Vessel containing an internal mixer and method of use

Abstract

A vessel including an internal mixer and actuator assembly and associated methods are described. In some embodiments, the vessel includes a mixer and an actuator, at least one of which may be disposed inside the vessel. The actuator may actuate the mixer to induce flow within the vessel, mixing the contents of the vessel with a small volume footprint and high mixing efficiency. In some embodiments, the actuator may be configured to deform the mixer, which may include one or more features that may be deformed out of plane, such as kirigami or origami. The actuator and mixer may be arranged in series or parallel. The actuator may be used without the mixer to induce flow within the vessel. The actuator may be powered pneumatically, hydraulically, electrically, and / or in other suitable manners.

Description

[Technical field]

[0001] This application claims the benefit of U.S. Provisional Application No. 63 / 315,508, filed March 1, 2022, and U.S. Provisional Application No. 63 / 315,495, filed March 1, 2022, the entire contents of each of which are incorporated by reference in their entirety.

[0002] The present technology relates generally to fluid mixing systems and related methods. More specifically, methods and apparatus are disclosed that include a vessel with an internal mixer. [Background technology]

[0003] Fluid mixers are traditionally used in a variety of applications to agitate fluids in a vessel. Fluid mixers allow the fluid agitation process to be performed automatically, sometimes continuously, potentially increasing throughput and efficiency compared to manual mixing processes. In some cases, mixers may include motor-driven components (such as propellers) to create a vortex to mix the fluids. Alternatively, fluid mixers include a fluid vessel resting on a rocking platform that moves in a controlled elliptical fashion to agitate the fluids to achieve the desired mixing. Summary of the Invention

[0004] In one embodiment, the mixing device includes a vessel configured to contain a fluid and a mixer disposed within the vessel. The mixer includes a substrate and a plurality of slots arranged in a pattern on the substrate. Additionally, the plurality of slots define one or more spines that extend at least partially along an axial direction of the substrate. The mixer also includes a plurality of flaps configured to move between an extended configuration and a contracted configuration when the substrate is axially deformed.

[0005] In another embodiment, a mixing device includes a vessel configured to contain a fluid and a mixer disposed within the vessel, the mixer configured to induce a flow in the fluid contained within the vessel upon axial deformation of the mixer.

[0006] In yet another embodiment, a method of mixing fluids disposed within a vessel includes displacing opposite ends of a mixer disposed within the vessel relative to one another to deform the mixer and induce flow of the fluids.

[0007] In some aspects, a mixing system is provided. In some embodiments, the mixing system can include a vessel configured to contain a fluid, a mixer disposed within the vessel, and an actuator disposed within the vessel and operably coupled to the mixer. The actuator can be configured to axially deform the mixer to induce a flow of the fluid contained within the vessel.

[0008] In some aspects, a mixing system is provided. In some embodiments, the mixing system can include a vessel configured to contain a fluid, a mixer disposed within the vessel, where the mixer is operably coupled to a first portion of the vessel, and an actuator disposed within the vessel. The actuator is operably coupled to a second portion of the vessel and the mixer, and the actuator can be configured to deform the mixer to induce a flow of the fluid contained within the vessel.

[0009] In some aspects, a method of mixing a fluid disposed within a vessel is provided. In some embodiments, the method can include axially deforming an actuator disposed within the vessel to axially deform a mixer disposed within the vessel and inducing a flow in the fluid disposed within the vessel when the mixer is axially deformed.

[0010] It should be understood that the foregoing concepts, and additional concepts described below, can be arranged in any suitable combination, and the disclosure is not limited in this respect. Moreover, other advantages and novel features of the present disclosure will become apparent from the following detailed description of various non-limiting embodiments when considered in conjunction with the accompanying figures. [Brief description of the drawings]

[0011] The accompanying drawings are not drawn to scale. In the drawings, identical or nearly identical parts that are shown in various figures may be represented by similar numerals. For clarity, not every part is labeled in every drawing. In the drawings:

[0012] [Figure 1] FIG. 1 is a photograph of one embodiment of a mixing system.

[0013] [Figure 2A-B] FIG. 2A is a photograph of one embodiment of a mixer.

[0014] FIG. 2B is a photograph of one embodiment of a mixer.

[0015] [Figure 2C-D] FIG. 2C is a photograph of one embodiment of a mixer.

[0016] FIG. 2D is a photograph of one embodiment of a mixer.

[0017] [Diagram 3] FIG. 3 is a schematic diagram of one embodiment of a mixing system.

[0018] [Figure 4A-B] FIG. 4A is a schematic diagram of one embodiment of a vessel with a mixer in a retracted configuration.

[0019] FIG. 4B is a schematic diagram of the vessel of FIG. 4A with the mixer in an extended configuration.

[0020] [Figure 5A-B] FIG. 5A is a schematic diagram of one embodiment of the vessel with the mixer in a retracted configuration.

[0021] FIG. 5B is a schematic diagram of the vessel of FIG. 5A with the mixer in an extended configuration.

[0022] [Figure 6] FIG. 6 is a schematic diagram of another embodiment of a container.

[0023] [Figure 7] FIG. 7 is a schematic diagram of yet another embodiment of a container.

[0024] [Figure 8A-B] FIG. 8A is a schematic diagram of one embodiment of a hanging container.

[0025] FIG. 8B is a schematic diagram of another embodiment of a hanging container.

[0026] [Figure 9] FIG. 9 is a schematic isometric view of one embodiment of a container.

[0027] [Figure 10] FIG. 10 is a graph of mixing times for several exemplary embodiments of the vessel.

[0028] [Figure 11A-11B] 11A-11B are schematic diagrams of a mixing system according to some embodiments.

[0029] [Figure 12A-12B] 12A-12B are schematic diagrams of a mixing system according to one embodiment.

[0030] [Figure 13A-13B] 13A-13B are schematic diagrams of a pneumatic mixing system according to one embodiment.

[0031] [Figure 14A-14B] 14A-14B are schematic diagrams of a pneumatic mixing system according to one embodiment.

[0032] [Figure 15A-15B] 15A-15B are schematic diagrams of a parallel mixing system and actuator according to one embodiment. [Fig. 15C-15D] 15C-15D are schematic diagrams of a parallel mixing system and actuator according to one embodiment.

[0033] [Figure 16A-16B] 16A-16B are schematic diagrams of a pneumatic mixing system according to one embodiment.

[0034] [Figures 17A-17C] 17A-17C are schematic diagrams of the operation process of the actuator of the pneumatic mixing system of FIGS. 16A-16B.

[0035] [Figures 18A-18C] 18A-18C are schematic diagrams of a mixing system according to one embodiment.

[0036] [Figure 19A-19B] 19A-19B are schematic diagrams of a parallel mixing system and actuator according to one embodiment.

[0037] [Figure 20] FIG. 20 is a schematic diagram of a mixing system according to one embodiment.

[0038] [Figures 21A-21C] 21A-21C are schematic diagrams of a mixing system according to one embodiment.

[0039] [Fig. 22A-22B] 22A-22B are schematic diagrams of an actuator of the mixing system of FIGS. 21A-21C.

[0040] [Figure 23A-23B] 23A-23B are schematic diagrams of a mixing system according to two embodiments.

[0041] [Figure 24A] FIG. 24A is an example control system of a mixing system according to some embodiments. [Figure 24B] FIG. 24B is an example control system of a mixing system according to some embodiments.

[0042] [Figure 25A] FIG. 25A is a measurement system of a mixing system according to some embodiments. [Figure 25B] FIG. 25B is a measurement system of a mixing system according to some embodiments.

[0043] [Figure 26] FIG. 26 is an example blend data for a blended system. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0044] Existing fluid handling systems traditionally use a structure (such as the propeller mentioned above) that is placed within the fluid and driven to generate a vortex within the fluid. In one exemplary system, a magnetic stir bar can be inserted into a container of fluid and placed on a platform that can magnetically rotate the stir bar. The inventors recognized that this category of fluid mixers can lack parallelization and throughput. Additionally, rigid actuators can induce high shear stresses within the fluid, which can disturb or damage biological material that may be contained within the fluid.

[0045] Alternative existing fluidic systems utilize a moving platform to agitate fluids in vessels placed on the moving platform. While this type of system may provide automated and controlled agitation of fluids, the inventors recognized that moving platforms (e.g., rocking cell culture platforms) typically require large footprints and expensive equipment. These drawbacks may limit the usefulness of these platforms. Furthermore, the throughput of these platforms can only be improved by increasing the footprint of the platform. In other words, while it is possible to mix multiple vessels in parallel, the platform must be appropriately sized to accommodate the vessels simultaneously.

[0046] In view of the above, the inventors have recognized advantages associated with a fluid mixer in which the mixer is disposed within a vessel containing a fluid. The mixer may include an elastic substrate, such as a flexible elastic sheet or a sheet including an elastic portion. The substrate may have a plurality of flaps formed thereon. In some embodiments, the plurality of flaps are formed by a plurality of slots arranged in a pattern on the flexible substrate of the mixer, such that the plurality of flaps are formed on different portions of the substrate. The flaps may be configured to deflect in a direction at least partially perpendicular to a plane in which the elastic substrate extends when the mixer is axially deformed. As the flaps periodically move between a first configuration and a second configuration (e.g., an extended configuration and a contracted configuration), the flaps induce flow within the vessel or agitate the surrounding fluid (e.g., by generating vortices). In this manner, the fluid within the vessel (flexible or rigid) is mixed. In some embodiments, the fluid flow may be generated by shedding of vortices at the edges of the flaps.

[0047] In some embodiments, the fluid in a container (flexible or rigid) described herein may be a liquid, such as a liquid solution. In some embodiments, the container may contain both a liquid solution and a gas (such as nitrogen) or a mixture of gases (such as air). In some embodiments, the liquid solution in the container may contain an additional composition that is mixed with and / or dispersed in the liquid. This additional composition may include, but is not limited to, pharmaceutical ingredients, bulk drug substances, buffers, cell culture media, active ingredients, drugs, foods, particles, other liquids, any combination thereof, or other suitable materials, but the disclosure is not so limited.

[0048] The embodiments of the mixing system described herein can provide a relatively small footprint compared to existing mixing systems and, in some cases, can facilitate parallel and / or automated operation of the mixing system. Additionally, the disclosed mixing system can be low cost and lightweight compared to existing bulky fluid mixers. It should also be recognized that in some embodiments, the mixing system can induce a gentler fluid flow in the fluid within the vessel (flexible or rigid) compared to mixers with rigid propellers. Thus, lower shear stress can be applied to the fluid. In embodiments where the fluid includes biological material such as cells, this reduction in shear stress can improve the viability of the cell culture.

[0049] In some embodiments, the axial deformation of the mixer changes the length of the mixer measured along the axial direction of the mixer parallel to the longitudinal axis of the mixer. For example, the mixer may be placed in a container in a contracted configuration in a substantially planar configuration. The container may then be deformed along an axis parallel to, and possibly aligned with, the longitudinal axis of the mixer, which may then deform the mixer in the same direction. Thus, the mixer may have a length that is substantially equal to or greater than the corresponding dimensions of the container in the extended configuration, but the length of the mixer (and container) in the extended configuration may be greater than the length of the mixer (and container) in the contracted configuration. It should be understood that the flap may be configured to deflect from the mixer in either the contracted or extended configuration, as the disclosure is not limited thereto.

[0050] In some embodiments, the mixer can be integrated into the container such that deformation of the container also causes the mixer to deform. For example, the mixer can be disposed between two opposing layers of one or more flexible films used to form the container. In this exemplary embodiment, the mixer is attached to the container such that deformation of the container also causes the mixer to deform and actuate the flap. In some embodiments, the mixer can be integrated into or attached to the container at a seam where opposing portions of two or more films can be joined together to form the flexible container. In such embodiments, the mixer can be manufactured using the same or different material as the film of the container. In some embodiments, the mixer can be attached to the film of the container by radio frequency welding, hot plate welding, induction welding, solvent welding, spin welding, laser welding, ultrasonic welding, extrusion-based sealing, hot sealing, cold sealing, adhesives, or any other suitable method, but the disclosure is not limited thereto. It should be understood that the mixer can be sealed or otherwise integrated into the container in such a manner as to prevent undesired leakage or other spillage of liquid from the container during use.

