liquid medium while applying pressure to at least a portion of the compressible container to compress the container; may include:

[0257] For example, the process (a) providing a compressible container comprising a population of cells in a liquid medium; (b) maintaining the population of cells in a liquid medium under static conditions for a first period of time; (c) maintaining the population of cells in a liquid medium under dynamic conditions for a first period of time; (d) maintaining the population of cells in the liquid medium under static conditions for a second period of time; (e) maintaining the population of cells in the liquid medium under dynamic conditions for a second period of time; (f) maintaining the population of cells in the liquid medium while applying pressure to at least a portion of the compressible container to compress the container; may include:

[0258] Suitably, maintenance under static conditions means that the population of cells in the liquid medium is not subjected to substantial movement or forces.

[0259] Suitably, maintaining under dynamic conditions means that the population of cells in the liquid medium is subjected to movement or forces.

[0260] There are many different types of dynamic cell culture techniques known in the art, and any dynamic culture technique can suitably be used in the processes of the present invention. For example, dynamic conditions can include any form of agitation of the liquid medium, such as rocking, rotating, stirring, wave, agitation, or swirling motion. Thus, suitably, maintaining a population of cells in a liquid medium under dynamic conditions can include applying rocking, agitation, wave, agitation, or swirling motion to the liquid medium. Suitably, each dynamic step of the process can include a different form of dynamic condition.

[0261] For example, a first dynamic step of the treatment may include maintaining a population of cells in a liquid medium under dynamic conditions that include applying a rocking motion to the liquid medium, and a second dynamic step of the treatment may include maintaining a population of cells in a liquid medium under dynamic conditions that include applying a wave motion to the liquid medium.

[0262] Suitably, the dynamic conditions applied to the cell population may be applied at a specific speed or frequency. Suitably, such speed or frequency can be changed. Suitably, the rocking motion can include any speed. Suitably, the rocking motion includes a speed defined in rocking per minute (rpm). For example, the rocking motion includes an rpm between 20 rpm and 60 rpm. For example, the rocking motion includes an rpm between 20 rpm and 60 rpm.

[0263] It is possible that each dynamic step of the treatment may include the same form of dynamic conditions, but applied at a different speed or frequency. For example, a first dynamic step of the treatment may include maintaining a population of cells in a liquid medium under dynamic conditions that include applying a rocking motion to the liquid medium at a speed of 60 rpm, and a second dynamic step of the treatment may include maintaining a population of cells in a liquid medium under dynamic conditions that include applying a rocking motion to the liquid medium at a speed of 20 rpm.

[0264] Suitably, different speeds may be used in the process, suitably during different dynamic steps, for example a first dynamic step may comprise applying an oscillating motion to the liquid medium at a speed of 60 rpm, and a second dynamic step may comprise applying an oscillating motion to the liquid medium at a speed of 20 rpm.

[0265] It should be understood that the compressing step (b) may also include maintaining the population of cells under dynamic conditions. Suitably, the liquid medium is agitated during compression of the compressible container, whereby the compression of said compressible container also provides dynamic conditions. Specifically, when a compressible container comprising bellows is used, upon compression, the liquid medium comes into contact with the folds of the bellows, and upon expansion, the liquid medium is lifted and falls from the folds of the bellows. Thus, suitably, the population of cells may be maintained under dynamic conditions by compression of the compressible container in step (b) of the treatment.

[0266] Suitably, the treatment itself lasts for a period of time sufficient to complete the desired treatment of the cells. Such periods of time will be known to those skilled in the art, but suitably the treatment can take minutes, hours, days, weeks or months, suitably between 1 minute and several months, suitably between 1 minute and 2 weeks, suitably between 1 hour and 2 weeks, suitably between 1 day and 14 days, suitably between 5 days and 14 days.

[0267] Suitably, each processing step lasts for a defined period of time.

[0268] Suitably, each treatment step may last for a period of time within the predefined ranges suitable to achieve the intended treatment of the cells.

[0269] Suitably, the process of the present invention comprises the step of applying pressure to at least a portion of the compressible container so as to compress the container.

[0270] Suitably, the pressure is applied linearly by compression of the compressible container.

[0271] Suitably, the pressure is applied by linear compression of a compressible container.

[0272] Suitably, by linear compression or linear it is meant that pressure is applied in the direction of the longitudinal axis of the compressible container, ie between the base and the top of the container.

[0273] Suitably, compressing the compressible container comprises applying a force to a top and / or base of the container to compress the container. Suitably, if the compressible container comprises a bellows, compressing the compressible container comprises applying a force to a top and / or base of the container to collapse the bellows of the container.

[0274] Suitably, the compressible container is compressed by a device on which the compressible container may be mounted. Suitably, the device is operable to apply pressure to at least a portion of the compressible container. Suitably, the device is operable to release pressure from the compressible container. Suitably, the device is operable to thereby compress and decompress the compressible container, as described elsewhere herein. In one embodiment, the device is an apparatus according to the first aspect of the invention, or a system according to the second or third aspect of the invention, as described elsewhere herein.

[0275] Suitably, the applied pressure is not constant. Suitably, the pressure is applied cyclically to at least a portion of the compressible container. Suitably, the cyclic pressure is applied to the compressible container, suitably by cyclic compression of the compressible container.

[0276] Suitably, by cyclic pressure it is meant that pressure is applied and released cyclically.

[0277] Suitably, by cyclic compression it is meant that the compressible container is cyclically compressed and decompressed.

[0278] Suitably, on compressing the compression vessel, pressure is applied to at least a portion of the compressible vessel and on decompressing the compressible vessel, pressure is released from at least a portion of the compressible vessel.

[0279] Suitably, therefore, step (b) comprises applying a cyclic pressure to at least a portion of the compressible container.

[0280] Suitably, step (b) may comprise applying cyclic pressure to at least a portion of the compressible container so as to compress and decompress the container.

[0281] Suitably, the cyclic pressure is applied at a suitable rate, suitably defined as cycles per minute (cpm). Suitably, the cyclic pressure may be applied at a rate of, for example, about 60 cpm.

[0282] Suitably, the cyclic pressure is applied with a suitable amplitude. Suitably, the amplitude may be defined as a fraction of the total height of the compressible container. For example, the cyclic pressure may be applied with an amplitude of 50% to 80% of the total height of the container. This means that with each compression of the compressible container, the height is reduced by a difference of 50-80% of the total height of the container. Alternatively, the amplitude may be defined as the distance a movable plate of the device or system travels to apply or release pressure from the compressible container. For example, the cyclic pressure may be applied with an amplitude of 5mm to 25mm. For example, the cyclic pressure may be applied with an amplitude between 5mm and 25mm.

[0283] The present invention may be defined by one or more of the following non-limiting examples, which may be used in any combination.

[0284] Example 1: An apparatus for use in performing one or more unit operations in cell processing, comprising: a holding element arranged to receive an upper portion of the container in the first plane; a movable plate spaced from the retaining element and positioned to operatively engage a base portion of the container, the movable plate defining a second plane substantially parallel to the first plane; an actuation mechanism operatively coupled to the movable plate for rotating the movable plate about at least one axis in the second plane to thereby reduce the distance between at least a portion of the second plane and the first plane; An apparatus comprising:

[0285] Example 2: The apparatus according to example 1, wherein the actuation mechanism is arranged to rotate the movable plate about an axis in a second plane.

[0286] Example 3: The apparatus according to example 1, wherein the actuation mechanism is arranged to rotate the movable plate about multiple axes in the second plane.

[0287] Example 4: A device according to any preceding example, wherein the actuation mechanism is arranged to rotate the movable plate between 0 and 90 degrees about the or each axis.

[0288] Example 5: A device according to any previous example, wherein a longitudinal axis extending perpendicular to the first plane and the second plane intersects the second plane at an origin, and wherein the actuation mechanism is arranged to pivot the movable plate about the origin.

[0289] Example 6: The apparatus according to example 5, wherein the origin is centered in the second plane.

[0290] Example 7: The apparatus according to example 5 or example 6, wherein the movable plate is pivotable about an origin such that each point in the second plane, excluding the origin, forms an angle between 0 degrees and 180 degrees, excluding 90 degrees, with the longitudinal axis.

[0291] Example 8: A device according to any previous example, wherein the actuation mechanism is further arranged to move the movable plate along a longitudinal axis substantially perpendicular to the first plane and the second plane, thereby reducing the distance between the second plane and the first plane.

[0292] Example 9: A device according to any previous example, wherein the retaining element comprises a platform operably engageable with the upper portion of the container, a clamping mechanism operably engageable with the upper portion of the container, or a sealing plate operably engageable with the upper portion of the container.

[0293] Example: 10. A device according to any preceding example, wherein the actuation mechanism comprises a base plate spaced from and substantially parallel to the movable plate, the base plate being operably coupled to the movable plate.

[0294] Example 11: An apparatus according to example 10, wherein the base plate comprises at least one actuator, the or each actuator being operably coupled to or operably engageable with the movable plate.

[0295] Example 12: An apparatus according to Example 10 or Example 11, wherein the base plate comprises at least one rail, the or each rail upstanding therefrom substantially perpendicular to the base plate, the movable plate being slidably coupled to the or each rail, and at least one actuator is arranged to slide at least a portion of the movable plate along the or each rail.

[0296] Example 13: The apparatus according to any one of Examples 10 to 12, wherein the base plate is operably coupled to the movable plate by at least one biasing element, the or each biasing element being arranged to bias the movable plate towards the base plate such that the second plane is substantially parallel to the first plane.

[0297] Example 14: A device according to example 13, wherein the or each biasing element comprises a spring, preferably a tension spring.

[0298] Example 15: The apparatus according to any one of Examples 10 to 14, wherein the base plate further comprises a rotatable support plate arranged to rotate about a longitudinal axis, the longitudinal axis being substantially perpendicular to the support plate, and the support plate comprises the or each actuator.

[0299] Example 16: The apparatus according to any one of Examples 10 to 15, wherein the or each actuator comprises a linear actuator.

[0300] Example 17: The apparatus according to any one of Examples 10 to 16, wherein the movable plate comprises at least one permanent magnet and the base plate comprises at least one corresponding electromagnet.

[0301] Example 18: An apparatus according to example 17, wherein the or each permanent magnet is distal from the center of the movable plate and the or each electromagnet is distal from the center of the base plate.

[0302] Example 19: The apparatus according to any one of Examples 10 to 18, wherein the base plate comprises at least one cam member, the or each cam member being operably engageable with the movable plate, and the or each cam member being driven by a motor.

[0303] Example 20: The apparatus according to any one of Examples 10 to 19, wherein the base plate comprises a central hub coaxial with and rotatable about a longitudinal axis perpendicular to the base plate, the central hub comprising connecting rods extending radially outward from the central hub and terminating in wheels, the wheels being operably engageable with the movable plate.

[0304] Example 21: The device according to example 20, wherein the central hub is rotated about the longitudinal axis by a motor.

[0305] Example 22: The apparatus according to any one of Examples 10 to 21, wherein the base plate comprises a first linkage operably coupled to the movable plate, the first linkage being driven by a first motor.

[0306] Example 23: The apparatus according to Example 22, wherein the base plate further comprises a second linkage operably coupled to the movable plate, the second linkage being driven by a second motor.

[0307] Example 24: The apparatus according to example 23, wherein the first linkage and the second linkage are operatively connected at opposite edges of the movable plate.

