Cell culture medium containers and dispensers

Abstract

A container (100) having a first end (102), a second end (104), and a deformable middle portion (106) and a method for manufacturing the container are disclosed. The container has a folded configuration and an unfolded configuration. The first end and the second end are rigid. The container is configured to store cell culture medium powder. Methods and systems (e.g., dispensers) for producing culture medium using the container are also disclosed. TIFF2023549285000002.tif200152

Description

Technical Field

[0001] Cross - Reference to Related Applications This application claims the benefit of U.S. Provisional Patent Application No. 63 / 073,356, filed on September 1, 2020, and U.S. Provisional Patent Application No. 63 / 238,720, filed on August 30, 2021, the content of each application being incorporated herein by reference in its entirety.

[0002] Field of the Invention The present disclosure generally relates to cell culture fluid formulations. More specifically, the present disclosure relates to cell culture fluid containers and dispensers.

Background Art

[0003] Background of the Invention Cell therapy extends life and saves lives. For example, cancer survival rates have increased significantly as cell therapy solutions have advanced. An important component in cell therapy solutions is the cell culture medium used to grow cells. Conventionally, cell culture media have been manufactured as bulk liquids and packaged in bottles, bags, or large drum cans in the range of 100 mL to 200 L, and then shipped to cell therapy technicians, bioproduction managers, and scientists. This approach has several drawbacks. Existing containers are bulky, spatially inefficient, and may increase shipping costs. At the point of use, technicians and scientists have to store the bulky containers on - site and may require a large storage space to make various cell culture media available on demand. Technicians and scientists may add other components to the medium and then need to resterilize because of the potential for contamination, adding manual steps to the process and introducing variability into the cell culture medium.

Summary of the Invention

[0004] A container having a first end, a second end, and a deformable intermediate portion, and a method for manufacturing the container are disclosed. The container has a folded configuration and an unfolded configuration. In some embodiments, the first end and the second end are rigid. In some embodiments, the container is configured to store cell culture medium powder. A method and system for preparing a culture medium using the container are also disclosed.

[0005] In some embodiments, the cell culture medium container comprises a rigid first end, a rigid second end, a deformable intermediate portion attached to the first and second ends and, together with the first and second ends, enclosing a region having a variable volume, cell culture medium powder within the region, a fluid-connected inlet to the region, and a fluid-connected outlet to the region, wherein the container has a folded configuration and an unfolded configuration.

[0006] In some embodiments, the volume of the region is larger in the unfolded configuration than in the folded configuration.

[0007] In some embodiments, the deployed configuration has a region volume that accommodates 500 mL, 5 L, or 2000 L of cell culture medium.

[0008] In some embodiments, the distance between the first rigid end and the second rigid end is greater in the unfolded configuration than in the folded configuration.

[0009] In some embodiments, the distance is 0 mm in the folded configuration, and 120 mm or 300 mm in the unfolded configuration.

[0010] In some embodiments, in the deployed configuration, the container has a height-to-width ratio greater than 1 / 2.

[0011] In some embodiments, the ratio is 1.2.

[0012] In some embodiments, the inlet is located at the rigid first end and the outlet is located at the rigid second end.

[0013] In some embodiments, the container further comprises a second inlet located at a rigid first end.

[0014] In some embodiments, the first entrance and the second entrance are parallel.

[0015] In some embodiments, the first inlet is a water inlet, and the second inlet is an air intake.

[0016] In some embodiments, the rigid first end is a rectangle with a width of 85 mm and a length of 85 mm.

[0017] In some embodiments, the first rigid end is circular.

[0018] In some embodiments, when the container is in an unfolded configuration, the intermediate portion has a rectangular cross-section.

[0019] In some embodiments, when the container is in an unfolded configuration, the middle section has a circular cross-section with a diameter of 73 mm.

[0020] In some embodiments, the rigid second end has a tapered surface inside the container, which tapers downward toward the center of the rigid second end.

[0021] In some embodiments, at least one of the rigid first end and the rigid second end is opaque to sterilization light.

[0022] In some embodiments, the rigid first end and the rigid second end include at least one of polyethylene, polylactic acid (PLA), and polycarbonate (PCL).

[0023] In some embodiments, the intermediate portion is a polyethylene bag or a polypropylene bag.

[0024] In some embodiments, the rigid first end, the rigid second end, and the intermediate portion comprise a recyclable material.

[0025] In some embodiments, the container further comprises an adapter attached to the inlet.

[0026] In some embodiments, the adapter comprises at least one of a luer lock adapter and a PVT adapter.

[0027] In some embodiments, the container further comprises a stirrer positioned within the region and having a length of 10 - 20 mm.

[0028] In some embodiments, the stirrer comprises polytetrafluoroethylene (PTFE).

[0029] In some embodiments, the container further comprises a QR code disposed on the rigid first end associated with the cell culture media powder.

[0030] In some embodiments, the rigid first end and the rigid second end comprise a tongue or groove configured to couple the container to the dispenser while the container is inserted into the dispenser.

[0031] In some embodiments, the intermediate portion is flexible when the container is in the deployed configuration.

[0032] In some embodiments, the surface of the rigid first end is configured to interface with the surface of the rigid second end.

[0033] In some embodiments, the intermediate portion stores a powder pouch containing the solution powder.

[0034] In some embodiments, the powder pouch is attached to the rigid first end.

[0035] In some embodiments, the container further comprises a barrier in an intermediate portion that separates the solution powder from at least one of the rigid first end and the rigid second end.

[0036] In some embodiments, the container further comprises a seal between the rigid second end and the intermediate portion.

[0037] In some embodiments, the container further comprises a seal between a rigid first end and an intermediate portion.

[0038] In some embodiments, the rigid first end and the rigid second end are configured such that, when the container is in an unfolded configuration, the rigid first end is rotated at a first angle from the rigid second end with respect to the orientation of the rigid first and rigid second ends, thereby locking the container in a folded configuration.

[0039] In some embodiments, the rigid first end includes a notch configured to engage with an opening in the rigid second end, thereby locking the container in a folded configuration.

[0040] In some embodiments, the rigid first end is provided with an opening.

[0041] In some embodiments, the container further comprises a cover configured to seal the opening.

[0042] In some embodiments, the container further comprises a filter having a pore size of 0.22 to 1 μm.

[0043] In some embodiments, the container further comprises a filter attached to the outlet.

[0044] In some embodiments, the outlet is mounted on a spring mechanism.

[0045] In some embodiments, the outlet is configured to be attached to the discharge pipe.

[0046] In some embodiments, the discharge pipe comprises at least one of a Luer lock fitting and a sealed nozzle.

[0047] In some embodiments, the container further comprises a filter attached to the discharge pipe.

[0048] In some embodiments, the discharge pipe is bendable or flexible.

[0049] In some embodiments, the container further comprises a pH sensor that senses the pH level associated with the cell culture medium powder.

[0050] In some embodiments, the container further comprises a dissolution sensor.

[0051] In some embodiments, the cell culture medium powder is pre-granulated by spraying a pH corrector.

[0052] In some embodiments, the intermediate portion of the folded configuration is configured to be vacuum-sealed.

[0053] In some embodiments, the container further comprises a material that seals the outlet, and the material is configured to rupture in response to an applied pressure exceeding a pressure threshold.

[0054] In some embodiments, the material used to block the outlet is 1 cm 2 It has an area of ​​.

[0055] In some embodiments, the material includes low-density polyethylene.

[0056] In some embodiments, the container further comprises a filter integrated with the outlet.

[0057] In some embodiments, a method for preparing a culture medium includes the steps of: receiving a first container in a folded configuration with a dispenser; unfolding the first container into an unfolded configuration; injecting water into the first container while the first container is being unfolded or while the first container is in an unfolded configuration, driving a stirrer inside the first container, and mixing the powder and water in the first container with the stirrer to prepare a culture medium; and dispensing the culture medium into a second container.

[0058] In some embodiments, the first container is a cell culture medium container as described herein.

[0059] In some embodiments, a method for preparing a culture medium further includes a step of receiving an input, wherein the input is a selection on a graphical user interface (GUI) of a dispenser, and a first container is unfolded in response to the receipt of the input.

[0060] In some embodiments, the method for preparing a culture medium further includes the step of receiving an input, wherein the input is a QR code scan of a QR code on a first container, and the first container is unfolded in response to the receipt of the input.

[0061] In some embodiments, the method for preparing the culture medium further includes the step of removing the cover of the second container before dispensing the culture medium into the second container.

[0062] In some embodiments, the method for preparing the culture medium further includes the step of dispensing the culture medium into a second container and then providing a cover to the second container.

[0063] In some embodiments, the method for preparing the culture medium further includes a step of sterilizing the dispenser.

[0064] In some embodiments, the method for preparing the culture medium further includes the step of injecting air into a first container.

[0065] In some embodiments, a method for preparing a culture medium further includes the step of providing a filter, wherein the culture medium is dispensed through the filter into a second container.

[0066] In some embodiments, the method for preparing the culture medium further includes the step of folding the first container from an unfolded configuration to a folded configuration.

[0067] In some embodiments, the agitator is driven magnetically.

[0068] In some embodiments, the first container is one of the cell culture medium containers described above.

[0069] In some embodiments, the method for preparing the culture medium further includes the step of applying pressure to the middle portion of a first container.

[0070] In some embodiments, the pressure is 5 to 12 psi.

[0071] In some embodiments, the method for preparing a culture medium further includes the step of applying a second pressure to the dispenser chamber, wherein the second pressure is different from the first pressure.

[0072] In some embodiments, the method for preparing the culture medium further includes the step of applying baffles to support the middle portion of a first container.

[0073] In some embodiments, the baffle is applied while the first container is being deployed or while the first container is in a deployed configuration.

[0074] In some embodiments, the method for preparing the culture medium further includes a step of performing in-line testing of the culture medium.

[0075] In some embodiments, the method for preparing the culture medium further includes the step of refrigerating the culture medium at -10 to 4 degrees Celsius.

[0076] In some embodiments, a method for preparing a culture medium further includes the steps of: heating a tube connected between a dispenser and a destination; and transporting the culture medium to the destination via the tube, wherein the tube is heated to the destination temperature of 30-40 degrees Celsius.

[0077] In some embodiments, the cell culture medium dispenser is configured to perform one of the above methods for preparing the culture medium.

[0078] In some embodiments, a method for manufacturing a cell culture medium container for storing culture medium powder includes the steps of: providing a rigid first end; providing a rigid second end; providing a deformable intermediate portion; attaching the deformable intermediate portion to the first end and the second end, wherein the first end, the second end and the intermediate portion surround a region having a variable volume; providing an inlet; fluidizing the inlet to the region; providing an outlet; fluidizing the outlet to the region; and loading cell culture medium powder into the region.

[0079] In some embodiments, the step of loading the region with culture solution powder includes loading the culture solution powder through an opening at a rigid first end.

[0080] In some embodiments, the manufacturing method further includes a step of creating a vacuum within the region.

[0081] In some embodiments, the step of creating a vacuum within the region includes the step of removing air from the region through an opening in a rigid first end.

[0082] In some embodiments, the manufacturing method further includes the step of providing a stirrer.

[0083] In some embodiments, the agitator includes PTFE.

[0084] In some embodiments, the manufacturing method further includes the step of providing a barrier in an intermediate portion that separates the cell culture medium powder from at least one of a rigid first end and a rigid second end.

[0085] In some embodiments, the step of creating a barrier further includes the step of folding an intermediate portion to create a barrier.

[0086] In some embodiments, the rigid first end is provided with an opening.

[0087] In some embodiments, the manufacturing method further includes the step of providing a cover configured to close the opening.

[0088] In some embodiments, the step of providing an inlet includes the step of positioning the inlet at a rigid first end, and the step of providing an outlet includes the step of positioning the outlet at a rigid second end.

[0089] In some embodiments, the manufacturing method further includes the step of providing a second inlet located at the rigid first end.

[0090] In some embodiments, the manufacturing method further includes the step of positioning the first inlet and the second inlet so that the first inlet and the second inlet are parallel to each other.

[0091] In some embodiments, the first rigid end is rectangular.

[0092] In some embodiments, the first rigid end is circular.

[0093] In some embodiments, when the container is in an unfolded configuration, the intermediate portion has a rectangular cross-section.

[0094] In some embodiments, when the container is in an unfolded configuration, the intermediate portion has a circular cross-section.

[0095] In some embodiments, the rigid second end has a tapered surface inside the container, which tapers downward toward the center of the rigid second end.

[0096] In some embodiments, the rigid first end and the rigid second end include at least one of polyethylene, PLA, and PCL.

[0097] In some embodiments, the intermediate portion is a polyethylene bag or a polypropylene bag.

[0098] In some embodiments, the rigid first end and the rigid second end and intermediate portion include a recyclable material.

[0099] In some embodiments, the manufacturing method further includes the step of attaching an adapter to the inlet.

[0100] In some embodiments, the adapter comprises at least one of a Luer lock adapter and a PVT adapter.

[0101] In some embodiments, the manufacturing method further includes the step of placing a QR code associated with cell culture medium powder on a rigid first end.

[0102] In some embodiments, the step of providing a rigid first end and a rigid second end includes the step of forming tongues or grooves on the rigid first end and the rigid second end, which are configured to connect the container and the dispenser while the container is being inserted into the dispenser.

[0103] In some embodiments, the intermediate portion includes a flexible material.

[0104] In some embodiments, the first rigid end and the second rigid end have an interface feature.

[0105] In some embodiments, the step of loading cell culture medium powder into the region further includes the step of supplying powder pouches containing the cell culture medium powder.

[0106] In some embodiments, the manufacturing method further includes the step of attaching the powder pouch to a rigid first end.

[0107] In some embodiments, the manufacturing method further includes the step of providing a seal between the rigid first end and the intermediate portion.

[0108] In some embodiments, the rigid first end includes a notch configured to engage with an opening in the rigid second end, thereby locking the container in a folded configuration.

[0109] In some embodiments, the manufacturing method further includes the step of supplying a filter having a pore size of 0.22 to 1 μm.

[0110] In some embodiments, the manufacturing method further includes the step of attaching a filter to the outlet.

[0111] In some embodiments, the manufacturing method further includes the step of mounting the outlet to a spring mechanism.

[0112] In some embodiments, the manufacturing method further includes the step of attaching a discharge pipe to the outlet.

[0113] In some embodiments, the discharge pipe comprises at least one of a Luer lock fitting and a sealed nozzle.

[0114] In some embodiments, the manufacturing method further includes the step of installing a filter attached to the discharge pipe.

[0115] In some embodiments, the discharge pipe is bendable or flexible.

[0116] In some embodiments, the manufacturing method further includes the step of providing a pH sensor that senses the pH level associated with the cell culture medium powder.

[0117] In some embodiments, the manufacturing method further includes the step of providing a dissolution sensor.

[0118] In some embodiments, the manufacturing method further includes a step of pre-granulating the cell culture medium powder by spraying a pH corrector.

[0119] In some embodiments, the cell culture medium powder is loaded into the region before the deformable intermediate portions are attached to the first and second ends.

[0120] In some embodiments, the container is one of the cell culture medium containers described above.

[0121] In some embodiments, the container is one of the containers used in the method for preparing the culture medium described above.

[0122] In some embodiments, the manufacturing method further includes a step of sealing an outlet with a material, wherein the material is configured to rupture in response to an applied pressure exceeding a pressure threshold.

[0123] In some embodiments, the material used to block the outlet is 1 cm 2 It has an area of ​​.

[0124] In some embodiments, the material includes low-density polyethylene.

[0125] In some embodiments, a dispenser for producing a cell culture medium, comprising: a graphical user interface (GUI) for controlling the dispenser; a slot for receiving and unfolding a first container; a second container access mechanism for opening and closing a second container, the second container access mechanism for dispensing the cell culture medium into the second container; a second container handling mechanism for moving the second container toward and away from the cell culture medium dispensing position; a filter supply mechanism for supplying a filter to the first container; a magnetic field generator for magnetically driving a stirrer within the first container; and a baffle for supporting the middle portion of the first container.

[0126] In some embodiments, the dispenser further comprises a pump for applying a first pressure to the middle portion of the first container.

[0127] In some embodiments, the first pressure is 5 to 12 psi.

[0128] In some embodiments, the pump is further used to apply a second pressure to the dispenser chamber, the second pressure being different from the first pressure.

[0129] In some embodiments, the dispenser further comprises a second pump for applying a second pressure to the dispenser chamber.

[0130] In some embodiments, the baffle is for supporting the middle portion of the first container.

[0131] In some embodiments, the baffle is applied while the first container is being deployed or while the first container is in a deployed configuration.

[0132] In some embodiments, the dispenser is configured to perform in-line testing of cell culture media.

[0133] In some embodiments, the dispenser is configured to refrigerate the culture medium at -10 to 4 degrees Celsius.

[0134] In some embodiments, the dispenser is configured to connect a tube between the dispenser and the destination and to heat the tube to the destination temperature at 30-40 degrees Celsius.

