Automated apparatus for preparing bioprocess solutions and automated system for preparing bioprocess solutions

Abstract

To provide automated apparatus for preparing bioprocess solutions, and to provide an automated system for preparing bioprocess solutions.SOLUTION: An automated apparatus includes: a first fluid inlet connected to a first fluid source; a volume sensor located near the fluid inlet to measure at least one of a volume or flow rate of the first fluid to the automated device; a plurality of tubes for fluid flow within the device; a mixing chamber having a lower port connected to the fluid inlet through the plurality of tubes and an upper port connected to the fluid inlet such that the first fluid enters the at least one mixing chamber through the lower port and the upper port; and a mixing control device including at least a plurality of valves disposed within the plurality of tubes, a processor, and a memory having instructions stored thereon, the mixing control device being operable to independently control a first valve associated with the lower port and a second valve associated with the upper port based on measurements received from the volume sensor.SELECTED DRAWING: Figure 1A

Description

Technical Field

[0001] Embodiments of the present technology generally relate to automated methods and apparatuses for mixing at least one material with at least one fluid. More particularly, embodiments of the present technology relate to automated methods and apparatuses that are particularly suitable for reconstituting a predetermined unit volume amount of a dry component into a bioprocess solution.

[0002] Cross - reference to related applications This application claims priority to U.S. Provisional Patent Application No. 62 / 527,878, filed Jun. 30, 2017, which is hereby incorporated by reference in its entirety.

Background Art

[0003] A bioprocess is a process that uses living cells or their components to obtain a desired product. In many bioprocesses, the use of various solutions is required. For example, the first step of a bioprocess may include cell culture, in which case it is often necessary to successfully culture new cells using a cell culture medium. In later steps of the bioprocess, the use of various buffer solutions may be required as part of the product purification process.

[0004] Bioprocess solutions are often hydrated from dry components immediately before use in large stainless - steel tanks or single - use mixing devices. Typical processes are time - consuming, costly, and do not add direct value to the desired product. Although the basic cell - culture methods have not changed much over the years, the volume of cell culture has continued to increase dramatically, thereby changing the requirements for medium preparation. Many research institutions, pharmaceutical companies, and biotechnology companies not only use cell - culture methods but often do so on a very large scale. Biotechnology companies may consume thousands of liters of liquid medium per day and employ a large number of manufacturing technicians and scientists to produce antibodies, growth factors, or recombinant proteins from cell culture for commercial use.

Summary of the Invention

Problems to be Solved by the Invention

[0005] The present invention provides an automated system and method for preparing a bioprocess solution using an in-line mixing device that helps reduce the time, labor, error risk, and contamination risk required in these processes, while also improving reliability and consistency.

Means for Solving the Problems

[0006] Overall, the embodiments described herein relate to automated methods and apparatuses for preparing dry components into a liquid solution (e.g., preparing a powdered bioprocess medium into a liquid bioprocess medium). As will be further described below, dry components tend to require less storage space, have a longer shelf life, be less expensive, and have shorter shipping and handling times than pre-packaged liquid solutions. Thus, when a liquid solution is needed, it is advantageous to utilize an automated method and apparatus designed to make the preparation of a liquid solution from dry components simple, direct, and reproducible rather than purchasing a pre-packaged liquid solution. Accordingly, the techniques according to some embodiments relate to an automated method for use with a mixing device for mixing dry components (e.g., powdered media) into a fluid such as a cell culture medium or buffer. More particularly, some embodiments of the present technology relate to an automated method for use with a mixing device, where both the automated method and the mixing device are suitable for reconstituting dry components into a predetermined unit volume amount of liquid.

[0007] Using this technology, various dry components can be reconstituted into a liquid solution. For example, as used herein, dry components can refer to powdered cell culture media, dry powdered media, dry buffer powders, granular media, dry salts, dry chemicals, dry components, dry materials, and unhydrated components.

[0008] Some embodiments described herein are based at least in part on the drawbacks and / or inconveniences of existing reconstitution techniques as recognized by the inventors of the present technology, or on the recognition of potential improvements by the inventors. For example, pre-packaged liquid cell culture media are sterilized, aliquoted into convenient sizes, and ready for immediate use. However, pre-packaged liquid cell culture media are generally photosensitive and have a predetermined shelf life. Therefore, pre-packaged liquid cell culture media need to be ordered regularly. Also, they need to be stored under refrigeration and, in their pre-packaged form, require a significant amount of manpower time to unpack and transport. Furthermore, the shipping costs of pre-packaged liquid cell culture media are becoming increasingly high.

[0009] In contrast, powdered cell culture media are provided in bulk or pre-measured packages. They tend to have a longer shelf life, be less expensive, and require less storage space and shipping and handling time than in the liquid case. However, powdered cell culture media need to be reconstituted into liquid cell culture media by aseptically aliquoting and dissolving the powdered media. The increased handling and preparation time for powdered cell culture media, especially for large-scale media preparation, often makes pre-packaged liquid cell culture media the preferred option despite the increased cost.

[0010] Furthermore, reconstituting dry components into liquid bioprocess solutions is generally a multi-step process. As an example, to prepare liquid cell culture media from solid powder, a known amount of powder for a specific volume of media is weighed and added to a volume of distilled water that is usually less than the final desired volume. The powder and water are stirred until the solid is completely dissolved. A specific amount of sodium bicarbonate is added and dissolved. Then, an acid or base is used to adjust the pH, and additional water is added to increase the media to the final volume. Next, the entire mixture is passed through a sterile filter. The media is then either collected in a single large sterile container or divided into several small sterile containers.

[0011] Reconstituting a solution based on the properties of the reconstituted dry component can be further difficult. For example, powdered tissue culture media have a very fine particle size and are hygroscopic. When mixed with water, they tend to form "balls" or "lumps". Therefore, when reconstituting with water or another aqueous liquid, sufficient agitation is required to break up the lumps that can form when first contacting the water. For small batch sizes, a sterile magnetic stir bar is added to the mixing container and the container is placed on a magnetic stirring plate. Adding a stir bar to the mixing container usually requires additional operations. However, in a typical laboratory environment, magnetic stirring plates are not a practical method for large-scale media preparation.

[0012] Furthermore, especially in a humid environment, due to hygroscopicity, powdered cell culture media absorb water during storage. The wet powdered media shorten the shelf life, become lumpy, and require vigorous agitation to reconstitute. Therefore, the shelf life of powdered cell culture media can be improved by pre-measuring, sealing, and providing in a dried aliquot.

[0013] Moreover, the reconstitution process requires several steps and several separate pieces of equipment. Generally, at least one container large enough to hold the entire final volume of the reconstituted media and one or more containers for receiving the sterilized media after filtration are required. The sterilized media are usually placed in an open-topped container. Therefore, most media preparation is done in a laminar flow hood. However, processing large amounts of media in the hood is difficult because there is often not enough space to hold the containers and the sterilized media. Accordingly, methods and devices are described herein that enable the preparation of large volumes of solution (e.g., cell culture media) in a manner that allows for minimal physical contact and is highly reliable and reproducible.