[0051] In some embodiments, one or more mixers and one or more actuators are integrated into the flexible container, such that deformation of the container may also cause the mixers to deform. For example, the mixers and actuators may be disposed between two opposing layers of one or more flexible films used to form the container. In some embodiments, the mixers and / or actuators may be integrated into or attached to the container at a seam where two or more opposing portions of the film may be joined together to form the flexible container. In such embodiments, the mixers may be manufactured using the same or different materials as the film of the container. In some embodiments, the mixers are attached to the film of the container by radio frequency welding, hot plate welding, induction welding, solvent welding, spin welding, laser welding, ultrasonic welding, extrusion-based sealing, hot sealing, cold sealing, adhesives, or any other suitable method, although the disclosure is not limited thereto. It should be understood that the mixers and actuators may be sealed or otherwise integrated into the container in such a manner as to prevent undesired leakage or other escape of fluids from the container during use.

[0052] In some embodiments, the container may be formed of a flexible material so as to deform with the actuator and mixer assembly. In other embodiments, the container may not deform with the actuator / mixer assembly. In other words, the mixer may be configured to deform by the actuator without a corresponding deformation of the container. This may be beneficial when a rigid container is used. In some such embodiments, the mixer and actuator assembly is attached to a corresponding portion of the container at one end and is free to move at the opposite end of the mixer and actuator assembly. For example, the mixer and actuator assembly is attached to a removable lid or base of the rigid container and the other end of the mixer and actuator assembly is free to move within the interior volume of the container. In another example, the mixer and actuator assembly may be configured to float on the surface of the fluid in the container. In some embodiments, a flexible connection between the mixer / actuator assembly and the container may be used to allow the actuator to appropriately deform the mixer without significantly deforming or inducing stresses on the container. It is to be understood that the present disclosure is not limited thereto and any suitable drive or actuation system may be used for any configuration of the mixing system, including but not limited to systems including flexible containers or systems including rigid containers.

[0053] In some embodiments, the container may be configured as disposable. In other words, the mixer, actuator, and / or container may be discarded after appropriate mixing has occurred, although multiple-use containers are also contemplated. It should be understood that depending on the attachment of the container and the integral mixer (and / or mixer-actuator assembly), the mixer may be made of a similar material as the container (for embodiments in which the mixer is manufactured together with the container) or may be made of a different material than the container (for embodiments in which the mixer is assembled to the container). It should also be understood that the actuator may be formed of the same or a different material as the mixer and / or container.

[0054] In some embodiments, the mixers described herein may be configured to move between the aforementioned contracted and extended configurations upon axial deformation of the associated mixer. For example, the mixers may be connected to actuators capable of displacing opposing portions of the mixers in opposite directions along an axial axis extending along or parallel to the longitudinal axis of the mixer. Thus, the opposing portions of the mixers are attached (removably or permanently) to links or other connections associated with the actuators. The actuators may displace associated portions of one or more mixers away from each other (or toward each other) to cause the mixers to transition between the contracted and closed configurations. It should be understood that any suitable type of actuator may be used to controllably displace opposing portions of the mixers.

[0055] It should be appreciated that in some embodiments, the container can be removed from the mixer and / or actuator and a new container can be placed to be received by the mixer and / or actuator. In this manner, the mixer and / or actuator can be reused and robustly integrated into a new mixing system.

[0056] In some embodiments, the mixer may be connected to an actuator capable of deforming the mixer along a longitudinal axis of the mixer or along an axial direction extending parallel to the longitudinal axis of the mixer. Thus, the mixer may be coupled or secured (removably or permanently) to a linkage or other connection associated with the actuator. The actuator then deforms an associated portion of the mixer, causing the mixer to transition between a contracted configuration and a closed configuration. In some embodiments, the actuator is welded, sealed, bonded, and / or attached directly to the mixer. Some examples of suitable actuators are described in more detail below, but it should be understood that any suitable type of actuator can be used to controllably displace the mixer. Suitable actuators include, but are not limited to, actuators including a crankshaft, actuators including a torsion spring, actuators including a ball screw, actuators including a cam, pneumatic actuators, piezoelectric actuators, solenoid actuators, hydraulic actuators, and / or other types of actuators capable of providing the desired deformation, but the disclosure is not so limited.

[0057] These alternative actuation mechanisms are used in embodiments where the mixer is not deformed by a corresponding deformation of the container. In other words, the mixer may be configured to deform without a corresponding deformation of the container. This may be beneficial when a rigid container is used. In some such embodiments, the mixer may be attached to a portion of the container at one end and free at the opposite end. For example, the mixer may be attached to a removable lid or the bottom of a rigid container. In another example, the mixer may float on the surface of the fluid within the fluid. An external driver, such as the actuation mechanisms described above, may then be used to align the mixer, deform the mixer, deflect the flaps, and mix the fluid without direct physical contact with the mixer. It should be understood that the present disclosure is not limited thereto and that any suitable drive or actuation system may be used for any configuration of the mixing system, including but not limited to systems including flexible containers or systems including rigid containers.

[0058] The inventors have also recognized advantages associated with a fluid mixing system that uses a mixer and associated actuator disposed within an interior volume of a vessel configured to contain a fluid, such as a liquid. During operation, the vessel may also contain one or more compositions in addition to the fluid, and as described in more detail below, it may be desirable to disperse and / or mix one or more other compositions with the fluid. The actuator can axially deform the mixer, which may be formed of an elastic material, to induce out-of-plane deflection. The elastic mixer can be cyclically moved by the actuator between its various configurations (e.g., extended and contracted configurations) to induce flow within the vessel or agitate the surrounding fluid within the vessel (e.g., by generating a vortex). In this manner, the fluid and other compositions disposed within the vessel can be mixed.

[0059] In some embodiments, the actuator is coupled to the mixer at at least one interface (e.g., at an end of the mixer), such that deformation or displacement of the actuator causes the mixer to deform. In other words, the actuator and mixer are arranged such that the mixer can deform together with the actuator, which deforms along at least one axis (e.g., uniaxial deformation), although complex motions involving movement in multiple directions are also contemplated. The actuator may be connected to one or more inputs (e.g., hydraulic, pneumatic, electrical, etc.) external to the vessel and serve to drive the actuator between the extended and retracted configurations. Locating the actuator inside the vessel reduces the overall footprint of the mixing system and increases the parallelization and throughput of the mixing system.

[0060] The mixing system of the present disclosure may use any suitable actuator or combination of actuators, as described in more detail below. In some embodiments, the actuators are hydraulically and / or pneumatically driven, where the inflow / outflow of fluid (e.g., air, gas, water) causes the actuator to deform in at least one axial direction, which in turn deforms the mixer, potentially inducing flow in the vessel. In some embodiments, the actuators are electrically driven, where an applied potential and / or current causes the actuator to deform in at least one axial direction, which in turn deforms the mixer. Of course, embodiments in which the actuators are driven by a combination of hydraulic, pneumatic, electrical, and / or other suitable inputs are also contemplated, as the present disclosure is not so limited. In some embodiments, a readily available source of compressed air may serve as the input source.

[0061] In some embodiments, the actuator and mixer may be arranged in series, and axial deformation of the actuator may result in an opposite axial deformation of the mixer. For example, contraction of the actuator may elongate the mixer, and expansion of the actuator may compress the mixer. For example, the actuator may be coupled or fixed at one end to the mixer and at the opposite end to a container (which may be rigid or flexible). The mixer may likewise be coupled or fixed at the opposite end to the container. In this way, the mixer may be deformed in the opposite direction of the actuator to induce a flow of fluid within the container.

[0062] In some embodiments, the actuator and mixer are arranged in parallel and can deform in a similar direction along the same axis. For example, the actuator and mixer can be coupled or fixed to each other at corresponding ends of each part, such that axial deformation of the actuator can result in a corresponding axial deformation of the mixer. In other words, a portion of the mixer that is disposed between opposite ends of the actuator can undergo the same deformation (both direction and magnitude) as the actuator. As previously mentioned, the mixer can include one or more features that can be deflected or otherwise moved by axial deformation of the mixer to induce flow in the vessel.

[0063] In some embodiments, the mixer can include an elastic substrate, such as a flexible elastic sheet or a sheet including elastic portions. In some embodiments, the substrate can include a plurality of flaps formed therein. In some embodiments, the plurality of flaps is formed by a plurality of slots arranged in a pattern on the flexible substrate of the mixer, with the plurality of flaps formed on different portions of the substrate. The flaps may be configured to deflect in a direction at least partially perpendicular to the plane in which the elastic substrate stretches when the actuator axially deforms the substrate. Thus, the flaps may induce a flow or agitate the surrounding fluid in the vessel. In some embodiments, the fluid flow may be generated by the shedding of vortices at the edges of the flaps.

[0064] In some embodiments, the mixers described herein may be formed by an elastic sheet that is deformable to transition the mixer between the contracted and extended configurations described above. The mixer may, in some embodiments, include a combination of spines, hinges, and slots formed in the elastic sheet to provide a desired function. For example, the slots, hinges, and / or spines may be formed in a pattern. In one such embodiment, the pattern includes a lattice of slots that form hinges and one or more spines of the mixer, where the hinges may be living hinges that correspond to small areas of material between adjacent sections of the patterned elastic sheet. The type of movement exhibited by a particular mixer is determined by the pattern and location of the slots formed in the mixer. In other words, different designs and placements of the slots can achieve different deformation modes. In some embodiments, the combination of slots, hinges, and spines of the mixer may be a kirigami structure. In such an embodiment, the mixer may elastically deform between the contracted and extended configurations when two or more opposing portions of the mixer deform axially. In other words, a portion of the mixer, such as a flap, may be deflected in a direction perpendicular (or different) to the direction of deformation applied to the mixer, and in some embodiments, may be oriented along the longitudinal axis of the mixer. In some embodiments, the cyclic deformation of one or more mixers between extended and retracted configurations may cause one or more flaps formed within the mixer to be cyclically extended and retracted. It should be understood that in some embodiments, the mixer pattern may be configured to allow deflection of the flap from the mixer when the container is deformed along an axis that is not substantially coaxial with the longitudinal axis of the mixer, and also to allow deflection of the flap in a direction that is not aligned with the longitudinal axis of the mixer.

[0065] One or more spines of the mixer may span at least a portion of the axial length of the mixer. In some embodiments, the spine may directly span at least a portion of the substrate forming the mixer along the axial length of the mixer, while in other embodiments, the one or more spines may follow a serpentine path that spans at least a portion of the substrate along the axial length of the mixer. In some embodiments, the spine, flaps, and slots may be formed in a single monolithic substrate. In other embodiments, various components of the mixer may be joined to form an integrated substrate.

[0066] It should be understood that the spines and slots corresponding to the mixer formed in a substrate, such as an elastic sheet, can have any configuration suitable for a desired application. In some embodiments, the slots are formed during manufacture of the mixer, and the slots may be part of the mixer without any material. In other words, the slots may be gaps or openings in the mixer structure that allow for certain deformations of the mixer. In other embodiments, the slots may be cut or otherwise removed from the mixer's substrate after manufacture. For example, the slots may include a pattern of cuts and / or openings formed in the substrate. It should be understood that the various features of the mixer may be formed using laser cutting, stamping, etching, any combination thereof, or other suitable techniques, but the present disclosure is not limited thereto.

[0067] In some embodiments, the flaps of the mixer may be configured to deflect out of the plane of the mixer when the mixer is deformed axially. Thus, the flaps may be sufficiently elastic to deflect away from the substrate and agitate nearby fluid in the vessel. It should be understood that the flaps may move linearly or non-linearly out of plane from the substrate by axial deformation or in any other suitable manner, as the disclosure is not limited in this respect.

[0068] It should also be appreciated that mixing of fluids by flaps deployed from the mixer's substrate may be determined by a variety of factors, including, but not limited to, the number of flaps on the substrate, the arrangement of the flaps on the substrate, the shape of the flaps, the actuation frequency, the actuation amplitude, the mechanical properties of the flaps (e.g., elastic modulus), the geometric properties of the flaps (e.g., thickness, length, width, and / or surface area of ​​the flaps), the properties of the fluids (e.g., viscosity), any combination thereof, or other suitable factors. It should be appreciated that any combination of the foregoing factors may be adjusted or varied to achieve a desired degree of fluid mixing by the mixing systems disclosed herein.