[0135] In some embodiments, a method for preparing a culture medium includes the steps of: unfolding a first container into an unfolded configuration; mixing powder and water in the first container to prepare a culture medium while the first container is unfolding or in an unfolded configuration; and dispensing the culture medium.

[0136] In some embodiments, the method for preparing the culture medium further includes the step of applying pressure to the middle portion of a first container.

[0137] In some embodiments, the pressure is 5 to 12 psi.

[0138] In some embodiments, the method for preparing a culture medium further includes the step of applying a second pressure to the dispenser chamber, wherein the second pressure is different from the first pressure.

[0139] In some embodiments, the method for preparing the culture medium further includes the step of applying baffles to support the middle portion of a first container.

[0140] In some embodiments, the baffle is applied while the first container is being deployed or while the first container is in a deployed configuration.

[0141] In some embodiments, the method for preparing the culture medium further includes a step of performing in-line testing of the culture medium.

[0142] In some embodiments, the method for preparing the culture medium further includes the step of refrigerating the culture medium at -10 to 4 degrees Celsius.

[0143] In some embodiments, a method for preparing a culture medium further includes the steps of: heating a tube connected between a dispenser and a destination; and transporting the culture medium to the destination via the tube, wherein the tube is heated to the destination temperature of 30-40 degrees Celsius. [Invention 1001] The first end of rigidity, The second end of rigidity, A deformable intermediate portion attached to the first end and the second end, which together with the first end and the second end encloses a region having a variable volume, The cell culture medium powder within the region, An inlet fluid-connected to the region, An outlet fluid-connected to the region and Equipped with, A cell culture medium container having both a folded configuration and an unfolded configuration. [Invention 1002] The container of the present invention 1001, wherein the rigid second end has a tapered surface inside the container, and the tapered surface tapers downward toward the center of the rigid second end. [Invention 1003] The container according to the present invention 1001 or 1002, wherein the intermediate portion is a polyethylene bag or a polypropylene bag. [Invention 1004] A container according to any of the invention 1001 to 1003, wherein the rigid first end, the rigid second end, and the intermediate portion include a recyclable material. [Invention 1005] A container according to any one of the present invention 1001 to 1004, further comprising a stirrer positioned within the aforementioned region. [Invention 1006] The first rigid end and the second rigid end are A tongue or groove is configured to connect the container and the dispenser while the container is inserted into the dispenser. A container according to any of the present invention 1001 to 1005, comprising the features described herein. [Invention 1007] A container according to any one of the present invention 1001 to 1006, further comprising a filter attached to the outlet. [Invention 1008] The first and second inlets are located at the rigid first end, The outlet is located at the rigid second end. A container according to any of the present invention 1001 to 1007. [Invention 1009] A container according to any of the invention 1001 to 1008, wherein the rigid first end and the rigid second end contain at least one of polyethylene, polylactic acid (PLA), and polycarbonate (PCL). [Invention 1010] A container according to any of the present invention 1001 to 1009, wherein the intermediate portion is flexible when the container is in the unfolded configuration. [Invention 1011] A container according to any one of the present invention 1001 to 1010, wherein the folded configuration is configured such that the intermediate portion is vacuum-sealed. [Invention 1012] A container according to any of the present invention 1001 to 1011, wherein at least one of the rigid first end and the rigid second end is impermeable to sterilization light. [Invention 1013] A method for producing a cell culture medium container according to any of invention 1001 to 1012, comprising the following steps: A step of providing a rigid first end; A step of providing a second rigid end; A process of creating a deformable intermediate section; A step of attaching the deformable intermediate portion to the first end and the second end, wherein the first end, the second end, and the intermediate portion enclose a region having a variable volume; The process of creating an entrance; A step of fluidly connecting the inlet to the region; The process of creating an outlet; The process of fluidly connecting the outlet to the region; and Steps to load cell culture medium powder into the area. Methods that include... [Invention 1014] A method for preparing a culture medium, comprising the following steps: A step of receiving one of the first containers of the present invention 1001 to 1012, which is in a folded configuration, into a dispenser; A step of unfolding the first container into its unfolded configuration; While the first container is being unfolded, or while the first container is in the unfolded configuration, Water is poured into the first container, The stirrer inside the first container is driven, A step of mixing the powder in the first container with the water using a stirrer in order to prepare the culture medium; and The process of dispensing the culture medium into a second container. Methods that include... [Invention 1015] A dispenser for producing cell culture medium, A graphical user interface (GUI) for controlling the dispenser, A slot for receiving and unfolding a first container according to any of invention 1001 to 1012, A second container access mechanism for opening and closing a second container, wherein the dispenser dispenses the cell culture medium into the second container; A second container handling mechanism for moving the second container toward and away from the cell culture medium dispensing position, A filter supply mechanism for supplying a filter to the first container, A magnetic field generator for magnetically driving the agitator inside the first container, A baffle for supporting the middle portion of the first container and A dispenser equipped with the following features. [Brief explanation of the drawing]

[0144] [Figure 1A] An example container is shown. [Figure 1B] An example container is shown. [Figure 2] An example dispenser is shown. [Figure 3A] An example dispenser is shown. [Figure 3B] An example dispenser is shown. [Figure 3C] An example dispenser is shown. [Figure 3D] An example dispenser is shown. [Figure 4] This illustrates the exemplary operation of an exemplary dispenser. [Figure 5] This shows an exemplary method for manufacturing an exemplary container. [Figure 6A] An example dispenser is shown. [Figure 6B]An example dispenser is shown. [Figure 6C] An example dispenser is shown. [Figure 6D] An example dispenser is shown. [Figure 6E] An example dispenser is shown. [Figure 6F] An example dispenser is shown. [Figure 6G] An example dispenser is shown. [Figure 6H] An example dispenser is shown. [Figure 6I] An example dispenser is shown. [Figure 6J] An example dispenser is shown. [Figure 6K] An example dispenser is shown. [Modes for carrying out the invention]

[0145] Detailed description of exemplary embodiments In the following description of embodiments, references are made to the accompanying drawings, which illustrate specific embodiments that form part of this specification and can be implemented. It should be understood that other embodiments may be used and structurally modified without departing from the scope of the embodiments disclosed.

[0146] The exemplary containers herein may, advantageously, reduce the transportation costs associated with transporting cell culture media, advantageously, increase shipping density, and advantageously, reduce the resources required to store cell culture media before use. In some embodiments, the container contains a powdered solution or culture medium and takes a miniaturized shipping form. When needed for use, the container can be unfolded, and the powder can be mixed with water to provide a desired amount of cell culture media (e.g., cell culture medium) on demand. For example, after removing the container from storage or loading, the user can insert the folded container into a dispenser, the dispenser unfolds the container with the powder, the dispenser adds water, and the dispenser mixes the water and powder to produce a desired amount of cell culture media. Some embodiments of the dispenser herein provide a sterilization light for sterilizing the container before mixing. Furthermore, in some embodiments, the containers of the disclosure contain recyclable or reusable materials, reducing waste and reducing the environmental footprint.

[0147] Figure 1A shows an exemplary container 100. In some embodiments, container 100 is a container for cell culture solution powder (e.g., cell culture medium powder). While the following discussion focuses on cell culture solutions (e.g., cell culture media), it will be understood by those skilled in the art that containers 100, 150, dispenser 200, and dispenser 300 may be used for other purposes. For example, although the examples of disclosure are described in relation to cell culture solutions (e.g., cell culture media), it will be understood that containers 100, 150, dispenser 200, and dispenser 300 may be used more generally for cell growth media. As another example, it will be understood that containers 100, 150, dispenser 200, and dispenser 300 may also be used with non-cell growth solutions such as salt solutions and dry buffer powders.

[0148] Those skilled in the art will acknowledge that for more common applications such as cell growth media and non-cell growth solutions, the requirements, processes, and elements may be adapted to these applications. For example, those skilled in the art will acknowledge that requirements, processes, and elements related to solubility and sterilization may be adapted accordingly.

[0149] As shown in the figures, the container 100 is in an unfolded configuration and may be foldable (for example, into the configuration shown in relation to Figure 1B). The container 100 includes a first end 102, a second end 104, and an intermediate portion 106 attached to the first end 102 and the second end 104. In some embodiments, the first end 102, the second end 104, and the intermediate portion 106 form a region 126 having a variable volume (for example, the volume of the container may vary depending on the configuration of the container 100). In some embodiments, the intermediate portion 106 is bonded to the first end 102 and the second end 104, which advantageously reduces the number of components included in the container. In some embodiments, the first end 102 and the second end 104 are rigid.

[0150] In some embodiments of this specification, a container material can be understood as rigid if it does not deform during transport. In addition, the rigidity of the rigid ends may cause the intermediate portion attached to the rigid ends to unfold in response to a force pulling the rigid ends apart. In some embodiments, one or both of the rigid ends are opaque to prevent light from coming into contact with the internal powder medium or solution and decomposing any of its components, which advantageously reduces the additional resterilization process and reduces mutability to the cell culture medium (e.g., cell culture culture medium). For example, existing containers are not opaque, and sterilization of the container may alter the chemical structure of the cell culture medium, thereby introducing mutability.

[0151] As an exemplary advantage, the miniaturized external form may, advantageously, allow for more efficient transport and reduce agitation of the powder during transport. Furthermore, the rigid first and second ends may provide protection to the contents to be stored in the container (e.g., when the container is in a folded configuration during transport), as the contents (e.g., cell culture medium powder) may be sensitive to contamination. As described and illustrated herein, the rigidity of the first and second ends allows the container to unfold in response to external forces separating the ends, and the rigid ends act as fasteners to a dispenser connected to the container, allowing the container to unfold to a larger volume.

[0152] In some embodiments, the first end 102 has a thickness 114A and the second end 104 has a thickness 114B. In some embodiments, the thicknesses 114A and 114B are each 10 mm. In some embodiments, the rigid first end and the rigid second end have a rectangular cross-section with corners on all four sides, as shown in Figure 1. In some embodiments, the first end 102 and the second end 104 are rectangular. For example, if the desired volume of solution is 500 mL, the rectangular first and second ends have a width of 85 mm and a length of 85 mm. As another example, if the desired volume of solution is 5 L, the rectangular first and second ends have a width of 170 mm and a length of 170 mm. As yet another example, if the desired volume of solution is 500 L, the rectangular first and second ends have a width of 85 cm and a length of 85 cm. As another example, if the desired volume of solution is 2000 L, the first and second ends of the rectangle have a width of 1.35 m and a length of 1.35 m. In some embodiments, the rigid first and second ends are circular. In some embodiments, the surfaces of the rigid first and second ends have a diameter of 73 mm.

[0153] While quantities of specific values ​​(e.g., dimensions, volume, etc.) are provided, it is understood that in some embodiments, the corresponding values ​​may not be exact. For example, dimensions or volumes may actually be functionally equivalent to exact values. As an example, the values ​​in these embodiments may differ from exact values, as long as the difference is within an acceptable range that does not functionally affect the accuracy, operation, and output of the system.

[0154] Although the first end 102 and the second end 104 are described as having dimensions within a specific range, it is understood that other dimensions may exist at the first and second ends without departing from the scope of this disclosure. Furthermore, it is understood that the dimensions described may not necessarily be uniform across the entire first or second end.

[0155] In some embodiments, the first end 102 and / or the second end 104 are opaque to sterilization light. In some embodiments, the sterilization light is ultraviolet, gamma-ray irradiation, or non-heating-based radiation configured to sterilize components used in the manufacturing process of cell culture media (e.g., cell culture mediums) (e.g., components of a cell culture media dispenser, such as exhaust and drain ports). An exemplary advantage is that having sterilization light-opaque container ends protects the cell culture media powder container from sterilization light while the components are being sterilized in the folded configuration (e.g., preventing the properties of the cell culture powder from being altered by the sterilization light).

[0156] In some embodiments, the second end 104 includes an internal surface 116 of the container that tapers downward toward the center of the second end 104 (for example, away from the direction of the first end 102). For example, a rigid second end includes a tapered surface 116 having a minimum thickness at its center, as shown. As an exemplary advantage, the tapered surface 116 may allow a stirrer (e.g., a magnetic stirring rod) to mix the powder in the container and the associated solution more efficiently by guiding the movement of the stirrer as it rotates when the solution is being mixed. The tapered surface 116 may also allow the container to drain more efficiently (e.g., the solution exits the container more efficiently). In some embodiments, a valve is fitted to an outlet 110 (described in more detail herein) located at the second end 104, and when the solution is being mixed, the valve is closed to prevent the solution from exiting the outlet 110. In some embodiments, the valve is configured to allow fluid to flow when pressed down under pressure. In some embodiments, before the production of the cell culture medium, the valve separates the contents from the filter to prevent the contents from clogging the filter.

[0157] In some embodiments, the first end 102 and the second end 104 include at least one of polyethylene, PLA, and PCL. The materials are advantageously included based on the environmental needs of the container user. In some embodiments, the first end 102, the second end 104, and the intermediate portion 106 (described in more detail herein) include one or more recyclable materials. As an exemplary advantage, by using cell culture medium (e.g., cell culture culture medium) powder containers containing recyclable materials, less plastic may be used, or types of plastic with faster decomposition properties may be used (e.g., compared to PET bottles compared to bottles that may be treated as biohazardous waste), waste may be minimized, thus reducing the environmental footprint of the cell culture medium manufacturing process. In some examples, the containers may be recycled (e.g., the same containers may be returned to the manufacturer for resterilization and reuse).

[0158] In some embodiments, the container 100 includes a stirrer 118 positioned in region 126. In some embodiments, the stirrer has a length of 10-20 mm and is rectangular or cylindrical. In some embodiments, for biological production applications (e.g., the container holds 2000 L of cell culture medium), the stirrer has a length greater than 20 mm. A cylindrical stirring rod can advantageously allow for more efficient mixing of the solution compared to other stirring rod shapes. Furthermore, a cylindrical stirring rod can advantageously reduce the likelihood of the middle section splitting during sealing, transport, etc. In some embodiments, the stirrer includes PTFE (e.g., PTFE-based material). In some embodiments, the stirrer 118 includes a magnetic material and is configured to mix the solution associated with the cell culture medium (e.g., cell culture medium) powder present in the container. In some embodiments, the magnetic stirring rod rotates (e.g., clockwise or counterclockwise with respect to surface 116) in response to an applied magnetic field (e.g., a time-varying magnetic field generated by a cell culture dispenser to which the container is connected) to mix the solution associated with the cell culture medium powder (e.g., cell culture medium) present in the container (e.g., mix the powder with supplied water). In some embodiments, the stirring rod may alternate between clockwise and counterclockwise rotations to improve mixing. In some embodiments, the center of the magnetic field is shifted away from the center of the container to move the position of the stirrer away from the center of the second end.

[0159] In some embodiments, the container 100 includes a QR code 120 attached to a first end 102 and associated with the contents to be stored in the container. In some embodiments, the QR code 120 is attached to an access port cover 124, hood, or cap that covers the opening (e.g., access port) of the first end 102. Although the QR code 120 has been described as being attached to the first end 102 or the access port cover 124, it is understood that the QR code 120 may also be attached to a second end 104 or an intermediate portion 106). For example, the QR code 120 may identify a cell culture medium (e.g., cell culture culture medium) powder to be stored in the container, and an associated formulation for preparing a specific cell culture medium (e.g., cell culture culture medium) preparation. A cell culture medium (e.g., cell culture culture medium) dispenser or system may be configured to use a QR code (e.g., by using a scanner, by using a camera) to quickly identify the contents of a container and the formulation associated with the contents, and to manufacture a cell culture medium (e.g., cell culture culture medium) based on the contents (e.g., supplying the appropriate amount of water, supplying the appropriate amount of air, determining the stirring time, determining the pH of the solution). In some embodiments, the dispenser is configured to communicate with a manufacturing facility to provide data on the use of the dispenser. While a QR code is used to describe the identification of the contents to be stored in the container, it is understood that other elements (e.g., barcodes, patterns, radio frequency identification, etc.) may identify the contents to be stored without departing from the scope of this disclosure.

[0160] In some embodiments, the first end 102 and the second end 104 include guides 122 configured to connect the ends to a dispenser having complementary ports for an inlet and an outlet (as shown in Figure 1A, the guides 122 are grooves that connect to complementary tongues on the dispenser to guide the container during insertion). In some embodiments, the container 100 includes another guide (not shown) located opposite the first end 102 from the upper guide 122 shown in Figure 1A, and another guide (not shown) located opposite the second end 104 from the lower guide 122 shown in Figure 1A. Advantageously, the guides 122 may be configured to allow the container to slide into the dispenser (e.g., a cell culture dispenser for producing cell culture media). In some embodiments, the positioning of the guides and inlet may advantageously restrict the placement of the container to a single orientation, allowing the user to insert the container into the machine quickly and efficiently. In some embodiments, the guide 122 firmly holds the container 100 in place so that separating forces can be applied to the ends 102 and 104. In some embodiments, the guide 122 firmly holds the folded container 100 while a dispenser (described further below) applies force to change the container 100 into an unfolded configuration. The guide 122 can also advantageously fix the container and its contents to the dispenser during the mixing process. Features of the guide 122 are described elsewhere in this specification.