[0308] Example 25: The apparatus according to Example 23, wherein the base plate further comprises a third linkage operably coupled to the movable plate, the third linkage being driven by a third motor.

[0309] Example 26: The apparatus according to example 25, wherein the first linkage, the second linkage, and the third linkage are operatively coupled to the movable plate in a triangular arrangement.

[0310] Example 29: The apparatus according to any one of Examples 1 to 9, wherein the actuation mechanism comprises a first motor operably coupled to the movable plate and configured to rotate the movable plate about at least one axis in the second plane.

[0311] Example 30: The apparatus according to Example 29, wherein the actuation mechanism further comprises a second motor operably coupled to the movable plate and configured to move the movable plate along a longitudinal axis substantially perpendicular to the first plane and the second plane, thereby reducing the distance between the second plane and the first plane.

[0312] Example 31: The apparatus according to Example 30, wherein the actuation mechanism further comprises a third motor operably coupled to the movable plate and configured to move the movable plate along the longitudinal axis, thereby reducing the distance between the second plane and the first plane.

[0313] Example 32: The actuation mechanism further includes a link mechanism, a crank housing slidable along the first longitudinal rail and including a rotatable crank extending substantially parallel to the longitudinal axis; a slider portion operably coupled to the movable plate, slidable along the second longitudinal rail, extending substantially parallel to the first longitudinal rail, the slider portion operably coupled to the rotatable crank by a connecting rod; Equipped with The apparatus according to Example 31, wherein a second motor is operably coupled to the rotatable crank to rotate the rotatable crank and move the slider portion along the second longitudinal rail, and a third motor is operably connected to the crank housing to move the crank housing along the first longitudinal rail.

[0314] Example 33: The apparatus according to Example 32, wherein the third motor comprises a ball screw motor or a lead screw motor operably coupled to a corresponding threaded portion of the crank housing, the threaded portion of the crank housing being movable along the first longitudinal rail.

[0315] Example 34: The apparatus according to any one of Examples 19 to 33, wherein the or each motor comprises a stepper motor.

[0316] Example 35: The apparatus according to any one of Examples 19 to 34, wherein the or each motor is operably connected to one or more gearboxes.

[0317] Example 36: A device according to any preceding example, further comprising a controller communicatively coupled to the actuation mechanism.

[0318] Example 37: The apparatus according to Example 36, further comprising one or more positioning sensors, the or each positioning sensor being communicatively coupled to a controller, the controller generating a signal to the actuation mechanism based on a signal received from the or each positioning sensor.

[0319] Example 38: A system for use in performing one or more unit operations in cell processing, comprising: An apparatus according to any of the preceding examples; a container having a base portion, an upper portion parallel to the base portion, and a compressible wall element extending substantially vertically between the base portion and the upper portion; Equipped with The system, wherein the container is at least partially disposed between the retaining element and the movable plate, and the actuation mechanism is arranged to move the movable plate such that at least a portion of the compressible wall element is at least partially compressed along a longitudinal axis perpendicular to the first plane and the second plane.

[0320] Example 39: A system for use in performing one or more unit operations in cell processing, comprising: a container having a base portion, an upper portion parallel to the base portion, and a compressible wall element extending substantially vertically between the base portion and the upper portion; a retaining element operably engaged with the top portion of the container to retain the top portion of the container in the first plane; a movable plate spaced from the retaining element and operably engaged with a base portion of the container, the movable plate defining a second plane substantially parallel to the first plane; an actuation mechanism operatively coupled to the movable plate for moving the movable plate about at least one axis in the second plane to at least partially compress at least a portion of the compressible wall element along a longitudinal axis perpendicular to the first plane and the second plane; A system comprising:

[0321] Example 40: A system according to example 39 or example 40, wherein the base part of the container is fixedly attached to the movable plate.

[0322] Example 41: A system according to example 39 or example 40, wherein the base portion of the container is removably engageable with or engaged with the base portion of the container.

[0323] Example 42: A method for treating cells, comprising: providing a cell treatment medium to a container, the container having a base portion, an upper portion parallel to the base portion, and a compressible wall element extending substantially vertically between the base portion and the upper portion; holding a top portion of the container in a first plane; engaging a base portion of the container with a movable plate defining a second plane substantially parallel to and spaced apart from the first plane; rotating the base portion of the vessel about at least one axis in a second plane, thereby inducing turbulent flow of the cell treatment medium within the vessel; A method comprising:

[0324] Example 43: The method according to Example 42, wherein the step of rotating the base portion of the container includes rotating the base portion of the container about an axis in a second plane.

[0325] Example 44: The method according to Example 42, wherein a longitudinal axis extending perpendicular to the first plane and the second plane intersects the second plane at an origin, and wherein the step of rotating the base portion of the container includes pivoting the base portion of the container about the origin.

[0326] Example 45: The method according to example 44, wherein the origin is centered in the second plane.

[0327] Example 46: A method of manufacturing an apparatus according to any one of examples 1 to 37 or a system according to any one of examples 38 to 41.

[0328] Example 47: A method for treating cells, comprising: (a) providing a compressible container comprising a population of cells in a liquid medium; (b) maintaining the population of cells in the liquid medium while applying pressure to at least a portion of the compressible container to compress the container; A method comprising:

[0329] Example 48: A method according to example 47, wherein the liquid medium is retained in a compressible container after compression is applied.

[0330] Example 49: A method of processing cells using the device of any one of Examples 1 to 37, wherein the device further comprises a container.

[0331] Example 50: The method according to example 49, wherein the container is adapted to contain a population of cells in a liquid medium.

[0332] Example 51: The method according to example 49 or example 50, wherein the container is compressible.

[0333] Example 52: (a) providing a population of cells in a liquid medium in a container; (b) operating the device to process the population of cells in the liquid medium; 52. The method according to any one of Examples 49 to 51, comprising:

[0334] Example 53: A method for treating cells, comprising: (a) providing a device according to any one of Examples 1 to 37, the device further comprising a container comprising a population of cells in a liquid medium; (b) operating the device to process the population of cells in the liquid medium; A method comprising:

[0335] Example 54: The method of Example 52 or 53, wherein treating the population of cells includes maintaining the population of cells in the liquid medium while applying pressure to at least a portion of the container to compress the container.

[0336] Example 55: A method of treating cells using the system of any one of Examples 38 to 41.

[0337] Example 56: The method according to example 55, wherein the container of the system is compressible.

[0338] Example 57: (a) providing a population of cells in a liquid medium in a container; (b) operating the system to process a population of cells in a liquid medium; The method according to Example 55 or Example 56,

[0339] Example 58: A method for treating cells, comprising: (a) providing a system according to any one of Examples 38 to 41, wherein the container comprises a population of cells in a liquid medium; (b) operating the system to process a population of cells in a liquid medium; A method comprising:

[0340] Example 59: The method according to Example 57 or 58, wherein treating the population of cells comprises maintaining the population of cells in the liquid medium while applying pressure to at least a portion of the container to compress the container.

[0341] Example 60: An apparatus for use in performing one or more unit operations in cell processing, comprising: a holding element arranged to receive an upper portion of the container in the first plane; a movable plate spaced from the retaining element and positioned to operatively engage a base portion of the container, the movable plate defining a second plane substantially parallel to the first plane; an actuation mechanism operably coupled to the movable plate for translating the movable plate along a longitudinal axis substantially perpendicular to the first plane and the second plane, thereby reducing a distance between the second plane and the first plane; An apparatus comprising:

[0342] Example 61: A method for treating cells, comprising: providing a cell treatment medium to a container, the container having a base portion, an upper portion parallel to the base portion, and a compressible wall element extending substantially vertically between the base portion and the upper portion; holding a top portion of the container in a first plane; engaging a base portion of the container with a movable plate defining a second plane substantially parallel to and spaced apart from the first plane; translating a base portion of the container along a longitudinal axis substantially perpendicular to the first plane and the second plane, thereby causing compression and / or decompression of the container; A method comprising:

[0343] Example embodiments of the present invention will now be described, by way of example only, with reference to the accompanying drawings in which: [Brief explanation of the drawings]