[0069] While most of the embodiments disclosed herein deploy the flaps of the mixer out of plane when the mixer is deformed, other embodiments configure the flaps of the mixer to deflect toward the plane of the mixer when the mixer is deformed axially. In these embodiments, the flaps are coplanar with the plane of the substrate in the extended configuration of the mixer and deflect out of plane of the substrate in the retracted configuration of the mixer. Additionally, embodiments are contemplated in which the flaps are not coplanar with the substrate in either the extended or retracted configuration. For example, the flaps can move between a first position at an angle from the substrate and a second position at an angle from the substrate between the extended and retracted configurations. In some embodiments, the flaps can move between one side of the plane and the other side of the plane between the extended and retracted configurations of the mixer.

[0070] It should be noted that some mixers may include a combination of different flap configurations. For example, a mixer may include one set of flaps that deflect from one side of the substrate in an extended configuration and a second set of flaps that deflect from the opposite side of the substrate in an extended configuration. This flap arrangement may induce a greater fluid flow compared to a mixer in which the flaps deflect from the plane of the substrate in only one direction. It should be understood that any suitable arrangement of flaps may be used as the disclosure is not limited thereto.

[0071] In some embodiments of the mixing system, the container can be placed on a suitable support structure. In this way, the container can be supported by the support structure before engaging with the actuator. In some embodiments, this support structure is automated, with a series of containers being moved sequentially to positions where the actuator can engage the container, such as a conveyor belt. In other embodiments, the container may be supported only by the actuator, in which case the connection to the actuator may act as a support. For example, the container may be suspended between two actuators, or between the actuator and a fixed structure. In these embodiments, the overall footprint of the mixing system may be reduced, as no platform or support is required for the container to rest on.

[0072] In embodiments in which the flexible container is suspended, the container may be suspended from a support configured to at least partially suspend the container from the support on at least one side. This configuration reduces the footprint of the mixing system, allowing multiple containers to be mixed in parallel in a smaller footprint space. Thus, the flexible container may be suspended from a support that includes a clamp, hook, or other attachment device to effectively hold the flexible container and prevent it from accidentally becoming detached, which could contaminate or damage the container. For example, in some embodiments, the container is connected to the support using a hook inserted into an eyelet on the container, a clamp configuration may be used, and / or any other suitable connection method may be used, as the disclosure is not so limited. It should be understood that the flexible container may be suspended in any suitable arrangement, as the disclosure is not so limited. Depending on the embodiment, the support is part of a reusable mixing system, and the support is configured to allow separate containers to be sequentially attached to and removed from the mixing system.

[0073] In some embodiments, the mixer can extend completely across a portion of the vessel. In other words, the mixer can extend from a first side of the vessel to an opposite second side. It should be understood that the mixer can extend at any suitable angle from the edge (e.g., vertical, 45° diagonal from the edge, or other suitable direction), but the disclosure is not so limited. In other embodiments, the mixer may be curved or non-linear and / or simply associated with a different portion of the vessel. For example, in some embodiments, the mixer may extend from a first side of the vessel to an adjacent second side. It should be understood, therefore, that the disclosure is not limited to the placement of the mixer within the vessel.

[0074] In some embodiments, the mixer and actuator assembly can extend across a portion of the vessel. In other words, the mixer and actuator assembly (in parallel, serial, and / or other suitable arrangement) can extend from a first side of the vessel to an opposite second side. It should be understood that the mixer and actuator assembly may extend at any suitable angle from the side of the vessel (e.g., vertically, at a 45° angle from the edge, or in any other suitable direction), as the disclosure is not limited thereto. It should be understood, therefore, that the disclosure is not limited to the arrangement of the mixer and actuator assembly within the vessel.

[0075] In embodiments in which the mixer extends from at least one side of the flexible container to the opposite side, it may be desirable for the length of the mixer to be shorter than the corresponding dimension of the film that extends between the opposite sides of the container. This allows the flexible container and the mixer to deform in a desired direction while filling the flexible container with fluid. In such embodiments, the axial length of the mixer (in either the extended or contracted configuration) may be at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 70%, 75%, 80%, 85%, 90%, or any other suitable percentage of the length measured along the outer surface of the container between the two opposite sides of the container (e.g., the distance measured between the two opposite sides is the distance measured along the outer surface of the film that extends between the two sides). Similarly, the axial length of the mixer may be 95%, 90%, 85%, 80%, 75%, 70%, 60%, 55%, 50%, 45%, 40%, 35%, 30%, 25%, 20% or less, and / or any other suitable percentage of the length of the cane can along the outer surface between the two opposing sides of the cane can. Combinations of the foregoing ranges are contemplated, including, for example, an axial length of the mixer between or equal to 5% and 95% of the length along the outer portion of the can extending between the opposing sides of the cane can. However, it should be understood that the mixer may be any length relative to the can as the disclosure is not limited thereto.

[0076] In some embodiments, the vessel can include multiple mixer and actuator assemblies distributed within the interior volume of the vessel. For example, there can be two or more assemblies distributed along the side of the vessel and extending to the opposite side or other portion of the vessel. Depending on the embodiment, the assemblies are evenly or unevenly distributed along the side of the vessel. In some embodiments, there can be at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or any other suitable number of assemblies along the edge of the vessel, although the disclosure is not limited thereto. It should be noted that each assembly may have a different arrangement and actuator (hydraulic, pneumatic, electric, etc.) type.

[0077] As mentioned above, in some embodiments, the mixer may be attached to only one portion of the vessel (e.g., if the vessel is rigid). In these embodiments, the length of the mixer (in either the extended or contracted configuration) may be at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, or other suitable percentage of the corresponding dimension of the vessel over which the mixer extends. The length of the mixer may be no more than 99%, 90%, 80%, 70%, 60%, 50%, and / or other suitable percentage of the corresponding dimension of the vessel. Combinations of these ranges are contemplated, including, for example, mixers having lengths between 5% and 100% of the corresponding dimension of the vessel, the mixer extending in a direction parallel to the stated dimension. In some embodiments, the length of the mixer may be substantially equal to the corresponding dimension of the vessel over which the mixer extends. Accordingly, it should be understood that the mixer can have any suitable size (i.e., length and / or width) relative to the vessel as the present disclosure is not limited thereto.

[0078] It should also be understood that the mixer can deform by any suitable amount of deformation depending on the volume of the associated vessel and the fluid contained therein. The overall deformation that may be applied may be influenced by parameters such as the volume of the fluid, the elasticity of the vessel material, the exterior surface area of ​​the vessel, the circumference of the vessel taken in a plane parallel to the longitudinal axis of one or more mixers of the system, and / or other suitable parameters. It should therefore be understood that the mixer can undergo any suitable change in its length between the extended and retracted configurations depending on the particular application, as the present disclosure is not limited thereto.

[0079] In some embodiments, the container can include multiple mixers distributed within the interior volume of the container. For example, there can be two or more mixers distributed along the side of the container and extending to the opposite side or other part of the container. Depending on the embodiment, the mixers are evenly distributed or unevenly distributed along the side of the container. In some embodiments, there can be at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or any other suitable number of mixers along the edge of the container, although the disclosure is not limited thereto. It should be noted that the multiple mixers can also have either the same mixer length or different mixer lengths.

[0080] In embodiments where the vessel includes multiple mixers, the mixers are controlled in a cyclical manner. For example, the vessel may include three mixers configured to deform sequentially. In this embodiment, the sequence of mixers may follow a wave pattern throughout the vessel and then induce continuous flow in different regions of the vessel's interior volume. If different mixers are actuated at different times, it should be understood that in such embodiments, the vessel may be flexible enough to allow for localized deformation of the flexible vessel and / or the different mixers may be actuable separately relative to the rigid vessel. It should be understood that the mixers may be controlled in any suitable manner, such as synchronously or asynchronously, as the disclosure is not limited in this respect. In embodiments where the vessel includes multiple mixers, the mixers may be controlled with different actuators. Alternatively, the mixers may be controlled with the same one or more actuators configured to deform the mixers in an alternative manner. It should be understood that the disclosure is not limited in this respect, and any suitable configuration between the actuators and the mixers may be used.

[0081] In embodiments where the vessel includes multiple mixer and actuator assemblies, the assemblies may be controlled in a cyclical manner. For example, the vessel may include three assemblies configured to deform sequentially. In this embodiment, the sequence of assemblies may follow a wave pattern throughout the vessel, which may then induce sequential flows in different regions of the vessel's interior volume. However, different mixers may be actuated simultaneously, as the disclosure is not so limited.

[0082] In some embodiments, the mixing system may include at least one processor for controlling an actuator that deforms the mixer. The processor may be responsible for operating the actuator, which may result in the deformation of the mixer. In some embodiments, all of the actuators may be controlled by a single processor, while in other embodiments, separate processors may be used to control separate actuators. It should be understood that the processor may control the actuators via any suitable communication mode, including, but not limited to, a wired or wireless communication link, as the disclosure is not limited in this respect. In some embodiments, the processor may be configured to operate the mixing system automatically and / or continuously.

[0083] In some embodiments, the mixing system may include at least one processor for controlling an actuator that deforms the mixer. The processor may be responsible for operating the actuator, which may result in the mixer being deformed. In some embodiments, the processor may be in communication with one or more controllers that function to operate the actuator. For example, the controller may be in communication with a fluid source connected to one or more pneumatic actuators. The controller may control the frequency, magnitude, duration, and / or other parameters of the actuation cycle. It should be understood that any suitable arrangement, type, and / or number of processors and controllers may be used in the mixing systems described herein, as the disclosure is not limited thereto.

[0084] In some embodiments, the actuator may be configured to operate at an appropriate frequency to induce a desired amount of flow in the vessel without excessive agitation. For example, in one embodiment, the actuator may induce the mixer to cycle from a contracted configuration to an extended configuration and then back to the contracted configuration at a frequency of 1.5 Hz. However, it should be noted that the operating frequency may be any suitable frequency, including frequencies of 0.01 Hz, 0.02 Hz, 0.05 Hz, 0.1 Hz, 0.5 Hz, 1 Hz, 5 Hz, 10 Hz, 20 Hz, 30 Hz, 40 Hz, 50 Hz, 60 Hz or more, and / or other suitable frequencies. The operating frequency may be less than or equal to 100 Hz, 90 Hz, 80 Hz, 70 Hz, 60 Hz, 50 Hz, 40 Hz, 30 Hz, 20 Hz, 10 Hz, and / or other suitable frequencies. Combinations of the above ranges are contemplated to include operating frequencies from 0.01 Hz to 100 Hz. However, higher and lower frequency ranges are also contemplated, as the disclosure is not limited thereto. It should be understood that the operating frequency may depend on the limiting factors of the operating system.

[0085] In some embodiments, the actuation of the mixer may further include an actuation amplitude. The actuation amplitude may correspond to the degree of deformation of the flap relative to the associated substrate. In some embodiments, the maximum actuation amplitude may be equal to the movement of the flap between a fully retracted and a fully extended configuration. However, individual actuation cycle amplitudes less than this full operating range may also apply. For example, in some embodiments, the actuation amplitude may be at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, or other suitable percentage of the full operating range of the mixer, but the disclosure is not so limited. Additionally, combinations of the above ranges are also envisioned where the actuation cycle amplitude is between or equal to any of the above ranges.

[0086] In some embodiments, the mixing system may be configured to operate at a predetermined operating frequency for any number of cycles to adequately mix or incubate the contents of the vessel, where the cycles may include movement of the mixer between extended and retracted configurations by the actuator. In some embodiments, the mixing system may operate for at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 15, 18, 20, 25, 30, 35, 40, 45, 50, or 100 cycles. The number of cycles applied by the system during mixing of the vessel may be up to 1000 cycles, 500 cycles, 100 cycles, 50 cycles, and / or any other suitable number, as the disclosure is not so limited. Combinations of the foregoing ranges are contemplated, including, for example, mixing systems that operate one or more mixers of the system to apply a range from 2 mixing cycles to 1000 mixing cycles, although ranges greater than and less than the above ranges are also contemplated. In some embodiments, depending on the operating frequency of the mixer, the mixing system can operate for any suitable period of time, including, but not limited to, 2 seconds, 15 seconds, 30 seconds, 1 minute, 5 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, 5 hours, 10 hours, 12 hours, 24 hours, 2 days, 5 days, 10 days, or other suitable period of time. Similarly, the mixing system can operate for less than 300 days, less than 200 days, less than 100 days, less than 50 days, less than 10 days, less than 1 day, and / or other suitable period of time when mixing the contents of a particular container. Combinations of the above ranges are contemplated, for example, mixing periods of 2 seconds to 300 days may be used. Thus, it should be understood that the mixer and container can be configured to operate using any suitable period and / or frequency to provide a desired amount of mixing over a given mixing period.