[0161] In some embodiments, the container 100 includes an opening (e.g., an access port) located at a rigid first end. In some embodiments, the opening is a sealable opening located at the rigid first end, configured to provide access to a region 126 for adding powder, and then to seal and / or vacuum the region 126 after the powder has been added. In some embodiments, the sealable opening is sealed by an access port cover 124, a sterile hood, or a cap, which is made of the same material as the rigid first end.

[0162] In some embodiments, the intermediate portion 106 is deformable (for example, to the configuration shown with respect to container 150; the intermediate portion is flexible as described herein, and the intermediate portion is foldable as described herein). In some embodiments, the container contains cell culture medium (e.g., cell culture culture medium) powder within region 126.

[0163] In some embodiments, in the unfolded configuration, the middle portion 106 of the container 100 is unfolded. In some embodiments, in the unfolded configuration, the maximum volume of the container 100 (for example, when the middle portion 106 is unfolded) is such that it can hold a specific amount of solution, and this volume is in the range of 500 mL to 2000 L. In some embodiments, in the unfolded configuration, the first end and the second end are separated by a distance 112. For example, if the volume of the container in the unfolded configuration holds a 500 mL solution, the distance 112 is 120 mm. As another example, if the volume of the container in the unfolded configuration holds a 5 L solution, the distance 112 is 300 mm. As yet another example, if the volume of the container in the unfolded configuration holds a 500 L solution, the distance 112 is 1.2 m. As yet another example, if the volume of the container in the unfolded configuration is for mixing a 2000 L solution, the distance 112 is 1.9 m.

[0164] By designing the intermediate section 106 to have a distance 112, mixing and container size can be advantageously optimized. For example, in the case of a container in an unfolded configuration for mixing 500 mL of solution, the distance 112 is 120 mm (e.g., the width of the intermediate section is 85 mm and the length of the intermediate section is 85 mm). The total volume of the exemplary container in the unfolded configuration is 867 mL, allowing the water level of the 500 mL of solution to rise during mixing (e.g., the solution swirls, causing the top surface of the solution to rise higher than the top surface of the 500 mL of solution if left standing), and allowing the intermediate section to fit within the first and second ends while the container is in a folded configuration (e.g., the intermediate section is not so large that it does not fit within the first and second ends).

[0165] The volume of the container in the deployed configuration may vary depending on the application. For example, a container with a deployed configuration volume for mixing 500 mL or 5 L of solution may be used in a laboratory setting to produce smaller amounts of cell culture medium (e.g., cell culture culture medium), while a container with a deployed volume for mixing 500 L or 2000 L of solution may be used in a factory setting (e.g., a bioprocess) to produce larger amounts of cell culture medium (e.g., cell culture culture medium).

[0166] In some embodiments, in the deployed configuration, the container has a height-to-width ratio greater than 1 / 2 (e.g., the height of the container is greater than the width of the container). For example, this ratio is 1.2. As an exemplary advantage, a container with a height-to-width ratio greater than 1 / 2 facilitates the solubilization of the contents within the container (e.g., the distance from the agitator to the contents being mixed decreases across the plane of the second end). For example, by using a 15 mm agitator (e.g., to mix the contents of the container) and rotating the agitator at 2000 RPM, the contents in a container with a height-to-width ratio greater than 1 / 2 (e.g., 1.2) have greater solubility (e.g., measured based on the conductivity of the contents). That is, the contents converge towards optimal solubility faster (e.g., about 400 seconds) compared to a container with a height-to-width ratio less than 1 / 2 (e.g., about 800 seconds).

[0167] In some embodiments, the volume of the container is greater in the unfolded configuration than in the folded configuration. In some embodiments, the distance between the first end and the second end is greater in the unfolded configuration than in the folded configuration. For example, in the unfolded configuration, the distance between the first end and the second end is 120 mm and the volume of the container is 867 mL. In the folded configuration, the distance between the first end and the second end is less than 120 mm (e.g., 0 mm) and the volume of the container is less than 500 mL (e.g., 20 mL).

[0168] In some embodiments, the intermediate portion 106 is flexible. For example, the material of the intermediate portion 106 stretches beyond its stationary shape in response to a tensile force. In some embodiments, the intermediate portion 106 is not flexible. For example, the material of the intermediate portion 106 does not stretch in response to a tensile force (for example, the intermediate portion is accordion-shaped, allowing extension of the intermediate portion when stretched, but the material does not stretch). In some embodiments, the intermediate portion 106 is deformable in response to an external force to change the configuration of the container and the mixing mode associated with the contents of the container.

[0169] In some embodiments, when the container is in an unfolded configuration, the intermediate portion 106 includes a rectangular cross-section (as shown in the figure). For example, in the case of a container with a volume for mixing 500 mL of solution in an unfolded configuration, the rectangular intermediate portion has a width of 85 mm and a length of 85 mm. As another example, in the case of a container with a volume for mixing 5 L of solution in an unfolded configuration, the rectangular intermediate portion has a width of 170 mm and a length of 170 mm. In some embodiments, when the container is in an unfolded configuration, the intermediate portion includes a circular cross-section (not shown). For example, the diameter of the circular cross-section is 73 mm.

[0170] The dimensions of container 100 are described in terms of the distance between two points, but it should be understood that the shape of the intermediate portion does not have to be a perfect cube (for example, the edges of the intermediate portion may not be straight).

[0171] In some embodiments, the intermediate portion 106 is a polyethylene bag, polypropylene bag, or other sterilizable plastic bag attached to the first end 102 and the second end 104. In some embodiments, the intermediate portion 106 is a multilayer bag comprising a polyethylene layer for heat sealing and nylon for reducing gas exchange. In some embodiments, the base of the bag is pressed into or clipped to the second end 104. For example, the second end 104 includes features that allow the base of the bag to be fitted into the second end 104 (e.g., the second end 104 includes a first part and a second part that hold the base of the bag together). In some embodiments, the container includes a first seal (not shown) between a rigid first end and the intermediate portion, and the container includes a second seal (not shown) between a rigid second end and the intermediate portion. The seals can advantageously protect the contents of the container (e.g., protecting powders from contamination and solutions from contamination during mixing).

[0172] In some embodiments, the cell culture medium (e.g., cell culture medium) powder is stored in powder pouches (not shown). For example, the intermediate section 106 is configured to house the powder pouches containing the powder. In some embodiments, the powder pouches contain a mesh of 20-50 μm. In some embodiments, when the container is in an unfolded configuration, the powder pouches are configured to move away from a rigid second end (e.g., to be attached to an intermediate section attached to a rigid first end).

[0173] In some embodiments, the container includes a barrier in the middle section that separates the powder from at least one of the first and second ends. In some embodiments, the barrier is at a certain height from the rigid second end when the container is in an unfolded configuration. In some embodiments, the barrier is positioned at a height selected to allow a predetermined amount of water to be added to the container before dissolution begins.

[0174] The powder pouches and / or barriers may, advantageously, allow the stirrer to remain away from the cell culture medium (e.g., cell culture culture medium) powder in the intermediate section before or during mixing, when sufficient water has been added to the container. When sufficient water has been added before or during mixing, the powder pouches and / or barriers may dissolve, causing the powder to fall to the rigid second end and initiating mixing.

[0175] In some embodiments, the container 100 includes inlets 108A, 108B and an outlet 110. In some embodiments, the inlet 108A or inlet 108B is located at a first end 102, and the outlet 110 is located at a second end 104. In some embodiments, the inlets 108A, 108B and the outlet 110 are fluid-coupled to a region 126 of the container. In some embodiments, two elements are fluid-coupled if a fluid (e.g., water, air, solution) can flow between them. For example, a fluid can flow between the inlet 108 and a region 126 in the container (e.g., water or air can travel from the inlet to region 126), and a fluid can flow between the region 126 in the container and the outlet 110 (e.g., a solution can flow from region 126 to the outlet). In some embodiments, the outlet 110 has a height of 16 mm. In some embodiments, the cell culture medium (e.g., cell culture culture medium) powder and / or agitator is loaded into the container through either the inlet or the outlet. In some examples, the cell culture medium (e.g., cell culture culture medium) powder and / or agitator is loaded into the intermediate section before the container is assembled. In some embodiments, the contents of the container are weighed and blended before being loaded into the container.

[0176] In some embodiments, the outlet 110 is positioned such that, when a filter is connected to the outlet, the connected filter does not physically obstruct the magnetic field generator from aligning with the second end of the container while the magnetic field generator is driving the agitator during mixing. For example, as described with reference to Figure 6H, the outlet of the container 608 is positioned such that, when a filter is connected to the outlet (by the filter connection mechanism 614), the connected filter does not physically obstruct the magnetic field generator 616.

[0177] In some embodiments, a material seals the outlet 110. In some embodiments, the material sealing the outlet is different from the material of the surface 116. In some embodiments, the material sealing the outlet includes low-density polyethylene. In some embodiments, the material sealing the outlet is configured to crack or rupture and open in response to an applied pressure (e.g., 5-10 psi) above a pressure threshold (e.g., 2-5 psi). In some embodiments, the material sealing the outlet is 1 cm 2 The outlet-blocking material has an area of ​​. The outlet-blocking material can advantageously keep the contents of container 100 (e.g., cell culture medium powder) sterile until the contents are to be used to manufacture a solution. During manufacture, when the solution is ready to exit the container, a pressure exceeding a pressure threshold is applied inside the container (e.g., by using compressed air, by folding the container 100), causing the material to tear or rupture, allowing the solution to exit the container 100 through the outlet 110. In some embodiments, before the manufacture of the cell culture medium, the outlet-blocking material separates the contents from the filter and prevents the contents from clogging the filter.

[0178] In some embodiments, the container 100 has a larger volume (e.g., 500 L, 2000 L) and is used in conjunction with a bioreactor. For containers with larger volumes, the cell culture medium powder (e.g., cell culture culture medium) can be loaded into the container from bags (e.g., 20 L) and drums through the opening of the container (e.g., the opening at the first end of the container).

[0179] In some embodiments, inlets 108A, 108B are located on the first end 102. In some embodiments, inlets 108A, 108B are located on the same side of the first end 102. In some embodiments, inlets 108A, 108B are parallel to each other so as to connect to corresponding attachments on the dispenser while the container 100 is inserted into the dispenser. In some embodiments, one of the inlets 108A, 108B is an air intake and the other is a water inlet. In some embodiments, the container includes one inlet, which is an air intake and / or water inlet. In some embodiments, the air intake is configured to connect to an exhaust port of a cell culture medium (e.g., cell culture culture medium) dispenser. In some embodiments, a HEPA filter is located at the air intake for sterilization by a controller airflow. In some embodiments, the water inlet is configured to connect to a drain port of a cell culture medium (e.g., cell culture culture medium) dispenser. In some embodiments, the water inlet is configured to transport United States Pharmacopeia (USP) grade water or highly purified water suitable for the production of cell culture media from a cell culture medium (e.g., cell culture culture medium) dispenser to an intermediate portion of the container.

[0180] As an example of an advantage, a dispenser configured to connect to the inlet and outlet of a container (e.g., a cell culture medium dispenser) can be better aligned with the container, even for different types of culture medium powders, because the fixed positioning of the inlet and outlet reduces the complexity of alignment between the container and the dispenser.

[0181] In some embodiments, the container 100 includes an adapter (not shown) attached to inlet 108A or inlet 108B. In some embodiments, the adapter includes at least one of a Luer lock adapter and a PVT adapter. As an exemplary advantage, the adapter allows for a simple but secure interface between the container and a cell culture medium (e.g., cell culture culture medium) dispenser.

[0182] In some embodiments, the container 100 includes a filter (not shown). In some embodiments, the filter is a sterile filter. In some embodiments, the filter is a filter cartridge. During mixing, the filter may be used to filter out undesirable by-products in the solution as the solution exits the container (e.g., through the outlet 110). In some embodiments, the filter has a pore size of 0.22 μm to 1 μm. In some embodiments, the filter is separately attached to the outlet 110. In some embodiments, the filter is integrated with the outlet 110 (e.g., the filter is part of the container assembly, the filter is part of the base of the container, the filter is pre-attached to the outlet before the cell culture medium is prepared, the filter is part of the outlet), which advantageously reduces the need to separately attach the filter to the outlet.

[0183] In some embodiments, the filter is supplied by a dispenser (e.g., dispenser 300, cell culture medium dispenser). For example, the filter is stored in the dispenser and the dispenser supplies the filter in response to an input (e.g., mechanical or electrical input from the user, determined by the dispenser). In some embodiments, the filter is placed on the outlet 110 of the container (e.g., using the spring mechanism described). In some embodiments, the filter is manually placed on the outlet 110 of the container. In some embodiments, the dispenser automatically places the filter on the container (e.g., before the solution leaves the container, when the solution is ready to be transferred to another container for storage).

[0184] As an example of the advantages, by providing a separate filter and installing it on the container at the time of use, the size of the container can be reduced (for example, to improve transport efficiency), and the possibility of damage or contamination of the contents of the container can be reduced. Furthermore, different types and sizes of filters may be provided, allowing for the selection of a filter more suitable for each application (for example, including the appropriate filter in the container may not be cost-effective or size-effective).

[0185] In some embodiments, the outlet 110 is configured to be attached to a discharge pipe (not shown). To optimize transport volume, the discharge pipe may be attached after dispatch and before mixing. In some embodiments, during or after mixing, the discharge pipe leads the solution to a second container for storing the solution. In some embodiments, the discharge pipe includes a Luer lock fitting, a sterilizable plastic tube, and a sealing nozzle. In some embodiments, the discharge pipe includes a filter used to filter out undesirable by-products in the solution as the solution exits the container. In some embodiments, the discharge pipe is bendable or flexible. A bendable or flexible discharge pipe may allow the tube to be transported more efficiently and may allow the tube to be more easily led to a second container for storing the solution during or after mixing.

[0186] In some embodiments, the outlet 110 is attached to a spring mechanism. This allows the outlet to open and close automatically in response to the insertion of a filter (e.g., a cell culture medium supplied by a dispenser 300) or in response to another force associated with the dispensing of a mixed solution.

[0187] In some embodiments, the container includes a pH sensor (not shown) that senses the pH level associated with the contents to be stored in the container. The pH level of the culture medium powder may, advantageously, be monitored throughout its lifespan (e.g., from when it is loaded into the container until it is shipped and mixed) to ensure product quality. In some embodiments, the culture medium powder is pre-granulated by spray-adding a predetermined amount of a pH corrector (e.g., an acid, a base). For example, the pH corrector may be added to the culture medium powder on a fluidized bed to facilitate drying and incorporation of the corrector into the powder. In some embodiments, the container includes a dissolution sensor (not shown) configured to determine the dissolution level associated with the contents of the container (e.g., when the solution is sufficiently mixed).

[0188] Although container 100 is described with respect to the elements shown in Figure 1A, the container may include more or fewer elements than expressly described without departing from the scope of the disclosure. For example, although container 100 is shown having two entrances, it will be understood that a different number of entrances may be included in the container without departing from the scope of the disclosure.

[0189] Figure 1B shows an exemplary container 150. In some embodiments, the container 150 is a container for cell culture medium powder (e.g., cell culture medium). Although the container 150 is a container for cell culture medium powder in some embodiments, it is understood that the container 150 may be used for other purposes. As shown in the illustration, the container 150 is in a folded configuration and can be unfolded (e.g., into the configuration shown with respect to Figure 1A). In some embodiments, in the folded configuration, the middle section 156 is enclosed by a first end 152 and a second end 154, and the contents are fixed within the middle section (e.g., culture medium powder, a stirrer, an element that can be stored in the container described with respect to Figure 1).

[0190] As an exemplary advantage, the contents (e.g., cell culture medium powder) can remain in the same foldable and unfoldable container from shipment to formulation, eliminating the need to transfer the contents from one container to another and potentially reducing the risk of contamination. Another exemplary advantage is that the foldable nature of the container allows for easy removal of the contents (e.g., by squeezing out the contents after use), making the container more recyclable or easier to re-sterilize and reuse.

[0191] In some embodiments, a container is changed from an unfolded configuration to a folded configuration, or from a folded configuration to an unfolded configuration, using a tool or machine. For example, when the container is in an unfolded configuration (e.g., when the contents of the container are loaded), the first and second ends of the container slide into or are fixed in slots of a tool or machine. The slots of the machine are spaced apart from each other at a certain distance in height from the container in the unfolded configuration. The tool or machine can change the container from an unfolded configuration to a folded configuration (e.g., after the container is ready to be packaged, shipped, or stored) by reducing the distance between the slots (e.g., the slots are controlled by a lowering mechanism to reduce the distance between the slots).

[0192] In some embodiments, container 150 includes elements similar to those described with respect to Figure 1A (for example, container 150 is container 100 but in a folded configuration). Therefore, for brevity, these similar elements will not be described again with respect to Figure 1B. For example, the first end 152 corresponds to the first end 102, the second end 154 corresponds to the second end 104, the middle section 156 corresponds to the middle section 106, the inlets 158A and 158B correspond to the inlets 108A and 108B, the outlet 160 corresponds to the outlet 110, the QR code 170 corresponds to the QR code 120, and the guide 172 corresponds to the guide 122.