[0344] [Figure 1(a)] FIG. 1 is a diagram of an example of the prior art. [Figure 1(b)] FIG. 1 is a diagram of an example of the prior art. [Figure 2(a)] FIG. 1 is a diagram of an example of the prior art. [Figure 2(b)] FIG. 1 is a diagram of an example of the prior art. [Figure 2(c)] FIG. 1 is a diagram of an example of the prior art. [Figure 2(d)] FIG. 1 is a diagram of an example of the prior art. [Figure 3(a)] FIG. 1 is a top view of an apparatus according to one embodiment of the present invention. [Figure 3(b)] FIG. 1 is a side view of an apparatus according to an embodiment of the present invention in a first configuration. [Figure 3(c)] FIG. 2 is a side view of an apparatus according to an embodiment of the present invention in a second configuration. [Figure 4] FIG. 10 is a side view of an apparatus according to another embodiment of the present invention. [Figure 5(a)] FIG. 2 is a side view of an apparatus according to another embodiment of the present invention in a first configuration. [Figure 5(b)] FIG. 10 is a side view of an apparatus according to another embodiment of the present invention in a second configuration. [Figure 6] FIG. 10 is a side view of an apparatus according to another embodiment of the present invention. [Figure 7]FIG. 10 is a side view of an apparatus according to another embodiment of the present invention. [Figure 8] FIG. 10 is a side view of an apparatus according to another embodiment of the present invention. [Figure 9] FIG. 10 is a side view of an apparatus according to another embodiment of the present invention. [Figure 10(a)] FIG. 2 is a first side view of an apparatus according to another embodiment of the present invention. [Figure 10(b)] FIG. 10 is a second side view of an apparatus according to another embodiment of the present invention. [Figure 10(c)] FIG. 10 is a first side view of a device according to another embodiment of the present invention with the central hub removed. [Figure 10(d)] FIG. 13 is a diagram of an example of a cam member for use in the device of FIGS. 10(a) to 10(c). [Figure 10(e)] 10(a)-10(c) show another example of a cam member for use in the device of FIG. 10(a)-FIG. 10(c). [Figure 11] FIG. 10 is a side view of an apparatus according to another embodiment of the present invention. [Figure 12] FIG. 10 is a side view of an apparatus according to another embodiment of the present invention. [Figure 13(a)] FIG. 2 is a side view of an apparatus according to another embodiment of the present invention in a first configuration. [Figure 13(b)] FIG. 10 is a side view of an apparatus according to another embodiment of the present invention in a second configuration. [Figure 13(c)] FIG. 10 is an enlarged view of an apparatus according to another embodiment of the present invention. [Figure 14(a)] FIG. 2 is a side view of an apparatus according to another embodiment of the present invention in a first configuration. [Figure 14(b)] FIG. 10 is a side view of an apparatus according to another embodiment of the present invention in a second configuration. [Figure 15] FIG. 10 is a side view of an apparatus according to another embodiment of the present invention. [Figure 16(a)] FIG. 10 is a side view of an apparatus according to another embodiment of the present invention. [Figure 16(b)] FIG. 10 is a perspective view of an apparatus according to another embodiment of the present invention. [Figure 16(c)]10 is another perspective view of an apparatus according to another embodiment of the present invention, including a container; FIG. [Figure 17(a)] FIG. 2 is a side view of an apparatus according to another embodiment of the present invention in a first configuration. [Figure 17(b)] FIG. 10 is a side view of an apparatus according to another embodiment of the present invention in a second configuration. [Figure 18(a)] FIG. 10 is a top view of an apparatus according to another embodiment of the present invention. [Figure 18(b)] FIG. 2 is a first side view of an apparatus according to another embodiment of the present invention. [Figure 18(c)] FIG. 10 is a perspective view of an apparatus according to another embodiment of the present invention. [Figure 18(d)] FIG. 10 is another side view of an apparatus according to another embodiment of the present invention. [Figure 19] FIG. 1 is a side view of a linear actuator for use in an apparatus according to the present invention. [Figure 20(a)] FIG. 1 is a diagram of a container containing water and food coloring prior to swirling agitation. [Figure 20(b)] FIG. 1 is a diagram of a container containing water and food coloring after swirling agitation. [Figure 21(a)] FIG. 1 is a diagram of a container containing water and food coloring prior to mixing. [Figure 21(b)] FIG. 1 is a diagram of a container containing water and food coloring after wave agitation. [Figure 22] FIG. 10 is a view during swirling agitation of a container with water and food coloring. [Figure 23] FIG. 10 is a view during another swirling agitation of a container with water and food coloring. [Figure 24] FIG. 10 is a view during yet another swirling agitation of a container with water and food coloring. [Figure 25] FIG. 10 is a view during another swirling agitation of a container with water and food coloring. [Figure 26] FIG. 10 is a diagram of a container with water and food coloring during linear compression agitation. [Figure 27] FIG. 10 is a diagram of another linear compression of a container with water and food coloring during agitation. [Figure 28]FIG. 10 is a diagram of yet another linear compression of a container with water and food coloring during agitation. [Figure 29(a)] FIG. 2 is a side view of the container in a first configuration. [Figure 29(b)] FIG. 10 is a side view of the container in a second configuration. [Figure 30(a)] 1 shows a system including a container and a device according to the invention through a compression movement; [Figure 30(b)] 1 shows a system including a container and a device according to the invention through a compression movement; [Figure 30(c)] 1 shows a system including a container and a device according to the invention through a compression movement; [Figure 30(d)] 1 shows a system including a container and a device according to the invention through a compression movement; [Figure 30(e)] 1 shows a system including a container and a device according to the invention through a compression movement; [Figure 31(a)] 1 is a side view of a system including a container and a device according to the invention in a first configuration; [Figure 31(b)] FIG. 10 is a side view of the system in a second configuration after rotation about an axis. [Figure 31(c)] FIG. 10 is a side view of the system in a third configuration. [Figure 32] FIG. 1 is a diagram of a mold for a container. [Figure 33(a)] FIG. 1 is a top-down view of a platform and vessel suitable for use with an apparatus and system according to the present invention. [Figure 33(b)] 1 is a side view of a platform and vessel suitable for use with devices and systems according to the present invention; [Figure 33(c)] 1 is a bottom view of a platform and container suitable for use with devices and systems according to the present invention; FIG. [Figure 33(d)] 1 is an exploded perspective view of a platform and container suitable for use with devices and systems according to the present invention; FIG. [Figure 34(a)] 1 is a schematic perspective view of an apparatus according to another embodiment of the present invention; [Figure 34(b)] FIG. 34(b) is a schematic front view of FIG. 34(a). [Figure 34(c)] FIG. 34(b) is a schematic diagram of one motor and linkage of the device of FIG. 34(a). [Figure 34(d)] FIG. 34(b) is a schematic diagram of another motor and linkage mechanism for the device of FIG. 34(a). [Figure 35] FIG. 34(b) is a detailed perspective view of the device of FIG. 34(a) and FIG. 34(b). [Figure 36(a)] FIG. 36 is a front view of the apparatus of FIG. 35 with the platform and vessel of FIGS. 33(a)-(d) attached. [Figure 36(b)] FIG. 36 is a front perspective view of the apparatus of FIG. 35 with the platform and container of FIGS. 33(a)-(d) attached. [Figure 36(c)] FIG. 36 is a rear perspective view of the apparatus of FIG. 35 with the platform and container of FIGS. 33(a)-(d) attached. [Figure 36(d)] FIG. 36 is a side view of the apparatus of FIG. 35 with the platform and vessel of FIGS. 33(a)-(d) attached. [Figure 36(e)] FIG. 36 is a top view of the apparatus of FIG. 35 with the platform and vessel of FIGS. 33(a)-(d) attached. [Figure 37] 1 is a diagram of a method according to the invention; [Figure 38] FIG. 1 is a diagram of an exemplary test administration timeline. [Figure 39] FIG. 10 is a diagram of exemplary primary T cell implementation timeline results using a device / system according to the present invention. [Figure 40] FIG. 10 is another exemplary primary T cell implementation timeline result using a device / system according to the present invention. [Figure 41] FIG. 39 illustrates additional results from the exemplary primary T cell implementation timeline shown in FIG. [Figure 42] FIG. 41 depicts further results from the exemplary primary T cell implementation timeline shown in FIG. 40. DETAILED DESCRIPTION OF THE INVENTION

[0345] The described example embodiments relate to devices, systems, and methods that relate primarily to, but are not limited to, processes in cell and / or gene therapy.

[0346] Certain terminology is used in the following description for convenience only, and not as a limitation. The words "upper," "lower," "upward," and "downward" designate directions in the drawings to which reference is made and relate to the described components when assembled and mounted. "Inner," "inwardly," "outer," and "outward" refer to directions toward and away from a designated centerline or geometric center (e.g., central axis) of the described element, with the specific meaning being readily apparent from the context of the description. Additionally, the terms "proximal" (i.e., closer to) and "distal" (i.e., away from) designate positions relative to a body or point of attachment.

[0347] Furthermore, as used herein, terms such as "connected" and "attached" are intended to include a direct connection between two members, with no other intervening material between them, as well as an indirect connection between two members, where one or more members are interposed between them. The terms include the words expressly mentioned above, derivatives thereof, and words of similar import.

[0348] Furthermore, unless otherwise expressly stated, the use of ordinal adjectives such as "first," "second," "third," etc., merely indicates that different instances of similar objects are being referred to and is not intended to imply that the objects so described must be in a given order in time, space, sequence, or in any other manner. Like reference numerals are used throughout to depict like features.

[0349] 3(a)-3(c) show a first embodiment of an actuation mechanism 100 according to the present invention. The actuation mechanism 100 comprises a movable plate 102 and a base plate 106. The movable plate 102 is axially translatable by virtue of a plurality of linear actuators 104. The base plate 106 may be rotatable about an axis by one or more actuators (not shown).

[0350] 4 shows a second embodiment of an actuation mechanism 200. The actuation mechanism 200 comprises a movable plate 202 and a linear actuator 204. The linear actuator 204 acts on the underside or surface of the movable plate 202 to raise and lower the movable plate 202 during use.

[0351] FIGS. 5(a) and 5(b) show another embodiment of an actuation mechanism 300. The actuation mechanism 300 comprises a movable plate 302 and a base plate 306. The base plate 306 is connected to the movable plate 302 by a linkage 304. The linkage 304 may be a series of pivotally connected rods, as shown in FIGS. 5(a) and 5(b). The actuation mechanism 300 may comprise one or more actuators (not shown) for raising or lowering the movable plate 302 relative to the base plate 306 during use. Additionally, the actuation mechanism 300 may comprise one or more actuators (not shown) for rotating the base plate 306 about an axis, as indicated by the arcuate arrows in FIGS. 5(a) and 5(b). It is noted that there may be one or more actuators that can both raise and lower the movable plate 302 and rotate the base plate 306 about an axis.

[0352] FIG. 6 illustrates another embodiment of an actuation mechanism 400. The actuation mechanism 400 includes a movable plate 402 and a base plate 406. The movable plate 402 is connected to the base plate 406 by a pivotable rod 408. A linear actuator 404 is also provided that acts on the underside or surface of the movable plate 402. There can be any number of linear actuators 404. In examples where there are several linear actuators 404, when the linear actuators 404 act in concert, i.e., simultaneously, the movable plate 402 is translated axially, causing the movable plate 402 to be raised or lowered. When the linear actuators 404 do not act in concert, i.e., when not simultaneously or at the same time, the movable plate 402 is caused to oscillate along one or more axes, depending on the number of linear actuators 404.

[0353] FIG. 7 illustrates another embodiment of an actuation mechanism 500. The actuation mechanism 500 includes a movable plate 502 and a base plate 506. The movable plate 502 and the base plate 506 are connected by a central rod 514 extending axially from the base plate 506 toward a pivot point 512 of the movable plate 502. A series of springs 504a, 504b are also provided. Any number of springs 504a, 504b may be used. The springs 504a, 504b bias the movable plate 502 toward the base plate 506. The springs 504a, 504b may be tension springs. Additionally, a connecting rod 508 is provided extending from the central rod 514 and terminating at a wheel 510. The central rod 514 may be driven by an actuator or motor such that the wheel 510 rotates about the central rod 514. In this method, the movable plate 502 is rotated about two axes perpendicular to each other to provide pivotal movement of the containers on the movable plate 502 .

[0354] 8 shows another embodiment of an actuation mechanism 600. The actuation mechanism 600 comprises a movable plate 602 and a base plate 606. The movable plate 602 is connected to the base plate 606 by a pivotable rod 608. The base plate 606 is provided with electromagnets 608a, 608b on its outer edge. The movable plate 602 is provided with permanent magnets 604a, 604b on its outer edge. The electromagnet 608a on the base plate 606 is aligned with the permanent magnet 604a on the movable plate 602. The electromagnet 608b on the base plate 606 is aligned with the permanent magnet 604b on the movable plate 602. In use, the electromagnets 608a, 608b are sequentially turned on and off to sequentially attract and repel the permanent magnets 604a, 604b on the movable plate 602. The interaction between the electromagnets 608a, 608b on the base plate 606 and the permanent magnets 604a, 604b on the moveable plate 602 causes the moveable plate 602 to pivot about the pivotable rod 608. In one example, the magnetic force acting on the moveable plate 602 causes the moveable plate 602 to move in a wave motion relative to the base 606.

[0355] 9 shows another embodiment of an actuation mechanism 700. The actuation mechanism 700 includes a movable plate 702 and a base plate 706. The base plate 706 is connected to the movable plate 702 by a linkage 704. The linkage 704 is a series of pivotally connected rods arranged in a scissor lift configuration. The actuation mechanism 700 may be provided with one or more actuators (not shown) that raise or lower the movable plate 702 relative to the plate 706 during use. That is, the distance between the base plate 706 and the movable plate 702 may be changed by using one or more actuators to raise and lower the movable plate 702 relative to the plate 706.

[0356] 10(a)-10(e) show another embodiment of an actuation mechanism 800. The actuation mechanism 800 comprises a movable plate 802 and a base plate 806. The base plate 806 is connected to the movable plate 802 by a central rod 810 extending axially from the base plate 806 toward a pivot point 812 of the movable plate 802. A first cam member 804a is provided at the base 806 in contact with the movable plate 802. A second cam member 804b is provided on the opposite side of the central rod 810, distal to the first cam member 804a. The first cam member 804a is driven by one or more motors (not shown). The second cam member 804b is driven by one or more motors (not shown). The first cam member 804a is driven by one or more motors to rotate about its pivot axis. The second cam member 804b is driven by one or more motors to rotate about its pivot axis. In use, the first cam member 804a is driven such that its surface engages the movable plate 802, causing it to move about the pivot point 812. The second cam member 804b may be driven either instead of or in addition to the first cam member 804a, such that its surface engages the movable plate 802, causing it to move about the pivot point 812. The first cam member 804a may be driven independently of the second cam member 804b.