[0014] One embodiment of the present technology relates to an automation method. The automation method includes providing a dry component that is reconstituted into a liquid bioprocess solution, and controlling, by a processing circuit, an automation system including at least one mixing chamber, a plurality of tubes for fluid flow within the system, and a plurality of valves provided within the tubes, in order to automatically prepare the liquid bioprocess solution from the dry component. Controlling the automation system can include performing a series of continuous mixing steps that cause the preparation of the liquid bioprocess solution. The method can further include obtaining one or more measurement values during the preparation of the liquid bioprocess solution, and each step is caused by at least one of the measurement value being below a measurement threshold, equal to the measurement threshold, or exceeding the measurement threshold. Each step can also include opening and closing at least one of the plurality of valves by the processing circuit to control the fluid flow within the automation system. The bioprocess solution can be a cell culture medium or a buffer solution.

[0015] A second embodiment of the present technology relates to an automation method. The automation method includes providing a dry component that is reconstituted into a liquid bioprocess solution, and providing an automation system including at least one mixing chamber, a plurality of tubes for fluid flow within the system, a plurality of valves provided within the tubes, and one or more inlets to the tubes. The automation method also includes connecting a purified water source to one of the one or more inlets. The automation method further includes controlling, by a processing circuit, the automation system to prepare the liquid bioprocess solution from the dry component by performing a series of continuous mixing steps, and each step includes opening and closing at least one of the plurality of valves to control the fluid flow within the automation system and obtaining one or more measurement values during the preparation of the liquid bioprocess solution, and each step is caused by at least one of the measurement value being below a measurement threshold, equal to the measurement threshold, or exceeding the measurement threshold. The bioprocess solution can be a cell culture medium or a buffer solution.

[0016] The third embodiment of the present technology relates to an automated device for preparing a liquid bioprocess solution from dry components. The automated device includes at least one mixing chamber, a plurality of tubes, a plurality of valves provided within the tubes, and a mixing control device. The mixing control device includes at least a processor and a memory storing instructions, and the mixing control device is configured to control the plurality of valves to prepare a liquid bioprocess solution from dry components. The automated device can also include one or more sensors configured to obtain one or more measurement values during the preparation of the liquid bioprocess solution, and the mixing control device is configured to control the plurality of valves in response to at least one of the measurement value being below a measurement threshold, equal to the measurement threshold, or exceeding the measurement threshold. The bioprocess solution can be a cell culture medium or a buffer solution.

[0017] The fourth embodiment of the present technology relates to an automated method. The automated method includes providing a bioprocess buffer in a dry form and controlling, by a processing circuit, an automated system including at least one mixing chamber, a plurality of tubes for the flow of fluid within the system, and a plurality of valves provided within the tubes to automatically prepare a liquid bioprocess buffer from the dry-form bioprocess buffer. Controlling the automated system can include performing, by the processing circuit, a series of continuous mixing steps that cause the preparation of the liquid bioprocess buffer. The method can further include obtaining one or more measurement values during the preparation of the liquid bioprocess buffer, and each step is caused by at least one of the measurement value being below a measurement threshold, equal to the measurement threshold, or exceeding the measurement threshold. Each step can also include opening and closing at least one of the plurality of valves by the processing circuit to control the flow of fluid within the automated system.

Brief Description of the Drawings

[0018] With reference to the accompanying drawings, the above features of the present technology, as well as other features, aspects, and advantages, will be described in relation to various embodiments of the present invention. However, the illustrated embodiments are merely examples and are not intended to limit the present invention.

[0019]

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DETAILED DESCRIPTION OF THE INVENTION

[0023] In the following detailed description, reference is made to the accompanying drawings, which form a part hereof. In the drawings, like reference numerals generally identify like components unless the context indicates otherwise. The illustrative embodiments described in the detailed description, drawings, and claims are not intended to be limiting. The detailed description is intended as an explanation of illustrative embodiments and is not intended to represent only the embodiments that can be implemented. As used herein, the term "illustrative" means "serving as an example, instance, or illustration" and should not necessarily be construed as preferred or advantageous over other embodiments. Other embodiments can be utilized and other changes can be made without departing from the spirit or scope of the subject matter presented herein. It will be readily understood that the aspects of the present disclosure described throughout this specification and shown in the drawings can be arranged, substituted, combined, and designed in a wide variety of different configurations. All of these configurations are explicitly contemplated and form a part of the present disclosure.

[0024] The embodiments described herein generally relate to devices / apparatuses, systems, and methods for preparing a solution from a dry component, for example, a cell culture medium from a dry powder cell culture medium or a buffer from a dry buffer powder. One or more of the provided embodiments can overcome one or more drawbacks, limitations, or deficiencies existing in the art with respect to the reconstitution of a solution, particularly with respect to the reconstitution of a dry form of a cell culture medium including a dry powder medium. For example, in some embodiments described herein, automated methods and apparatuses mix dry components into a liquid bioprocess solution such that the mixing process is user-friendly, can be used to reconstitute a relatively large volume of solution, and can result in a completely mixed and non-aggregated solution.

[0025] The present disclosure refers to the systems and methods described herein in connection with preparing a liquid cell culture medium from a powdered cell culture medium. However, it should be understood that the systems and methods described herein can be adapted for the preparation of other types of solutions. For example, the systems and methods described herein can be used to prepare buffers for chromatography and downstream processing of biopharmaceutical bulk drug substances. As another example, the systems and methods described herein can be used to prepare various "bioprocess solutions", or solutions used in processes to obtain a desired product using live cells or their components. Further, the systems and methods described herein are considered to be adaptable for many more extensive commercial or industrial uses. As an example, many liquid pharmaceuticals are prepared at a hospital pharmacy at regular frequencies and amounts. Saline solutions, nutritional formulations, imaging reagents, dyes, sterilizing solutions, and anesthetics are reconstituted as liquids. Additional alternative uses include, but are not limited to, the preparation of insecticides, fertilizers, and various beverages (e.g., milk, iced tea, etc.) generally prepared from powders, all of which could have been reconstituted using embodiments of the systems and methods described herein. In this regard, the dry components that can be reconstituted using the present systems and methods are not limited to powdered cell culture media, and can include dry powder media, dry buffer powders, granular media, dry salts, dry chemicals, dry components, dry materials, and anhydrous components.

[0026] Figure 1A is an overall system diagram of one embodiment of the mixing device 10. Preferably, the mixing device 10 is made of a material suitable for a cell culture environment, such as a non-toxic medical-grade plastic or other non-toxic material that does not contaminate the culture medium. The mixing device 10 includes a first mixing chamber 12, a second mixing chamber 14, and a filter unit 16 connected to each other by tubes of various lengths (e.g., flexible hoses). As will be described in more detail below, the tubes further include various valves provided in the tubes to selectively permit (e.g., when the valve is in the open position) and stop (e.g., when the valve is in the closed position) the flow of fluid through the valve. In an exemplary embodiment, the valve is a pinch valve, but in other embodiments, the valve can be another type of valve, such as a ball valve, or can include other types of valves. In various embodiments, the mixing device 10 is designed to reconstitute a powdered cell culture medium into a liquid medium. For example, the mixing device 10 can be a single-use device in which the necessary medium components (e.g., powdered cell culture medium, sodium bicarbonate, etc.) are pre-packaged. However, those skilled in the art will understand that the mixing device 10 can be used to reconstitute other forms of undissolved cell culture medium (e.g., granular cell culture medium), prepare a bioprocess buffer from a dry form, or more generally reconstitute a liquid from a powder.