[0193] In some embodiments, in the folded configuration, the middle portion 156 of the container 150 is folded. In some embodiments, in the folded configuration, the first end and the second end are in contact (for example, when the container is in the folded configuration, the distance between the first end and the second end is 0 mm). In some embodiments, the thickness of the container in the folded configuration is 20 mm. In some embodiments, the shipping thickness of the container in the folded configuration (e.g., the thickness of the container and the height of the outlet) is 36 mm.

[0194] In some embodiments, the container 150 is configured to be stacked with another container. In some embodiments, the surface of the first end 152 is configured to interface with the surface of the second end 154. In some embodiments, the top surface of the first end 102 of the first container is configured to interface with the bottom surface of the second end 154 of the second container. In some embodiments, the top surface of the rigid first end and the bottom surface of the rigid second end are flat, allowing adjacent containers to be stacked. In some embodiments, the top surface of the rigid first end and the bottom surface of the rigid second end include features (e.g., grooves, guides, notches, inserts) that allow the two surfaces to interface tightly, allowing multiple containers to be efficiently and tightly packed for transport and storage (e.g., compared to space-inefficient, bulkier containers). Thus, by using the containers of disclosure to store cell culture powder, it is advantageous that the transport costs associated with transporting the powder can be reduced, the shipping density can be increased, and the resources (e.g., storage space) required to store the powder before use can be reduced. In some embodiments, during transport or storage, the outlet 160 of the container 150 is placed within protective packaging to prevent damage to the outlet (and its interface with the filter).

[0195] In some embodiments, the middle section 156 of the container 150 is vacuum-sealed to prevent contamination and maximize the shelf life of the container contents. For example, the first end includes an opening (e.g., an access port) which is configured to allow a vacuum to be created (e.g., allowing a tube to remove air from the container area 126). In some embodiments, after the air has been removed from the middle section, the middle section is sealed (e.g., the opening allows access to the portion of the bag to be sealed), and the opening is covered by an access port cover 174, a hood, or a cap to ensure a vacuum in the middle section.

[0196] In some embodiments, barriers are used to prevent contamination, extend the shelf life of container contents during transport and storage, or separate different contents within a container. In some embodiments, the barrier is formed by an intermediate section 156 when the container is in a folded configuration. For example, the intermediate section 156 includes a foldable bag. When the container is in a folded configuration, the bag is folded such that the folds of the bag function as a sealed barrier for the contents within the barrier (for example, the contents are separated by the barrier from at least one of the first and second ends). In some embodiments, the sealed barrier within the intermediate section 156 is configured to maintain a vacuum within the intermediate section 156 when the container is in a folded configuration.

[0197] In some embodiments, the barrier of the intermediate portion 156 is formed when the container changes from an unfolded configuration to a folded configuration (e.g., when the container contents are loaded, after the contents are loaded, after the first contents are loaded, before the second contents are loaded). In some embodiments, the intermediate portion is folded in a specific manner by a tool (e.g., an off-center slit through which the intermediate portion passes) such that the folds of the intermediate portion (e.g., folds of a bag) form a barrier when the container changes from an unfolded configuration to a folded configuration (e.g., during a method of manufacturing a cell culture vessel, such as the manufacturing method described herein).

[0198] In some embodiments, the barrier of the intermediate section 156 separates the first and second contents within the container while the container is in a folded configuration. When the container changes from a folded configuration to an unfolded configuration (for example, before the contents are mixed), the barrier opens, allowing the first and second contents to come together in the intermediate section.

[0199] Although container 150 is described with respect to the elements shown in Figure 1B, the container may include more or fewer elements than expressly described without departing from the scope of the disclosure. For example, although container 150 is shown having two entrances, it will be understood that a different number of entrances may be included in the container without departing from the scope of the disclosure.

[0200] In some embodiments, the first end 152 and the second end 154 include guides 172 configured to connect the ends to a dispenser configured to connect to an inlet and an outlet. In some embodiments, the guides 172 are located at both ends of the first end 102 and at both ends of the second end 154, as shown in the figure. Advantageously, the guides 172 may be configured to allow the container to slide into a dispenser configured to connect to the container (e.g., a cell culture medium dispenser connected to a container for producing cell culture medium), so that the container is securely positioned within the dispenser.

[0201] In some embodiments, before preparing the cell culture medium (e.g., cell culture culture medium), the guide 172 slides into the slot of the cell culture medium (e.g., cell culture culture medium) dispenser. In some embodiments, when the container is placed in the cell culture medium (e.g., cell culture culture medium) dispenser (e.g., slides into the slot of the cell culture medium (e.g., cell culture culture medium) dispenser like a cassette tape), the container is in a folded configuration. In some embodiments, after the container is firmly placed in the dispenser, the guide 172 holds the rigid first end and the rigid second end in a fixed position relative to the slot with which the guide 172 interfaces. In some embodiments, with the guide 172 holding the rigid first end and the rigid second end in a fixed position relative to the slot, the cell culture medium (e.g., cell culture culture medium) dispenser causes the slot to split vertically so that the intermediate portion 156 unfolds. Thus, the containers 100, 150 advantageously allow the contents to be efficiently transported and adapted to machinery for culture medium formulation.

[0202] In some embodiments, the first end 152 and the second end 154 are configured such that when the container is in an unfolded configuration, the first end 102 is rotated by a first angle from the second end 154 with respect to the orientation of the first end 102 and the second end 154 to lock the container 150 in a folded configuration (e.g., rotated like a cap). In some embodiments, the container 150 is locked in a folded configuration by rotating the first end 102 clockwise relative to the second end 154, and the container 150 is unlocked from a folded configuration by rotating the first end 102 counterclockwise relative to the second end 154 (e.g., the container can be unfolded).

[0203] In some embodiments, the first end 152 includes a notch configured to engage with an opening in the second end 154 and lock the container in a folded configuration. In some embodiments, the first end 152 includes a notch that can interface (e.g., engage, connect, link) with a corresponding opening on the second end 154 to lock the container in a folded configuration. The user may separate the first end 152 and the second end 154 from each other to separate the two rigid ends from each other.

[0204] By enabling the locking of the first and second ends when the container is in a folded configuration, the contents of the container can be advantageously secured during transport and / or storage. In some embodiments, the middle portion of the container is under vacuum when the container is in a folded configuration. The vacuum in the middle portion can be advantageously maintained by enabling the container to be locked.

[0205] Figure 2 shows an exemplary dispenser 200. In some embodiments, the dispenser 200 is a cell culture medium (e.g., cell culture culture solution) dispenser. For example, a cell culture medium (e.g., cell culture solution) dispenser is used with smaller containers (e.g., 500 mL, 5 L) (e.g., in a laboratory). In another example, a cell culture medium (e.g., cell culture solution) dispenser is used with larger containers (e.g., 500 L, 2000 L) (e.g., in a bioreactor). As shown in the figure, the dispenser 200 includes a filtration system 202, a first handling system 204, and a second handling system 206. In some embodiments, the dispenser 200 includes the first handling system 204 and the second handling system 206, and the filtration system 202 is included in a different dispenser.

[0206] In some embodiments, the filtration system 202 is an ultrapure water (UPW) filtration system. For example, the UPW filtration system includes a water inlet configured to receive water (e.g., UPW water, USP water, water from an external source). In some embodiments, the water passes through the UPW filter of the filtration system and enters the reservoir of the filtration system 202. In some embodiments, the water circulates between the filter and the reservoir to maintain or increase the purity of the water. In some embodiments, the water in the filtration system is supplied to a first handling system 204 (e.g., pumped).

[0207] In some embodiments, the first handling system 204 includes a container chamber, an inlet, a container handling mechanism, and a mixing system. In some embodiments, the container chamber is an enclosure for inserting, unfolding, and / or folding containers (e.g., container 100, container 150, container 308, container 608). In some embodiments, the container chamber is sterilized (e.g., using sterile light). For example, before mixing the contents of the containers, the container chamber is sterilized (e.g., by the dispenser 200, or by a device other than the dispenser 200). In some embodiments, the dispenser 200 includes a heating chamber for heating water and air to sterilize the dispenser's piping. In some embodiments, the dispenser 200 includes an ozone generator for removing contaminants in the chamber (e.g., to purify water, to purify air).

[0208] In some embodiments, the inlet of the first handling system 204 is an inlet configured to connect to the inlet of the container (e.g., inlet 108A, inlet 108B, inlet 158A, inlet 158B). In some embodiments, the inlet supplies water and / or air to the container (e.g., from the filtration system 202). In some embodiments, the inlet of the first handling system 204 is advantageously aligned with the inlet of the container when the container is inserted, allowing for more efficient placement of the container into the dispenser. In some embodiments, the inlet is cleaned or sterilized (e.g., using sterile light). For example, before mixing the contents of the container, the inlet is cleaned or sterilized (e.g., by the dispenser 200, or by a device other than the dispenser 200).

[0209] In some embodiments, the container handling mechanism includes an insertion mechanism (e.g., slot 304) configured to accept a container (e.g., a slot is configured to align with guides on the container (e.g., guides 122, guide 152)) when the container is inserted, and to secure the container after insertion. In some embodiments, the insertion mechanism includes two parts (e.g., slots 304A, 304B) configured to be spaced apart. Since the container is secured to the insertion mechanism, when the container is in a folded configuration, the insertion mechanism unfolds the container as the insertion mechanism moves apart. In some embodiments, the insertion mechanism includes two parts (e.g., slots 304A, 304B) configured to be closer together. Since the container is secured to the insertion mechanism, when the container is in an unfolded configuration, the insertion mechanism folds the container as the insertion mechanism moves closer together.

[0210] In some embodiments, the mixing system includes hardware for driving a stirrer used to mix the contents of a container. For example, the mixing system includes a magnetic field generator for driving a magnetic stirrer for mixing. As an example, the magnetic field generator generates a time-varying magnetic field that drives or induces the stirrer to rotate as intended to mix the contents of the container.

[0211] In some embodiments, the first handling system 204 supplies a filter (e.g., a filter cartridge). For example, the filter is supplied from a dispenser 200 and loaded onto a rail aligned with the container. The filter is connected to the outlet of the container, and the contents of the container (e.g., cell culture medium) pass through the filter before dispensing the contents into a second container. In some embodiments, after the contents have been dispensed into the second container, the first handling system 204 discards the used filter. In some embodiments, the filter is integrated with the outlet, which advantageously reduces the need to separately attach the filter to the outlet and / or discard the filter. Thus, the first handling system 204 does not separately attach the filter to the outlet or arrange the filter separately.

[0212] In some embodiments, after the contents have been dispensed into the second container, the first handling system 204 disposes of the used container. In some embodiments, the used container is discharged and reused as described herein.

[0213] In some embodiments, the second handling system 206 includes a second container chamber and a second container access mechanism. In some embodiments, the second container chamber is an enclosure for inserting a second container (e.g., container 306, culture bottle) and for dispensing contents from a first container (e.g., container 100, container 150, container 308, container 608) into the second container. In some embodiments, the container chamber is sterilized (e.g., using sterile light). For example, before dispensing contents from the first container, the second container chamber is sterilized (e.g., by dispenser 200, or by a device other than dispenser 200).

[0214] In some embodiments, the second container access mechanism includes a motor-driven element configured to loosen the screw of the cap of the second container (for example, according to a determination that the solution in the container is ready for dispensing). In some embodiments, while the cap of the second container 306 is being removed, the second container is lowered (for example, by the second container access mechanism) to separate the cap from the second container. In some embodiments, the second container access mechanism includes a motor-driven element configured to tighten the screw of the cap of the second container (for example, according to a determination that the solution in the container has been completely transferred). In some embodiments, the motor-driven element for tightening and loosening the cap screw is the same element. In some embodiments, while the cap of the second container is being attached, the second container is lifted (for example, by the second container access mechanism) to engage the cap with the second container. In some embodiments, the interface between the second container access mechanism and the cap of the second container is adjustable to accommodate different container sizes (for example, the diameter of the interface is adjustable).

[0215] In some embodiments, the dispenser 200 includes a user interface, hardware, and software for operating the dispenser. In some embodiments, the dispenser 200 includes a scanner (e.g., a QR code scanner) for scanning information on a container (e.g., scanning QR code 120, scanning QR code 170). Advantageously, the commands for operating the dispenser 200 can be updated by software and firmware updates.

[0216] Figures 3A–3D show exemplary dispensers 300. In some embodiments, exemplary dispenser 300 is dispenser 200. In some embodiments, dispenser 300 is a cell culture medium (e.g., cell culture solution) dispenser. Although exemplary dispenser 300 is described in relation to smaller containers (e.g., 500 mL), it is understood that larger containers (e.g., 5 L, 500 L, 2000 L) may be used in a similar manner (e.g., unfolded, their contents mixed) without departing from the scope of the present disclosure. For example, larger containers may be used to prepare larger volumes of solution for bioreactors.

[0217] Figure 3A shows the dispenser 300 before the placement of cell culture medium (e.g., cell culture culture medium) powder containers (e.g., container 100, container 150). In some embodiments, the dispenser 300 includes a display configured to present a GUI 302 and a slot 304. In some embodiments, the dispenser 300 is configured to dispense the cell culture medium into a second container 306.

[0218] In some embodiments, the GUI 302 is displayed on a touchscreen and configured to receive input for the production of a cell culture medium (e.g., cell culture culture medium). In some embodiments, before mixing, the GUI 302 prompts the user to place or insert containers (e.g., container 100, container 150) containing the culture medium powder to be used to produce the cell culture medium (e.g., cell culture culture medium). In some embodiments, the GUI 302 includes user-configurable choices that define aspects of the cell culture medium (e.g., cell culture culture medium) production process.

[0219] In some embodiments, slot 304 is configured to receive containers (e.g., container 100, container 150) containing culture medium powder used to prepare cell culture media (e.g., cell culture medium). In some embodiments, container guides (e.g., guides 122, guides 172) are configured to interface with the slot so that the container can be slid into the slot using the guides. In some embodiments, once the container has slid fully into the slot, slot 304 secures the container and prevents it from moving (e.g., during mixing). In some embodiments, dispenser 300 includes intake and drain ports (not indicated) that can be connected to inlets (e.g., inlets 108A, 108B, inlets 158A, 158B) when the container slides into the slot or before the contents of other containers are mixed. In some embodiments, the exhaust and drain ports are aligned with the inlets (e.g., inlets 108A, 108B or 158A and 158B) such that when the container is slid into the slot, the dispenser outlet connects to the container inlets without any additional adjustments to align the container with the dispenser. In some embodiments, the exhaust and drain ports of the dispenser 300 supply air and water (e.g., USP grade water, water suitable for the production of cell culture media).

[0220] Although the slot 304 of the dispenser 300 is described as guiding the container 308 during insertion and holding the container 308 securely during deployment, it is understood that the insertion of the container may be guided, or other components may be used to keep the container fixed during deployment. For example, components having different mechanical properties (e.g., enabling the container to snap into the dispenser), electromagnetic properties, or adhesive properties may be used with or in place of the slot 304.

[0221] In some embodiments, the second container 306 stores a solution (e.g., a solution prepared by the dispenser 300) (e.g., a culture medium bottle) associated with the contents of the installed or inserted container 308. In some embodiments, the solution exits the container's outlet (e.g., outlet 110, outlet 160) before being transferred to the second container 306.

[0222] Figure 3B shows the dispenser 300 with a cell culture medium (e.g., cell culture culture medium) powder container 308 installed or inserted into the dispenser. Although container 308 is described as a cell culture medium (e.g., cell culture culture medium) powder container used with a cell culture dispenser, it is understood that container 308 may be used for other purposes. In some embodiments, the cell culture medium (e.g., cell culture culture medium) powder container 308 is container 100 or container 150. As shown in the figure, container 308 is in a folded configuration, but container 308 may be installed or inserted into the dispenser 300 in other configurations. In some embodiments, container 308 is installed or inserted by sliding the container into the slot 304 using guides on the container (e.g., guide 122, guide 172). Once the container 308 is placed in or fully inserted into the dispenser, the rigid ends of the container 308 (e.g., first end 102, second end 104, first end 152, second end 154) are fixed relative to the slot 304. In some embodiments, the exhaust and drain ports of the dispenser 300 are also aligned with the inlets 108A, 108B or 158A, 158B so that when the container is slid into the slot, the dispenser outlet connects to the container inlet without any additional adjustments to align the container with the dispenser. In some embodiments, the exhaust and drain ports of the dispenser 300 are supplied with air and water (e.g., USP grade water, water suitable for the production of cell culture media). In some embodiments, (for example, when the container 308 is in an unfolded configuration as shown in Figure 3D) alignment and connection between the exhaust and drain ports of the dispenser 300 and the inlets 108A, 108B or inlets 158A, 158B are subsequently performed.

[0223] In some embodiments, when the container 308 is set up or inserted, the GUI 302 is updated to prompt the user to start the cell culture manufacturing process. In some embodiments, the GUI 302 is updated to display selectable options for starting the cell culture manufacturing process.