[0357] In one example, the first cam member 804a and the second cam member 804b are driven simultaneously. The cam members 804a, 804b can have non-circular profiles to cause the movable plate 802 to move non-linearly. As shown in this specific example, the first cam member 804a is arranged to rotate out of phase with the second cam member 804b to raise one side of the movable plate 802 and lower the other side of the movable plate 802. As will be explained later, the cam members 804a, 804b can be provided with angled surfaces or non-circular profiles to tilt the movable plate 802 from one side to the other during use. Examples of cam members 804a, 804b are shown in FIGS. 10(d) and 10(e). FIG. 10(d) shows the cam member 804a with a circular profile. FIG. 10(e) shows the cam member 804a with an elongated circular profile. As shown in Fig. 10(b), the cam members 804a, 804b may additionally be provided with tension springs 808a, 808b that provide a resilient force between the base plate 806 and the movable plate 802. Fig. 10(c) shows an example in use in which the first cam members 804a and 804b are mirror images of each other. The upper surfaces of the cam members 804a, 804b are at the same height so that the movable plate 802 is positioned horizontally.

[0358] FIG. 11 illustrates another embodiment of an actuation mechanism 900. The actuation mechanism 900 includes a movable plate 902 and a base plate 906. The movable plate 902 and base plate 906 are connected by a central hub 914 that extends axially from the base plate 906 toward a pivot point 912 of the movable plate 902. A series of springs 904a, 904b are provided. Any number of springs 904a, 904b may be used. The springs 904a, 904b bias the movable plate 902 toward the base plate 906. In this example, the springs 904a, 904b are tension springs. A connecting rod 908 extends radially from the central hub 914 and terminates at a wheel 910. The central rod 914 may be driven by an actuator or motor such that the wheel 910 rotates about the central hub 914. In this method, the movable plate 902 is rotated about two axes perpendicular to each other to provide pivoting movement of the containers on the movable plate 902. In one example, the wheels 910 are driven by a motor and move around in a circular motion, which causes the movable plate 902 to move in a symmetrical wave motion.

[0359] 12 shows another embodiment of an actuation mechanism 1000. The actuation mechanism 1000 comprises a movable plate 1002 and a base plate 1006. The movable plate 1002 and base plate 1006 are connected by a central hub 1014 that extends axially from the base plate 1006 toward a pivot point 1012 on the movable plate 1002. Springs 1004a, 1004b are provided to bias the movable plate 1002 toward the base plate 1006. In this embodiment, the central hub 1014 is provided on the base plate 1006. The central hub 1014 is connected to a support plate 1010. A linear actuator 1008 is provided between the support plate 1010 and the base plate 1006. The linear actuator 1004 acts on the underside or surface of the movable plate 1002 to raise and lower the movable plate 1002 during use. The support plate 1010 can be rotated by a motor (not shown).

[0360] 13(a) and 13(b) show another embodiment of an actuation mechanism 1100. The actuation mechanism 1100 comprises a movable plate 1102 and a base plate 1106. A motor 1114 is positioned on the base plate 1106 and operably coupled to a support plate 1104. The support plate 1104 is positioned between the base plate 1106 and the movable plate 1102. The motor 1114 operates to rotate the support plate 1104 relative to the base plate 1106. In one example, the motor 1114 is raised and lowered relative to the base plate 1106. The support plate 1104 is connected to the movable plate 1102 by a linkage 1108. The linkage 1108 can be a series of pivotally connected rods. The linkage 1108 can be enclosed by a housing, such as a bellows-based housing, to prevent access to the linkage 1108 during use. The actuation mechanism 1100 may include an actuator 1112 to raise or lower the movable plate 1102 relative to the support plate 1104 during use. In this specific embodiment, a cam system is provided. The cam system has a first cam member 1110a and a second cam member 1110b. The cam members 1110a, 1110b are integrated with the linkage 1108 in this example. However, the cam members 1110a, 1110b may additionally or alternatively be integrated with the actuator 1112. The cam members 1110a, 1110b are driven so that their surfaces engage the movable plate 1102. This moves the movable plate 1102 relative to the base plate 1106.

[0361] 14(a) and 14(b) show another embodiment of an actuation mechanism 1200. The actuation mechanism 1200 comprises a movable plate 1202 and a base plate 1206. A motor 1216 is positioned on the base plate 1206 and operably coupled to a support plate 1204. The support plate 1204 is positioned between the base plate 1206 and the movable plate 1202. The motor 1216 operates to rotate the support plate 1204 relative to the base plate 1206. In one example, the motor 1216 is raised and lowered relative to the base plate 1206. The support plate 1204 is connected to the movable plate 1202 by a linkage 1214. The linkage 1214 may be enclosed by a housing, such as a bellows-based housing, to prevent access to the linkage 1214 during use. The linkage 1214 may be a series of pivotally connected rods. In use, the linkage 1214 moves the movable plate 1202 relative to the support plate 1204, and therefore relative to the base plate 1206. In this specific embodiment, the actuation mechanism 1200 comprises a central hub 1210 extending axially towards the movable plate 1202. Additionally, a connecting rod 1212 is provided extending radially from the central hub 1210 and terminating in a linear actuator 1208. In use, the central hub 1210 is driven by an actuator or motor (not shown) such that, when the linear actuator 1208 is actuated, the linear actuator 1208 is driven to provide a pivoting movement to a container positioned on the movable plate 1202.

[0362] 15 shows another embodiment of an actuation mechanism 1300. The actuation mechanism 1300 includes a movable plate 1302 and three linkages: a first linkage 1304a, a second linkage 1304b, and a third linkage 1304c. The linkages 1304a, 1304b, and 1304c extend from the bottom surface of the movable plate 1302. The first linkage 1304a extends from the movable plate 1302 toward a base plate 1306a at a first pivot point 1310a. The second linkage 1304b extends from the movable plate 1302 toward a base plate (not shown) at a second pivot point 1310b. The third linkage 1304c extends from the movable plate 1302 toward the base plate 1306b at a third pivot point 1310c. A first actuator 1308a is positioned between the first linkage 1304a and the base plate 1306a. A second actuator 1308b is positioned between the second linkage 1304b and the base plate (not shown). A third actuator 1308c is positioned between the third linkage 1304c and the base plate 1306b. In use, the actuators 1308a, 1308b, and 1308c are driven sinusoidally out of phase with each other to create a wave effect on the movable plate 1302. In one example, the actuators 1308a, 1308b, and 1308c are linear actuators that slide along rails such that the pivot points move in sync to move the movable plate 1302 in a wave motion.

[0363] FIG. 16(a) shows another embodiment of an actuation mechanism 1400. The actuation mechanism 1400 includes a movable plate 1402 and a base plate 1406. In this specific embodiment, three motors 1408a, 1408b, and 1408c are provided. Three linkages extending from the movable plate 1404 are also provided: a first linkage 1404a, a second linkage 1404b, and a third linkage 1404c. The motors 1408a, 1408b, and 1408c are each used to drive a respective linkage 1404a, 1404b, and 1404c. More specifically, the first motor 1408a drives the first linkage 1404a. The second motor 1408b drives the second linkage 1404b. A third motor 1408c drives a third linkage 1404c. The linkages 1404a, 1404b, 1404c are driven in coordination to move the movable plate 1402 in a wave motion. Referring to Figures 16(b) and 16(c), a holding element 1450 is provided. A container 1480 having a base portion is provided. The container 1480 will be described in more detail with reference to subsequent figures.

[0364] Specifically, it is noted that the apparatus comprises an actuation mechanism 1400, a movable plate 1402, and a holding element 1450. The system further comprises a container 1480.

[0365] More specifically, the base of the container 1480 is disposed on the movable plate 1402 such that the container 1480 is disposed between the retaining element 1450 and the movable plate 1402. The container 1480 has compressible walls. When the movable plate 1402 is moved using the aforementioned actuation mechanism 1400, the top of the container 1480 is pressed against the retaining element 1450. This compresses the walls of the container 1480.

[0366] 17(a) and 17(b) show another embodiment of an actuation mechanism 1500. The actuation mechanism includes a movable plate 1502 and two linear actuators 1504a and 1504b. The first linear actuator 1504a is provided on a first side of the movable plate 1502. The second linear actuator 1504b is provided on the opposite side of the movable plate 1502. The linear actuators 1504a and 1504b are positioned to act on the bottom surface of the movable plate 1502. There can be any number of linear actuators 1504. When the linear actuators 1504 act in concert, i.e., simultaneously, the movable plate 1502 is translated axially. When the linear actuators 1504 do not act in concert, i.e., when not simultaneously or at the same time, the movable plate 1502 is oscillated along one or more axes, depending on the number of linear actuators 1504. In this particular embodiment, a further linear actuator 1504c, in this example a larger linear actuator 1504c, is provided at the bottom of the actuation mechanism below the linear actuators 1504a, 1504b. In use, the larger linear actuator 1504c is provided to lower the actuation mechanism from the higher position shown in Figure 17(a) to the lower position shown in Figure 17(b).

[0367] 18(a)-18(d) show another apparatus 1600 according to the present invention. The apparatus 1600 comprises a movable plate 1602 and a base plate 1606. The movable plate 1602 and the base plate 1606 are operatively connected by a first linkage 1604a and a second linkage 1604b. The first linkage 1604a is driven by a first motor 1608a and is connected to a first gearbox 1610a and the first linkage 1604a. The second linkage 1604b is driven by a second motor 1608b and is connected to a second gearbox 1610b and the second linkage 1604b. Each motor 1608a, 1608b, specifically gearbox 1610a, 1610b, is coupled to a motor pivot shaft 1612a, 1612b which is further coupled to a motor coupling 1614a, 1614b to drive a linkage 1604a, 1604b.

[0368] 18(b), the first linkage 1604a stands upright from the base plate 1606 and is connected at one end to the movable plate 1602. The second linkage 1604b stands upright from the base plate 1606 and is connected at the other opposite end to the movable plate 1602. Specifically, the first linkage 1604a includes a pivot bar 1616a connected to the lower surface of the movable plate 1602. The second linkage 1604b also includes a pivot bar 1616b connected to the lower surface of the movable plate 1602. The movable plate 1602 is also connected to a central pivot clamp 1618 that is pivotable about a central pivot bar 1620. Additionally, each linkage 1604a, 1604b includes a hard stop 1622a, 1622b that defines the lowest point or plane that the movable plate 1602 can reach.

[0369] 18(c), the device 1600 further comprises a sensor mount 1624 capable of receiving a sensor 1626, the sensor 1626 comprising a sensor cable 1628. The sensor cable 1628 communicatively connects the sensor 1626 to a controller (not shown), which may further be communicatively connected to the motors 1608a, 1608b.

[0370] Additionally, the device 1600 includes a telescoping rail 1630 mounted on a rail mounting plate 1631, the telescoping rail 1630 being vertically movable and operatively connected to the movable plate 1602. Thus, the movable plate 1602 is movable along the rail 1630.

[0371] Additionally, each linkage 1604a, 1604b includes a hinge 1632 and a bearing 1634. There are generally four pivot bearing blocks 1636, 1638, 1640 (a fourth not shown) through which the linkages 1604a, 1604b extend and are supported.