[0027] First, in various embodiments, the first mixing chamber 12 contains a dry powder medium that is reconstituted in a liquid medium. It is contemplated that a pre-measured amount of the dry powder medium is provided to the first mixing chamber 12. In some embodiments, the first mixing chamber 12 can be pre-packaged with a pre-measured amount of the dry powder medium therein. Further, in various embodiments, the first mixing chamber 12 is designed to facilitate the mixing of the medium with purified water and / or other powders or liquids such as dissolved sodium bicarbonate or adjuvants. For example, the first mixing chamber 12 can include an upper cone and / or a lower cone respectively connected to the upper end and / or the lower end of the first mixing chamber 12 to promote the generation of a swirling vortex motion when fluid enters the first mixing chamber 12. The swirling vortex motion promotes the mixing of the dry powder medium, purified water, dissolved sodium bicarbonate, adjuvants, and the like. Various configurations and embodiments of the first mixing chamber 12 are described in U.S. Patent Application No. 15 / 087,826, entitled "Medium Mixing Chamber," filed on March 31, 2016, which is hereby incorporated by reference in its entirety.

[0028] The first mixing chamber 12 includes three ports, namely, a top port 20, an upper port 22, and a lower port 24, through which fluid can flow into and out of the first mixing chamber 12. In an exemplary embodiment, ports 22 and 24 are disposed in the first mixing chamber 12 such that fluid enters the first mixing chamber 12 at a substantially tangential angle to the inner wall of the first mixing chamber 12 through ports 22 and 24, thereby further facilitating the mixing of the various medium components within the first mixing chamber 12.

[0029] The top inflow / outflow pipe 30 is connected to the first mixing chamber 12 at the top port 20. As shown in FIG. 1A, the top inflow / outflow pipe 30 connects the first mixing chamber 12 to a common inflow pipe 32 and an upper filter inflow pipe 34. Similarly, the common inflow pipe 32 is connected to an auxiliary substance inflow pipe 36 and a compressed air inflow pipe 38. The auxiliary substance inflow pipe 36 is configured to be connected to an auxiliary substance source (not shown) at an auxiliary substance inlet 40. The auxiliary substance source can include any type of auxiliary substance used in a cell culture medium, such as an amino acid auxiliary substance, a cholesterol auxiliary substance, a lipid auxiliary substance, etc. The compressed air inflow pipe 38 is configured to be connected to a compressed air source (not shown) at a compressed air inlet 42. Thus, when fluids (e.g., medium auxiliary substances, compressed air) are introduced into the apparatus 10 through the auxiliary substance inflow pipe 36 and the compressed air inflow pipe 38, the fluids flow into the common inflow pipe 32. Then, the fluids flow into the top inflow / outflow pipe 30 and enter the first mixing chamber 12 through the top port 20.

[0030] As shown in FIG. 1A, the compressed air inflow pipe 38 also includes a compressed air valve 44. When in the open position, the compressed air valve 44, as described, allows compressed air to flow from the compressed air source through the compressed air valve 44 into the first mixing chamber 12. Conversely, when the compressed air valve 44 is in the closed position, the compressed air valve 44 prevents compressed air from flowing through the valve 44. However, as further shown in FIG. 1A, the auxiliary substance inflow pipe 36 does not include a valve. Thus, unlike compressed air, the auxiliary substance can flow into the first mixing chamber 12 at any time when the auxiliary substance is introduced into the apparatus 10 through the auxiliary substance inflow pipe 36.

[0031] The upper inlet pipe 46 is connected to the first mixing chamber 12 at the upper port 22. The upper inlet pipe 46 is connected to a fluid inlet pipe 48. The water inlet pipe 48 is configured to be connected to a fluid source (not shown) by a fluid inlet 50. In an exemplary embodiment, the fluid source includes and supplies purified water (e.g., distilled deionized water (ddH2O)). In an exemplary embodiment, the water source includes at least 1,000 L of purified water. Further, the upper inlet pipe 46 includes an upper inlet valve 52. Thus, when the upper inlet valve 52 is in the open position and water is introduced into the apparatus 10 by the water inlet pipe 48, the water flows from the water inlet pipe 48, through the open upper inlet valve 52, and into the upper inlet pipe 46. From the upper inlet pipe 46, the water flows into the first mixing chamber 12 by the upper port 22. When the upper inlet valve 52 is in the closed position, water cannot flow into the first mixing chamber 12 by the upper port 22.

[0032] As shown in FIG. 1A, the water inlet pipe 48 is further connected to a lower flow pipe 54, a second chamber pipe 56, and a lower filter pipe 58. The lower flow pipe 54 is connected to the first mixing chamber 12 by a lower port 24, and a second chamber outlet pipe 60 branches from the lower flow pipe 54 in the middle of the length of the lower flow pipe 54. The lower flow pipe 54 further includes a lower port valve 62 proximate to the pipe portion where the water inlet pipe 48, the lower flow pipe 54, the second chamber pipe 56, and the lower filter pipe 58 are connected. Thus, when the lower port valve 62 is in the open position, fluid can flow into and out of the first mixing chamber 12 through the lower flow pipe 54 and the lower port 24, but when the lower port valve 62 is in the closed position, fluid cannot flow through the valve 62.

[0033] The second mixing chamber 14 contains additives to the cell culture medium. In an exemplary embodiment, the second mixing chamber 14 contains sodium bicarbonate powder, and the second mixing chamber 14 is designed to facilitate the mixing of sodium bicarbonate and purified water. Further, the second mixing chamber 14 can be pre-packaged with a pre-measured amount of sodium bicarbonate therein. In some embodiments, the second mixing chamber 14 is configured similarly to the first mixing chamber 12 (e.g., including upper and / or lower cones respectively connected to the upper end and / or lower end of the second mixing chamber 14 to facilitate the generation of a swirling vortex motion when fluid enters the second mixing chamber 14). In other embodiments, the second mixing chamber 14 is configured differently from the first mixing chamber 12. The various configurations and embodiments of the second mixing chamber 14 are described in U.S. Patent Application No. 15 / 087,826, entitled "Media Mixing Chamber", filed on March 31, 2016, which is hereby incorporated by reference in its entirety as described above.

[0034] The second mixing chamber 14 includes two ports through which fluid can flow into and out of the second mixing chamber 14, namely, a second chamber top port 64 and a second chamber bottom port 66. In an exemplary embodiment, the port 66 is arranged such that fluid enters the second mixing chamber 14 through the port 66 at an angle substantially tangential to the inner wall of the second mixing chamber 14, thereby further facilitating the mixing of sodium bicarbonate within the second mixing chamber 14.