[0224] In some embodiments, the contents of container 308 are identified by dispenser 300, and the cell culture manufacturing process is carried out based on the identification of the contents in container 308. In some embodiments, the contents are identified using a QR code on container 308 (e.g., QR code 120, QR code 170). In some embodiments, dispenser 300 includes a scanner or camera configured to identify the contents of the container by scanning identification information on the container (e.g., QR code, barcode, patterned code, radio frequency identification). In some embodiments, the camera of dispenser 300 or a second camera is configured to monitor the chamber of the dispenser, and images or videos from the camera may be viewed on the display of dispenser 300 or on the display of a second device communicating with dispenser 300. For example, the sterility of the chamber is monitored based on the camera, and based on the monitoring, dispenser 300 performs a sterilization operation according to a determination that the chamber requires sterilization. As another example, the production of cell culture medium is monitored using a camera, and based on the monitoring, the dispenser 300 adjusts production parameters (e.g., stirrer speed, mixing time). In some embodiments, a second device (e.g., a mobile device) is used to scan identification information (e.g., the second device scans the identification information using an application and communicates the identification information with the dispenser 300). In some embodiments, the GUI 302 presents information about the contents in the container 308 identified by the dispenser 300. In some embodiments, the GUI 302 presents selectable or configurable options for the user to input or update information about the identified contents.

[0225] Figure 3C shows the dispenser 300 when a cell culture medium (e.g., cell culture culture medium) powder container 308 is being unfolded. In some embodiments, the dispenser 300 unfolds the cell culture medium (e.g., cell culture culture medium) powder container 308 in response to an input associated with a command requesting to start a cell culture medium (e.g., cell culture culture medium) manufacturing process. In some embodiments, as described with respect to Figure 3B, the rigid ends of the container (e.g., first ends 102, 152, second ends 104, 154) are locked in a fixed position in their respective slots 304. More specifically, the rigid first end of the container 308 is locked in a fixed position in slot 304A, and the rigid second end of the container 308 is locked in a fixed position in slot 304B.

[0226] In some embodiments, when the dispenser 300 unfolds the container 308, the dispenser moves slots 304A and 304B away from each other in a direction parallel to the intended unfolding direction (e.g., perpendicularly). As the rigid ends are locked in place in their respective slots, the intermediate portions of the container 308 (e.g., intermediate portion 106, intermediate portion 156) unfold (towards an unfolded configuration of the container, such as the configuration shown in Figure 1), and the volume within the container increases as the rigid ends move further away from each other.

[0227] In some embodiments, when the container 308 is being dispensed by the dispenser 300, the GUI 302 displays the progress of the cell culture medium (e.g., cell culture culture medium) manufacturing process. In some embodiments, the current process, container contents, solution being manufactured, and progress are shown in the GUI 302.

[0228] Figure 3D shows the dispenser 300 when the cell culture medium (e.g., cell culture culture medium) powder container 308 is in an unfolded configuration. In some embodiments, the unfolded configuration of the cell culture medium (e.g., cell culture culture medium) power container 308 is the unfolded configuration of the container 100 described with respect to Figure 1.

[0229] In some embodiments, compared to Figure 3C, slots 304A and 304B are further apart from each other, resulting in a larger volume within the container. In some embodiments, at this point shown in Figure 3D, slots 304A and 304B (behind GUI 302) stop moving away from each other. In some embodiments, the desired volume is reached by achieving the corresponding separation between the rigid ends of the container. In some embodiments, the volume of the container is necessary to thoroughly mix the contents within container 308 and the associated solution.

[0230] In some embodiments, when the desired volume of the container 308 is reached and slots 304A and 304B stop unfolding the container 308, the dispenser 300 aligns and connects the exhaust port and drain port of the dispenser 300 with the inlets 108A, 108B or inlets 158A, 158B.

[0231] In some embodiments, after the exhaust and drain ports of the dispenser 300 are aligned and connected to the inlet of the container 308, mixing of the solution begins. In some embodiments, the exhaust and drain ports of the dispenser 300 begin supplying an appropriate amount of air and water (e.g., USP grade water, water suitable for the production of cell culture media) into the container 308. In some embodiments, in addition, the dispenser 300 generates a magnetic field near the rigid second end of the container 308 (e.g., the rigid end connected to slot 304B) to start the rotation of the agitator contained in the container (e.g., clockwise with respect to the surface of the rigid second end, counterclockwise with respect to the surface of the rigid second end).

[0232] In some embodiments, the contents of a container are mixed using a stirrer for a predetermined amount of time. In some embodiments, the amount of time is determined based on the cell culture medium being prepared (e.g., cell culture medium). In some embodiments, identification information on the container 308 (e.g., QR code, barcode, patterned code, radio frequency identification) includes information about the mixing time, and this information is input to the dispenser 300 when the contents of the container are identified.

[0233] In some embodiments, when the solution is determined to be complete (for example, after a predetermined amount of time has elapsed, or when the solubility of the liquid is determined to be achieved by measurement), the solution is discharged from the outlet of container 308 (e.g., outlet 110, outlet 160) into the second container 306. In some embodiments, the solution passes through a filter, which is contained within container 308. In some embodiments, before the solution is discharged, the dispenser 300 opens the cover (e.g., cap) of the second container 306 to allow the solution to be transferred from container 308 to the second container 306. For example, the dispenser 300 includes a motor-driven element configured to loosen the screw of the cap of the second container 306 in accordance with the determination that the solution in container 308 is ready for dispensing. In some embodiments, while the cap of the second container 306 is being removed, the second container is lowered to separate the cap from the second container 306.

[0234] In some embodiments, after the solution is transferred to the second container 306, the solution is suitable for or transferred to promote cell growth. Although the contents of the container are described in relation to cell growth (e.g., cell culture medium), it is understood that the description of the contents of the container is not limited to cell growth. For example, cell growth may include tissue growth. As another example, cell culture may include tissue culture.

[0235] In some embodiments, the dispenser 300 performs the reverse process (e.g., after the solution is prepared and ready to be dispensed in the second container 306). For example, the dispenser 300 includes a motor-driven element configured to tighten the screw of the cap of the second container 306 according to a determination that the solution in the container 308 has been completely transferred. In some embodiments, while the cap of the second container 306 is attached, the second container is lifted to fit the cap onto the second container 306. In some embodiments, the interface between the dispenser 300 and the cap of the second container 306 is adjustable to accommodate different container sizes (e.g., the diameter of the interface is adjustable).

[0236] In some embodiments, the dispenser 300 includes an enclosure or chamber (not shown). As an exemplary advantage, the enclosure allows for a sterile environment during solution preparation or when the solution is transferred from a cell culture fluid (e.g., cell culture medium) container. In some embodiments, the dispenser 300 includes a heating chamber that heats water and air to sterilize the dispenser's tubing. In some embodiments, the dispenser 300 includes an ozone generator for removing contaminants within the chamber (e.g., for purifying water and purifying air).

[0237] In some embodiments, when the container 308 is deployed to its deployed configuration and the solution begins to mix, the GUI 302 presents the progress of the cell culture fluid (e.g., cell culture medium) manufacturing process. In some embodiments, the current step, container contents, solution being manufactured, and progress are presented to the GUI 302.

[0238] In some embodiments, the container 308 is used within a bioreactor. Instead of the second container 306, as shown, the solution made from the contents of the container 308 is transferred to a bioprocess container (e.g., the bioreactor provides a connection that allows fluid to flow from the container 306 to the bioprocess container).

[0239] Figure 4 shows an exemplary method of operation 400 for an exemplary dispenser. In some embodiments, method 400 is a method of operation for container 100, container 150, container 308, or container 608. In some embodiments, method 400 is performed using dispenser 300 or dispenser 600. Although method 400 is shown as including the steps described, it is understood that different sequences of steps, additional steps, or fewer steps may be performed to operate the exemplary containers without departing from the scope of the present disclosure. In some embodiments, the steps of method 400 are performed in response to the selection of a GUI object on the dispenser's GUI (e.g., GUI 302, GUI 602).

[0240] In some embodiments, method 400 includes the step (step 402) of receiving a first container in a folded configuration within a dispenser. For example, dispenser 300 receives a container 308 inserted into the dispenser, as described with respect to Figure 3B. In some embodiments, the first container is inserted after the dispenser door (e.g., door 610) is opened, as described with respect to Figure 6B.

[0241] In some embodiments, method 400 includes a step of sterilizing the dispenser. For example, before inserting the container 308 or before mixing, the components of the dispenser 300 (e.g., the chamber into which the first container 308 is inserted, the chamber into which the second container 306 is placed, the inlet of the dispenser 300) are sterilized (e.g., by the dispenser 300, or by a device other than the dispenser 300). In some embodiments, the components are sterilized using sterile light (e.g., UV light). As another example, the dispenser is sterilized after the cell culture medium has been prepared and dispensed. In some embodiments, the dispenser includes a heating chamber for heating water and air to sterilize the dispenser's piping. In some embodiments, the dispenser includes an ozone generator for removing contaminants in the chamber (e.g., to purify water, to purify air).

[0242] In some embodiments, method 400 includes a step (step 404) of unfolding the first container into an unfolded configuration. For example, dispenser 300 unfolds container 308 as described with respect to Figure 3C. In another example, dispenser 600 unfolds container 608 as described with respect to Figure 6G.

[0243] In some embodiments, method 400 includes a step of receiving input. In some embodiments, the input is a selection on the dispenser's GUI, and the first container is unfolded in response to the receipt of the input. For example, the user provides input by making a selection on GUI 302, and in response to that selection, dispenser 300 unfolds container 308 and mixing begins. In some embodiments, the input is a QR code scan of the QR code of the first container, and the first container is unfolded in response to the receipt of the input. For example, the QR code of container 308 (e.g., QR code 120, QR code 170) is scanned (e.g., by dispenser 300, by a device different from device 300), and in response to the scan, dispenser 300 unfolds container 308 and mixing begins. As another example, as illustrated with reference to Figure 6C, after container 608 has been inserted into dispenser 600, the user selects GUI object 622C to proceed with input for preparing the cell culture medium.

[0244] In some embodiments, Method 400 includes the step of injecting water into the first container (step 406) while the first container is being unfolded or in an unfolded configuration. For example, as described with reference to Figures 3C and 3D, the dispenser 300 injects water (e.g., USP-grade water) into the container 308 while the dispenser 300 is unfolding the container 308 or in an unfolded configuration. In some embodiments, Method 400 includes the step of injecting air into the first container while the first container is being unfolded or in an unfolded configuration. For example, as described with reference to Figures 3C and 3D, the dispenser 300 injects air into the container 308 while the dispenser 300 is unfolding the container 308 or in an unfolded configuration. As another example, as described with reference to Figure 6H, water is injected into the container 608.

[0245] In some embodiments, method 400 includes the step of applying baffles to a first container. In some embodiments, baffles are applied to the first container while the first container is being unfolded or while the first container is in an unfolded configuration. For example, as described with respect to Figure 6H, baffles are applied to the middle portion of container 608 to support the middle portion of the container while the cell culture medium solution is being prepared. In some embodiments, baffles are applied before the unfolding of the first container.

[0246] In some embodiments, method 400 includes the step (step 408) of driving a stirrer in the first container while the first container is being unfolded or in an unfolded configuration. For example, as described with reference to Figures 3C and 3D, dispenser 300 drives a stirrer in container 308 while dispenser 300 is unfolding container 308 or when container 308 is in an unfolded configuration. In some embodiments, the stirrer is magnetically driven. For example, as described herein, dispenser 300 provides a time-varying magnetic field to control the movement of the stirrer to mix the powder and water. As an example, the stirrer is driven to rotate at 2000 RPM. As another example, as described with reference to Figure 6H, a magnetic field generator 616 magnetically drives the stirrer to mix the contents of container 608.

[0247] In some embodiments, Method 400 includes the step (step 410) of mixing the powder and water in the first container with a stirrer to prepare a culture medium while the first container is being unfolded or in an unfolded configuration. For example, as described with reference to Figures 3C and 3D, while the dispenser 300 is unfolding the container 308 or when the container 308 is in an unfolded configuration, a stirrer in the container 308 mixes the powder (e.g., cell culture medium powder) with the injected water. In another example, as described with reference to Figure 6H, a magnetic field generator 616 magnetically drives the stirrer to mix the contents of the container 608.

[0248] In some embodiments, method 400 includes a step of dispensing culture medium into a second container (step 412). For example, after the powder and water have finished mixing and the culture medium has been prepared, dispenser 300 dispenses the culture medium from the first container 308 into the second container 306. In another example, as illustrated with reference to Figure 6I, dispenser 600 dispenses cell culture medium from the first container 608 into the second container 606.

[0249] In some embodiments, method 400 includes the step of removing the cover of the second container before dispensing the culture medium into the second container. For example, before dispensing the culture medium into the second container 306, the dispenser 300 loosens the screw of the cap of the second container 306. As another example, as described with reference to Figure 6E, the second container access mechanism 612 loosens the screw of the cap of the second container 606 before dispensing the culture medium into the second container 606. In some embodiments, method 400 includes the step of providing a cover to the second container after dispensing the culture medium into the second container. For example, after the culture medium has been dispensed into the second container 306, the dispenser screws on the cap of the second container 306.

[0250] In some embodiments, method 400 includes a step of supplying a filter. For example, before dispensing the culture medium into the second container 306, a suitable filter, such as those described herein, is supplied (e.g., by a dispenser 300). In some embodiments, the culture medium is dispensed into the second container through the filter. For example, before dispensing the culture medium into the second container 306, the filter removes undesirable contents (e.g., contaminants) from the solution in the first container 308 before the culture medium is dispensed into the second container 306. As another example, as described with respect to Figure 6F, a filter coupling mechanism 614 supplies the filter and connects the filter to the outlet of the container 608. In some embodiments, the filter is integrated with the outlet 110, which advantageously reduces the need to separately attach the filter to the outlet. For example, as described with respect to Figure 1A, the filter is integrated with the outlet 110. In some embodiments, the dispenser does not include the filter coupling mechanism 614 because the filter is integrated with the outlet.

[0251] In some embodiments, method 400 includes the step of folding a first container from an unfolded configuration to a folded configuration. For example, after mixing the powder and water and / or when the culture medium is ready to be dispensed into the second container 306, container 308 is folded from its unfolded configuration (e.g., by dispenser 300) to empty the contents of the container. In another example, as illustrated with reference to Figure 6I, after the cell culture medium has been prepared, dispenser 600 folds container 608 using slot 604.

[0252] In some embodiments, Method 400 includes a step of performing in-line inspection of the culture medium. For example, the quality of the culture medium is inspected as described with respect to the description of the dispenser 600 before dispensing the culture medium (e.g., into a second container 306, a second container 606, or a bioreactor) or before allowing the second container to be removed (e.g., the medium is inspected before the dispenser door is opened for removal).

[0253] In some embodiments, Method 400 includes a step of refrigerating the cell culture medium. For example, before dispensing the culture medium (e.g., into a bioreactor) or before allowing the removal of a second container (e.g., the medium is stored and refrigerated before the dispenser door is opened for removal), the culture medium is refrigerated to a temperature of -10 to 4 degrees Celsius, as described in relation to the description of the dispenser 600.

[0254] In some embodiments, Method 400 includes the steps of transporting the cell culture medium to a destination and heating the cell culture medium while it is being transported. In some embodiments, the step of heating the cell culture medium includes heating the tube through which the cell culture medium is transported to the same temperature as the destination. For example, as described in relation to the description of dispenser 600, the tube is heated to the same temperature as the destination while the cell culture medium is being transported or guided through the tube to the destination. As an example, the tube is heated to the same temperature as a connected bioreactor (for example, to favorably maintain the state of the cell culture medium before dispensing it into the bioreactor). In some embodiments, the tube is heated to a temperature of 30-40 degrees Celsius (e.g., 37 degrees Celsius).

[0255] Further examples and exemplary advantages associated with Method 400 are described with respect to Figures 1A–1B, 2, 3A–3D, and 6A–6K. For brevity, these examples and advantages will not be described again.

[0256] Figure 5 shows an exemplary method 500 for manufacturing an exemplary container. In some embodiments, method 500 is a method for manufacturing container 100, container 150, container 308, or container 608. Although method 500 is shown as including the steps described, it will be understood that different sequences of steps, additional steps, or fewer steps may be performed to manufacture an exemplary container without departing from the scope of the present disclosure.

[0257] In some embodiments, method 500 includes a step (step 502) of providing a rigid first end. For example, the first end 102 is provided for manufacturing a container 100. In another example, the first end 102 is provided for manufacturing a container 150. In some embodiments, the first end is formed by at least one of stamping, molding, and 3D printing. It is understood that the described methods for forming the first end are not intended to be limiting.

[0258] In some embodiments, the first end is rectangular or circular. In some embodiments, the first end comprises at least one of PLA and PCL. In some embodiments, the first end comprises a recyclable material. In some embodiments, the step of providing the first end comprises forming a tongue or groove (e.g., guide 122, guide 172) on the first end configured to couple the container to a complementary groove or tongue on the dispenser while the container is inserted into the dispenser (e.g., dispenser 300). In some embodiments, the first end comprises interfacing features (e.g., for stacking as described with respect to FIG. 1B). In some embodiments, the first end comprises a notch configured to mate with an opening of the second end and lock the container in a folded configuration (e.g., as described with respect to FIG. 1B).