[0372] In use, the apparatus 1600 is arranged to rotate the movable plate 1602 about the central pivot bar 1620, thereby imparting a wave or rocking motion to a container engaged by the movable plate 1602. Also in use, the movable plate 1602 can be translated along a longitudinal axis disposed centrally and vertically through the movable plate 1602, thereby imparting a compressive motion to a container engaged by the movable plate 1602.

[0373] A user can operate device 1600 according to a pre-set program stored in a control device (not shown) that performs a desired movement when executing a series of movement instructions. Alternatively, a user can input parameters into a control device (not shown) to operate device 1600 according to a desired range of movement.

[0374] Although two linkages 1604a, 1604b are shown in this embodiment, any number of linkages can be used, and although the linkages 1604a, 1604b are driven by motors 1608a, 1608b, they may alternatively be driven by other mechanisms, such as actuators, e.g., linear actuators.

[0375] 19 shows an example of a linear actuator 1700. The linear actuator 1700 can act on or be engaged with a portion or surface of any of the movable plates as described herein. Alternatively or additionally, in embodiments where multiple linear actuators are provided, the linear actuator 1700 can be coupled to a portion or surface of any of the movable plates as described herein.

[0376] FIGS. 20(a) and 20(b) show the container before and after a swirling motion, respectively. Specifically, FIG. 20(a) shows the container 1800 including a central origin 1802 whose longitudinal axis, extending perpendicular to the base of the container 1800, intersects the plane of the base of the container. Such a longitudinal axis is further described in connection with FIGS. 28(a)-30(c). The container 1800 contains water and several drops of food coloring 1804 to demonstrate the various stirring methods described herein. As seen in FIG. 20(b), after a swirling motion is imparted to the water and food coloring 1804 by pivoting the container 1800 about the central origin 1802, the food coloring begins to mix, as indicated by 1806. The continuous swirling provides thorough dispersion of the food coloring 1804 within the water in the container 1800. This provides an illustration of the mixing of cell treatment media within the container 1800 during use.

[0377] FIGS. 21(a) and 21(b) show the container before and after wave motion, respectively. Specifically, FIG. 21(a) shows container 1900 including an axis 1902 extending perpendicular to the longitudinal axis as described in connection with FIGS. 20(a) and 20(b) and extending in the plane of the base of container 1900. Like container 1800 of FIGS. 20(a) and 20(b), container 1900 contains water and food coloring to demonstrate the various stirring methods described herein. As seen in FIG. 21(b), after imparting wave motion to the water and food coloring by rotating, tilting, or pivoting container 1900 about axis 1902 (FIG. 21(a)), the food coloring begins to mix, specifically toward the wall elements of container 1900. Specifically, as indicated by reference numeral 1904, there is constructive interference toward the wall elements of container 1900, which can aid in mixing of the water and food coloring. Continuous undulating agitation provides thorough dispersion of the food coloring in the water of vessel 1900. This provides an illustration of the mixing of the cell treatment medium in vessel 1900 during use.

[0378] Figures 22(a)-22(c) show a container with water and food coloring to simulate mixing of cell treatment media within the container. Figure 22(a) shows the container with food coloring dropped into the water at time t=0 seconds. Figure 22(b) shows the container with the food coloring beginning to mix with the water at a time after t=0. Figure 22(c) shows the container with the food coloring mixing with the water at a time after t=0, after the illustration in Figure 22(b). Throughout Figure 22, a swirling motion, such as that described in connection with Figures 20(a) and 20(b), at 20 revolutions per minute is imparted to water and food coloring in a container with a volume of 500 ml of water.

[0379] Figures 23(a)-23(c) show a container with water and food coloring to simulate mixing of cell treatment media within the container. Figure 23(a) shows the container with food coloring dropped into the water at time t=0 seconds. Figure 23(b) shows the container with the food coloring beginning to mix with the water at a time after t=0 seconds. Figure 23(c) shows the container with the food coloring mixing with the water at a time after t=0 seconds, after the illustration in Figure 23(b). Throughout Figure 23, a swirling motion, such as that described in connection with Figures 20(a) and 20(b), is imparted at 30 revolutions per minute to water and food coloring in a container with a volume of 500 ml of water.

[0380] Figures 24(a)-24(c) show a container with water and food coloring to simulate mixing of cell treatment media within the container. Figure 24(a) shows the container with food coloring dropped into the water at time t=0 seconds. Figure 24(b) shows the container with the food coloring beginning to mix with the water at a time after time t=0 seconds. Figure 24(c) shows the container with the food coloring mixing with the water at a time after t=0 seconds, after the illustration of Figure 24(b). Throughout Figure 24, a swirling motion, such as that described in connection with Figures 20(a) and 20(b), is imparted at 60 revolutions per minute to water and food coloring in a container with a volume of 500 ml of water.

[0381] Thus, as can be seen by comparing Figures 22(c), 23(c), and 24(c), the swirling motion does not appear to adequately mix food coloring in water in a relatively large volume of fluid, such as 500 ml, as demonstrated, which is a good model for cell processing media in a container.

[0382] As shown in Figures 25(a) and 25(b), a container contains water and food coloring to simulate the mixing of cell treatment media within the container. Figure 25(a) shows the container with food coloring dripped into the water at time t = 0 seconds. Figure 25(b) shows the container with the food coloring beginning to mix with the water at time t = 60 seconds. Unlike Figures 22(a) through 24(c), throughout Figures 25(a) and 25(b), a wave motion, such as that described in connection with Figures 21(a) and 21(b), is imparted to water and food coloring in a container with a volume of 50 ml of water at 20 revolutions per minute.

[0383] Thus, as can be seen by comparing Figure 25(b) with Figures 22(c), 23(c), and 24(c), the swirling motion is more suitable for mixing the contents of the vessel at smaller fluid volumes, even at lower revolutions per minute, and therefore may be preferable for small volumes of fluid in cell processing.

[0384] Figures 26(a)-26(c) show a container with water and food coloring to simulate mixing of cell treatment media within the container. Figure 26(a) shows the container with food coloring dropped into the water at time t=0 seconds. Figure 26(b) shows the container with the food coloring beginning to mix with the water at a time after t=0 seconds. Figure 26(c) shows the container with the food coloring mixing with the water at a time after t=0 and after the illustration in Figure 26(b). Throughout Figure 26, a linear compression motion, compression along the vertical axis as described in more detail below, is applied to the water and food coloring in a container with a volume of 500 ml of water at 20 revolutions per minute. As seen in Figure 26(c), at the low cycles per minute, mixing appears to be primarily due to the dispersion of the food coloring in the water.

[0385] Figures 27(a)-27(c) show a container with water and food coloring to simulate mixing of cell treatment media within the container. Figure 27(a) shows the container with food coloring dropped into the water at time t=0 seconds. Figure 27(b) shows the container with the food coloring beginning to mix with the water at a time after t=0 seconds. Figure 27(c) shows the container with the food coloring mixing with the water at a time after t=0 seconds, after the illustration of Figure 27(b). Throughout Figure 27, a linear compression motion, compression along the vertical axis as described in more detail below, is applied to the water and food coloring in a container with a volume of 500 ml of water at 40 revolutions per minute. As can be seen in Figure 27(c), mixing is improved with increasing cycles per minute.

[0386] Figures 28(a)-28(c) show a container with water and food coloring to simulate mixing of cell processing media within the container. Figure 28(a) shows the container with food coloring dripped into the water at time t=0 seconds. Figure 28(b) shows the container with the food coloring beginning to mix with the water at a time after t=0 seconds. Figure 28(c) shows the container with the food coloring mixing with the water at a time after t=0 seconds, after the illustration in Figure 28(b). Throughout Figure 28, a linear compression motion, which is compression along the vertical axis as described in more detail below, is applied at 80 revolutions per minute to water and food coloring in a container with a volume of 500 ml of water. As shown in Figure 28(b), large bubbles are occasionally created during the linear compression, which can help aerate the mixture and can be useful in cell processing methods. As shown in Figure 28(c), good mixing is achieved for larger volumes of fluid at higher cycles per minute.

[0387] Thus, the inventors have surprisingly found that a swirling motion is suitable for adequately mixing fluids in a container at small volumes, particularly less than 100 ml. Furthermore, the inventors have surprisingly found that a linear compressive motion is suitable for adequately mixing fluids in a container at larger volumes, particularly 100 ml or greater. Thus, the agitation mechanism should be able to provide both ranges of motion so that fluids of any volume can be adequately mixed.

[0388] Figures 29(a) and 29(b) show a container according to the present invention. The container 2000 comprises a top portion 2002, a base portion 2004 extending parallel to the top portion 2002, and a wall element 2006 between the top portion 2002 and the base portion 2004. The wall element 2006 is compressible along the longitudinal axis L of the container 2000. The wall element 2006 may include one or more Z-folds 2008 or may form a concertina shape so as to be compressible along the longitudinal axis L. Figure 29(a) shows the container 2000 before compression. Figure 29(b) shows the container 2000 after compression of a portion of the wall element 2006. In general, the top portion 2002 and the base portion 2004 each generally define a plane, each plane being parallel to each other and substantially perpendicular to the longitudinal axis L.

[0389] 30(a)-30(e) show an apparatus 2100 including a container 2000 according to the present invention. The apparatus 2100 comprises a holding element 2110 and a movable plate 2120. The movable plate 2120 can be any movable plate as described herein and can be moved by any actuation mechanism as described herein. The holding element 2110 holds the upper portion of the container 2000 in a first plane P1, and the movable plate 2120 forms a second plane P2 substantially parallel to the first plane P1 for moving the base portion of the container 2000. Prior to movement of the movable plate 2120, i.e., actuation and movement, the first plane P1 and the second plane P2 extend substantially horizontally and substantially perpendicular to the longitudinal axis L.

[0390] As shown in Figure 30(a), the container 2000 can be compressed along the longitudinal axis L such that the first plane P1 remains stationary and the movable plate 2120, and therefore the second plane P2, is moved. Compression along the longitudinal axis L can cause mixing of the medium within the container 2000, as previously described. In the example shown, 50 ml of transduction can be performed. The liquid can have a depth of approximately 2.75 mm.

[0391] As shown in Figure 30(b), the container 2000 containing the medium 2102 can be expanded or depressurized along the longitudinal axis L such that the first plane P1 remains stationary and the movable plate 2120, and therefore the second plane P2, is moved. Expansion along the longitudinal axis L can be beneficial in cell processing methods, for example, for cell culture or growth. In the illustrated example, an expansion of 500 ml can be performed. The liquid can have a depth of approximately 27 mm.

[0392] 30(c), the container 2000 can undergo further compression, thus agitating the medium 2102 in the container 2000 along the axis L, as indicated by the arrow. This causes the container 2000, specifically its wall elements, to compress along the longitudinal axis L. That is, the first plane P1 remains stationary, while the movable plate 2120 and the second plane P2 are moved.

[0393] As shown in Figure 30(d), as the headspace within vessel 2000 above media 2102 is reduced, media 2102 residing within the wall elements of vessel 2000 is forced inward toward longitudinal axis L. This movement causes agitation within vessel 2000 of media 2102, which can be beneficial for several steps in cell processing methods.

[0394] 30(e), as the vessel 2000 is expanded or decompressed along the longitudinal axis L, the media 2104, 2106 that collected within the wall elements of the vessel 2000 during compression is forced, dripped, or trickled into the collection of media 2102, thereby causing further agitation within the vessel, which may be beneficial for some steps in the cell processing method.