[0035] As shown in FIG. 1A, the second chamber outflow pipe 60 is connected to the second mixing chamber 14 at the second chamber top port 64. The second chamber outflow pipe 60 also includes a second chamber outflow valve 68 proximate to where the second chamber outflow pipe 60 branches from the lower flow pipe 54. Further, as shown in FIG. 1A, the second chamber pipe 56 is connected to the second mixing chamber 14 at the second chamber lower port 66. The second chamber inflow pipe 56 further includes a second chamber inflow valve 70 proximate to the pipe portion where the water inflow pipe 48, the lower flow pipe 54, the second chamber pipe 56, and the lower filter pipe 58 connect. Thus, fluid (e.g., purified water from a water source) can flow into and out of the second mixing chamber 14 only when the second chamber inflow valve 70 and the second chamber outflow valve 68 are in the open position. When the second chamber inflow valve 70 and the second chamber outflow valve 68 are in the closed position, fluid cannot flow into or out of the second mixing chamber 14.

[0036] The lower filter pipe 58 connects the upper filter inflow pipe 34 to the pipe portion where the water inflow pipe 48, the lower flow pipe 54, the second chamber pipe 56, and the lower filter pipe 58 converge at the position where the lower filter pipe 58 and the upper filter inflow pipe 34 merge. Next, the merged lower filter pipe 58 and upper filter inflow pipe 34 are connected to the filter unit 16. As shown in FIG. 1A, the filter unit 16 includes a filtration pipe portion 72 by which the filter unit 16 is connected to the merged lower filter pipe 58 and upper filter inflow pipe 34. The filtration pipe portion 72 is also connected to an outlet 74 that ends at the device outlet 76. The device outlet 76 is configured to be connected to a collection container that collects the medium solution mixed and discharged by the device 10. In various embodiments, the collection container can be made of glass, plastic, or metal and can be preformed or flexible.

[0037] Filter 16 is configured to filter the solution flowing into the filter by the filter tube portion 72. For example, filter 16 can remove undissolved powder medium from the solution by a membrane within filter 16. Filter 16 can further be configured to sterilize the solution flowing into the filter before the solution flows out of the device through the outlet 74. Additionally, since air does not pass through the membrane of filter 16 when filter 16 is wet, filter 16 can further include a top segment with a hydrophobic vent that allows air to escape from filter 16. This vent prevents air from being trapped in filter 16 and interfering with the filtration process.

[0038] Filters of the type envisioned in this technology can be purchased from many suppliers. For example, filter 16 can include nylon or cellulose acetate. Additionally, in the case of media products, filter 16 is typically a 0.2 μ filter, but it is contemplated that other filter sizes can be selected for specific functions. For example, the preparation of an electrophoresis buffer requires a solution that is not contaminated but not necessarily sterile, and a 0.45 μ filter is sufficient. Similarly, the preparation of a more viscous solution may require a larger pore size. In short, filter 16 can be of any desired size, volume, pore size, etc. Further, for other uses of the technology disclosed herein, it may not be necessary to add a filtration device. Thereafter, the liquid moves directly through the outlet 74 to the collection container. Alternatively, in some embodiments, a hydrophobic vent filter is used somewhere upstream of filter 16 to allow air entrained in the dissolved medium to escape so as not to fill filter 16.

[0039] As shown in FIG. 1A, the lower filter tube 58 further includes a water bypass valve 78 proximate to the tube portion to which the water inlet tube 48, the lower flow tube 54, the second chamber tube 56, and the lower filter tube 58 are connected. For this reason, when the water bypass valve 78 is in the open position and the water supply source is open, fluid flows from the fluid supply source through the water inlet 48 into the lower filter tube 58. From the lower filter tube 58, the fluid flows into the filter 16 through the filter tube portion 72. In this way, the fluid can bypass both the first mixing chamber 12 and the second mixing chamber 14 and flow directly to the filter 16 (e.g., to reduce the back pressure of the filter 16). When the water bypass valve 78 is in the closed position, the water bypass valve 78 prevents fluid (e.g., water from the water supply source, the bicarbonate solution mixed by the second mixing chamber 14) from bypassing the first mixing chamber 12 and flowing directly to the filter 16.

[0040] Similarly, as shown in FIG. 1A, the upper filter inlet tube 34 further includes an upper filter inlet valve 80. Thus, when the upper filter inlet valve 80 is in the open position, the upper filter inlet tube 34 allows fluid to flow through the upper filter inlet tube 34 into the filter 16. More specifically, when the first mixing chamber 12 is filled with a solution (e.g., a solution of purified water, powder medium, bicarbonate, and / or auxiliary substances), the solution flows out of the first mixing chamber 12 through the top port 20 and into the top inlet / outlet 30. Next, the solution flows into the upper filter inlet tube 34 and, when the upper filter inlet valve 80 is in the open position, into the filter 16 through the filter tube portion 72. On the other hand, when the upper filter inlet valve 80 is in the closed position, fluid cannot flow through the upper filter inlet tube 34 into the filter 16.

[0041] Further, in various embodiments, the mixing device 10 can include various sensors for obtaining measurement values within the mixing device 10. These sensors can include, for example, a pressure sensor (e.g., for detecting the water pressure within the device 10), a conductivity sensor (e.g., for detecting the conductivity, and thus the concentration, of the solution within the device 10), a volumetric sensor such as a rotary flow meter (e.g., for detecting the volume and flow rate of the fluid consumed in the mixing process), a pH sensor (e.g., for detecting the pH of the solution within the device 10), a viscometer (e.g., for measuring the viscosity of the fluid within the device 10), and the like. As shown in FIG. 1B, in an exemplary embodiment, the mixing device 10 includes at least a pressure sensor 90 located in the upper filter inlet pipe 34, a conductivity sensor 92 located in the combined upper filter inlet pipe 34 and lower filter pipe 58, and a volumetric sensor 94 located in the water inlet pipe 48. The pressure sensor 90 is configured to measure the pressure of the fluid flowing into the filter 16 (e.g., to ensure that the back pressure of the filter 16 does not become too high). The conductivity sensor 92 is configured to measure the conductivity of the solution flowing into the filter 16, thereby indirectly measuring the concentration of the solution flowing into the filter 16 and ultimately out of the device 10. Finally, the volumetric sensor 94 is configured to measure the volume and flow rate of the water consumed during the mixing process.

[0042] In various embodiments, as described in further detail below, the powdered medium is mixed with the liquid medium in the mixing device 10 by an automated method. Using the mixing device 10 to prepare the liquid medium from the dry powdered medium by an automated method is an improvement over the current art because it enables easy and efficient preparation of the liquid medium. Further, by having programming logic that controls the automated method (e.g., implemented by a processing circuit that executes instructions stored on a non-transitory machine-readable medium as part of a computing system), the preparation of the liquid medium from the dry powdered medium is made reproducible and consistent.