[0259] In some embodiments, the rigid first end comprises an opening. The opening may advantageously be used in other steps of method 500 before being covered by an access port (e.g., access port cover 124, access port cover 174). In some embodiments, method 500 comprises providing a cover configured to close the opening. For example, an access port cover (e.g., access port cover 124, access port cover 174) is provided to close the opening of the rigid first end.

[0260] In some embodiments, method 500 comprises disposing a QR code associated with a cell culture fluid (e.g., cell culture medium) powder on the rigid first end. For example, QR code 120 is disposed on access port cover 124, or QR code 170 is disposed on access port cover 174. It is understood that the illustrated position of the QR code is not intended to be limiting. The QR code may be disposed on other parts of the container.

[0261] In some embodiments, method 500 includes a step (step 504) of providing a rigid second end. For example, a rigid second end 104 is provided for manufacturing a container 100. In another example, a rigid second end 154 is provided for manufacturing a container 150. In some embodiments, the second end is formed by at least one of stamping, molding, and 3D printing. It is understood that the described methods for forming the second end are not intended to be limiting.

[0262] In some embodiments, the rigid second end has a tapered surface inside the container (as described with respect to Figure 1A), the tapered surface tapers downward toward the center of the rigid second end. In some embodiments, the second end includes at least one of polyethylene, PLA, and PCL. In some embodiments, the second end includes a recyclable material. In some embodiments, the step of providing the second end includes forming a tongue or groove (e.g., guide 122, guide 172) on the second end, which is configured to connect the container to a complementary groove or tongue on the dispenser (e.g., dispenser 300) while the container is being inserted into the dispenser. In some embodiments, the second end includes an interface feature (for stacking, as described with respect to Figure 1B).

[0263] In some embodiments, method 500 includes a step of providing an intermediate portion (step 506). For example, an intermediate portion 106 is provided for manufacturing a container 100. In another example, an intermediate portion 156 is provided for manufacturing a container 150. In some embodiments, the intermediate portion is deformable. In some embodiments, when the container is in an unfolded configuration, the intermediate portion includes a rectangular or circular cross-section (as described with respect to Figure 1A, for example). In some embodiments, the intermediate portion is a polyethylene bag or a polypropylene bag. In some embodiments, the intermediate portion includes a recyclable material. In some embodiments, the intermediate portion includes a flexible material.

[0264] In some embodiments, method 500 includes the step of providing an inlet (step 508). In some embodiments, the inlet is located at a first end. For example, inlet 108A or inlet 108B is provided for manufacturing container 100. As another example, inlet 158A or inlet 158B is provided for manufacturing container 150. In some embodiments, method 500 includes the step of fluidizing the inlet to a region of the container (e.g., a region 126 enclosed by a first end, a second end, and an intermediate portion). In some embodiments, method 500 includes the step of attaching an adapter to the inlet. In some embodiments, the adapter comprises at least one of a Luer lock adapter and a PVT adapter.

[0265] In some embodiments, Method 500 includes the step of providing a second inlet located at the rigid first end. For example, inlet 108B or inlet 108A is provided for manufacturing container 100. In another example, inlet 158B or inlet 158A is provided for manufacturing container 150. In some embodiments, Method 500 includes the step of positioning the first and second inlets so that they are parallel to each other. For example, inlets 108A, 108B are arranged in a parallel configuration within container 100. In another example, inlets 158A, 158B are arranged in a parallel configuration provided within container 150.

[0266] In some embodiments, method 500 includes the step of providing an outlet (step 510). In some embodiments, the outlet is located at a second end. For example, an outlet 110 is provided for manufacturing a container 100. In another example, an outlet 160 is provided for manufacturing a container 150. In some embodiments, method 500 includes the step of fluidizing the outlet to a region of the container (e.g., a region 126 enclosed by a first end, a second end, and an intermediate portion). In some embodiments, method 500 includes the step of mounting the outlet to a spring mechanism. In some embodiments, method 500 includes the step of attaching a discharge pipe to the outlet. In some embodiments, the discharge pipe includes at least one of a Luer lock fitting and a sealing nozzle. In some embodiments, the discharge pipe is bendable or flexible.

[0267] In some embodiments, the method includes the step of blocking the outlet with a material on the second end. The outlet-blocking material is configured to rip or break in response to an applied pressure (e.g., 5-10 psi) above a threshold pressure (e.g., 2-5 psi). In some embodiments, the outlet-blocking material is different from the material on the second end. In some embodiments, the outlet-blocking material is 1 cm 2 It has an area of ​​.

[0268] In some embodiments, method 500 includes the step of attaching intermediate portions to first and second ends (step 512). For example, intermediate portion 106 is attached to first end 102 and second end 104 to manufacture container 100. In another example, intermediate portion 156 is attached to first end 102 and second end 154 to manufacture container 150. In some embodiments, the step of attaching intermediate portions to first and second ends includes the step of bonding the intermediate portions to the first and second ends. An exemplary advantage is that the amount of plastic components included in the container is reduced. In some embodiments, method 500 includes the step of providing a seal between the rigid first end and the intermediate portion.

[0269] In some embodiments, Method 500 includes the step of loading cell culture medium (e.g., cell culture culture medium) powder into a region. In some embodiments, the cell culture medium (e.g., cell culture culture medium) powder is loaded into a region (e.g., region 126) through an opening of a container (e.g., covered by an access port cover 124, covered by an access port cover 174). In some embodiments, after the container contents (e.g., cell culture medium (e.g., cell culture medium) powder) are loaded through the opening, the access port covers (e.g., access port cover 124, access port cover 174) cover the opening. In some embodiments, the cell culture medium (e.g., cell culture medium) powder is loaded into a region through an inlet of a container. In some embodiments, the cell culture medium powder is loaded into a region after deformable intermediate portions are attached to a first end and a second end. In some embodiments, the cell culture medium powder is loaded into a region before the deformable intermediate portions are attached to the first end and the second end.

[0270] In some embodiments, the step of loading cell culture medium (e.g., cell culture culture medium) powder into the region includes the step of supplying a powder pouch, such as those described herein, containing the cell culture medium (e.g., cell culture culture medium) powder. In some embodiments, method 500 includes the step of attaching the powder pouch to a rigid first end.

[0271] In some embodiments, Method 500 includes a step of pre-granulating the cell culture medium (e.g., cell culture culture medium) powder by spraying a pH corrector. For example, before loading the cell culture medium (e.g., cell culture culture medium) powder into a container, the cell culture medium (e.g., cell culture culture medium) powder is pre-granulated by spraying a pH corrector to favorably control the pH level of the cell culture medium (e.g., cell culture culture medium) powder. In some embodiments, Method 500 includes a step of providing a pH sensor (e.g., a pH sensor that senses the pH level of the cell culture medium (e.g., cell culture culture medium) powder) that senses the pH level associated with the cell culture medium (e.g., cell culture culture medium) powder. In some embodiments, Method 500 includes a step of providing a dissolution sensor (e.g., to monitor the solubility of the contents of the container).

[0272] In some embodiments, method 500 includes the step of providing a stirrer. In some embodiments, the stirrer includes PTFE. Further exemplary stirrs are described herein, but for brevity, they will not be described again. In some embodiments, the stirrer is loaded into the area through an opening of the container (e.g., covered by an access port cover 124, covered by an access port cover 174). In some embodiments, after the stirrer is loaded through the opening, the access port covers (e.g., access port cover 124, access port cover 174) cover the opening. In some embodiments, the stirrer is loaded into the area through an inlet of the container.

[0273] In some embodiments, Method 500 includes the step of providing a barrier within an intermediate portion that separates a cell culture medium (e.g., cell culture culture medium) powder from at least one of a rigid first end and a rigid second end. In some embodiments, the step of providing a barrier further includes the step of folding the intermediate portion to create a barrier. For example, when a container is in a folded configuration, the intermediate portion (e.g., a foldable bag) is folded such that the folds of the intermediate portion function as a sealed barrier for the contents within the barrier (e.g., the contents are separated by the barrier from at least one of the first end and the second end). In some embodiments, a barrier is provided as described herein, and the barrier is not part of the intermediate portion.

[0274] In some embodiments, the intermediate barrier is formed when the container changes from an unfolded configuration to a folded configuration (e.g., when the container contents are loaded, after the contents are loaded, after the first contents are loaded, before the second contents are loaded). In some embodiments, the intermediate portion is folded in a specific manner by a tool (e.g., an off-center slit through which the intermediate portion passes) such that the folds of the intermediate portion (e.g., the folds of a bag) form a barrier when the container changes from an unfolded configuration to a folded configuration.

[0275] In some embodiments, method 500 includes the step of creating a vacuum within a region. In some embodiments, the step of creating a vacuum within a region includes the step of removing air from the region through an opening at a rigid first end (e.g., inserting a tube through the opening to remove air from region 126). In some embodiments, after the vacuum is created, an access port cover (e.g., access port cover 124, access port cover 174) covers the opening to maintain the vacuum within the region. In some embodiments, the vacuum is created through the inlet of the container.

[0276] In some embodiments, Method 500 includes the step of supplying a filter having a pore size of 0.22 to 1 μm. In some embodiments, Method 500 includes the step of attaching a filter to an outlet. For example, the filter is connected to the outside of the outlet of the container (e.g., outlet 110, outlet 160) (for example, as described with respect to Figures 3A to 3D and Figure 4). In another example, the filter is connected to the inside of the outlet of the container (e.g., outlet 110, outlet 160). For example, the filter is loaded into an area and connected to the outlet. In some embodiments, Method 500 includes the step of attaching a filter to an exhaust pipe (e.g., a discharge pipe attached to an outlet).

[0277] Further examples and exemplary advantages associated with Method 500 are described with respect to Figures 1A–1B, 2, 3A–3D, and 6A–6K. For brevity, these examples and advantages will not be described again.

[0278] Figures 6A–6K show exemplary dispensers 600. In some embodiments, exemplary dispenser 600 is dispenser 200 or dispenser 300. In some embodiments, dispenser 600 is a cell culture medium (e.g., cell culture culture medium) dispenser. While exemplary dispenser 600 is described in relation to smaller containers (e.g., 500 mL), it is understood that larger containers (e.g., 5 L, 500 L, 2000 L) may be used in a similar manner (e.g., unpacked and their contents mixed) without departing from the scope of the present disclosure. For example, larger containers may be used to produce larger volumes of solution for bioreactors. In addition, it is understood that the process of producing cell culture medium using the dispensers may involve more steps, fewer steps, or steps in a different order than those described with respect to Figures 6A–6K. In some embodiments, the operation of the Dispenser 600 of the Disclosure enables the rapid preparation (e.g., in 20 minutes) of cell culture media in a user-friendly, accurate, and sterile manner.

[0279] Figure 6A shows dispenser 600 before the installation of cell culture medium (e.g., cell culture culture medium) powder containers (e.g., container 100, container 150). In some embodiments, dispenser 602 includes a display configured to present a GUI 602, a slot 604, a door 610 (shown in a later figure), a second container access mechanism 612 (shown in a later figure), a filter coupling mechanism 614 (shown in a later figure), a magnetic field generator 616 (shown in a later figure), a baffle 618 (shown in a later figure), a second container handling mechanism 620 (shown in a later figure), and a camera or scanner (not shown). In some embodiments, dispenser 600 is configured to prepare cell culture medium from container 608 and dispense the cell culture medium into a second container 606, as described in detail herein.

[0280] In some embodiments, the dispenser 600 includes at least one pump (not shown). In some embodiments, the dispenser 600 includes a pump for supplying air into the container 608 (e.g., during the unfolding of the middle section of the container 608). In some embodiments, the dispenser 600 includes a pump for supplying air from the container 608 (e.g., during the folding of the middle section of the container 608). In some embodiments, the dispenser 600 includes a pump for cleaning and / or sterilizing the chamber after use. For example, the pump may drain the liquid from the chamber and / or supply water or a cleaning solution for cleaning and / or sterilizing the chamber.

[0281] In some embodiments, the dispenser 600 includes a first pump configured to apply a first pressure and a second pressure. In some embodiments, the first and second pressures are different. In some embodiments, the dispenser 600 includes a pump configured to apply a variable pressure. In some embodiments, by including one or more pumps capable of applying different pressures, the dispenser 600 advantageously allows different tasks to be performed (e.g., different tasks that cannot be performed by a single pump applying one pressure). For example, the pump applies a first pressure (e.g., 10-30 psi) to pump air into the container 608. In another example, the pump applies a second pressure (e.g., less than 12 psi, unpressurized) to pump air out of the container 608. In yet another example, the pump applies a third pressure (e.g., less than 12 psi, unpressurized) to clean and / or sterilize the chamber after use.

[0282] In some embodiments, some components of the dispenser 600 are components described with respect to Figure 1, Figure 2, or Figure 3. For example, GUI 602 is GUI 302, slot 604 is slot 304, second container 606 is second container 306, container 608 is container 308, container 100, or container 150, and a camera or scanner is described with respect to Figure 3. In some embodiments, the dispenser 600 includes a filtration system 202, a first handling system 204, and a second handling system 206, as described with respect to Figure 2. For brevity, some embodiments and advantages of these components are not described here.

[0283] In some embodiments, GUI 602 indicates the status of dispenser 600 and / or presents selectable inputs for the user to control dispenser 600 (e.g., to produce cell culture medium). For example, as shown in Figure 6A, in some embodiments, GUI 602 indicates that dispenser 600 is ready to produce cell culture medium and presents GUI object 622A. In response to the selection of GUI object 622A, dispenser 600 starts the cell culture production process (e.g., as described with respect to Figure 4). In some embodiments, GUI 602 indicates other states of dispenser 600. For example, dispenser 600 may be connected to a wireless network to communicate with other devices (e.g., a server for providing information associated with cell culture medium, a second device for wirelessly controlling dispenser 600), and GUI object 622B indicates the network status (e.g., connected to a WiFi network). In some embodiments, the GUI 602 includes additional GUI objects to indicate temperature (e.g., chamber temperature, ambient temperature, and selection of GUI objects that allow the user to adjust the chamber temperature), the progress of the current manufacturing operation (and GUI elements for controlling the current manufacturing operation), the pH level (e.g., sensed by the dispenser's pH sensor), and / or the culture medium being manufactured.

[0284] In some embodiments, the cell culture manufacturing process begins in response to the selection of GUI object 622A. For example, as shown in Figure 6B, the door 610 opens in response to the selection, and GUI 602 indicates the door is open.

[0285] In some embodiments, as shown in Figure 6C, after the door 610 is opened, the GUI 602 is updated to prompt the user to insert a container 608 (e.g., a pod) into slot 604. In some embodiments, the container 608 is inserted into slot 604 as described with respect to slot 304 and Figures 3A-3D. In addition, as shown, during this time the user may place a second container 606 in the chamber of the dispenser 600.

[0286] In some embodiments, as shown in Figure 6D, GUI 602 prompts the user to insert container 608 into slot 604, after which the user may insert container 608 (in a folded configuration) into slot 604. In some embodiments, during this time, GUI 602 includes GUI objects 622C and 622D. In response to the selection of GUI object 622C, dispenser 600 proceeds to the next step of the cell culture manufacturing process. In some embodiments, if container 608 is not inserted (or not properly inserted) or the second container 606 is not placed (or not properly placed) in the chamber, dispenser 600 does not respond to the selection of GUI object 622C, or GUI 602 does not display GUI object 622C. Warnings may be displayed in GUI 602 to prompt the user to properly insert container 608 or properly place the second container 606. In response to the selection of GUI object 622D, dispenser 600 can return to the previous page on GUI 602 (e.g., door open, homepage).

[0287] In some embodiments, in response to the selection of GUI object 622C, the dispenser 600 proceeds to the next step of the cell culture manufacturing process. In some embodiments, as shown in Figure 6E, in response to the selection of GUI object 622C, the door 610 closes and the second container access mechanism 612 moves toward the door so that the mechanism 612 is above the second container 606. In some embodiments, the second container access mechanism 612 is configured to open and close the second container 606 as described with respect to Figures 2 and 3A-3D. For brevity, some descriptions and advantages are not described here. After the second container access mechanism 612 is positioned above the second container 606, the second container access mechanism 612 opens the second container 606 (for example, by loosening the screw on the cap of the second container 606). In some embodiments, after the second container 606 is opened, the second container access mechanism 612 holds the cap while the cell culture medium is being manufactured. As described in more detail herein, the second container access mechanism 612 may hold the cap until the cell culture medium is dispensed, and the mechanism 612 may retighten the cap onto the second container 606. In some embodiments, in response to the selection of GUI object 622C, GUI 602 updates to indicate that the current step of the cell culture manufacturing process is being performed. In some embodiments, the updated GUI 602 includes GUI objects for modifying the cell culture manufacturing process being performed (e.g., stopping, updating manufacturing parameters).