[0087] It should be understood that the mixer and / or actuator disposed within the vessel may be formed of any suitable material that is compatible with the fluid contained within the vessel. In some embodiments, the material of the mixer and / or actuator may be more rigid than the material of the vessel. In some embodiments, the mixer and / or actuator may include a multi-layer construction. In other embodiments, the mixer and / or actuator may include one or more composite materials for ease of manufacture and longevity. In still other embodiments, the mixer and / or actuator may include thermoplastics, elastomers, composites, metals, any combination thereof, or any other suitable material, although the disclosure is not so limited. Thus, it should be understood that the mixer and / or actuator may be made from any suitable material, or combination of materials, that exhibit sufficient strength and elasticity to perform the desired functions described herein.

[0088] In some embodiments, the actuator may be disposed inside the vessel, but may have a coating or outer layer formed of any suitable material compatible with the fluid contained in the vessel, regardless of any material disposed inside the actuator and arranged to actuate the mixer. In other words, the actuator may be formed of any suitable material or combination of materials suitable for actuation, but may also include a coating or outer layer to reduce the risk of contamination. Contamination may occur from fluid flowing from the interior volume of the vessel to the actuator, and / or from the actuator to the interior volume of the vessel. Thus, the coating or outer layer of the actuator may seal the actuator against the surrounding interior volume of the vessel, substantially preventing the inflow and outflow of fluid into and out of the actuator. In some embodiments, the coating or outer layer of the actuator may be deposited on the actuator using any suitable technique, including, but not limited to, welding, spraying, adhesive, mechanical bonding, combinations thereof, and / or other suitable techniques.

[0089] In some embodiments, the container, the outer coating of the actuator, and / or the mixer may be flexible and deformable enough to mix the contents contained within the container. Thus, the container, the outer coating of the actuator, and / or the mixer may be made of a single layer or multi-layer film. In some embodiments, the container, the outer coating of the actuator, and / or the mixer may be composed of one or more polymer layers, including but not limited to polypropylene, polyethylene, ethylene vinyl alcohol, polyamide, polychlorotrifluoroethylene, cyclic olefin copolymer, polycarbonate, ethylene vinyl acetate, polyvinyl chloride, polyvinylidene chloride, polystyrene, polyethylene terephthalate, thermoplastic elastomers, polymethyl methacrylate, polysulfone, polyester, polyolefin, epoxy, phenolic, novolac, thermoset, thermoplastic, composite, any combination thereof, or any other suitable polymer or flexible material, although the disclosure is not so limited. The vessel, the outer coating of the actuator, and / or the mixer may be made of a material that can withstand temperatures below 0° C., e.g., −20° C., and / or temperatures above 30° C., e.g., 37° C. As mentioned above, in some embodiments, the vessel is rigid and may be formed of any suitable rigid material, including ceramic, metal, polymer, combinations thereof, and / or any other material.

[0090] The vessels, outer coatings of actuators, and / or mixers disclosed herein may be made of any suitable material that is compatible with the composition of the fluids (e.g., biocompatible for bioreactor applications), although it should be understood that the disclosure is not so limited. The material can also withstand sterilization (e.g., withstand gamma irradiation, autoclaving, and / or other suitable sterilization procedures) in applications sensitive to biological or other contamination.

[0091] As previously mentioned, the mixer may be made of the same material as the vessel, although in other embodiments the mixer may be made of a different material than the vessel. It should be noted that the mixer may be made of any suitable material that is compatible with the fluid contents (e.g., biocompatible for bioreactor applications) and flexible enough to allow deflection of the flaps, although the disclosure is not so limited. The mixer may also be made of a material that is suitably sterilizable for biological applications (e.g., able to withstand gamma irradiation procedures). The mixer may also be made of a material that can withstand high and low temperature conditions.

[0092] In some embodiments, the surfaces of the vessel configured to contact the fluid during operation, the outer coating of the actuator, and / or the mixer may include a layer to reduce fouling (i.e., the layer may be an anti-biofouling layer). In this way, the mixing system can be used for a long period of time. Thus, the mixing system may include a layer of an anti-fouling material disposed on one or more surfaces exposed to the fluid. Suitable types of anti-fouling layers include, but are not limited to, low density polyethylene, very low density polyethylene ethylene vinyl acetate copolymer, polyester, polyamide, polyvinyl chloride, polypropylene, polyfluoroethylene, polyvinylidene fluoride, polyurethane or fluoroethylene propylene, any combination thereof, or other suitable materials capable of reducing fouling, but the disclosure is not limited thereto. In some embodiments, a gas and / or water vapor barrier layer is disposed on one or more surfaces of the mixing system, and the barrier layer may include a material such as an ethylene / vinyl alcohol copolymer blend in polyamide or an ethylene vinyl acetate copolymer.

[0093] It should also be understood that the mixing systems described herein can be used with any suitable size container. For example, the container volume can be at least 1 mL, 2 mL, 10 mL, 20 mL, 50 mL, 100 mL, 200 mL, 500 mL, 1 L, 2 L, 10 L, 50 L, 100 L, 500 L, or other suitable volume. The container volume can be up to 1000 L, 500 L, 100 L, 50 L, 10 L, 1 L, and / or other suitable volume. Combinations of the above are contemplated, for example, the container volume can range from 1 mL to 1000 L. However, both larger and smaller volumes are contemplated, as the mixing systems described herein are not limited by the size or scale of the container.

[0094] It is to be understood that the mixing system described herein can be used for any suitable application, such as mixing of fluid solutions (including, for example, buffers, cell culture media), homogenization of solutions, such as homogenization of frozen samples (which may include, for example, active substances or pharmaceuticals), cell culture applications including, but not limited to, CHO cells, HEK cells, T cells, stem cells, iPSC cells, combinations thereof, and / or other suitable types of cells. In some embodiments, the mixing system can be used to uniformly and rapidly thaw frozen solutions or frozen products. In other embodiments, the mixing system can be used for intravenous fluid delivery applications, where a container of fluid (which may include cells) can be delivered to a patient during a therapeutic window. In other embodiments, the mixing system can be used in a bioreactor. In yet other embodiments, the mixing system can be used in conjunction with a cell culture platform. In still other embodiments, the mixing system can be used to homogenize or mix buffers and ingredients contained within a container (flexible or rigid). It is to be understood that the mixing system can be used for any suitable application, as the present disclosure is not limited thereto.

[0095] In some embodiments, disposable vessels with integrated mixers and / or actuators are low cost and subject the contents of the vessel to less shear stress, potentially reducing the risk of damage to the contents (e.g., primary T cells or iPSC cells) and improving mixing efficiency.

[0096] In some embodiments, pneumatically actuated mixers and / or actuators can be perforated to act as a sparging system that couples mixing with the introduction of fluid (e.g., oxygen). In such embodiments, pores formed within the actuator are fluidly coupled to a pneumatic volume within the actuator, such that when pressurized gas is introduced into the pneumatic actuator, the gas can also flow through the pores into the surrounding fluid.

[0097] Although the presently disclosed mixers are disclosed as being integrated into flexible vessels and / or new vessels, in some embodiments it may be desirable to include such functionality in existing equipment. Thus, in some embodiments, pneumatically actuated mixers and / or actuators can be integrated into existing cell culture vessels to achieve adequate mixing efficiency while minimizing shear stress on the cells.

[0098] In some embodiments, the mixing system of the present disclosure can be used to keep cells in suspension within a therapeutic infusion bag. Specifically, the mixing system can be integrated with a bag containing a cellular therapeutic (e.g., T cells, stem cells) to be delivered to a patient via intravascular infusion (and / or other suitable delivery methods to the patient). During the infusion process, which typically lasts from minutes to hours, the cells may settle or clump due to the effects of gravity, resulting in an inconsistent dose. The mixing system described herein can be used to keep the cells evenly dispersed within the bag during delivery for proper processing and delivery of a uniform dose.

[0099] In various embodiments described herein, a bioreactor may include compartments configured to house live organisms or cells that produce biological compounds. These cells or organisms may be suspended in a liquid disposed within the reactor or attached to solid particles and / or surfaces disposed within the reactor. The environment within the bioreactor may be monitored and maintained for healthy growth of the cells. Temperature, pH, dissolved oxygen, gas flow rates, etc. are examples of potential process parameters that may be controlled to ensure healthy, reproducible, and reliable growth of the cells or organisms.

[0100] In some embodiments, the cells, organisms, and / or particles with attached cells can be suspended in the liquid contained within the bioreactor, allowing the use of the entire volume within the bioreactor or other desired portion thereof, allowing the generation of high density cell cultures. To keep the cells, organisms, and / or particulates in suspension, the bioreactor medium can be stirred, shaken, and / or mixed using the systems and methods described herein. The mixing rate can affect the mix ratio, dissolution of oxygen into the medium, and flow profiles that lead to shear stress on the organisms. Thus, the mixing rate can be optimized and controlled for a particular mixture. Some cells, such as stem cells and T cells, are very sensitive to shear stress, so the mixing rate may need to be appropriately controlled to avoid damaging the cells. As previously mentioned, the systems and methods described can advantageously provide low shear rate mixing, which may help increase the viability of the cell culture.

[0101] It should be noted that while mechanical actuators are primarily described for actuation of the mixers described herein, any suitable mechanism capable of applying deformations to the mixer to induce movement between contracted and extended configurations may be used as the disclosure is not so limited. For example, electromagnetic actuation, pneumatic actuation, photoresponsive actuation, and / or any other suitable type of actuation method may be used, as the disclosure is not so limited. Thus, the mixer may be made of magnetic materials (e.g., polymers with embedded magnetic particles), photoresponsive materials, gas-filled channels (for pneumatic actuation), dielectric elastomers, electroactive responsive materials, and / or other suitable materials depending on the type of actuation applied to the mixer. Thus, the mixer may be made of magnetic materials (e.g., polymers with embedded magnetic particles), photoresponsive materials, gas-filled channels (for pneumatic actuation), dielectric elastomers, electroactive responsive materials, and / or other suitable materials depending on the type of actuation applied to the mixer.

[0102] With reference to the figures, certain non-limiting embodiments are described in further detail. It should be understood that the various systems, components, functions, and methods described in connection with these embodiments are not limited to only the specific embodiments described herein, but can be used individually and / or in any combination.

[0103] FIG. 1 illustrates an embodiment of a mixing system in which a container 100 is formed from two flexible films 110 and 120 that are at least partially joined around the container to form an interior volume therebetween. The system includes a mixer 130 disposed between the flexible sheets 110, 120 so as to extend from a first side of the container to an opposite second side. In the illustrated embodiment, both ends of the mixer are sealed between two opposing portions of the flexible films at seams 115 of the container 100 that correspond to the joined perimeters of the films. In operation, the container 100 can be positioned near one or more actuators 10a and 10b that engage ends of the mixer. In operation, the one or more actuators can deform the container 100 and the mixer 130 along an axis that extends between the actuators or between the actuators and a fixed support associated with the other opposite portion of the mixer. As the vessel 100 deforms along the deformation axes of the actuators 10a, 10b, the mixer 130 may also be deformed along an axis parallel to the axis extending between the two actuators, in this case parallel to the longitudinal axis of the mixer. As described in more detail below, this may actuate the mixer to move between first and second configurations (e.g., extended and contracted configurations) to agitate or otherwise induce flow of fluid within the vessel 100.

[0104] 2A-2D show various embodiments of a mixer. Mixer 230 includes a substrate 237. As previously mentioned, a mixer can include various features, such as slots, flaps, spines, etc., disposed on the substrate. As shown, substrate 237 generally defines a surface on which mixer features may be disposed. In the illustrated embodiment, a substantially planar substrate 237 is shown in a retracted configuration. While the illustrated substrate is substantially planar in the retracted configuration, it should be understood that in other embodiments, the substrate may not be planar in the retracted configuration.

[0105] 2A-2D, the mixer 230 may include two opposing ends with two opposing tabs 238a and 238b that may be configured to be sealed within or extend beyond the seam 115 of the container 100 (see FIG. 1). Although rectangular shaped tabs are shown in the figures, the tabs may have any suitable shape or arrangement to be sufficiently attached to the container 100 to indirectly deform the mixer due to deformation of the container and / or to be engaged by an actuator or other support during operation.