[0043] In an automated method, a computing system controls the opening and closing of valves (e.g., valves 44, 52, 62, 68, 70, 78, and 80) and the supply sources of components (e.g., water supply source, compressed air supply source, auxiliary substance supply source) used in the automated method to control the mixing of a powder medium into a liquid medium. The computing system opens and closes the valves and component supply sources in response to various triggers. For example, the computing system can receive measurements from the mixing device 10 related to the mixing process (e.g., from pressure sensor 90, conductivity sensor 92, and volume sensor 94). The computing system can then open and close the valves and / or component supply sources in response to receiving measurements at a specific level, below or above a specific level, within a specific range, etc. As another example, the computing system can open and close the valves and / or component supply sources in response to a specific elapsed time.

[0044] Accordingly, FIG. 2 shows a computing system configured to control the mixing device 10 according to an automated method, and this computing system is embodied as a mixing control device 100. As shown in FIG. 2, the mixing control device 100 includes a communication interface 102 and a processing circuit 104. The communication interface 102 is configured to facilitate communication between the mixing control device 100 and an external system or device. Accordingly, as shown in FIG. 2, the communication interface 102 can receive data related to the mixing process from a group of sensors 150 included in the mixing device 10, such as pressure data from the pressure sensor 90, conductivity data from the conductivity sensor 92, and volume / flow rate data from the volume sensor 94. Further, the communication interface 102 can receive commands from a user via the user device 170. For example, the communication interface 102 can receive a command from the user via the user device 170 to start the execution of the automated mixing method.

[0045] As shown in FIG. 2, the communication interface 102 can send commands to one or more of the valve groups 152 such as the valves 44, 52, 62, 68, 70, 78, and 80 described above. Similarly, the communication interface 102 can send instructions or commands to the component supply source groups 154 such as the water supply source 160 (e.g., connected to the water inlet 50), the auxiliary substance supply source 162 (e.g., connected to the auxiliary substance inlet 40), and the compressed air supply source 164 (e.g., connected to the compressed air inlet 42). For example, the communication interface 102 can send commands to open or close any valve within the valve group 152 or any component supply source within the component supply source group 154.

[0046] The communication interface 102 can include a wired or wireless communication interface (e.g., a jack, an antenna, a transmitter, a receiver, a transceiver, a wire terminal, etc.) for data communication with an external system or device. In various embodiments, the communication can be direct (e.g., local wired or wireless communication) or via a communication network (e.g., WAN, Internet, cellular network, etc.). For example, the communication interface 102 can include an Ethernet card and ports for sending and receiving data via an Ethernet (registered trademark)-based communication link or network. In another example, the communication interface 102 can include a WiFi transceiver for communicating via a wireless communication network or a cellular or mobile phone communication transceiver.

[0047] The processing circuit 104 includes a processor 106 and a memory 108. The processor 106 can be a general-purpose or special-purpose processor, an application-specific integrated circuit (ASIC), one or more field-programmable gate arrays (FPGAs), a group of processing components, or other suitable processing components. The processor 106 is configured to execute computer code or instructions stored in the memory 108 or received from other computer-readable media (e.g., CDROM, network storage, remote server, etc.).

[0048] The memory 108 can include one or more devices (e.g., a memory unit, a memory device, a storage device, etc.) for storing data and / or computer code for completing and / or facilitating the various processes described in the present disclosure. The memory 108 can include random access memory (RAM), read-only memory (ROM), hard drive storage, a temporary storage device, non-volatile memory, flash memory, optical memory, or any other suitable memory for storing software objects and / or computer instructions. The memory 108 can include a database component, an object code component, a script component, or any other type of information structure for supporting the various activities and information structures described in the present disclosure. The memory 108 can be communicatively connected to the processor 106 via the processing circuit 104 and can include computer code for executing one or more processes described herein (e.g., by the processor 106). When the processor 106 executes instructions stored in the memory 108 to complete the various activities described herein, the processor 106 generally configures the hybrid control device 100 (more particularly, the processing circuit 104) to complete such activities.

[0049] The hybrid control device 100 further includes a measurement control device 110 and a method execution control device 112. As shown in FIG. 2, the measurement control device 110 is configured to receive measurement values from the sensor group 150 via the communication interface 102. Additionally, in various embodiments, the measurement control device 110 is composed of an internal timer for tracking the elapsed time during the execution of the automation method. The measurement control device 110 provides one or more of the received measurement values and / or the tracked elapsed time to the method execution control device 112 during the execution of the automation method. Additionally, the measurement control device 110 can receive data indicating the progress of the automation method from the method execution control device 112 during the execution of the automation method. For example, the measurement control device 110 can receive an indication from the method execution control device 112 that a predetermined step of the automation method is currently being executed.

[0050] The method execution control device 112 is configured to provide commands to one or more of the valve group 152 and the component supply source group 154. In various embodiments, the method execution control device 112 provides commands in response to (a) user commands received via the communication interface 102 and (b) data received from the measurement control device 110. In one example, the method execution control device 112 can open and close a specific valve of the valve group 152 and / or a specific component supply source of the component supply source group 154 in response to a user command to start the execution of the automation method. In a second example, the method execution control device 112 can open and close a specific valve of the valve group 152 and / or a specific component supply source of the component supply source group 154 in response to the received measurement value being at a specific level. In a third example, the method execution control device 112 can open and close a specific valve of the valve group 152 and / or a specific component supply source of the component supply source group 154 in response to a specific elapsed time. Additionally, the method execution control device 112 can be further configured to provide feedback data to the measurement control device 110. For example, the method execution control device 112 can provide a notification to the measurement control device 110 indicating that a predetermined step of the automation method has been executed.

[0051] FIG. 3 shows a flowchart illustrating an example of an automated method 200 for mixing a powder medium into a liquid medium using the mixing device 10. FIGS. 4A-4G show the flow of fluid through the mixing device 10 during steps of the automated method 200. As described below, the series of steps shown in FIGS. 3 and 4A-4E illustrate a precise protocol for successfully using the mixing device 10 to reconstitute a powder medium into a liquid medium. By using this precise protocol, the timing that is key to the success of the automated method 200 is obtained. For example, in an exemplary embodiment, the mixing control device 100 mixes an amount of powdered cell culture medium that is less than 50% of the volume of the first mixing chamber 12 using the protocol of the automated method 200.

[0052] However, those skilled in the art will understand that the automated method 200 is intended to be an example and does not limit the use of the mixing device 10 to the types and orders of steps described with respect to the automated method 200. Rather, the mixing control device 100 can use other embodiments of the automated method using the mixing device 10 to mix dry media powder into a liquid medium and, more generally, to mix dry powder into a liquid. For example, other embodiments of the automated method used with the mixing device 10 can include the use of different solution components, include fewer or additional steps, include different steps, provide the steps of the automated method 200 in a different order, and so on. Further, in other embodiments of the automated method used with the mixing device 10, the steps can include different "triggers" or additional "triggers" for the steps, apart from those described below.