[0288] In some embodiments, as shown in Figure 6F, after the second container access mechanism 612 opens the second container 606, the mechanism 612 returns to its initial position. After the second container 606 is opened, the filter coupling mechanism 614 moves to align the filter (e.g., a filter as disclosed herein) with the outlet of the container 608 (e.g., outlet 110, outlet 160). After the filter is aligned with the outlet, the filter coupling mechanism 614 couples (e.g., attaches) the filter to the outlet. In some embodiments, the filter is integrated with the outlet, which advantageously reduces the need to separately attach the filter to the outlet. For example, as described with respect to Figure 1A, the filter is integrated with outlet 110. In some embodiments, the dispenser does not include the filter coupling mechanism 614 because the filter is integrated with the outlet.

[0289] In some embodiments, as shown in Figure 6G, the container 608 unfolds as described with respect to Figures 3A-3D (for example, slot 604B of slot 604 is slot 304B of slot 304). In some embodiments, while the container 608 is unfolding, air and / or water are injected into the container 608 (for example, using the pump of dispenser 600) for the preparation of cell culture medium, as described with respect to Figures 3A-3D. In some embodiments, as shown in Figure 6H, the baffle 618 moves toward the container 608 in the unfolded configuration. In this example, the baffle 618 moves toward the container 608 after the container 608 is in the unfolded configuration, so the baffle does not physically prevent the container 608 from unfolding. However, it should be understood that the timing of the described baffle application is not intended to be limiting. In some embodiments, the baffle does not physically prevent the container from unfolding, and the baffle moves toward before the container unfolds.

[0290] In some embodiments, the baffle structure is concentric with the container 608 such that the structure supports the intermediate portion of the container while a force is acting on the intermediate portion (for example, to prevent the intermediate portion from breaking). For example, as shown in the figure, the two components of the baffle 618 include planes parallel to the intermediate portion, optimizing the contact point between the intermediate portion and the baffle, and thus optimizing support for the intermediate portion.

[0291] It is understood that the geometric shapes and mechanisms of the baffles described are not intended to be limiting. The baffles may include a different number of components (e.g., more than two) or different shapes than those described, as long as the baffles can provide support for the middle portion of the container 608 when a force is acting on the middle portion. For example, the baffles may include four components (e.g., each component supporting one-quarter of the middle portion). As another example, the shape of the baffles may be cylindrical, hexagonal, octagonal, etc.

[0292] In some embodiments, the baffle 618 advantageously provides support to the material of the intermediate portion of the container 608 (e.g., intermediate portion 106) while a force acts on the intermediate portion (e.g., caused by mixing cell culture medium or pressurization applied in the intermediate portion (5-10 psi)) when the container 608 is in an unfolded configuration. By providing support to the intermediate portion of the container while a force acts on it, the baffle may allow the use of more compact (e.g., thinner) material in the manufacture of the intermediate portion. A more compact intermediate portion material may increase the efficiency of content storage and / or allow both ends of the container (e.g., first end 102, second end 104) to fit together uniformly when the container is in a folded configuration (e.g., may allow the container to be properly closed). For example, a thinner intermediate portion material may allow more cell culture medium powder to be stored and allow the container to be properly closed when the container is in a folded configuration.

[0293] In some embodiments, after the container 608 is in an unfolded configuration, the magnetic field generator 616 moves (as described with respect to Figures 1A-1B, Figure 2, and Figures 3A-3D) to align with the second end of the container 618. After the magnetic field generator 616 is aligned with the second end of the container 618 (for example, when the magnetic field generator 616 is completely below the second end of the container 618), the magnetic field generator 616 generates a magnetic field as described with respect to Figures 1A-1B, Figure 2, and Figures 3A-3D to drive the agitator inside the container 608 and mix the contents of the container.

[0294] In some embodiments, the magnetic field generator 616 continues to magnetically drive the stirrer until the desired cell culture medium is prepared. In some embodiments, the magnitude, direction, and / or frequency may be varied to drive the stirrer in different ways while the cell culture medium is being prepared. In some embodiments, the solution may be stirred for a predetermined amount of time (e.g., based on the contents of the container). In some embodiments, the dispenser 600 includes sensors (not shown) (e.g., a pH sensor, a timing sensor, an optical system for quantifying turbidity (e.g., in the solution)) for determining whether the desired cell culture medium has been prepared. In some embodiments, after the desired cell culture medium has been prepared (e.g., after stirring is complete), the magnetic field generator 616 returns to its initial position.

[0295] In some embodiments, as shown in Figure 6I, the second container handling mechanism 620 lifts the second container 608 toward the outlet of the container 606 and the filter. In some embodiments, the second container handling mechanism 620 is configured to fix the second container 608 in place (e.g., to prevent the container from moving, to prevent the container from coming into contact with contaminants) while the cell culture medium is being prepared (e.g., mixed).

[0296] In some embodiments, the second container handling mechanism 620 raises the second container 608 toward the container 606 in accordance with the determination that the desired cell culture medium has been prepared (for example, after a predetermined amount of time, the dispenser 600 determines that the solution has been prepared (for example, based on sensor data)).

[0297] In some embodiments, after the second container 608 is lifted to a suitable distance from the filter (e.g., a distance that allows the cell culture medium to be dispensed cleanly or efficiently), the dispenser 600 causes the cell culture medium to be dispensed from container 606. In some embodiments, the dispenser applies pressure (e.g., 5-10 psi, by using a fluid-coupled pump to the container to fold container 608 back into a folded configuration) to the middle portion of the unfolded container, pushing the cell culture medium toward the outlet of container 606. In some embodiments, the outlet is blocked by a material configured to rip or rupture in response to an applied pressure (e.g., 5-10 psi) exceeding a pressure threshold (e.g., 2-5 psi). Thus, as shown in the figure, in response to the pressure applied by the dispenser in the middle portion, the material blocking the outlet rips or ruptures, allowing the cell culture medium to exit the outlet, pass through a filter coupled to the outlet, and be dispensed into the second container 608. In some embodiments, after the second container 608 has been lifted to a suitable distance from the filter, the dispenser 600 folds the container 608 back into its folded configuration (for example, the slot 604 moves toward each other so that the first and second ends of the container 608 are brought closer together), and pushes the cell culture medium out of the container 608 through the outlet of the container.

[0298] In some embodiments, after the desired cell culture medium is dispensed into the second container 608, the second container handling mechanism 620 lowers the second container 608 back to its initial position. In some embodiments, after the desired cell culture medium is dispensed into the second container 608, the filter coupling mechanism 614 discards the filter, as described with respect to Figures 1A-1B, Figure 2, and Figures 3A-3D. In some embodiments, the filter is integrated with the outlet, which advantageously reduces the need to separately attach the filter to the outlet. For example, as described with respect to Figure 1A, the filter is integrated with the outlet 110. In some embodiments, the dispenser does not include the filter coupling mechanism 614 because the filter is integrated with the outlet, and the filter is discarded together with the second container 608.

[0299] In some embodiments, as shown in Figure 6J, the cell culture medium is dispensed into the second container 608, and after the second container 608 is lowered, the second container access mechanism 612 moves to align with the second container 608. In some embodiments, the second container access mechanism 612 held the cap of the second container 608 (for example, after the mechanism 612 opened the cap). In some embodiments, after the second container access mechanism 612 has aligned with the second container 608, the mechanism 612 closes the second container 608 (for example, by tightening the cap screw onto the second container 608).

[0300] In some embodiments, as shown in Figure 6K, after the second container 608 is closed, the dispenser 600 causes the door 610 to open, allowing the user to remove the second container 608 and its contents. In some embodiments, after the door 610 is opened, the GUI 602 updates to prompt the user to remove the filled second container 608 and / or container 606 (which is empty after the cell culture medium has been prepared and is for disposal or recycling).

[0301] In some embodiments, during this time, GUI 602 includes GUI object 622E. The user may select GUI object 622E after container 608 and the second container 606 have been removed (for example, to inform the dispenser 600 that the containers have been removed). In response to the selection of GUI object 622E, the dispenser 600 closes the door 610. In some embodiments, in response to the selection of GUI object 622E, GUI 602 updates to display the home page. In some embodiments, GUI object 622E is not displayed until container 608 and the second container 606 have been removed from the dispenser 600 (for example, based on sensors in the dispenser 600). In some embodiments, GUI object 622E is not selectable until container 608 and the second container 606 have been removed from the dispenser 600 (for example, based on sensors in the dispenser 600).

[0302] In some embodiments, in response to the closing of the door 610, the dispenser 600 prepares for the preparation of another cell culture medium (for example, the dispenser 600 is sterilized as described with respect to Figures 2 and 3A-3D).

[0303] In some embodiments, the dispenser 600 is configured for in-line testing of cell culture media. For example, in-line testing of media is performed to determine the quality of the media (e.g., amino acid levels, protein levels, salt levels, etc.). In some embodiments, in-line testing of media is performed by sensors in the dispenser 600. In some embodiments, the dispenser 600 produces cell culture media of higher values ​​(e.g., for bioreactors). In-line testing is advantageous in that it verifies the suitability of the media before dispensing it into the bioreactor to prevent low-quality media from being dispensed into cells in the bioreactor (e.g., low-quality media could kill thousands or millions of dollars worth of cells in the bioreactor).

[0304] In some embodiments, the dispenser 600 is configured to refrigerate the cell culture medium. In some embodiments, the cell culture medium is refrigerated at a temperature of -10 to 4 degrees Celsius. For example, prior to the removal of the cell culture medium (e.g., removal of the second container 606, removal of the container containing the cell culture medium, dispensing the cell culture medium into the bioreactor), the dispenser chamber provides cooling (e.g., by lowering the chamber temperature) until it is ready for the removal of the cell culture medium (e.g., removal of the second container 606, removal of the container containing the cell culture medium, dispensing the cell culture medium into the bioreactor). In some embodiments, by refrigerating the cell culture medium, the dispenser advantageously allows the cell culture medium to be stored under ideal conditions and prevents degradation of the cell culture medium. In some embodiments, the cell culture medium is refrigerated in a thermally separated chamber of the dispenser, different from (e.g., a chamber for producing the cell culture medium), which advantageously allows the first cell culture medium to be stored and refrigerated in this chamber while a second cell culture medium is being produced in another chamber of the dispenser.

[0305] In some embodiments, the dispenser 600 is configured to include a tube configured to be heated, or to be connected to a tube configured to be heated. In some embodiments, the tube is configured to transport or lead the cell culture medium to a destination (e.g., a bioreactor, a second vessel). In some embodiments, while the cell culture medium is being transported or led to the destination, the tube is heated to the same temperature as the destination. For example, the tube is heated to the same temperature as the connected bioreactor (e.g., to favorably maintain the state of the cell culture medium before dispensing it into the bioreactor). In some embodiments, the tube is heated to a temperature of 30-40 degrees Celsius (e.g., 37 degrees Celsius).

[0306] While the contents of the container are described in relation to cell proliferation (e.g., cell culture medium), it should be understood that the description of the contents of the container is not strictly limited to cell proliferation. For example, cell proliferation may include tissue proliferation. As another example, cell culture may include tissue culture.

[0307] In one aspect, the cell culture medium container comprises a rigid first end, a rigid second end, a deformable intermediate portion attached to the first and second ends and, together with the first and second ends, enclosing a region having a variable volume, cell culture medium powder within the region, an inlet fluid-connected to the region, and an outlet fluid-connected to the region, and the container comprises a folded configuration and an unfolded configuration.

[0308] In some aspects of the above container, the volume of the region is larger in the unfolded configuration than in the folded configuration.

[0309] In some aspects of the above container, in the unfolded configuration, the volume of the region accommodates 500 mL, 5 L, or 2000 L of cell culture medium.

[0310] In some aspects of the above-described container, the distance between the rigid first end and the rigid second end is greater in the unfolded configuration than in the folded configuration.

[0311] In some aspects of the above container, the distance is 0 mm in the folded configuration and 120 mm or 300 mm in the unfolded configuration.

[0312] In some aspects of the above-described container, in the unfolded configuration, the container has a height-to-width ratio greater than 1 / 2.

[0313] In some aspects of the above container, the ratio is 1.2.

[0314] In some aspects of the above-described container, the inlet is located at the rigid first end, and the outlet is located at the rigid second end.

[0315] In some aspects of the above-described container, the container further comprises a second inlet located at the rigid first end.

[0316] In some aspects of the above-described container, the first inlet and the second inlet are parallel.

[0317] In some aspects of the above container, the first inlet is a water inlet, and the second inlet is an air intake.

[0318] In some aspects of the above container, the rigid first end is a rectangle with a width of 85 mm and a length of 85 mm.

[0319] In some aspects of the above container, the rigid first end is circular.

[0320] In some aspects of the above-described container, when the container is in an unfolded configuration, the intermediate portion has a rectangular cross-section.

[0321] In some aspects of the above-mentioned container, when the container is in an unfolded configuration, the middle section has a circular cross-section with a diameter of 73 mm.

[0322] In some aspects of the above-described container, the rigid second end has a tapered surface inside the container, and the tapered surface tapers downward toward the center of the rigid second end.

[0323] In some aspects of the above container, at least one of the rigid first end and the rigid second end is impermeable to sterilization light.

[0324] In some aspects of the above-described container, the rigid first end and the rigid second end include at least one of polyethylene, PLA, and PCL.

[0325] In some aspects of the above container, the intermediate portion is a polyethylene bag or a polypropylene bag.

[0326] In some aspects of the above-described container, the rigid first end, the rigid second end, and the intermediate portion contain recyclable material.

[0327] In some aspects of the above-described container, the container further comprises an adapter attached to the inlet.

[0328] In some aspects of the above container, the adapter comprises at least one of a Luer lock adapter and a PVT adapter.

[0329] In some aspects of the above-described container, the container is further equipped with a stirrer positioned within the region and having a length of 10-20 mm.

[0330] In some aspects of the above container, the agitator contains PTFE.

[0331] In some aspects of the above container, the container further comprises a QR code located on a rigid first end associated with the cell culture medium powder.

[0332] In some aspects of the above-described container, the rigid first end and the rigid second end are provided with a tongue or groove configured to connect the container and the dispenser while the container is being inserted into the dispenser.

[0333] In some aspects of the above-mentioned container, the intermediate portion is flexible when the container is in an unfolded configuration.

[0334] In some aspects of the above-described container, the surface of the rigid first end is configured to interface with the surface of the rigid second end.

[0335] In some aspects of the above container, the middle section houses a powder pouch containing the solution powder.

[0336] In some aspects of the above container, the powder pouch is attached to the rigid first end.

[0337] In some aspects of the above-described container, the container further comprises a barrier in an intermediate portion that separates the solution powder from at least one of the rigid first end and the rigid second end.

[0338] In some aspects of the above-described container, the container further includes a seal between the rigid second end and the intermediate portion.

[0339] In some aspects of the above-described container, the container further includes a seal between the rigid first end and the intermediate portion.

[0340] In some aspects of the above-described container, the rigid first end and the rigid second end are configured such that, when the container is in an unfolded configuration, the rigid first end is rotated by a first angle from the rigid second end with respect to the orientation of the rigid first and rigid second ends, thereby locking the container in a folded configuration.

[0341] In some aspects of the above-described container, the rigid first end is provided with a notch configured to engage with an opening in the rigid second end, thereby locking the container in a folded configuration.

[0342] In some aspects of the above-described container, the rigid first end is provided with an opening.

[0343] In some aspects of the above-described container, the container further comprises a cover configured to seal the opening.

[0344] In some aspects of the above-described container, the container further comprises a filter having a pore size of 0.22 to 1 μm.

[0345] In some aspects of the above-described container, the container further comprises a filter attached to the outlet.

[0346] In some aspects of the above-mentioned container, the outlet is attached to a spring mechanism.

[0347] In some aspects of the above-described container, the outlet is configured to be attached to a discharge pipe.

[0348] In some aspects of the above container, the discharge pipe is provided with either a Luer lock fitting or a sealing nozzle.

[0349] In some aspects of the above-described container, the container further comprises a filter attached to the discharge pipe.

[0350] In some aspects of the above-mentioned container, the discharge pipe is bendable or flexible.

[0351] In some aspects of the above container, the container further includes a pH sensor that senses the pH level associated with the cell culture medium powder.

[0352] In some aspects of the above-mentioned container, the container is further equipped with a dissolution sensor.

[0353] In some aspects of the above container, the cell culture medium powder is pre-granulated by spraying a pH corrector.

[0354] In some aspects of the above container, the middle section is configured to be vacuum-sealed in the folded configuration.

[0355] In some aspects of the above-described container, the container further comprises a material that seals the outlet, and the material is configured to rupture in response to an applied pressure exceeding a pressure threshold.

[0356] In some aspects of the above container, the material sealing the outlet is 1 cm 2 It has an area of ​​.

[0357] In some aspects of the above-mentioned container, the material includes low-density polyethylene.

[0358] In some aspects of the above-mentioned container, the container further includes a filter integrated with the outlet.