[0106] The illustrated mixer 230 may further include a number of slots 236 formed in a substrate 237 configured to allow the mixer to deform. Specifically, the slots 236 may be areas of the substrate 237 free of material, or in other cases, the slots may be thin cuts in the substrate. In either case, the pattern of slots may also define a number of living hinges 240 distributed on the substrate, the living hinges corresponding to areas of the substrate having locally reduced areas that may undergo local deformations greater than the average deformation of the substrate as the mixer deforms to allow the desired transitions between different configurations during operation. It should be understood that the slots may be any openings or cuts provided in the substrate to allow elastic deflection of the flaps, as the disclosure is not limited in this respect.

[0107] The illustrated mixer 230 may also include one or more spines 239 that correspond to a continuous strip of material extending from one end of the mixer to an opposite end of the mixer. Thus, the spines 239 may span at least a portion of the axial dimension AX1 of the mixer 230. In some embodiments, the spines 239 may follow a serpentine path between the tabs of the mixer 230, as shown in FIGS. 2A-2D.

[0108] The mixer 230 may further include a number of flaps 235 formed in the substrate. Depending on the embodiment, the flaps may correspond to shapes cut out of the mixer's substrate (see FIGS. 2A-2B), or the flaps may simply correspond to the edges of the mixer (see flat edges in FIG. 2C and finger-like curved edges in FIG. 2D), and in either case, the flaps 235 may be configured to at least partially deflect out of the plane of the substrate 237 upon axial deformation, as previously described. This may be due to localized deformation of the living hinges 240 defined by the pattern of slots 236, which generate an out-of-plane moment when the mixer is deformed, causing the fins to deform in a desired direction. Given the various configurations of the mixer, it should be understood that the flaps, slots, and other components of the mixer may be located in any suitable location and have any suitable configuration on the substrate, as the disclosure is not limited thereto.

[0109] FIG. 3 is a front view of a mixing system. The mixing system may include a container 100 having a plurality of films 110, 120 bonded along the periphery to form an interior volume, as previously described. In the illustrated embodiment, the container 100 is a flexible container. In some embodiments, a mixer 130 may be disposed between the films 110, 120 of the container 100. As previously described, the mixer 130 may be attached to the container 100 at a seam 115, as shown in FIG. 1. The container may also be engaged with actuators 10a, 10b that, in some embodiments, are aligned with the longitudinal axis AX1 of the mixer. Although two actuators 10a, 10b are shown in FIG. 3, it should be understood that the disclosure is not limited in this respect and any number of actuators may be used. The container 100 may also be disposed on a support 140, such that the container is supported on the underside of the support prior to and / or during engagement with the actuators 10a, 10b. In other embodiments, the vessel 100 is suspended between the actuators 10a, 10b, with either the actuators or another structure acting as the support 140. Such an arrangement may be beneficial to reduce the overall footprint of the mixing system. As previously mentioned, the actuators 10a, 10b may be operatively coupled to and controlled in conjunction with a processor and / or controller 150, although embodiments using analog systems without a processor are also envisioned.

[0110] 4A and 4B show one exemplary embodiment of a vessel undergoing an actuation cycle. The mixer in FIG. 4A is in a contracted configuration 130A, where the mixer is not subjected to axial deformation along the axial dimension AX1 from the actuators 10a, 10b and is in an initial, undeformed state. In this configuration, the mixer 130A may have a first mixer length ML1. The actuators 10a, 10b apply a force F in an opposite direction along the axial dimension AX1, as shown in FIG. 4B. Deformation of the vessel 100 may cause the mixer to deform to a second deformation state corresponding to the illustrated extended configuration 130B. Thus, the mixer 130B may have a second mixer length ML2 that is longer than the first mixer length ML1. The flap 135 of the mixer 130B may then deflect away from the mixer 130B to a flap height FH. As previously described, the height FH of the flap in the extended configuration may correspond to the actuation amplitude. It should be noted that the embodiment of FIG. 4B includes flaps 135 that extend in two opposite directions perpendicular to the plane of the nominal plane in which the substrate of the mixer 130B is located. In other embodiments, the flaps 135 may extend in only one direction out of the plane of the mixer 130B. In still other embodiments, the flaps 135 may extend in any suitable direction out of the plane of the mixer 130B as the disclosure is not so limited. As previously discussed, movement of the flaps 135 between the retracted and extended configurations 130A and 130B of the mixer may induce localized fluid flow within the vessel, resulting in mixing of the fluids.

[0111] 5A and 5B show another embodiment of the container undergoing an actuation cycle. In this embodiment, the flaps 135 may be initially oriented out of plane from the mixer's substrate in a contracted configuration 130A before the mixer is deformed. After a deformation is applied to the mixer by a force F applied to the mixer as the actuators 10a, 10b deform the container 100 along the axial dimension AX1, the flaps may be deformed into the nominal plane of the mixer as the substrate elongates.

[0112] Also, note that while multiple substantially similar flaps 135 are shown in Figures 5A and 4B, the flaps 135 may be a combination of different flap shapes configured to create flow in the fluid. For example, a mixer may include flaps of different sizes and shapes at different locations along the length of the mixer.

[0113] FIG. 6 illustrates a top view of one exemplary embodiment of the vessel 100. As previously described, the mixer 130 is attached to the vessel 100 along two opposing portions of the vessel's opposing seam 115. Thus, deformation of the vessel 100 may cause the mixer 130 to deform and subsequently deflect the flaps 135 to mix the fluids within the vessel. The mixer 130 has a mixer width MW measured perpendicular to the axial dimension AX, which in the illustrated embodiment is the longitudinal axis of the mixer. Depending on the application, the mixer width MW may be any suitable percentage of the vessel's width CW. Additionally, the mixer length ML may be any suitable percentage of the vessel's length CL, as previously described. Although FIG. 6 illustrates the mixer 130 as being centrally located along the vessel's width, the disclosure is not limited thereto and the mixer 130 may be located anywhere along the vessel's width.

[0114] It should be understood that in the illustrated embodiment of the flexible container 100, the mixer length ML may be substantially equal to the container length CL or other relevant dimension of the container due to the mixer. This is because the seam 115 of the mixer 130 and the container 100 is connected on opposite sides of the container. However, as discussed above, the length along the exterior surface of the flexible container between the opposite ends of the mixer may be longer than the length of the mixer to allow for filling of the container with fluid. However, in embodiments where the container 100 is rigid and the mixer 130 is only attached to a portion of the container 100, the mixer length ML may differ from the corresponding dimension of the container.

[0115] It should be understood that the width and length of the vessel are interchangeable, as the mixer can be positioned in any direction on the vessel. For example, the mixer may span the larger dimension of a rectangular vessel. In another example, the mixer may span the smaller dimension of a rectangular vessel. In yet another example, the mixer may span the angle between adjacent sides of a rectangular vessel. It should be noted that the mixer may span any portion of the vessel. Also, it should be understood that while the figures depict a rectangular vessel, the disclosure is not limited thereto, and alternative vessel shapes may be used, including, but not limited to, circular, triangular, or other suitable shapes.

[0116] In some embodiments, the vessel 100 may include multiple mixers 130. For example, the vessel 100 may include multiple mixers distributed along the length of one or more sides of the mixer, see the three mixers 130A, 130B, 130C shown in FIG. 7. In such embodiments, each mixer 130A, 130B, 130C may include a respective pair of actuators 10a, 10b configured to deform the vessel 100 in a localized portion close to the axial dimension of the mixer 130A, 130B, 130C. However, embodiments are also contemplated in which a single actuator or pair of actuators are operably coupled to each mixer. When separate actuators are associated with different mixers, the mixers 130A, 130B, 130C may operate in conjunction with a processor and / or controller 150 (shown in FIG. 3) such that all actuators 10a, 10b are synchronized. In other embodiments, the mixers 130A, 130B, 130C may be operated sequentially or according to any other suitable order as the disclosure is not so limited. Although similarly sized mixers 130A, 130B, 130C are evenly distributed along vessel 100, it should be understood that any suitable combination of mixer size, placement, orientation, and / or distribution may be used as the disclosure is not limited in this respect. For example, vessel 100 may include one mixer spanning the length of the vessel and a second mixer spanning the width of the vessel.

[0117] 8A and 8B show an embodiment of a suspended container 100 as indicated by the direction of gravity G. In some embodiments, the container 100 may be suspended directly from the actuators 10a, 10b, as shown in FIG. 8A. In such an embodiment, a single lower actuator may be used and the upper actuator may be replaced by a support attached to the container and configured to support the container. In this manner, the actuators 10a, 10b, or the actuators and supports, may support and deform the container 100. Of course, although a vertical orientation is shown in the illustrated embodiment, the invention is not limited thereto and the container may also be suspended in a horizontal orientation.

[0118] In other embodiments, the container 100 may be connected to a clamp 30 or other connection operably coupled to the support 31 such that the container hangs vertically below the support relative to the direction of gravity G. Thus, the container 100 may be supported even when not engaged with an actuator 10a, 10b engageable with the mixer 130. As previously mentioned, alternative hanging embodiments are contemplated including, for example, a horizontal hanging arrangement.

[0119] FIG. 9 illustrates an exemplary embodiment of a rigid container 100 with a mixer 130 at least partially disposed within the container and at least partially immersed in the fluid 160 contained within the interior volume of the container. As previously described, when the mixer 130 is disposed within the rigid container 100, the mixer 130 is connected to the container 100 at only one point, allowing the mixer 130 to deform sufficiently in response to a stimulus (e.g., the mechanical deformation described above or other stimuli) to deflect the flap 135 from the mixer 130. For example, the mixer 130 may be disposed adjacent to the bottom of the container 100 and attached to the rigid container 100 at the end 101 connected to the bottom of the container 100. However, it should be understood that the invention is not so limited and the mixer 130 may be attached to the rigid container 100 at any suitable location. In some embodiments, the mixer 130 may not be attached to the rigid container 100 and may be dispersed within the fluid 160. For example, the mixer 130 may be made of a material that allows the mixer 130 to deform in response to a suitable external stimulus without contacting the rigid container 100.

[0120] FIG. 10 is a graph of the mixing time t (in seconds) for various embodiments (i.e., configurations) of the mixer 130 as characterized by the decolorization method (i.e., iodometric titration). In these processes, an operating frequency of 2 Hz and an operating amplitude of 15 mm were used. The decolorization protocol in ISBN: 978-3-89746-171-0 was used to characterize the mixing time of the various mixers 130. It should be understood that all of the embodiments of the mixer 130 shown in FIG. 10 have reduced mixing time t of the vessel. This reduction in mixing time t may increase the overall throughput and efficiency of the laboratory or environment in which the mixers described herein are used.

[0121] 11A-11B show a mixing system including a mixer 1020 and an actuator 1030 disposed within a vessel 100, according to some embodiments. The mixer 1020 is deformable between a contracted state 1020A and an extended state 1020B along an axial direction AX1, with the actuator 1030 moving between an extended state 1030A and a contracted state 1030B. The movement of the actuator 1030 may be controlled by one or more controllers and processors 60 configured to control one or more inputs 50 operatively coupled to corresponding actuators (e.g., fluid sources, electrical signals, etc.). In this manner, the controller and processor 60 may drive the actuators to deform along the axial direction AX1, thereby deforming the mixer 1020. The inputs 50 may communicate with the actuators 1030 through at least one port 1040 in the case of a pneumatic or hydraulic system, while other suitable connections (e.g., fluidic, electrical) may be used in the case of other types of actuators (e.g., one or more electrical contacts). In some embodiments, the mixer 1020 includes one or more features (e.g., flaps) that may deflect out of plane when the mixer 1020 is deformed axially, which may result in fluid flow within the vessel 100.

[0122] The mixing system shown in Figures 11A-11B represents a mixer and actuator assembly arranged in series. For example, a first tab 1021 of the mixer 1020 is coupled or fixed (removably or permanently) to the container 100 at a first end of the container 100A, and a second tab 1022 of the mixer 1020 is coupled or fixed (removably or permanently) to the actuator 1030. The actuator 1030 may be coupled or fixed (removably or permanently) to a second end of the container 100B. Thus, the axial length L1 of the container 100 may be substantially equal to the sum of the axial length L2 of the mixer 1020 and the axial length L3 of the actuator 1030. Of course, embodiments are also contemplated in which the connection features are located between various components (e.g., between the container and the mixer, between the mixer and the actuator, between adjacent mixers, between adjacent actuators), such that the sum of the axial length L2 of the mixer and the axial length L3 of the actuator may be less than the axial length L1 of the container.