[0395] Compression can compress the media out of the folds as the container is repeatedly raised and lowered. A set time period of compression pause may be provided, i.e., compression may be held or stopped so that the container is in a compressed state for a predetermined time period. This allows cell settling before media exchange. The compression step can result in excellent mixing and gas transfer. Such processing can also be scalable. Thus, there can be several advantages associated with such compression processing described herein for cell processing methods.

[0396] 31(a)-31(c) show a further apparatus 2200 of the present invention. The apparatus 2200 comprises a holding element 2210 for receiving and holding an upper portion of the container 2000 in a first plane P1. The apparatus 2200 further comprises a movable plate 2220 for acting on or engaging a base portion of the container 2000, the movable plate 2220 defining a second plane P2. The first plane P1 and the second plane P2 are substantially parallel and extend substantially perpendicular to the longitudinal axis L.

[0397] As shown in Figure 31(a), a static phase or step of the method is shown, and the vessel 2000 is not agitated in any way. This may be beneficial for some steps in the cell processing method.

[0398] As shown in FIG. 31(b), an agitation phase or step of the method is shown, in which the vessel 2000 is agitated to cause agitation or turbulence of the medium within the vessel 2000. In this specific example, the agitation phase includes rotating the movable plate 2220 around at least one axis in plane P2, such as axis A indicated in FIG. 31(a). Plane P2 moves when the movable plate 2220 moves. Thus, as the movable plate 2220 moves, plane P2, or a portion thereof, moves toward plane P1, which remains stationary. Thus, the distance between at least a portion of plane P2 and plane P1 is reduced. The movement of the movable plate 2220 around axis A compresses a portion of the wall elements of the vessel 2000, as shown in FIG. 31(b). When the movable plate 2220 rotates or tilts in the opposite direction, the opposite portion of the wall elements of the vessel 2000 is compressed. Thus, a wave motion as described above can be imparted to the medium in vessel 2000. Additionally, movable plate 2220 can be pivotable about an origin where longitudinal axis L intersects second plane P2 such that the origin remains stationary while all other points move. In this example, a swirling motion as described above can be imparted to the medium in vessel 2000. In other examples, movable plate 2220 can be rotatable about any number of axes in second plane P2 or can be arranged to be tilted to impart any desired stirring effect to the medium in vessel 2000.

[0399] As shown in Figure 31(c), a compression phase or step of the method is shown in which the container 2000, and specifically the wall elements, are compressed along the longitudinal axis L such that the second plane P2 is moved closer towards the first plane P1. Thus, as shown in Figure 31(c), the headspace above the medium in the container 2000 is changed, e.g., air may be forced out of the container 2000. Furthermore, the compression may result in agitation as previously described.

[0400] 32 shows a mold or insert 2300 for making a container as described herein. Mold 2300 may be suitable for blow molding, such that the container may be formed by blow molding. Mold 2300 includes a series of protrusions or ridges 2303 arranged to provide a series of Z-folds or concertina-like arrangement of the containers described herein.

[0401] Figures 33(a)-33(d) show examples of a container 2400, platform 2410, and other components that may be used in combination with the devices or systems described herein. Figure 33(d) shows a container 2400 having a top portion that is substantially open, thereby forming a fluid passageway, and a base portion that is substantially closed. There is a wall element extending between the top portion and the base portion, as described in connection with Figures 29(a) and 29(b). The wall element may include a compressible portion, such as a Z-fold as shown in Figures 33(b) and 33(d). The container 2400 may form a bellows, such as a four-fold bellows, or a concertina-like arrangement.

[0402] 33(d), the vessel 2400 can be attached to a platform 2410, which, on its underside, can be interpreted as a cell processing platform. A clip 2412 can also be provided, which can form a retention element as described herein. The clip 2412 can be provided in two halves as shown. The vessel 2400 can be sealed using an O-ring 2414 that is wedged between the upper portion of the vessel 2400 and the underside of the platform 2410. The clip 2412 can be coupled to the platform 2410 using a bolt 2416 and a corresponding nut 2418.

[0403] Platform 2410 can have many features. For example, platform 2410 can have a series of fluid inlets with attachment elements for attaching various devices. Platform 2410 can have one or more, preferably one, fluid outlets in fluid communication with the fluid inlets. For example, as shown in FIG. 33(d), the attachment element of the inlet of platform 2410 can be connected to a secondary container 2420 having a neck 2422 with threads for screwing into the corresponding threads of the attachment mechanism 2424 of platform 2410. The attachment mechanism 2424 can also include an O-ring 2426 to ensure a fluid seal or a liquid seal. Platform 2410 can also include a male connection element 2428 for connecting platform 2410 to one or more pipes or other devices. The male connection element 2428 is fluidly connected to the fluid inlet of platform 2410 by a tube 2430, such as a flexible tube, held in place by a cable tie 2432. A filter 2434 may be present between the flexible tube 2430 and the male connection element 2428. Platform 2410 may include a tube 2436 for connecting to other devices, connected to the inlet of platform 2410. The tube 2436 can be a flexible tube. The tube 2436 is connected to the fluid inlet of platform 2410 by a cable tie 2438. Platform 2410 can also include a cap 2440 for covering one or more elements, such as the sampling element 2442 or the inlet of platform 2410.

[0404] During use, secondary container 2420 acts as a breathing container for container 2400. That is, when container 2400 is compressed or decompressed, or moved, for example, by a movable plate of the present invention, secondary container 2420 allows for the counterbalance of increases and / or decreases in pressure in container 2400. Specifically, when container 2400 acts at its base beside the movable plate, fluid, such as air, can be pushed from container 2400 through platform 2410 and into secondary container 2420. Similarly, when container 2400 is pulled downward or decompressed, fluid, such as air, can be drawn from secondary container 2420 through platform 2410 and into container 2400. Thus, secondary container 2420 acts as a breathing container in that it accounts for pressure changes in container 2400.

[0405] Figures 34(a)-34(d) show another apparatus 2500 and its components according to the present invention. As best shown in Figures 34(a) and 34(b), apparatus 2500 comprises a movable plate 2502 having two protruding arms 2502a, 2502b formed thereon for frictionally engaging a sidewall adjacent the base of a container 2580. Apparatus 2500 is depicted without retention elements for clarity only, although retention elements are discussed in more detail below in connection with Figures 35(a)-35(e).

[0406] The apparatus includes a linkage 2504 connecting a movable plate 2502 to a first motor 2508a, a second motor 2508b, and a third motor 2508c. Each motor has a respective gearbox 2510a, 2510b, 2510c. The first motor 2508a is arranged to rotate the movable plate 2502 about an axis formed in the plane of the movable plate 2502. The second motor 2508b and the third motor 2508c are arranged to move the movable plate 2502 longitudinally, as described in more detail below.

[0407] Specifically, the illustrated linkage 2504 includes a first longitudinal rail 2504 a and a second longitudinal rail 2504 b. Each longitudinal rail 2504 a, 2504 b is generally formed as a complementary pair of rails in this particular embodiment. The linkage 2504 further includes a crank housing 2512 including a crank 2514 driven by a shaft 2516 connected to a second motor 2508 b, the crank housing 2512 being slidable upwardly and / or downwardly along the first longitudinal rail 2504 a.

[0408] The linkage 2504 further includes a slider portion 2520 connected to the movable plate 2502, which is slidable upward and / or downward along the second longitudinal rail 2504b. The crank 2514 is connected to the slider portion 2520 by a connecting rod 2518. The slider portion 2520 also includes a shaft (not shown) extending therethrough to couple the movable plate 2502 to the first motor 2508a.

[0409] 34(c), the previously discussed crank arrangement is shown in more detail. Specifically, there is provided a crank 2514 driven by a shaft 2516 by a second motor (not shown). The crank 2514 is coupled to a connecting rod 2518 that terminates in a slider portion 2520. The crank 2514 has a diameter of 40 mm in the depicted example, although other diameters are equally contemplated. The crank 2514 may be interchangeable such that it can be replaced with a crank of larger or smaller diameter so that the displacement of the movable plate during use can be adjusted accordingly. For example, for larger displacements, a larger diameter crank may be used. For example, for smaller displacements, a smaller diameter crank may be used.

[0410] In use, as the crank 2514 is rotated, thus moving the connecting rod 2518, the slider portion 2520 is moved axially upward, and then as the crank 2514 continues to rotate, the slider portion 2520 is moved axially downward. The slider portion 2520 is thereby movable by the crank 2514 between a first or home position and a second or raised position. The slider portion 2520 then returns to the first or home position on subsequent rotations of the crank 2514. In this manner, the crank arrangement allows for rapid upward and downward movement of the movable plate, imparting a complete compression and decompression cycle to a received container with each rotation of the crank 2514 during use.

[0411] 34(d), the third motor 2508c is shown in more detail. Specifically, the third motor 2508c is shown as a lead screw or ball screw motor, including a drivable threaded shaft 2522. The drivable threaded shaft 2522 is threadedly engaged with a corresponding threaded portion 2524 forming part of the crank housing 2512 (see FIG. 34(a)). As a result, when the threaded shaft 2522 is driven, the threaded portion 2524 of the crank housing 2512 is moved axially either upward or downward, depending on the direction of rotation of the driven shaft 2522. As a result, the crank housing 2512 is movable along the first longitudinal rail 2504a (see FIG. 34(a)). Thus, by virtue of the crank arrangement discussed above, the movable plate 2502 (see FIG. 34(a)) is similarly movable along the second longitudinal rail 2504b (see FIGS. 34(b) and 34(c)). In this manner, a lead screw or ball screw arrangement allows for slower upward and downward movement of the movable plate.

[0412] 34(a)-34(d), during use, the container 2580 is received within the apparatus 2500, specifically between the movable plate 2502 and a retaining element (not shown). The first motor 2508a is actuated to rotate the movable plate 2502 about an axis in the plane of the movable plate 2502. Additionally, the second motor 2508b is actuated, either intermittently or continuously, to cause axial translation of the movable plate 2502 along a longitudinal axis parallel to the first longitudinal rail 2504a and the second longitudinal rail 2504b. As previously discussed, the second motor 2508b rotates the shaft 2516, thereby rotating the crank 2514. As the crank 2514 rotates, the connecting rod 2518 is moved, causing the slider portion 2520 to move axially along the second longitudinal rail 2504b. Due to the configuration of the crank arrangement, the slider portion 2520, and therefore the movable plate 2502, is moved axially upward and downward, thereby imparting compression and decompression motion to the container 2580. Furthermore, due to this configuration, the axial movement of the slider 2520 by the second motor 2508b is limited to a predetermined area along the longitudinal axis. Furthermore, the third motor 2508c is actuated to cause rotation of the driven shaft 2522, thereby translating the crank housing 2512 axially upward or downward, depending on the direction of rotation of the driven shaft 2522. The crank housing 2512 is thereby caused to move axially along the first longitudinal rail 2504a, thereby imparting a slow compressive or decompressive movement to the container 2580.

[0413] For the sake of completeness, one skilled in the art will readily appreciate that motors 2508a, 2508b, 2508c may be operated in any order or indeed in combination with one another. The foregoing description of the use of device 2500 is not intended to be limiting in any way.

[0414] Figures 35 and 36(a) to 36(d) show another apparatus 2600 of the present invention, which operates according to the same principles as described above for apparatus 2500 of Figures 34(a) to 34(d).