[0359] In one aspect, a method for preparing a culture medium includes the steps of: receiving a first container in a folded configuration with a dispenser; unfolding the first container into an unfolded configuration; injecting water into the first container while the first container is being unfolded or while the first container is in an unfolded configuration, driving a stirrer inside the first container, and mixing the powder and water in the first container with the stirrer to prepare a culture medium; and dispensing the culture medium into a second container.

[0360] In some aspects of the above method for preparing the culture medium, the first container is a cell culture medium container.

[0361] In some aspects of the above method for preparing the culture medium, the method for preparing the culture medium further includes a step of receiving an input, wherein the input is a selection on the GUI of a dispenser, and a first container is unfolded in response to the receipt of the input.

[0362] In some aspects of the above method for preparing the culture medium, the method for preparing the culture medium further includes a step of receiving an input, wherein the input is a QR code scan of a QR code on a first container, and the first container is unfolded in response to the receipt of the input.

[0363] In some aspects of the method for preparing the culture medium described above, the method for preparing the culture medium further includes the step of removing the cover of the second container before dispensing the culture medium into the second container.

[0364] In some aspects of the method for preparing the culture medium described above, the method for preparing the culture medium further includes the step of providing a cover to the second container after dispensing the culture medium into the second container.

[0365] In some aspects of the above method for preparing the culture medium, the method further includes a step of sterilizing the dispenser.

[0366] In some aspects of the above method for preparing the culture medium, the method for preparing the culture medium further includes the step of injecting air into the first container.

[0367] In some aspects of the above method for preparing the culture medium, the method for preparing the culture medium further includes the step of providing a filter, wherein the culture medium is dispensed through the filter into a second container.

[0368] In some aspects of the above method for preparing the culture medium, the method further includes the step of folding the first container from an unfolded configuration to a folded configuration.

[0369] In some aspects of the above method for preparing the culture medium, the agitator is driven magnetically.

[0370] In some aspects of the method for preparing the culture medium described above, the first container is one of the cell culture medium containers described above.

[0371] In some aspects of the method for preparing the culture medium described above, the method for preparing the culture medium further includes the step of applying pressure to the middle portion of the first container.

[0372] In some aspects of the above method for preparing the culture medium, the pressure is 5-12 psi.

[0373] In some aspects of the above method for preparing the culture medium, the method further includes a step of applying a second pressure to the dispenser chamber, wherein the second pressure is different from the first pressure.

[0374] In some aspects of the method for preparing the culture medium described above, the method for preparing the culture medium further includes the step of applying baffles to support the middle portion of the first container.

[0375] In some aspects of the method for preparing the culture medium described above, the baffle is applied while the first container is being unfolded or while the first container is in an unfolded configuration.

[0376] In some aspects of the above method for preparing the culture medium, the method further includes a step of performing in-line testing of the culture medium.

[0377] In some aspects of the above method for preparing the culture medium, the method further includes a step of refrigerating the culture medium at -10 to 4 degrees Celsius.

[0378] In some aspects of the above method for preparing the culture medium, the method further includes the steps of: heating a tube connected between a dispenser and a destination; and transporting the culture medium to the destination via the tube, wherein the tube is heated to the temperature of the destination, between 30 and 40 degrees Celsius.

[0379] In one aspect, the cell culture medium dispenser is configured to perform one of the above methods for preparing the culture medium.

[0380] In one aspect, a method for manufacturing a cell culture medium container for storing culture medium powder includes the steps of: providing a rigid first end; providing a rigid second end; providing a deformable intermediate portion; attaching the deformable intermediate portion to the first end and the second end, wherein the first end, the second end, and the intermediate portion surround a region having a variable volume; providing an inlet; fluidly connecting the inlet to the region; providing an outlet; fluidly connecting the outlet to the region; and loading cell culture medium powder into the region.

[0381] In some aspects of the above manufacturing method, the step of loading the culture solution powder into the region includes the step of loading the culture solution powder through the opening of the rigid first end.

[0382] In some aspects of the above manufacturing method, the manufacturing method further includes a step of creating a vacuum within the area.

[0383] In some aspects of the above manufacturing method, the step of creating a vacuum within the region includes the step of removing air from the region through an opening at the rigid first end.

[0384] In some aspects of the above manufacturing method, the manufacturing method further includes the step of providing a stirrer.

[0385] In some aspects of the above manufacturing method, the agitator contains PTFE.

[0386] In some aspects of the above manufacturing method, the manufacturing method further includes the step of providing a barrier in an intermediate portion that separates the cell culture medium powder from at least one of the rigid first end and the rigid second end.

[0387] In some aspects of the above manufacturing method, the step of creating a barrier further includes the step of folding the intermediate portion to create the barrier.

[0388] In some aspects of the above manufacturing method, the rigid first end is provided with an opening.

[0389] In some aspects of the above manufacturing method, the manufacturing method further includes the step of providing a cover configured to close the opening.

[0390] In some aspects of the above manufacturing method, the step of providing an inlet includes the step of positioning the inlet at a rigid first end, and the step of providing an outlet includes the step of positioning the outlet at a rigid second end.

[0391] In some aspects of the above manufacturing method, the manufacturing method further includes the step of providing a second inlet located at the rigid first end.

[0392] In some aspects of the above manufacturing method, the manufacturing method further includes the step of positioning the first inlet and the second inlet so that they are parallel to each other.

[0393] In some aspects of the above manufacturing method, the first rigid end is rectangular.

[0394] In some aspects of the above manufacturing method, the first rigid end is circular.

[0395] In some aspects of the above manufacturing method, when the container is in an unfolded configuration, the middle section has a rectangular cross-section.

[0396] In some aspects of the above manufacturing method, when the container is in an unfolded configuration, the intermediate portion has a circular cross-section.

[0397] In some aspects of the above manufacturing method, the rigid second end has a tapered surface inside the container, and the tapered surface tapers downward toward the center of the rigid second end.

[0398] In some aspects of the above manufacturing method, the rigid first end and the rigid second end include at least one of polyethylene, PLA, and PCL.

[0399] In some aspects of the above manufacturing method, the intermediate part is a polyethylene bag or a polypropylene bag.

[0400] In some aspects of the above manufacturing method, the rigid first end, the rigid second end, and the intermediate portion include recyclable material.

[0401] In some aspects of the above manufacturing method, the manufacturing method further includes the step of attaching an adapter to the inlet.

[0402] In some aspects of the above manufacturing method, the adapter comprises at least one of a luer lock adapter and a PVT adapter.

[0403] In some aspects of the above manufacturing method, the manufacturing method further includes the step of placing a QR code associated with the cell culture medium powder on the first rigid end.

[0404] In some aspects of the above manufacturing method, the step of providing a rigid first end and a rigid second end includes the step of forming tongues or grooves on the rigid first end and the rigid second end, which are configured to connect the container and the dispenser while the container is being inserted into the dispenser.

[0405] In some aspects of the above manufacturing method, the intermediate portion includes a flexible material.

[0406] In some aspects of the above manufacturing method, the first rigid end and the second rigid end have an interface feature.

[0407] In some aspects of the above manufacturing method, the step of loading cell culture medium powder into the region further includes the step of supplying powder pouches containing the cell culture medium powder.

[0408] In some aspects of the above manufacturing method, the manufacturing method further includes the step of attaching the powder pouch to a rigid first end.

[0409] In some aspects of the above manufacturing method, the manufacturing method further includes the step of providing a seal between the rigid first end and the intermediate portion.

[0410] In some aspects of the above manufacturing method, the rigid first end is provided with a notch configured to fit into an opening in the rigid second end, thereby locking the container in a folded configuration.

[0411] In some aspects of the above manufacturing method, the manufacturing method further includes the step of supplying a filter having a pore size of 0.22 to 1 μm.

[0412] In some aspects of the above manufacturing method, the manufacturing method further includes the step of attaching a filter to the outlet.

[0413] In some aspects of the above manufacturing method, the manufacturing method further includes the step of mounting the outlet to the spring mechanism.

[0414] In some aspects of the above manufacturing method, the manufacturing method further includes the step of attaching a discharge pipe to the outlet.

[0415] In some aspects of the above manufacturing method, the discharge pipe is equipped with either a Luer lock fitting or a sealed nozzle.

[0416] In some aspects of the above manufacturing method, the manufacturing method further includes the step of attaching a filter to the discharge pipe.

[0417] In some aspects of the above manufacturing method, the discharge pipe is bendable or flexible.

[0418] In some aspects of the above manufacturing method, the manufacturing method further includes a step of providing a pH sensor that senses the pH level associated with the cell culture medium powder.

[0419] In some aspects of the above manufacturing method, the manufacturing method further includes the step of providing a dissolution sensor.

[0420] In some aspects of the above manufacturing method, the manufacturing method further includes a step of pre-granulating the cell culture medium powder by spraying a pH corrector.

[0421] In some aspects of the above manufacturing method, the cell culture medium powder is loaded into the region before the deformable intermediate portions are attached to the first and second ends.

[0422] In some aspects of the above manufacturing method, the container is one of the cell culture medium containers described above.

[0423] In some aspects of the above manufacturing method, the container is one of the containers used in the above method for preparing the culture medium.

[0424] In some aspects of the above manufacturing method, the manufacturing method further includes a step of sealing an outlet with a material, wherein the material is configured to rupture in response to an applied pressure exceeding a pressure threshold.

[0425] In some aspects of the above manufacturing method, the material used to seal the exit is 1 cm 2 It has an area of ​​.

[0426] In some aspects of the above manufacturing method, the material includes low-density polyethylene.

[0427] In one aspect, a dispenser for producing a cell culture medium, comprising: a graphical user interface (GUI) for controlling the dispenser; a slot for receiving and unfolding a first container; a second container access mechanism for opening and closing a second container, the second container access mechanism for dispensing the cell culture medium into the second container; a second container handling mechanism for moving the second container toward and away from the cell culture medium dispensing position; a filter supply mechanism for supplying a filter to the first container; a magnetic field generator for magnetically driving a stirrer inside the first container; and a baffle for supporting the middle portion of the first container.

[0428] In some aspects of the dispenser described above, the dispenser further comprises a pump to apply a first pressure to the middle portion of the first container.

[0429] In some aspects of the dispenser described above, the first pressure is 5-12 psi.

[0430] In some aspects of the dispenser described above, the pump is also used to apply a second pressure to the dispenser chamber, which is different from the first and second pressures.

[0431] In some aspects of the dispenser described above, the dispenser further comprises a second pump for applying a second pressure to the dispenser chamber.

[0432] In some aspects of the dispenser described above, the baffle is for supporting the middle portion of the first container.

[0433] In some aspects of the dispenser described above, the baffle is applied while the first container is being deployed or while the first container is in a deployed configuration.

[0434] In some aspects of the dispenser described above, the dispenser is configured to perform in-line testing of cell culture media.

[0435] In some aspects of the dispenser described above, the dispenser is configured to refrigerate the culture medium at -10 to 4 degrees Celsius.

[0436] In some aspects of the dispenser described above, the dispenser is configured to have a tube connected between the dispenser and the destination, and the tube is heated to the destination temperature at 30-40 degrees Celsius.

[0437] In one aspect, a method for preparing a culture medium includes the steps of: unfolding a first container into an unfolded configuration; mixing powder and water in the first container to prepare a culture medium while the first container is unfolding or in an unfolded configuration; and dispensing the culture medium.

[0438] In some aspects of the method for preparing the culture medium described above, the method for preparing the culture medium further includes the step of applying pressure to the middle portion of the first container.

[0439] In some aspects of the above method for preparing the culture medium, the pressure is 5-12 psi.

[0440] In some aspects of the above method for preparing the culture medium, the method further includes a step of applying a second pressure to the dispenser chamber, wherein the second pressure is different from the first pressure.

[0441] In some aspects of the method for preparing the culture medium described above, the method for preparing the culture medium further includes the step of applying baffles to support the middle portion of the first container.

[0442] In some aspects of the method for preparing the culture medium described above, the baffle is applied while the first container is being unfolded or while the first container is in an unfolded configuration.

[0443] In some aspects of the above method for preparing the culture medium, the method further includes a step of performing in-line testing of the culture medium.

[0444] In some aspects of the above method for preparing the culture medium, the method further includes a step of refrigerating the culture medium at -10 to 4 degrees Celsius.

[0445] In some aspects of the above method for preparing the culture medium, the method further includes the steps of: heating a tube connected between a dispenser and a destination; and transporting the culture medium to the destination via the tube, wherein the tube is heated to the temperature of the destination, between 30 and 40 degrees Celsius.

[0446] The manner of disclosure is fully described with reference to the accompanying drawings, but it should be noted that various changes and modifications will become apparent to those skilled in the art. Such changes and modifications should be understood to fall within the scope of the manner of disclosure as defined by the accompanying claims.

[0447] The terms used in the descriptions of the various aspects of the description herein are intended to describe, and not to limit, a particular aspect. Where used in the descriptions of the various aspects of the description and in the appended claims, the singular forms “a,” “an,” and “the” are intended to include the plural form unless the context makes it clear otherwise. The terms “and / or” as used herein will be understood to refer to and encompass one or any possible combination of the related description items. The terms “includes,” “including,” “comprises,” and / or “comprising,” where used herein, specify the presence of a described feature, integer, process, operation, element, and / or component, but will not exclude the presence or addition of one or more other features, integers, processes, operations, elements, components, and / or groups thereof.

Claims

1. A system comprising a dispenser for producing a cell culture medium, The dispenser includes a container handling mechanism which comprises an insertion mechanism having two parts configured to be spaced apart, The insertion mechanism is, Accepting containers, After receiving the container, the container is fixed to the two parts, and To unfold the container toward its deployed configuration, the two parts are separated. It is configured in such a way, The container is, The first end of rigidity, The second end of rigidity, A deformable intermediate portion attached to the first end and the second end, which together with the first end and the second end encloses a region having a variable volume, The cell culture medium powder within the region, An inlet fluid-connected to the region, An outlet fluid-connected to the region and Equipped with, It has both a folded configuration and an unfolded configuration. system.

2. The system according to claim 1, wherein the rigid second end has a tapered surface inside the container, and the tapered surface tapers downward toward the center of the rigid second end.

3. The system according to claim 1 or 2, wherein the intermediate portion is a polyethylene bag or a polypropylene bag.

4. The system according to any one of claims 1 to 3, wherein the rigid first end, the rigid second end, and the intermediate portion include a recyclable material.

5. The system according to any one of claims 1 to 4, further comprising a stirrer positioned within the aforementioned region.

6. The first rigid end and the second rigid end are A tongue or groove is configured to connect the container and the dispenser while the container is inserted into the dispenser. A system according to any one of claims 1 to 5, comprising:

7. The system according to any one of claims 1 to 6, further comprising a filter or a fitting configured to connect the filter to the outlet.

8. The container further comprises a second inlet, The first inlet and the second inlet are located at the rigid first end, The outlet is located at the rigid second end. The system according to any one of claims 1 to 7.

9. The system according to any one of claims 1 to 8, wherein the rigid first end and the rigid second end comprise at least one of polyethylene, polylactic acid (PLA), and polycarbonate (PCL).

10. The system according to any one of claims 1 to 9, wherein the intermediate portion is flexible when the container is in the deployed configuration.

11. The system according to any one of claims 1 to 10, wherein the intermediate portion in the folded configuration is configured to be vacuum-sealed.

12. The system according to any one of claims 1 to 11, wherein at least one of the first rigid end and the second rigid end is impermeable to sterilization light.

13. The system according to any one of claims 1 to 12, wherein the volume of the container in the deployed configuration is 500 L.

14. A step of providing a rigid first end; A step of providing a second rigid end; A process of creating a deformable intermediate section; A step of attaching the deformable intermediate portion to the first end and the second end, wherein the first end, the second end, and the intermediate portion enclose a region having a variable volume; The process of creating an entrance; A step of fluidly connecting the inlet to the region; The process of creating an outlet; The process of fluidly connecting the outlet to the region; and Steps to load cell culture medium powder into the area. A method for producing a cell culture medium, which includes, A method comprising a tongue or groove, wherein the rigid first and second ends are configured to connect the container to a complementary groove or tongue on the dispenser while the container is being inserted into the dispenser.

15. A method for preparing a culture medium, comprising the following steps: A step of receiving the container, which is included in the system according to any one of claims 1 to 13 and is in a folded configuration, with the dispenser included in the system according to any one of claims 1 to 13; A step of unfolding the container into its deployed configuration; While the container is being unfolded, or while the container is in the unfolded configuration, Pour water into the container, The agitator inside the container is driven, A step of mixing the powder in the container with the water using a stirrer in order to prepare the culture medium; and The process of dispensing the culture medium into further containers. Methods that include...

16. The dispenser further comprises a graphical user interface (GUI) for controlling the dispenser, The two parts described above define slots for receiving and unfolding the container, The aforementioned system, A further container access mechanism for opening and closing a further container, wherein the dispenser dispenses the cell culture medium into the further container; A further container handling mechanism is provided, configured to move the further container toward and away from the cell culture medium dispensing position. A filter supply mechanism for supplying a filter to the container, A magnetic field generator for magnetically driving a stirrer inside the container, A baffle for supporting the intermediate portion of the container and Furthermore, The system according to any one of claims 1 to 13.

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