[0123] It should be noted that depending on the specific construction and arrangement of the mixing system and the type of actuator used, the axial length of each of the mixer 1020 and / or actuator 1030 may be any suitable percentage of the axial length L1 of the vessel. For example, the axial length L2 of the mixer in either the contracted state 1020A or the expanded state 1020B may be at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, and / or any other suitable percentage of the axial length L1 of the vessel. The axial length L2 of the mixer in either the contracted state 1020A or the expanded state 1020B may be no more than 100%, 90%, 80%, 70%, 60%, 50%, 40%, 30%, 20%, 10%, and / or any other suitable percentage of the axial length L1 of the vessel. Combinations of the above are also contemplated, for example, the mixer's axial length L2 can be between 10% and 100%, between 20% and 90%, and / or other suitable percentage ranges of the container's axial length L1 in either the contracted state 1020A or the expanded state 1020B.

[0124] Similarly, the axial length L3 of the actuator in either the extended state 1030A or the contracted state 1030B may be at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, and / or any other suitable percentage of the axial length L1 of the container. The axial length L3 of the actuator may be no more than 100%, 90%, 80%, 70%, 60%, 50%, 40%, 30%, 20%, 10%, and / or any other suitable percentage of the axial length L1 of the container in either the extended state 1030A or the contracted state 1030B. Combinations of the foregoing are also contemplated, for example, the axial length L3 of the actuator may be in the range of 10%-100%, 20%-90%, and / or any other suitable percentage of the axial length L1 of the container in either the extended state 1030A or the contracted state 1030B.

[0125] It should be noted that the mixer 1020 and / or the actuator 1030 may undergo any suitable amount of axial deformation along the axial direction AX1 between the extended and contracted configurations. The mixer 1020 and / or the actuator 1030 may undergo at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 120%, 150%, 200%, 300%, 500%, 750%, and / or other suitable axial deformation along the axial direction AX1 in either compression or extension. The mixer 1020 and / or actuator 1030 may also undergo 750%, 500%, 300%, 200%, 150%, 120%, 100%, 90%, 80%, 70%, 60%, 50%, 40%, 30%, 20%, 10%, 5% or less, and / or other suitable axial deformation along the axial direction AX1, either in compression or extension. Combinations of the foregoing are also contemplated, such as the mixer 1020 and / or actuator 1030 that may undergo 5% to 750%, 20% to 200%, 10% to 500%, and / or other suitable axial deformation along the axial direction AX1, either in compression or extension. Of course, depending on the type of actuator and the requirements of the mixing system, the mixer and / or actuator may undergo any suitable amount of axial deformation, and the disclosure is not so limited.

[0126] It should be noted that in the series configuration shown in Figures 11A-11B, the deformations of the mixer and the actuator can be complementary. For example, if the actuator deforms axially by 50% increasing its axial length, the mixer can deform axially in the opposite direction by the same amount. In other words, axial expansion of the actuator can cause axial compression of the mixer.

[0127] In some embodiments, the actuator 1030 may undergo uniaxial deformation along the direction AX1, as shown in Figures 11A-11B, although embodiments are envisioned in which the actuator undergoes multi-axial deformation, including deformation along the axial direction AX1.

[0128] 12A-12B show a mixing system with an actuator 1030 and two or more mixers interconnected and coupled to the actuator (e.g., via tabs 1022), such that deformation of the actuator 1030 may cause deformation of both or all of the mixers. In some embodiments, the mixers 1120 may be positioned along a plane formed by the axial directions AX1 and AX2, as shown in FIG. 12A. In this manner, the mixers may induce flow in different regions of the vessel 100, enhancing the mixing efficiency of the overall system. In some embodiments, the mixers 1121, 1221 may be positioned along a plane formed by the axial directions AX1 and AX3, as shown in FIG. 12B, to help induce flow in upper and lower regions of the vessel 100. It should be understood that any suitable number of mixers, one or more, may be used to enhance mixing efficiency. These mixers may be positioned in any suitable manner along any plane within the vessel to help mix different regions of the fluid within the vessel. As shown in FIG. 12A-12B, the mixers may all be actuated by one actuator 1030. In other embodiments, multiple actuators may be used to actuate the mixer. In some embodiments, the mixer may be monolithic, but may also include sections that mix different portions of the vessel, as shown in the exemplary embodiment of FIG. 4B.

[0129] 13A-13B show a mixing system using a pneumatic actuator 1032 according to some embodiments. As described above with respect to FIGS. 11A-11B, the mixing system may include a mixer 1020 and an actuator 1032 disposed inside a vessel 100. The mixer 1020 and the actuator 1032 are coupled to each other such that the actuator can deform the mixer 1020, which in some embodiments may induce a flow of fluid within the interior volume of the vessel 100.

[0130] The pneumatic actuator 1032 may be fluidly connected to an input source (e.g., air) 50 via one or more ports 1040. The pneumatic actuator 1032 may include a flexible tubular bladder that is inflated by the input source 50. The bladder is encased in a woven or braided shell and serves to translate the radial expansion of the member upon inflation into uniaxial contraction. For example, FIG. 13A illustrates the pneumatic actuator 1032 in an extended state 1032A, where fluid from the input source 50 inflates the internal bladder, causing axial expansion of the actuator. FIG. 13B illustrates the pneumatic actuator 1032 in a contracted state 1032B, where fluid is forced out of the internal bladder, resulting in axial contraction of the actuator 1032 along an axial direction AX1. Note that the pneumatic actuator 1032 may also undergo deformation along a secondary axial direction AX2, which is complementary to deformation along the axial direction AX1, as shown in FIGS. 13A-13B. In some embodiments, the pneumatic actuator 1032 may act similarly to an artificial muscle or a McKibben muscle, although of course other modes of pneumatic actuators are contemplated.

[0131] 14A-14B show a mixing system with a flexible, deployable linear actuator 1034 driven by a fluid input source 50. In some embodiments, the soft actuator 1034 can be structured similar to an accordion with one or more bellows with an internal cavity. The internal cavity of the soft actuator 1034 can be inflatable such that a flow of fluid from the input source 50 (e.g., air, water, etc.) to the actuator 1034 can induce an axial expansion, and a flow of fluid from the actuator 1034 can induce an axial contraction. Thus, the actuator 1034 can deform linearly based on the fluid pressure therein. In some embodiments, the input source 50 can include one or more pumps (e.g., pneumatic pumps) configured to cyclically inflate / deflate the actuator 1034. The pumps can be controlled by one or more processors 60 that either directly control the pumps or provide one or more pneumatic controls (e.g., valves, variable restrictions, etc.) not shown, depending on the embodiment.

[0132] 15A-15D show a mixing system with a mixer 1020 and an actuator 1036 configured in parallel. As shown, the mixer 1020 and the actuator 1036 can be coupled to each other at a connection 1025 on opposite sides of the vessel. The connection can be a removable or permanent attachment of the actuator and the mixer. The actuator 1036 can be movable between a contracted state 1036A shown in FIG. 15A and an extended state 1036B shown in FIG. 15B. The mixer 1020 can deform axially with the actuator through the connection 1025. In some embodiments, the actuator 1036 is driven by one or more input sources 50 in communication with a processor and / or controller 60, which can control various parameters of the actuation process, such as duration, frequency, magnitude, etc.

[0133] In some embodiments, as shown in Figures 15A-15B, the mixer 1020 may be coupled or secured to the container 100 by a first tab 1021 at a first end 100A of the container and a second tab 1022 at a second end 100B of the container. Thus, in the embodiment shown in Figures 15A-15D, the container 100 may deform along with the actuator 1036. For example, as shown in Figures 15A-15B, the axial length L1 of the container 100 may change as the actuator 1036 moves between a contracted state 1036A and an extended state 1036B. Of course, embodiments with a rigid (i.e., non-flexible) container with one or more mixers and one or more actuators in parallel are also possible.

[0134] 15C-15D are views of the mixing system of FIGS. 15A-15B along an axial direction AX1. As shown, as the actuator moves between the contracted state 1036A and the extended state 1036B, the mixer may move between the contracted state 1020A and the extended state 1020B due to one or more connections 1025. In some embodiments, the mixer may include one or more flaps 1023 that may deflect out of plane when the mixer is in the extended state 1020B. This out of plane deflection of the flaps 1023 may induce localized fluid flow within the vessel. It should be understood that any suitable arrangement of flaps and / or other suitable features may be employed to achieve fluid agitation upon axial deformation of the mixer.

[0135] 15A-15D is a pneumatically actuated tube in fluid communication with the input source 50 and may be configured to pass a fluid (e.g., air) through the tube to deform the actuator 1036. In some embodiments, the tube may have greater axial deformation (e.g., along the axial direction AX1) than radial deformation. In other words, the tube may be configured to maximize the axial deformation of the actuator and minimize the radial deformation to provide more efficient actuation.

[0136] In some embodiments, the actuator 1036 shown in FIGS. 15A-15D may be formed of a shape memory material. Thus, the actuator 1036 may be configured to deform axially (e.g., elongate uniaxially) in response to a temperature change that may be applied via the input source 50. Due to one or more connections 1025 between the mixer 1020 and the actuator 1036, uniaxial deformation of the actuator 1036 may cause axial deformation of the mixer 1020, which may induce a fluid flow within the vessel 100. As mentioned above, in some embodiments, the actuator 1036 may be coated with an outer layer that may isolate the actuator from the surrounding environment. It should be understood that any suitable shape memory material that undergoes sufficient axial deformation within a desired temperature range for a given application may be used, as the present disclosure is not limited by the material composition of the shape memory alloy. In embodiments in which the mixing system is used for cell culture, the shape memory material may be selected to undergo axial deformation at a physiologically acceptable temperature.

[0137] 16A-16B show a mixing system in which a mixer 1020 and an origami actuator 1038 are arranged in series, both disposed inside the vessel 100. The origami actuator 1038 may include a rigid but deformable internal structure 1382 housed within a flexible bladder. The origami actuator 1038 may be movable between an extended state 1038A when the bladder is inflated (e.g., via the port 1040 and the input source 50) and a contracted state 1038B when the bladder is deflated. In some embodiments, the internal structure 1382 may include one or more holes 1384 to reduce hydraulic resistance of fluids (air, water, etc.) entering and leaving the bladder.

[0138] 17A-17C illustrate the operation of an origami actuator according to some embodiments. As shown, the origami actuator can include a rigid, deformable internal structure in the form of a rigid, foldable internal structure 1382 configured to fold along a plurality of joints. For example, the rigid internal structure can include a series of planar segments connected to one another in series by corresponding living hinges or another suitable rotatable connection disposed between adjacent planar segments. The rigid foldable structure can be disposed within a bladder 1381 that extends along its length and at least partially surrounds the rigid foldable structure. The bladder 1381 is flexible and can be inflated / deflated by a fluid (air, water, etc.) flowing into and out of the interior volume of the bladder via a port 1386. In some embodiments, the port 1386 can be in fluid communication with the port 1040 shown in FIGS. 16A-16B and then in fluid communication with the input source 50. The internal structure 1382 can be formed of a folded sheet of rigid material such that it can be axially deformed by bending flexible joints at each fold. Bladder 1381 may be sufficiently flexible to conform around inner structure 1382 when deflated.

[0139] It should be noted that the bladder 1381 may be formed of any suitable flexible material or combination of materials suitable for the intended application of the mixing system. The bladder 1381 may be sufficiently sealed to reduce the risk of fluid flow from the bladder 1381 into the interior volume of the vessel, and similarly, the risk of fluid flow from the interior volume of the vessel into the bladder.

[0140] FIG. 17A illustrates an extended state 1038A of the origami actuator, in which the bladder 1381 is substantially expanded. The actuator has an axial length L3 along an axial direction AX1, and as the bladder 1381 collapses, the axial length L3 may be shortened, as shown in FIGS. 17B-17C. When fluid is discharged (e.g., pumped) from the bladder 1381 through the outlet port 1386, the bladder 1381 may deform along with the internal structure 1382, which may also deform axially or linearly due to the discharge of fluid from the bladder 1381. Thus, the overall axial length L3 of the actuator may be shortened (see axial length L3 in FIG. 17C compared to FIG. 17A), which may facilitate axial deformation (e.g., expansion) of a mixer connected to the actuator, as shown in FIGS. 16A and 16B.