[0415] FIG. 35 shows an apparatus 2600 including a movable plate 2602 operated by a linkage 2604, motors 2608a, 2608b, 2608c, and gearboxes 2610a, 2610b, 2610c, as described in connection with FIGS. 34(a)-(d). Further description will not be provided for the sake of brevity. The apparatus 2600 further includes a holding element 2650. The holding element 2650 is formed from an upper plate 2652 arranged to receive an upper portion of a container during use, and a lower plate 2654. The movable plate 2602 is disposed between the upper plate 2652 and the lower plate 2654. The upper plate 2652 is connected to the lower plate 2654 by a plurality of legs 2656 extending between the upper plate 2652 and the lower plate 2654, and the ends of the legs 2656 are coupled to each of the plates 2652, 2654. The upper plate 2652 generally includes a concave surface 2658 for receiving an upper portion of a container during use, as described further below. The upper plate 2652 also includes a plurality of clamps 2660 arranged to clamp an upper portion of a container to the upper plate 2652 during use.

[0416] Apparatus 2600 also includes a frame 2662 formed around an actuation mechanism, including linkage 2604, motors 2608a, 2608b, 2608c, and gearboxes 2610a, 2610b, 2610c. While not shown in this figure for clarity, frame 2662 also includes a plurality of panels that enclose components of the actuation mechanism, thereby preventing user access during use. Additionally, the panels may prevent ingress of liquids or other cell processing components, such as media, cells, or the like, into the actuation mechanism. Frame 2662 and the panels may be construed as forming a housing for the actuation mechanism.

[0417] FIGS. 36(a)-36(e) illustrate the apparatus 2600 depicted in FIG. 35 and to which the container 2400 and platform 2410 of FIGS. 33(a)-33(d) are attached. Specifically, a base portion of the container 2400 is engageable with a movable plate 2602. In this specific embodiment, the base portion of the container 2400 can be freely engaged and disengaged with the movable plate 2602; however, in other examples, the base portion of the container 2400 can be fixedly coupled to the movable plate 2602 via adhesive, fastening means, or the like. Furthermore, the platform 2410 coupled to the upper portion of the container 2400 is received within a concave surface 2658 (see FIG. 35) and clamped to the concave surface 2658 by a plurality of clamps 2660. The container 2400 is thereby positioned between the movable plate 2602 and the retaining element 2650 to allow for compression, decompression, or other movement of the container 2400 during use.

[0418] 34(a)-34(d) to cause a desired movement of the container 2400. Specifically, the first motor 2608a controls the rotational movement of the base of the container 2400 about an axis formed in the plane of the movable plate 2602, the second motor 2608b controls the fast compression / decompression of the container 2400, specifically by axially translating the base of the container 2400 toward or away from the retaining element 2650, and the third motor 2608c controls the slow compression / decompression of the container 2400, specifically by axially translating the base of the container 2400 toward or away from the retaining element 2650. The first motor 2608a may thus be useful for imparting a pivoting or rocking motion to the base of the container 2400. The second motor 2608b may thus be useful for imparting a compressive mixing motion, i.e., a rapid compression followed by a rapid decompression, to the container 2400. The third motor 2608c may be useful for imparting a breathing motion, for example, by expelling fluid, such as air or medium, from the container 2400 into the secondary container 2420, as described in more detail in relation to Figures 33(a)-33(d). Separate motors may thereby be provided for individual motions imparted to the container 2400, or indeed for compound motions during use.

[0419] In certain examples described herein, there may be a method 2700 for cell processing, illustrated by Figure 37. Method 2700 may include step 2710 of providing a compressible container containing a population of cells in a liquid medium. Method 2700 may include step 2720 of statically processing the population of cells in the liquid medium in the compressible container. Method 2700 may include step 2730 of dynamically processing the population of cells in the liquid medium in the compressible container.

[0420] Step 2720 of statically treating the population of cells in a liquid medium may include not subjecting the population of cells to movement or force, i.e., may be a static aspect of cell treatment.

[0421] The step 2730 of dynamically treating the population of cells in the liquid medium may include agitating the population of cells in the liquid medium. The step of agitating the population of cells in the liquid medium may include imparting a wave motion to the population of cells and the liquid medium, imparting a gyration motion to the population of cells and the liquid medium, compressing the compressible container, or a combination thereof. The step of compressing the compressible container may include compressing the compressible container along a longitudinal axis that is perpendicular to the top and base portions of the container.

[0422] A separate step, or in combination with any other step 2740, of compressing a compressible container containing a cell population in a liquid medium may be provided.

[0423] Further embodiments and examples are provided below with reference to Figures 38-42.

[0424] (Example) The invention will now be described with reference to the following non-limiting examples demonstrating various embodiments of the invention. It should be noted that the vessel 2400 and platform 2410 of Figures 33(a)-33(d) were used in combination with the apparatus 1600 of Figures 18(a)-18(d) for the following examples.

[0425] material The following materials were used: CD3+ T cells, healthy donor 1 (HD1) (isolated from leukopak, Access Biologicals LLC) · X-VIVO 15(LZBE02-053Q, Lonza) 5% normal human AB serum (H4522, Sigma) rhlL-2 (100 units.mL -1 )·(202-IL-050, R&D Systems) Activator: CTS Dynabeads (3:1 bead-to-cell ratio) (40203D, ThermoFisher) Transduction: GFP lentiviral vector (MOI: 1) (0010VCT, Takarabio)

[0426] method The following methods were utilized: · Seeding density (day 0) = 1x10 6 cells.mL -1 Inoculation volume (day 0) = 50 mL Feed: Fed-batch, volume doubled from the set point at the end of the static period (day 3). Not dictated by cell density from sampling. Additional media volume includes fresh IL2 cytokine (100 units / mL). Control: FEP static culture bags (CellGenix VueLife) with increased volume (see below) to replicate manual processing for both static and initial expansion phases, with the same seeding density and feeding strategy (no agitation). Viable cell density and fold extension: Cellometer Auto 2000, Nexcelom

[0427] Testing Timeline A general test run timeline is shown in Figure 38. Specifically, an inoculum is provided on day 0. A lentiviral vector is added on day 1. From days 0 to 3, static and / or intermittent rocking motion is applied to the vessel by the device. A feed, i.e., the supply of nutrients to the medium, occurs on day 3, and a sample is also taken on day 3 for testing. From days 3 to 5, a rocking motion is applied to the vessel by the device. An additional feed occurs on day 5, and a sample is also taken on day 5 for testing. Finally, from days 5 to 7, linear compression is applied to the vessel by the device. An additional feed occurs on day 6, and a sample is also taken on day 6 for testing. Final readouts, such as cell viability and total viable cell count, are taken on day 7 or later. This test run provides a general process for culturing cells using the device; more specific examples are described below.

[0428] Example 1 For primary T cell run 1 (FIGS. 39 and 41), cells and culture media were placed into a bioreactor, specifically vessel 2400 shown in FIGS. 33(a)-33(d). The cell culture process was substantially as described above in the study run timeline. In this specific example, an inoculum was provided on day 0 in a 50 ml volume utilizing the materials described above, followed by the addition of the lentiviral vector. A sample was taken on day 3, and a 150 ml feed volume was provided to the vessel. Additional samples were taken on days 4, 5, and 6. An additional feed at a 100 ml feed volume was provided on day 6. Additional feeds were provided on days 7, 8, 9, and 10, with feed volumes of 100 ml, 400 ml, 100 ml, and 50 ml, respectively. Samples were taken on days 7, 8, 9, 10, and 11.

[0429] Also, the following processing steps were used, specifically the following stirring steps: 1. Days 0-3 and 4-5: None (i.e., static culture) 2. Days 3-4: Oscillatory movement A (60 rpm, 20 mm displacement amplitude) 3. Days 5-6: Oscillatory movement B (20 rpm, 10 mm displacement amplitude) 4. Days 6-11: Linear compression (60 cpm, 20 mm displacement amplitude)

[0430] The relevant agitation steps (either numbered 1, 2, 3, or 4) are indicated at appropriate time intervals in Figures 39 and 41. Total viable cells are shown for this particular agitation regime in Figures 39 and 41, with Figure 41 showing cell viability.

[0431] Key results of primary T cell run 1 were as follows: One container can be used for all volumes, meaning no manual transfers are required. · Oscillating behavior A (days 3-4): Cell death was observed Cell yield after 4 days of compression mixing was 1x10 9 exceeded. Final viability was within the release criteria (80% or higher).

[0432] Example 2 For primary T cell run 2 (FIGS. 40 and 42), cells and culture media were placed into a bioreactor, specifically vessel 2400 shown in FIGS. 33(a)-33(d). The cell culture process was substantially as described above in the study run timeline. In this specific example, an inoculum was provided on day 0 in a volume of 50 ml, followed by the addition of the lentiviral vector. A sample was taken on day 3, and a 150 ml feed volume was provided to the vessel. Further samples were taken on days 4 and 5. A further feed at a 200 ml feed volume was provided on day 5. A further feed was provided, and a sample was taken on day 6 at a 400 ml feed volume. Samples were then taken on days 7 and 8.

[0433] Also, the following processing steps were used, specifically the following stirring steps: 1. Days 0-3: None (i.e., static culture) 2. Days 3-4: Oscillatory movement C (20 rpm, 20 mm displacement amplitude) 3. Days 4-5: Oscillatory movement B (20 rpm, 10 mm displacement amplitude) 4. Days 6-8: Linear compression (60 cpm, 20 mm displacement amplitude)

[0434] The relevant agitation steps (either numbered 1, 2, 3, or 4) are indicated at appropriate time intervals in Figures 40 and 42. Total viable cells are shown in Figures 40 and 42 for this particular agitation regime, with Figure 42 showing cell viability.

[0435] Key results from primary T cell run 2 were as follows: One container can be used for all volumes, meaning no manual transfers are required. · Rocking movement C (days 3-4): Cell death was observed After 5 days of stirring, the cell yield was 6x10 6 exceeded. Overall viability within release criteria (80% or more) As shown in Figure 40, approximately 60% less culture medium was used in our vessel over 8 days compared to a standard wave perfusion protocol (estimated based on the standard protocol for perfusion culture of T lymphocytes in the WAVE Bioreactor System 2 / 10, GE Healthcare Life Sciences (Application Note 28-9650-52 AC)).

[0436] It will be understood by those skilled in the art that the above embodiments have been described by way of example only and not by way of limitation, and that various modifications and changes can be made thereto without departing from the scope of the present invention as defined by the appended claims. Various changes to the detailed designs as described above are possible, for example, changes in shape, size, arrangement, assembly, etc.

[0437] Specifically, any of the discussed actuation mechanisms may be utilized in any embodiment of the device, system, or method discussed herein. Further, any of the discussed retention elements may be utilized in any embodiment of the device, system, or method discussed herein. Still further, any of the discussed containers, platforms, or other similar cell processing components may be utilized in any embodiment of the device, system, or method discussed herein.