[0053] First, during the transportation, installation, and setup of the mixing device 10, close (202) all valves (e.g., valves 44, 52, 62, 68, 70, 78, and 80). This helps prevent leakage and contamination during the setup process of the mixing device 10. For example, during setup, unpack the first mixing chamber 12 and the second mixing chamber 14, which are provided with pre-measured amounts of powdered medium and sodium bicarbonate in chambers 12 and 14 respectively, and set them up as shown in FIG. 1A. Alternatively, set up the first mixing chamber 12 and the second mixing chamber 14 as shown in FIG. 1A and place a measured amount of powdered medium and sodium bicarbonate into chambers 12 and 14. Next, configure the first mixing chamber 12 and the second mixing chamber 14 together with the filter 16 and the tubes to create the mixing device 10 as shown in FIG. 1A. Further, connect a compressed air source to the compressed air inlet 42, connect a purified water supply source containing a certain amount of water to the water inlet 50, and, if necessary, connect an auxiliary substance supply source to the auxiliary substance inlet 40. Also connect a collection container to the device outlet 76.

[0054] Next, the mixing control device 100 opens (204) the water supply source, the lower port valve 62, and the upper filter inlet valve 80. As shown in FIG. 4A, when the water supply source and the lower port valve 62 are opened, water flows from the water supply source through the water inlet pipe 48 and the lower port valve 62 into the lower flow pipe 54. Then, the water flows from the lower flow pipe 54 through the lower port 24 into the first mixing chamber 12, at which point the water begins to mix with the powdered medium contained in the first mixing chamber 12.

[0055] Furthermore, since the upper filter inlet valve 80 is open, when the first mixing chamber 12 begins to be filled with water from the bottom of the chamber 12, as shown in FIG. 4B, the displaced air is discharged from the top port 20 of the first mixing chamber 12. The displaced air flows through the top inlet / outlet 30 and the upper filter inlet pipe 34. The displaced air exits the mixing device 10 by flowing out through the outlet 74 through the filter 16. Alternatively, when the filter membrane of the filter 16 becomes wet, the membrane may prevent air from passing through the membrane and the filter 16. Thus, alternatively, air can exit the mixing device 10 through hydrophobic vents provided in the filter 16 (e.g., provided in the top segment of the filter 16). This is beneficial as it reduces the amount of air trapped within the first mixing chamber 12.

[0056] Finally, the water that flows into the first mixing chamber 12 through the lower port 24 and mixes with the powder medium to form the medium solution fills the first mixing chamber 12. In some embodiments, the first mixing chamber 12 is filled with solution immediately after the mixing process begins (e.g., during step 204). In other embodiments, the first mixing chamber 12 is filled with solution later in the mixing process (e.g., after step 204). In any case, when this occurs, the solution follows the same path as the displaced air, as shown in FIG. 4B. The solution exits the first mixing chamber 12 through the top port 20, flows into the filter 16 through the top inlet / outlet 30, the upper filter inlet pipe 34, and the filter tube portion 72. After being filtered and sterilized by the filter 16, the solution flows into the outlet 74, exits the mixing device 10 through the device outlet 76, and is collected there by the collection container. Although not shown in FIGS. 4C - 4E, when the solution begins to flow out of the first mixing chamber 12 through the top port 20, the solution flows out of the first mixing chamber 12 and out of the device 10 through the device outlet 76 through the filter 16 as long as water continues to flow into the first mixing chamber 12 (e.g., until step 216 described below).

[0057] After a predetermined elapsed time, the mixing control device 100 closes the lower port valve 62 and opens the upper inflow valve 52 (206). For example, in one embodiment, the mixing control device 100 waits for 1 minute before closing the lower port valve 62 and opening the upper inflow valve 52. As shown in FIG. 4C, this stops the inflow of water into the first mixing chamber 12 through the lower port 24. Instead, water flows from the water inflow pipe 48 to the upper inlet 46. From the upper inlet 46, water flows into the first mixing chamber 12 through the upper port 22 and continues to mix with the powder medium in the first mixing chamber 12. The switching of the water flow to the first mixing chamber 12 from the lower port 24 to the upper port 22 helps maintain a uniform dissolution rate of the powder medium in the chamber 12 without clogging the filter 16 with high concentrations of solutes, undissolved particles, and air that may occur when water flows into the chamber 12 through the lower port 24. Furthermore, by switching the water flow, a desirable beneficial dissolution rate can be promoted.

[0058] During the above steps of the automation method 200, the mixing control device 100 continuously monitors the pressure in the upper filter inlet pipe 34 (e.g., by the pressure sensor 90). When the pressure in the upper filter inlet pipe 34 reaches a predetermined level, the mixing control device 100 opens the water bypass valve 78 (208). For example, in one embodiment, when the pressure in the upper filter inlet pipe 34 reaches 20 psig (pounds per square inch gauge pressure), the mixing control device 100 opens the water bypass valve 78. As shown in FIG. 4D, when this occurs, water continues to flow into the first mixing chamber 12 through the upper inlet 46 and the upper port 22. However, water also flows from the water supply source through the water inlet pipe 48 into the lower filter pipe 58. From the lower filter pipe 58, the water mixes with the solution (not shown) flowing out of the first mixing chamber 12 at the location where the upper filter inlet pipe 34 and the lower filter pipe 58 merge. Thereafter, the solution flows into the filter 16 through the filter pipe portion 72. After filtration, the water flows out of the device 10 through the outlet 74 and into the collection container. By opening the water bypass valve 78, it is possible for water to bypass the first mixing chamber 12 and the second mixing chamber 14 and flow directly to the filter 16, which helps to reduce the back pressure in the filter 16. It also helps to maintain the flow necessary for the first mixing chamber 12 to function properly.

[0059] The mixing control device 100 keeps the water bypass valve 78 open for a predetermined time to allow water to flow directly to the filter 16. After the predetermined time has elapsed, the mixing control device 100 closes the water bypass valve 78 (210). For example, in one embodiment, the mixing control device 100 closes the water bypass valve 78 after 2 minutes have passed. Thereafter, the direct water flow to the filter 16 stops, and the mixing device 10 returns to the state of step 206 as shown in FIG. 4C. By closing the water bypass valve 78, the mixing control device 100 helps to avoid premature depletion of a certain amount of water (e.g., a certain amount of 1000 L of purified water) required for the automation method 200.

[0060] The hybrid control device 100 also continuously monitors the conductivity of the solution entering the filter (e.g., by conductivity sensor 92). Since the solution is conductively related to the solution concentration (e.g., the higher the solution conductivity, the higher the solution concentration, and vice versa), by monitoring the conductivity of the solution entering the filter, the hybrid control device 100 can indirectly monitor the concentration of the solution exiting the first mixing chamber 12. When the conductivity of the solution reaches a predetermined conductivity, the hybrid control device 100 closes the upper inlet valve 52 and opens the lower port valve 62 (212). For example, in one embodiment, the hybrid control device 100 closes the upper inlet valve 52 and opens the lower port valve 62 when the conductivity of the solution entering the filter is 6 mS / cm (millisiemens per centimeter) or less. Thus, the water flow to the first mixing chamber 12 switches from the upper port 22 to the lower port 24, returning the mixing device 10 to the state of step 204 shown in FIG. 4A. By switching the water flow from the upper port 22 to the lower port 24 when the conductivity of the solution reaches 6 mS / cm, it helps to ensure that a sufficient concentration of solute (e.g., powdered medium) in the solution being mixed in the first mixing chamber 12 is maintained (e.g., so that a certain amount of water provided by the water supply source is not used up without being mixed into a sufficiently concentrated solution).