[0141] The internal structure 1382 (including the holes 1384 shown in FIGS. 16A-16B) can be formed using any suitable materials and techniques. In some embodiments, the internal structure may be laser cut, folded, and then heat sealed to the bladder 1381 to form the actuator. Weakness in the folded structure may allow the internal structure to deform axially like an accordion as fluid exits the bladder 1381.

[0142] 18A-18C illustrate an origami actuator 1048 according to another embodiment. The actuator 1048 and its internal structure 1482 are similar in operation to the actuator 1038 outlined in FIGS. 16A-17C, but may also include one or more paddles 1485 in fluid communication with an inflatable bladder 1481. The paddles 1485 may be arranged in any suitable manner along the actuator 1048 and serve to enhance mixing efficiency within the vessel. As shown in the sequence of FIGS. 18A-18C, the paddles 1485 may be inflatable with the bladder 1481 such that the outflow of fluid from the bladder may cause the paddles to deflate and then actuate. Specifically, the paddles may be inflatable structures that extend outward from one or more exterior portions of the bladder 1481. Thus, as the bladder expands, the paddles may move with the bladder and extend further into the fluid, resulting in further mixing of the fluid as the paddles move through the fluid to a fully expanded configuration. In some embodiments, the paddles rotate in an expansion / deflation cycle to induce flow within the vessel (not shown). In some embodiments, the expansion of the paddles themselves may induce localized fluid flow. It should be understood that non-inflatable paddles that rotate or otherwise move in accordance with the collapse / expansion of the bladder 1481 are also contemplated. The paddles 1485 shown in Figures 18A-18C are not limited to origami actuators and may be combined with any of the actuators and / or mixers described herein.

[0143] 19A-19B show an origami actuator 1039 and mixer 1020 in a parallel configuration, according to some embodiments. The actuator 1039 has a similar structure to the origami actuator shown in FIGS. 16A-17C, with a rigid collapsible inner structure housed in a flexible inflatable bladder. However, in the embodiment depicted in FIGS. 19A-19B, the actuator 1039 overlies the mixer 1020, and the actuator 1039 can be extended to extend the mixer and contracted to contract the mixer. In contrast, when the origami actuator 1038 and mixer 1020 are placed in series, as shown in FIGS. 16A-17C, the actuator extends to contract the mixer and contracts the mixer to extend the mixer. The actuator 1039 in FIGS. 19A-19B can be coupled or secured (removably or permanently) to the container 100 with one or more tabs. For example, the actuator 1039 and mixer 1020 may be attached to the first end 100A of the container by tabs 1021. As with the parallel configuration described above with respect to Figures 15A-15D, the container 100 may be sufficiently flexible to deform along with the actuator and mixer. For example, the axial length L1 of the container along the axial direction AX1 may be longer in the extended state 1039B (Figure 19B) of the origami actuator than in the contracted state 1039A (Figure 19A) of the origami actuator. Of course, embodiments using a rigid container 100 with a parallel actuator / mixer assembly are also contemplated, as the disclosure is not limited thereto.

[0144] While various pneumatic actuators are described for actuation of the mixer, it should be understood that any suitable mechanism capable of applying deformation to the mixer to induce movement between contracted and extended configurations may be used as the disclosure is not limited thereto. For example, electromagnetic actuation, pneumatic actuation, light responsive actuation, and / or any other suitable type of actuation method may be used, but the disclosure is not so limited.

[0145] In some embodiments, the mixing system may employ a uniaxial dielectric elastomer actuator. The uniaxial dielectric actuator may include multiple stacked pieces of thin dielectric film coated with compliant electrodes. The actuator may be used in a series configuration with the mixer (see FIGS. 11A-11B) and may be in electrical communication with an input source (e.g., a power supply) via a port (see port 1040 in FIGS. 11A-11B). Application of an actuation voltage to the actuator results in an electrostatic field induced displacement perpendicular to the plane of the electrodes. The stacked dielectric films act as a series of compliant capacitors, with alternating polarities for each layer, electrically connected in parallel. Thus, an actuation voltage may be applied to two separated compliant electrodes connected to the associated conductive layers. The dielectric elastomer actuator may thus convert electrical energy into mechanical work to axially deform the mixer and induce flow in the vessel. The dielectric elastomer actuator may be formed of any suitable material, but may also include a coating or outer layer to reduce the risk of fluid inflow from the vessel's internal volume into the actuator.

[0146] In other embodiments, the uniaxial dielectric actuator may include a roll or tube actuator. In a rolled configuration, the actuator is formed of a flat elastomeric sheet with complementary electrodes disposed on either side of the flat sheet. The flat sheet may be rolled to bring the two sides of the flat sheet closer together. An actuation voltage may be applied to the rolled actuator (e.g., via power supply 50 and port 1040, as shown in Figures 11A-11B) to deform the actuator axially and, in turn, deform the mixer. In some embodiments, the actuator may be in a tubular configuration substantially similar to the rolled configuration, with a single roll instead of multiple coaxial rolls. Of course, other arrangements or configurations of the uniaxial dielectric elastomeric actuator are contemplated, as the disclosure is not limited thereto.

[0147] FIG. 20 illustrates a mixing system employing a pneumatic soft actuator 1530 according to some embodiments. The mixing system may include an inflatable soft actuator 1530 with an internal channel configured for fluid flow. The internal channel may be integrated into the actuator. The actuator 1530 may be coupled to a mixer 1520 having similar characteristics to any of the mixers described herein. The soft actuator 1530 may be designed to undergo out-of-plane deformation during expansion with fluid from the input source 50 and the controller and / or processor 60. For example, the actuator 1530 may include one or more ridges to induce expansion in a particular direction to actuate the mixer and induce flow in the vessel. Expansion and subsequent actuation of the actuator may induce in-plane and / or out-of-plane deformation of the mixer 1520 along a plane formed by the axial directions AX1 and AX2. In some embodiments, high pressure fluid in the actuator 1530 may cause the mixer 1520 to expand, and low pressure fluid in the actuator 1530 may cause the mixer 1520 to contract. Cycling between high and low pressure can be achieved by expanding and collapsing the actuator. Any suitable soft actuator can be used to deform the mixer as the disclosure is not limited in this respect. The soft actuator can be formed of a flexible and / or elastic material (e.g., silicone, rubber) to facilitate its actuation.

[0148] In some embodiments, the actuator 1530 may be formed as an expandable channel within the mixer 1520, with the actuator integrated directly into the body of the mixer. Thus, changes in the expansion of the actuator 1530 may exert pressure on the mixer 1520 and induce a change in configuration. In other embodiments, the actuator 1530 may be a separate piece from the mixer 1520 and secured thereto by any suitable bonding (e.g., gluing, welding, fusing) technique. Actuation of the actuator similarly exerts pressure on the mixer and induces mixing within the vessel. Any suitable arrangement of mixers and actuators is contemplated, with it being understood that the disclosure is not limited thereto.

[0149] 21A-21C show a pneumatic wound actuator 1630 according to some embodiments. The mixing system may include one or more wound actuators 1630 disposed within a container (flexible or rigid) to induce fluid flow. The actuator may include an energy storage member 1635 disposed in parallel with an expandable body 1632. For example, the energy storage member may be a torsion spring or other coiled elastic structure that can be deformed between an unbiased coil configuration and an extended configuration. The energy storage member 1635 and the expandable body 1632 are coupled together, and expansion of the expandable body may overcome the energy storage in the energy storage member 1635, causing the assembly to deform. As shown in the sequence of FIG. 21A-21C, expansion of the body 1632 and / or the processor 60 (e.g., from the input source 50 and controller) may cause the assembly to unfold or unwrap from the original wound configuration shown in FIG. 21A to a partially unwrapped configuration shown in FIG. 21B to a fully unwrapped configuration shown in FIG. 21C. The energy storage member 1635 is pre-formed in a fully coiled configuration, and collapse of the body 1632 allows the system to return to its original coiled configuration. Thus, repeated cycles of expansion and collapse can induce fluid flow within the vessel. In some embodiments, the actuator 1630 can operate similar to a party horn.

[0150] The actuators 1630 can be positioned along any suitable plane so long as it is spatially efficient in the application to induce highly efficient fluid flow within the vessel. The mixing time of the system can be controlled by the roll and unroll speeds of the body 1632, as well as the unroll / unroll frequency, both of which can be controlled by pneumatic valves, as described in more detail below.

[0151] It should be understood that in some embodiments, the actuators 1630 of Figures 21A-21C can be used to induce fluid flow without the use of a mixer. Multiple roll actuators 1630 can be used in any suitable arrangement in a single vessel to enhance mixing. In other embodiments, the actuators of Figures 21A-21C can be integrated with any of the mixers described herein.

[0152] 22A-22B show an exploded roll actuator 1630 and a cross-sectional view of the actuator, according to some embodiments. The actuator 1630 can be formed from one or more flexible sleeves 1633 and an energy storage member 1634. In some embodiments, the energy storage member can be a constant force spring, although other embodiments of the energy storage member are contemplated. The sleeve 1633 can be arranged to form one chamber for the energy storage member 1635 and another chamber 1638 for the fluid, as shown in FIG. 22B. The sleeve can be sealed to reduce the risk of leakage from the actuator to or from the reservoir.

[0153] In some embodiments, the system of FIGS. 21A-22B may be inflated at a pressure of about 0.4 bar. Thus, the sleeve may be formed of a material that can expand and deform at this pressure (and / or other suitable pressures). The pressure may be selected to overcome the preformed energy storage member. Thus, the inflation pressure of the actuator may be any suitable pressure greater than 0.4 bar and less than 0.4 bar as the disclosure is not so limited. It should be noted that the inflation pressure of the roll actuator may also depend on the properties (such as viscosity and density) of the fluid placed in the container. As described below, the speed of the rolling / unrolling process may be controlled by a needle valve that controls the inflow and outflow of air to the actuator. In some embodiments, the frequency of the cycles may be controlled by another valve.

[0154] In some embodiments, actuators of the present disclosure described as employing pneumatic actuation may alternatively or in combination use a voltage actuated shape memory alloy material. The material can be heated to alternate between various actuation configurations to induce flow in the vessel (or actuate a mixer to induce flow). To limit heat transfer to the fluid in the vessel, insulating actuator sleeve material can be used to keep the contents of the vessel at the appropriate temperature.

[0155] It should be understood that any of the actuators described herein may be used to independently mix fluids without the use of a mixer. An actuator disposed within a vessel may be sufficient to induce flow and mix the contents of the vessel. Embodiments are contemplated that use mixers and actuators as described above.

[0156] In some embodiments, the mixers and / or actuators can be arranged in a fractal fashion to enhance mixing efficiency. As shown in FIG. 23A, in some embodiments, the mixers and / or actuators 1710 can be arranged in a linear fashion extending in one direction. To enhance mixing efficiency, as shown in FIG. 23B, fractal shaped mixers and / or actuators 1720 can be used in combination with or in place of the linear actuators 1710. Various configurations of the fractal mixers and actuators can induce fluid flow in different portions of the vessel to enhance efficiency. In some embodiments, the fractal structure 1720 can include one or more portions 1720A, 1720A that can be actuated via the same or different actuation mechanisms to achieve a desired flow pattern throughout the vessel. It should be understood that the fractal structure shown in FIG. 23B is exemplary and represents any suitable multi-directional mixers and / or actuators that can aid in enhancing mixing efficiency. FIG. 24A illustrates an exemplary control system for any of the mixing systems described herein. The control system can be compact (e.g., small footprint) to facilitate use of the mixing system in a variety of applications. In some embodiments, fluid (e.g., compressed air or a compressor connected to a fluid source) flows from an input source 50 to a pressure reducer 2110 and a needle valve 2112, which can be electronically operated by a controller 2118 and a relay to control the operation of the actuator. The control system may also include a 3 / 2-way valve 2114 that controls the frequency of the actuation cycle and thus the mixing time. In some embodiments, a needle valve 2116 can be used to control the flow rate of fluid from the input source to the actuator, which may also contribute to the frequency of the actuation cycle. As mentioned above, the cycle frequency can affect the mixing rate as well as the shear stress of the fluid in the vessel. Thus, the frequency can be tailored to the application. For example, if the vessel contains cells, the frequency can be controlled to ensure that the cells are subjected to an acceptable level of shear stress during mixing.FIG. 24B is a block diagram for visually understanding the control system of FIG. 24A.

[0157] It should be understood that the control systems of FIGS. 24A-24B are exemplary and that any other suitable control system for controlling the actuators and / or mixers of the present disclosure may be employed.