[0438] While the foregoing examples illustrate exemplary uses of the disclosed devices and systems, those skilled in the art will understand that they are equally applicable to other cell types, media types, transduction and activation reagents, etc. Likewise, those skilled in the art will understand that other mixing / agitation regimes, such as, for example, the speeds, time durations, or amplitudes of the rocking, swirling, and / or compressing regimes discussed herein, are equally contemplated as part of the present invention. [Explanation of symbols]

[0439] 100 Operating mechanism 102 Movable board 106 Foundation plate 200 Operating Mechanism 202 Movable board 204 Linear Actuator 300 Operating Mechanism 300 Operating Mechanism 302 Movable board 306 Foundation plate 400 Operating mechanism 402 Movable board 404 Linear Actuator 406 Foundation plate 408 Pivotable Rod 500 Operating mechanism 502 Movable board 504a, 504b springs 506 Foundation plate 508 Connecting Rod 510 wheels 506 Foundation plate 512 Pivot point 514 Center Rod 600 Operating Mechanism 602 Movable board 604a, 604b permanent magnets 606 Foundation plate 608 Pivotable rod 608a, 608b electromagnet 700 Operating Mechanism 702 Movable board 704 Link Mechanism 706 Foundation plate 800 Operating Mechanism 802 Movable board 804a First cam member 804b Second cam member 806 Foundation plate 808a, 808b tension spring 810 Center Rod 812 Pivot point 900 Operating mechanism 902 Movable board 904a, 904b springs 906 Foundation plate 908 connecting rod 910 wheels 912 Pivot point 914 central hub 1000 Operating Mechanism 1002 Movable board 1004a, 1004b springs 1006 Foundation plate 1010 Support plate 1012 Pivot point 1014 Center rod, center hub 1100 Operating mechanism 1102 Movable board 1104 Support plate 1106 Foundation plate 1108 Link mechanism 1110a first cam member 1110b Second cam member 1112 Actuator 1114 Motor 1200 Operating mechanism 1202 Movable board 1204 Support plate 1206 Foundation plate 1208 Linear Actuator 1210 central hub 1212 Connecting rod 1214 Link mechanism 1216 Motor 1300 Operating mechanism 1302 Movable board 1304a First link mechanism 1304b Second link mechanism 1304c Third link mechanism 1306a Foundation plate 1306b Foundation plate 1308a First Actuator 1308b Second Actuator 1308c Third Actuator 1310a First Pivot Point 1310b Second Pivot Point 1310c Third pivot point 1400 Operating mechanism 1402 Movable board 1404a First link mechanism 1404b Second link mechanism 1404c Third link mechanism 1406 Foundation plate 1408a First motor 1408b Second Motor 1408c Third Motor 1450 Holding Element 1480 Container 1500 Operating mechanism 1502 Movable board 1504a First Linear Actuator 1504b Second Linear Actuator 1504c Linear Actuator 1600 equipment 1602 Movable board 1604a First link mechanism 1604b Second link mechanism 1606 Foundation plate 1608a First motor 1608b Second Motor 1610a First Gearbox 1610b second gearbox 1612a, 1612b Motor pivot shaft 1614a, 1614b Motor connection part 1616a, 1616b Pivot bar 1618 Center Pivot Clamp 1620 Center pivot bar 1622a, 1622b Stop 1624 Mounting section 1626 Sensor 1628 Sensor Cable 1630 Telescopic Rail 1631 Rail mounting plate 1632 Hinge 1634 Bearings 1636, 1638, 1640 Pivot bearing blocks 1700 Linear Actuator 1800 containers 1802 Center origin 1804 Food coloring 1806 mixed 1900 container 1902 Axis 2000 containers 2002 Upper part 2004 Basic part 2006 Wall Elements 2100 equipment 2102, 2104, 2106 Medium 2110 Holding element 2120 Movable board 2200 equipment 2210 Holding element 2220 Movable board 2300 type, cast-in insert 2400 containers 2410 Platform 2412 clips 2414 O-ring 2416 volts 2418 Nut 2420 Secondary container 2422 Neck 2424 Mounting mechanism 2426 O-ring 2428 Male connecting element 2430 tube 2432 Cable Tie 2434 Filter 2436 Tube 2438 Cable Tie 2440 Cap 2442 Sampling Elements 2500 equipment 2502 Movable board 2502a, 2502b arms 2504 Link mechanism 2504a First longitudinal rail 2504b Second longitudinal rail 2508a First Motor 2508b Second Motor 2508c Third Motor 2510a, 2510b, 2510c gearbox 2512 crank case 2514 Crank 2516 Shaft 2518 Connecting Rod 2520 Slider part 2522 Drivable Thread Shaft 2524 Threaded part 2580 Container 2600 equipment 2602 Movable board 2604 Link mechanism 2608a, 2608b, 2608c motors 2610a, 2610b, 2610c gearbox 2650 Holding Element 2652 Upper plate 2654 Lower plate 2656 legs 2658 Concave surface 2660 Clamp 2662 frames A-axis L vertical axis P1 First plane P2 Second plane

Claims

1. 1. An apparatus for use in performing one or more unit operations in cell processing, comprising: a retaining element arranged to receive an upper portion of the compressible container in the first plane; a movable plate spaced from the retaining element and positioned to operatively engage a base portion of the container, the movable plate defining a second plane substantially parallel to the first plane; an actuation mechanism operatively coupled to the movable plate for rotating the movable plate about at least one axis in the second plane, thereby reducing a distance between at least a portion of the second plane and the first plane; Equipped with The actuation mechanism is further arranged to move the movable plate along a longitudinal axis substantially perpendicular to the first plane and the second plane, thereby reducing the distance between the second plane and the first plane and compressing the compressible container between the movable plate and the retaining element.

2. The apparatus of claim 1 , wherein the actuation mechanism is arranged to rotate the movable plate about an axis in the second plane.

3. The apparatus of claim 1 , wherein the actuation mechanism is arranged to rotate the movable plate about multiple axes in the second plane.

4. 4. Apparatus according to any one of claims 1 to 3, wherein the actuation mechanism is arranged to rotate the movable plate between 0 and 90 degrees about the or each axis.

5. 5. The apparatus of claim 1, wherein a longitudinal axis extending perpendicular to the first plane and the second plane intersects the second plane at an origin, and the actuation mechanism is arranged to pivot the movable plate about the origin.

6. The apparatus of claim 5 , wherein the origin is centrally located within the second plane.

7. 7. The apparatus of claim 5 or 6, wherein the movable plate is pivotable about the origin such that each point in the second plane, excluding the origin, forms an angle with the longitudinal axis between 0 and 180 degrees, excluding 90 degrees.

8. 8. The device of claim 1, wherein the retaining element comprises a platform operably engageable with the upper portion of the compressible container, a clamping mechanism operably engageable with the upper portion of the compressible container, or a sealing plate operably engageable with the upper portion of the compressible container.

9. 9. The apparatus of claim 1, wherein the actuation mechanism comprises a base plate spaced apart from and substantially parallel to the movable plate, the base plate being operably coupled to the movable plate.

10. 10. The apparatus of claim 9, wherein the base plate comprises at least one actuator, the or each actuator being operably coupled to or operably engageable with the movable plate.

11. 11. The apparatus of claim 9 or 10, wherein the base plate comprises at least one rail, the or each rail upstanding therefrom substantially perpendicular to the base plate, the movable plate being slidably connected to the or each rail, and at least one actuator arranged to slide at least a portion of the movable plate along the or each rail.

12. 12. The apparatus of any one of claims 9 to 11, wherein the base plate comprises a first linkage operatively connected to the movable plate, the first linkage being driven by a first motor.

13. 13. The apparatus of claim 12, wherein the base plate further comprises a second linkage operatively coupled to the movable plate, the second linkage being driven by a second motor.

14. The apparatus of claim 13 , wherein the first linkage and the second linkage are operatively connected at opposite edges of the movable plate.

15. 15. The apparatus of claim 13 or 14, wherein the base plate further comprises a third linkage operatively coupled to the movable plate, the third linkage being driven by a third motor.

16. 16. The apparatus of claim 15, wherein the first linkage, the second linkage, and the third linkage are operatively coupled to the movable plate in a triangular arrangement.

17. 9. The apparatus of claim 1, wherein the actuation mechanism comprises a first motor operably coupled to the movable plate and configured to rotate the movable plate about at least one axis in the second plane.

18. 18. The apparatus of claim 17, wherein the actuation mechanism further comprises a second motor operably coupled to the movable plate and configured to move the movable plate along a longitudinal axis substantially perpendicular to the first plane and the second plane, thereby reducing the distance between at least a portion of the second plane and the first plane.

19. 20. The apparatus of claim 18, wherein the actuation mechanism further comprises a third motor operably coupled to the movable plate and configured to move the movable plate along the longitudinal axis, thereby reducing the distance between at least a portion of the second plane and the first plane.

20. The actuation mechanism further includes a link mechanism, the link mechanism comprising: a crank housing slidable along a first longitudinal rail and including a rotatable crank extending substantially parallel to the longitudinal axis; a slider portion operably coupled to the movable plate, slidable along a second longitudinal rail, extending substantially parallel to the first longitudinal rail, the slider portion operably coupled to the rotatable crank by a connecting rod; Equipped with 20. The apparatus of claim 19, wherein the second motor is operably coupled to the rotatable crank to rotate the rotatable crank and move the slider portion along the second longitudinal rail, and the third motor is operably connected to the crank housing to move the crank housing along the first longitudinal rail.

21. 21. The apparatus of claim 20, wherein the third motor comprises a ball screw motor or a lead screw motor operably coupled to a corresponding threaded portion of the crank housing such that the crank housing is movable along the first longitudinal rail.

22. 22. The device of any one of claims 1 to 21, further comprising a controller communicatively coupled to the actuation mechanism.

23. 23. The apparatus of claim 22, further comprising one or more positioning sensors, the or each positioning sensor communicatively coupled to the controller, the controller generating a signal to the actuation mechanism based on a signal received from the or each positioning sensor.

24. 1. A system for use in performing one or more unit operations in cell processing, comprising: An apparatus according to any one of claims 1 to 23; a container having a base portion, an upper portion parallel to the base portion, and a compressible wall element extending substantially vertically between the base portion and the upper portion; Equipped with the container is at least partially disposed between the retaining element and the movable plate, and the actuation mechanism is arranged to move the movable plate such that at least a portion of the compressible wall element is at least partially compressed along a longitudinal axis perpendicular to the first plane and the second plane.

25. 25. The system of claim 24, wherein the base portion of the container is fixedly attached to the movable plate.

26. 1. A method of treating cells, comprising: providing a cell treatment medium to a vessel having a base portion, an upper portion parallel to the base portion, and a compressible wall element extending substantially vertically between the base portion and the upper portion; holding the top portion of the container in a first plane; engaging the base portion of the container with a movable plate defining a second plane substantially parallel to and spaced apart from the first plane; rotating the base portion of the vessel about at least one axis in the second plane, thereby inducing turbulence in the cell treatment medium within the vessel; compressing the container along a longitudinal axis substantially perpendicular to the first plane and the second plane; A method comprising:

27. 27. The method of claim 26, wherein the step of rotating the base portion of the container comprises rotating the base portion of the container about an axis in the second plane.

28. 27. The method of claim 26, wherein a longitudinal axis extending perpendicular to the first plane and the second plane intersects the second plane at an origin, and wherein the step of rotating the base portion of the container includes pivoting the base portion of the container about the origin.

29. 29. The method of claim 28, wherein the origin is centered within the second plane.

30. 30. A method of treating cells using the system of claim 28 or 29.

31. (a) providing a population of cells in a liquid medium in said container; (b) operating the system to process the population of cells in the liquid medium; 31. The method of claim 30, comprising:

32. 32. The method of claim 30 or 31, wherein treating the population of cells comprises maintaining the population of cells in the liquid medium while pressure is applied to at least a portion of the container to compress the container.

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