[0061] In addition to monitoring the pressure within the upper filter inlet pipe 34 and the conductivity of the solution entering the filter 16, the mixing control device 100 further continuously monitors the amount of water consumed (e.g., by the volume sensor 94) during the execution of the automated method 200. When a predetermined total amount of water is consumed, the mixing control device 100 closes the lower port valve 62, opens the second chamber inlet valve 70, and opens the second chamber outlet valve 68 (214). For example, in one embodiment, the mixing control device 100 closes the lower port valve 62, opens the second chamber inlet valve 70, and opens the second chamber outlet valve 68 when the total amount of water consumed reaches 800 L or more. As shown in FIG. 4E, when this occurs, water flows from the water source through the water inlet pipe 48 into the second chamber pipe 56. From the second chamber pipe 56, the water flows through the second chamber lower port 66 into the second mixing chamber 14, where it mixes with the sodium bicarbonate powder within the second mixing chamber 14. When the second mixing chamber 14 is filled with water, the water and bicarbonate solution is pushed out from the second chamber top port 64 and pushed into the second chamber outlet 60. The bicarbonate solution then flows from the second chamber outlet 60 into the lower flow pipe 54 and finally enters the first mixing chamber 12 through the lower port 24. When the bicarbonate solution enters the first mixing chamber 12, the bicarbonate solution mixes with the water and powder medium contained within the first mixing chamber 12. In this way, the sodium bicarbonate powder (and / or other additives contained within the second mixing chamber 14) is separately dissolved before being added to the solution within the first mixing chamber 12.

[0062] The mixing control device 100 maintains the valves in this configuration for a predetermined time. After the predetermined time has elapsed, the mixing control device 100 closes the second chamber inlet valve 70, closes the second chamber outlet valve 68, and opens the lower port valve 62 (216). For example, in one embodiment, the mixing control device 100 closes the second chamber inlet valve 70, closes the second chamber outlet valve 68, and opens the lower port valve 62 when at least 5 minutes have elapsed. This stops the water flow through the second mixing chamber 14, resumes the water flow from the water source to the first mixing chamber 12 through the lower port 24, and returns the mixing device 10 to the configuration of steps 204 and 212 shown in FIG. 4A.

[0063] Finally, when the mixing control device 100 determines that the total amount of water consumed (e.g., by the volume sensor 94) has reached a predetermined total amount, the mixing control device 100 closes the water supply source and the upper filter inlet valve 80. The mixing control device 100 further opens the compressed air valve 44 and the water bypass valve 78 (218). For example, in one embodiment, when 1,000 L of water is consumed during the mixing process, the mixing control device 100 closes the water supply source and the upper filter inlet valve 80 and opens the compressed air valve 44 and the water bypass valve 78. When this occurs, compressed air flows from the compressed air supply source through the compressed air inlet 42 into the compressed air inlet 38. From the compressed air inlet 38, the compressed air flows into the common inlet 32 and through the top inlet / outlet 30 into the top port 20 and into the first mixing chamber 12. The compressed air flowing into the first mixing chamber 12 discharges the solution remaining in the chamber 12 from the chamber 12 through the lower port 24 into the lower flow tube 54. The discharged solution then flows through the lower flow tube 54 into the lower filter tube 58 and into the filter 16 by the filter tube portion 72. After being filtered, the solution flows through the outlet 74 into a collection container connected to the device outlet 76. In this way, using compressed air, the solution remaining in the first mixing chamber 12 can be discharged from the device 10 into the collection container to obtain a target volume yield (e.g., 1,000 L of prepared liquid medium).

[0064] During any step of the automated method 200, an auxiliary substance can be added to the solution being mixed in the first mixing chamber 12. FIG. 4G shows the flow of a predetermined auxiliary substance into the first mixing chamber 12. The auxiliary substance flows into the auxiliary substance inlet 36 of the device 10 through the auxiliary substance inlet 40 and follows the tube of the auxiliary substance inlet 36 into the common inlet 32. If the solution being mixed in the first mixing chamber 12 is still contained in the chamber 12, the auxiliary substance flows from the common inlet 32 into the top inlet / outlet 30 and into the first mixing chamber 12 through the top port 20. If the solution being mixed in the first mixing chamber 12 fills the chamber 12 and is flowing out of the top port 20, the auxiliary substance mixes with the solution flowing out of the chamber 12 in the upper filter inlet tube 34.

[0065] However, while the automated method 200 described above relates to the reconstitution of powdered cell culture media, it should be understood that embodiments of the mixing device 10 can be used with embodiments of the automated method to reconstitute various dry components into a liquid, e.g., various bioprocess powders into a bioprocess solution. Further, the liquid solvent used can be considered to be water, alcohol, or other organic substances. Solubility characteristics, the solvent used, the amounts required, and the chemical interactions between the solvent and the reconstituted chemical substances serve to provide guidelines for the embodiments of the automated method used to reconstitute the powder and the configuration of the mixing device used in a given embodiment of the automated method. Further, the preferred embodiments described herein add liquid to these dry components for the purpose of reconstituting the dry components, but the mixing device is considered to be equally effective for the reconstitution of concentrates or a series of combinations of liquids and powders.

[0066] Various modified forms of the technology can be constructed for various end uses. For example, the mixing device 10 can include only the first mixing chamber 12. Both the powdered medium and a secondary additive such as sodium bicarbonate can be fed together into the first mixing chamber 12. Thus, only one chamber is required to dissolve the solid in the liquid. As another example, the mixing device 10 can include one or more additional mixing chambers in addition to the first mixing chamber 12 and the second mixing chamber 14 (e.g., for separately mixing additional secondary additives).

[0067] The foregoing description has detailed certain embodiments of the systems, devices, and methods disclosed herein. However, it will be understood that, no matter how detailed the foregoing may be in text, the devices and methods may be implemented in various ways. Also, as noted above, the use of particular terms when describing certain features or aspects of the technology is not meant to imply that the term is redefined herein to include particular characteristics of the feature or aspect of the technology with which the term is associated. Accordingly, the scope of the present disclosure should be construed in accordance with the appended claims and their equivalents.

[0068] It will be understood by those skilled in the art that various modifications and changes can be made without departing from the scope of the technology described. Such modifications and changes are intended to fall within the scope of the embodiments as defined by the appended claims. Also, it will be understood by those skilled in the art that parts included in one embodiment are interchangeable with other embodiments, and that one or more parts of the illustrated embodiments can be included in any combination with other illustrated embodiments. For example, any of the various components described and / or shown in the drawings can be combined with, interchanged with, or excluded from other embodiments.

[0069] Embodiments of the present specification have been described with reference to the drawings. The drawings show specific details of specific embodiments for implementing the systems and methods described herein. However, describing the embodiments using the drawings should not be construed as imposing limitations that may exist in the drawings on the present disclosure.

[0070] Regarding the use of plural and / or singular terms in this specification, those skilled in the art can translate from plural to singular and / or from singular to plural as appropriate for the context and / or application. Various singular / plural exchanges can be explicitly described in this specification for clarity.