[0158] The mixing operation of the mixing systems described herein can be evaluated using an automated image analysis system. An exemplary system includes evaluating the grayscale level of the image after mixing to reduce human error in the analysis. An exemplary data analysis process includes reading a recorded video of a vessel with a mixing system inside. Extracting a region of interest in one or more frames of the video. An exemplary frame and vessel 100 are shown in FIG. 25A. Each frame can be saved and the average RGB value of the region of interest can be converted to a grayscale intensity value. This data can be plotted as a function of time, as shown in the exemplary plot of FIG. 25B. Signal processing such as data smoothing (e.g., cubic spline interpolation) can be employed to improve signal quality. In some embodiments, outlying events such as changes in focus or light intensity may be discarded. From the remaining data, a complete mixing time can be extracted, defined as the time after which the grayscale value varies by less than 1%. In some embodiments, other mixing times can also be extracted, such as the time it takes to achieve 95% of the complete mixed grayscale value.

[0159] Figure 26 shows an exemplary data table of measured mixing times as a function of the actuation cycle characteristics of a mixing system using a pneumatic rolling actuator as shown in Figures 21A-21C. The data shown in the table suggests that reasonable mixing times can be achieved by varying the control characteristics.

[0160] It should be understood that the above-described process for evaluating the mixing efficiency is exemplary and that other analytical processes for evaluating the mixing efficiency of the mixing systems herein are also contemplated.

[0161] The above embodiments of the technology described herein may be implemented in any of a number of ways. For example, the embodiments may be implemented using hardware, software, or a combination thereof. When implemented in software, the software code may be executed on any suitable processor or collection of processors, whether provided in a single computing device or distributed across multiple computing devices. Such a processor may be implemented as an integrated circuit, including one or more processors within an integrated circuit component, including commercially available integrated circuit components known in the art under names such as CPU chips, GPU chips, microprocessors, microcontrollers, or coprocessors. Alternatively, the processor may be implemented in a custom circuit, such as an ASIC, or a semi-custom circuit resulting from the configuration of a programmable logic device. As yet another alternative, the processor may be part of a larger circuit or semiconductor device, whether commercially available, semi-custom, or custom. As a specific example, some commercially available microprocessors may have multiple cores, one or a subset of those cores may constitute a processor. However, the processor may be implemented using any suitable form of circuit.

[0162] Further, it should be noted that a computing device may be realized in a variety of forms, such as a rack-mounted computer, a desktop computer, a laptop computer, a tablet computer, etc. Additionally, a computing device may be incorporated into devices that are not generally considered to be computing devices but that have suitable processing capabilities, such as a personal digital assistant (PDA), a smartphone, a tablet, or other suitable portable or fixed electronic device.

[0163] A computing device may also have one or more input and output devices. These devices may be used, among other things, to present a user interface. Examples of output devices that may be used to provide a user interface include a display screen for visually presenting output and a speaker or other sound generating device for audibly presenting output. Examples of input devices that may be used for a user interface include a keyboard, individual buttons, and pointing devices such as a mouse, touchpad, or digital tablet. As another example, a computing device may receive input information via speech recognition or other audible form.

[0164] Such computing devices may be interconnected by one or more networks in any suitable form, such as a local area network or a wide area network, such as an enterprise network or the Internet. Such networks may be based on any suitable technology and operate according to any suitable protocol, and may include wireless networks, wired networks, fiber optic networks, etc.

[0165] Also, the various methods and processes outlined herein may be coded as software executable on one or more processors using any one of a variety of operating systems or platforms. Additionally, such software may be written using any of a variety of suitable programming languages ​​and programming or scripting tools, and may be compiled as executable machine language code or intermediate code that runs on a framework or virtual machine.

[0166] In this regard, the embodiments described herein may be embodied as a computer-readable storage medium (or a plurality of computer-readable media) (e.g., a computer memory, one or more floppy disks, compact disks (CDs), optical disks, digital video disks (DVDs), magnetic tapes, flash memory, RAM, ROM, EEPROM, circuitry in a field programmable gate array or other semiconductor device, or other tangible computer storage medium) having one or more programs encoded thereon, which, when executed on one or more computers or other processors, performs methods for implementing the various embodiments described above. As is evident from the foregoing examples, a computer-readable storage medium may retain information for a sufficient period of time to provide computer-executable instructions in a non-transitory form. Such computer-readable storage media may be portable, and the programs stored thereon may be loaded into one or more different computing devices or other processors to implement various aspects of the present disclosure, as described above. The term "computer-readable storage medium" as used herein encompasses only non-transitory computer-readable media that may be considered an article of manufacture (i.e., a product) or a machine. Alternatively or additionally, the present disclosure may be embodied as a computer-readable medium other than a computer-readable storage medium, such as a propagated signal.

[0167] As used herein, the terms "program" or "software" are used in a general sense to refer to any type of computer code or set of computer-executable instructions that can be used to program a computing device or other processor to implement various aspects of the present disclosure as described above. Additionally, according to one aspect of this embodiment, it should be understood that one or more computer programs that, when executed, perform the methods of the present disclosure need not reside on a single computing device or processor, but may be distributed in a modular manner among a number of different computers or processors to implement various aspects of the present disclosure.

[0168] Computer-executable instructions may be in various forms, such as program modules, executed by one or more computers or other devices. Generally, program modules include routines, programs, objects, components, data structures, etc. that perform particular tasks or implement particular abstract data types. Typically the functionality of the program modules may be combined or distributed as desired in various embodiments.

[0169] The embodiments described herein may be embodied as methods, which are provided as examples. The acts performed as part of the method may be ordered in any suitable manner. Thus, embodiments may be constructed in which acts are performed in an order different from that shown, which may include performing some acts simultaneously even though in the example embodiments they are shown as sequential acts.

[0170] Additionally, some actions are described as being performed by a "user." It should be understood that a "user" does not necessarily have to be a single individual, and that in some embodiments, actions attributed to a "user" may be performed by a team of individuals and / or an individual in combination with computer-assisted tools or other mechanisms.

[0171] While the present teachings have been described in conjunction with various embodiments and examples, it is not intended that the present teachings be limited to such embodiments or examples. Rather, the present teachings encompass various alternatives, modifications, and equivalents, as will be appreciated by those skilled in the art. Accordingly, the foregoing description and drawings are merely exemplary.

[0172] Although several embodiments of the present disclosure have been described and illustrated herein, those skilled in the art can readily envision a variety of other means and / or structures for performing the functions and / or results and / or obtaining one or more advantages described herein, and each such variation and / or modification is deemed to be within the scope of the present disclosure. More generally, those skilled in the art will readily appreciate that all parameters, dimensions, materials, and configurations described herein are intended to be exemplary, and that the actual parameters, dimensions, materials, and / or configurations will depend on the particular application or applications in which the teachings of the present disclosure are used. Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, numerous equivalents to the specific embodiments of the disclosure described herein. Thus, the foregoing embodiments are presented by way of example only, and it will be understood that within the scope of the appended claims and their equivalents, the present disclosure may be practiced otherwise than as specifically described and claimed. The present disclosure is directed to each individual feature, system, article, material, kit, and / or method described herein. Furthermore, any combination of two or more such features, systems, articles, materials, kits, and / or methods is within the scope of the present disclosure, unless such features, systems, articles, materials, kits, and / or methods are mutually inconsistent.

[0173] The terms used herein, for example, relating to the shape, orientation, arrangement, and / or geometric relationships of one or more articles, structures, forces, fields, flows, directions / trajectories, and / or subparts thereof, and / or combinations thereof, and / or other tangible or intangible elements characterized by such terms not enumerated above, shall be understood not to necessarily adhere to the mathematical definitions of such terms, unless otherwise defined or indicated, but rather to indicate adherence to the mathematical definitions of such terms to the extent possible with respect to the subject matter so characterized, as understood by one of ordinary skill in the art most closely related to such subject matter.

Claims

1. 1. A mixing device comprising: a vessel configured to contain a fluid; and A mixer disposed within a vessel, the mixer comprising: substrate, a plurality of slots arranged in a pattern on the substrate, the plurality of slots defining one or more spines extending at least partially along an axial direction of the substrate; and the mixer including a plurality of flaps configured to move between an extended configuration and a contracted configuration when a substrate is axially deformed; Including, the plurality of flaps are configured to induce fluid flow when the substrate is axially deformed; The mixing device.

2. 10. The mixing device of claim 1, wherein the container includes a seam extending around the periphery of the container, and the mixer is attached to the container at the seam.

3. The mixing device of claim 1 , wherein the plurality of flaps are configured to be flush with the substrate in the retracted configuration.

4. The mixing device of claim 1 , wherein the plurality of flaps are configured to extend outwardly from the plane of the substrate in the extended configuration.

5. 5. The mixing device of claim 4, wherein the mixer is a first mixer and the mixing device further comprises a second mixer including a plurality of flaps, the plurality of flaps configured to move between an extended configuration and a contracted configuration when a substrate of the second mixer is axially deformed, and the plurality of flaps of the second mixer configured to extend outward from a plane of the substrate of the second mixer in a different direction than the plurality of flaps of the first mixer.

6. 10. The mixing device of claim 1, wherein the mixer further comprises a plurality of paddles extending from the base plate.

7. 1. A mixing device comprising: a vessel configured to contain a fluid; and a mixer disposed within the container; The mixer is configured to induce a flow in a fluid within the vessel when deformed axially. The mixing device.

8. 8. The mixing device of claim 7, wherein the plurality of flaps are configured to be flush with a base plate of the mixer in the retracted configuration.

9. 8. The mixing device of claim 7, wherein the plurality of flaps are configured to extend outwardly from the plane of the base of the mixer in the extended configuration.

10. 1. A method of mixing fluids disposed in a container, comprising: displacing opposite ends of a mixer disposed within the vessel relative to one another to deform the mixer and induce a fluid flow; The method.

11. The method of claim 10 , wherein the plurality of flaps are flush with the mixer in the retracted configuration.

12. The method of claim 10 , wherein the plurality of flaps extend outwardly from the plane of the base plate of the mixer in the extended configuration.

13. 1. A mixed system comprising: a vessel configured to contain a fluid; a mixer disposed within the vessel; and an actuator disposed within the vessel and operably coupled to the mixer; The actuator is configured to axially deform the mixer to induce fluid flow within the vessel. The mixing system.

14. 14. The mixing system of claim 13, wherein the actuator comprises one or more bladders configured to expand to place the mixer in the contracted configuration, and the one or more bladders configured to collapse to place the mixer in the extended configuration.

15. 14. The mixing system of claim 13, wherein the actuator comprises a plurality of bladders.

16. 14. The mixing system of claim 13, wherein the actuator includes an expansion tube configured to expand axially to place the mixer in an extended configuration, and the expansion tube configured to collapse axially to place the mixer in a contracted configuration.

17. 14. The mixing system of claim 13, wherein the actuator includes an energy storage member coupled to a bladder, the energy storage member and the bladder configured to transition between a rolled configuration and an unrolled configuration upon actuation.

18. 1. A mixed system comprising: a mixer disposed within the vessel, the mixer operably coupled to the first portion of the vessel; and an actuator disposed within the vessel, the actuator operably coupled to the second portion of the vessel and the mixer, the actuator configured to deform the mixer to induce a flow of fluid within the vessel; The mixing system comprising:

19. 20. The mixing system of claim 18, wherein the mixer includes a plurality of flaps configured to move between an extended configuration and a contracted configuration when the mixer is axially deformed, and wherein the plurality of flaps are configured to induce fluid flow when the mixer is axially deformed.

20. 1. A method of mixing fluids disposed in a container, comprising: axially deforming an actuator disposed within the vessel to axially deform a mixer disposed within the vessel; and Inducing a flow in a fluid placed in a vessel when the mixer is deformed in the axial direction The method comprising:

21. 21. The method of claim 20, wherein inducing fluid flow comprises moving a plurality of flaps between an extended configuration and a retracted configuration when the mixer is axially deformed.

22. Inflating one or more bladders of the actuator to axially expand the mixer; and Axial contraction of the mixer by deflating one or more bladders of the actuator.

21. The method of claim 20, further comprising:

23. 21. The method of claim 20, wherein the actuator further comprises a plurality of paddles extending from at least one of the actuator and the mixer.

24. 1. A method of mixing fluids disposed in a container, comprising: introducing a fluid into a bladder of an actuator disposed within a container; Unwinding the actuator; and Inducing a flow in a fluid disposed within a container when the actuator is unwound The method comprising:

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