[0071] Generally, those skilled in the art will understand that the terms used in this specification and in particular in the appended claims are generally intended to be "open" terms (e.g., the term "including" should be construed as "including but not limited to", the terms "comprising" and "having" should be construed as "including at least" and "having at least", respectively, and the term "includes" should be construed as "including but not limited to", etc.). Further, if a specific number of introductions of claim descriptions is intended, such intention is explicitly stated in the claims, and those skilled in the art will understand that such intention does not exist if there is no such description. For example, for the sake of understanding, the following appended claims may include the use of introductory phrases such as "at least one" and "one or more" to introduce claim descriptions. However, the use of such phrases should not be construed as implying that the introduction of a claim description by the indefinite article such as "one or more" or "at least one" and "a" or "an" in the same claim limits a particular claim including such claim description to an embodiment including only one such description. Generally, "a" and / or "an" should be construed as meaning "at least one" or "one or more", and the same applies to the use of definite articles used to introduce claim descriptions.

[0072] Also, in cases where conventional expressions similar to “at least one of A, B, and C” are used, generally, such syntax is intended in a sense that those skilled in the art would understand this conventional expression (e.g., “a system having at least one of A, B, and C” includes, but is not limited to, a system having A alone, B alone, C alone, A and B together, A and C together, B and C together, and / or A, B, and C together). In cases where conventional expressions similar to “at least one of A, B, or C” are used, generally, such syntax is intended in a sense that those skilled in the art would understand this conventional expression (e.g., “a system having at least one of A, B, or C” includes, but is not limited to, a system having A alone, B alone, C alone, A and B together, A and C together, B and C together, and / or A, B, and C together). It will be further understood by those skilled in the art that any disjunctive and / or clause presenting two or more alternative terms in any of the specification, claims, or drawings should be understood to contemplate the possibility of including one of the terms, any of the terms, or both of the terms. For example, the phrase “A or B” is understood to include the possibilities of “A” or “B” or “A and B”.

[0073] For the purposes of the present disclosure, the term “coupled” means that two members are joined directly or indirectly to each other. Such a joining may be fixed or movable. Such a joining can be achieved by two members or two members and an additional intermediate member being integrally formed as a single unitary body with each other, or by two members or two members and an additional intermediate member being attached to each other. Such a joining may be essentially permanent or essentially removable or releasable.

[0074] The techniques described in this specification have many applications. Although specific embodiments of the technology have been described in detail, it will be apparent to those skilled in the art that the disclosed embodiments can be modified in light of the design considerations described herein. Accordingly, the foregoing description should be regarded as illustrative rather than restrictive, and the true scope of the invention is defined by the appended claims.

Claims

1. 1. An automated method comprising: Providing dry ingredients to be reconstituted into a liquid bioprocessing solution; controlling, by a processing circuit, an automated system including at least one mixing chamber, a number of tubes for fluid flow within the system, and a number of valves within the tubes and controlled by the processing circuit, for automatically preparing the bioprocess solution from the dry components; A method comprising:

2. The method of claim 1 , wherein the liquid solution prepared is a cell culture medium.

3. 10. The method of claim 1, wherein the bioprocess solution is a buffer solution.

4. The method of claim 1 , wherein the dry ingredients are in powder form.

5. The method of claim 1 , wherein the dry ingredients are in granular form.

6. controlling the automated system includes controlling, by the processing circuitry, the automated system to perform a series of sequential mixing steps; 10. The method of claim 1, wherein the series of continuous mixing steps results in preparation of the liquid bioprocess solution.

7. 7. The method of claim 6, further comprising obtaining one or more measurements during preparation of the liquid bioprocess solution, each step being triggered by at least one of a measurement falling below, equal to, or exceeding a measurement threshold.

8. The method of claim 7 , wherein the one or more measurements include at least one of pressure, conductivity, volume of water consumed during brewing, flow rate, or elapsed time.

9. The method of claim 6 , wherein each step includes opening and closing at least one of the plurality of valves by the processing circuitry to control fluid flow within the automated system.

10. The method of claim 1 , wherein the automated system further comprises two or more inlets to the tube, each inlet configured to direct a flow of fluid to the automated system.

11. 1. An automated method comprising: Providing dry ingredients to be reconstituted into a liquid bioprocessing solution; providing an automated system including at least one mixing chamber, a number of pipes for fluid flow within the system, a number of valves in the pipes, and one or more inlets to the pipes; connecting a purified water source to one of the one or more inlets; To prepare the liquid bioprocessing solution from the dry components: performing a series of sequential mixing steps, each step including opening and closing at least one of the plurality of valves to control fluid flow within the automated system; obtaining one or more measurements during preparation of the liquid bioprocess solution; The processing circuit controls the automation system. Including, A method wherein each step is triggered by at least one of a measurement value falling below, equal to, or exceeding a measurement threshold.

12. 12. The method of claim 11, wherein the bioprocess solution is a cell culture medium.

13. 13. The method of claim 12, wherein the bioprocess solution is a buffer solution.

14. The method of claim 11 , wherein the dry ingredients are in powder form.

15. The method of claim 11 , wherein the dry ingredients are in granular form.

16. The method of claim 11 , wherein the one or more measurements include at least one of pressure, conductivity, volume of water consumed during brewing, flow rate, or elapsed time.

17. The automated system includes two or more inlets, and the method further comprises: connecting a compressed air source to one of the two or more inlets; opening the compressed air source to drain the prepared liquid bioprocessing solution from the automated system; The method of claim 11 further comprising:

18. the automated system includes at least a first mixing chamber containing the dry ingredients and a second mixing chamber containing an additive; 12. The method of claim 11, wherein at least one of said steps comprises mixing said additive with purified water in said second mixing chamber before being added to said first mixing chamber.

19. 1. An automated apparatus for preparing a liquid bioprocess solution, comprising: At least one mixing chamber; A plurality of tubes; A plurality of valves disposed within the pipe; a mixing controller including at least a processor and a memory having instructions stored thereon, the mixing controller being configured to control the plurality of valves to prepare a liquid bioprocess solution from dry components; 4. An automated device comprising:

20. and one or more sensors configured to obtain one or more measurements during preparation of the liquid cell culture medium; 20. The automated device of claim 19, wherein the mixing control device is configured to control the plurality of valves in response to at least one of the measurement value falling below, equal to, or exceeding a measurement threshold.

21. 21. The automated device of claim 20, wherein the one or more sensors include at least one of a pressure sensor, a conductivity sensor, a volume sensor, or a timer.

22. 20. The automated device of claim 19, further comprising two or more inlets to the tube, each inlet configured to direct a flow of fluid to the automated system.

23. one of the two or more inlets is configured to be coupled to a compressed air source; 23. The automated apparatus of claim 22, wherein the mixing control device is further configured to open the compressed air source to drain the prepared liquid bioprocess solution from the automated apparatus.

24. The automated device includes at least a first mixing chamber containing dry ingredients and a second mixing chamber containing additives; 20. The automated device of claim 19, wherein the mixing control device is configured to control the plurality of valves such that the additive is mixed with purified water in the second mixing chamber and then added to the first mixing chamber.

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