AUTOMATED METHOD AND APPARATUS FOR PREPARING BIOPROCESS SOLUTIONS - Patent application

Abstract

To provide an automated apparatus for preparing bioprocess solutions.SOLUTION: Provided is an automated apparatus for preparing a bioprocess solution. The apparatus comprises: a first mixing chamber containing ingredients of the bioprocess solution; a first port and a second port, which allow fluid to enter the mixing chamber; a third port for allowing a liquid bioprocess solution prepared from the ingredients to exit the mixing chamber; a plurality of tubes for fluid flow within the apparatus; a sensor arranged to measure a property of the liquid bioprocess solution exiting the mixing chamber; a first valve configured to control flow to the first port; and a second valve configured to control flow to the second port. If the characteristic meets or exceeds a threshold, the apparatus is operable to perform at least one of closing the first valve and opening the second valve.SELECTED DRAWING: Figure 1A

Description

[Technical field]

[0001] Embodiments of the present technology generally relate to automated methods and apparatus for mixing at least one material with at least one fluid, and more particularly, to automated methods and apparatus that are particularly suited for reconstituting a predetermined unit volume of dry components 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 June 30, 2017, which is incorporated herein by reference in its entirety. [Background technology]

[0003] A bioprocess is a process that uses living cells or their components to obtain a desired product. Bioprocessing often requires the use of various solutions. For example, the first step of a bioprocess may involve cell culture, which often requires the successful cultivation of new cells using cell culture media. Later steps in a bioprocess may require the use of various buffers as part of the product purification process.

[0004] Bioprocessing solutions are often hydrated from dry ingredients just prior to use in large stainless steel tanks or single-use mixing devices. The typical process is time consuming, expensive, and does not add direct value to the desired product. Although basic cell culture methods have not changed much over the years, cell culture volumes continue to increase dramatically, thereby changing the requirements for media preparation. Many laboratories, 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 media per day and employ large numbers of manufacturing engineers and scientists to produce antibodies, growth factors, or recombinant proteins from cell cultures for commercial use. Summary of the Invention [Problem to be solved by the invention]

[0005] The present invention provides an automated system and method for preparing bioprocess solutions using in-line mixing devices that helps reduce the time, effort, risk of error, and risk of contamination required in these processes, while also improving reliability and consistency. [Means for solving the problem]

[0006] In general, the embodiments described herein relate to automated methods and devices for preparing dry components into liquid solutions (e.g., preparing powdered bioprocessing media into liquid bioprocessing media). As described further below, dry components tend to require less storage space than reconstituted liquid solutions, have a longer shelf life, are less expensive, and require less shipping and handling time than pre-packaged liquid solutions. Thus, when a liquid solution is required, it is advantageous to utilize automated methods and devices designed to make the preparation of a liquid solution from dry components simple, straightforward, and reproducible, rather than purchasing a pre-packaged liquid solution. Thus, the technology according to some embodiments relates to an automated method used in conjunction 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 technology relate to an automated method used in conjunction with a mixing device, where both the automated method and the mixing device are suitable for reconstituting dry components into a predetermined unit volume of liquid.

[0007] Using this technology, various dry components can be reconstituted into liquid solutions. 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 ingredients, dry materials, and unhydrated components.

[0008] Some embodiments described herein are based at least in part on the shortcomings and / or inconveniences of existing reconstitution techniques as recognized by the inventors of the present technology, or on the recognition by the inventors of potential improvements. For example, prepackaged liquid cell culture media are sterilized, aliquoted into convenient sizes, and ready to use. However, prepackaged liquid cell culture media are generally light sensitive and have a given shelf life. Thus, prepackaged liquid cell culture media need to be ordered periodically. Also, they need to be stored under refrigeration, and in prepackaged form, they require significant manpower time to unpack and transport. Furthermore, the cost of shipping prepackaged liquid cell culture media is becoming increasingly expensive.

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

[0010] Furthermore, reconstitution of dry ingredients into a liquid bioprocessing solution is generally a several-step process. As an example, to prepare liquid cell culture medium from a solid powder, a known amount of powder for a specific volume of medium is weighed out and added to a volume of distilled water, 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 to dissolve. The pH is then adjusted using an acid or base, and additional water is added to increase the medium to its final volume. The entire mixture is then passed through a sterile filter. The medium is then collected in a single large sterile container or divided into several smaller sterile containers.

[0011] There can be additional difficulties in reconstituting a solution based on the properties of the dry ingredients being reconstituted. For example, powdered tissue culture media has a very fine particle size and is hygroscopic. When mixed with water, it has a tendency to "ball" or "clump". Thus, when reconstituted with water or another aqueous liquid, sufficient agitation is required to break up any clumps that may form upon initial contact with water. If the batch size is small, a sterile magnetic stir bar is added to the mixing vessel and the vessel is placed on a magnetic stir plate. Adding a stir bar to the mixing vessel typically requires an additional operation. However, in a typical laboratory environment, a magnetic stir plate is not a practical method for large volume media preparation.

[0012] Additionally, due to their hygroscopic nature, powdered cell culture media will absorb water upon storage, especially in humid environments. Wet powdered media will shorten their shelf life, become lumpy, and require vigorous agitation to reconstitute. Therefore, the shelf life of powdered cell culture media can be improved if they are provided in pre-measured, sealed, and dried aliquots.

[0013] Moreover, the reconstitution process requires several steps and several separate pieces of equipment. Generally, at least one container large enough to accommodate the entire final volume of the reconstituted medium and one or more containers to receive the sterile medium after filtration are required. The sterilized medium is usually placed in an open-top container. Therefore, most medium preparation is performed in a laminar flow hood. However, processing large volumes of medium in the hood is difficult because there is often not enough space to accommodate the containers and the sterile medium. Therefore, methods and devices are described herein that allow the preparation of large volumes of solutions (e.g., cell culture medium) with minimal physical contact and in a reliable and reproducible manner.

[0014] One embodiment of the present technology relates to an automated method. The automated method includes providing dry components to be reconstituted into a liquid bioprocess solution, and controlling, by the processing circuit, an automated system including at least one mixing chamber, a plurality of tubes for fluid flow in the system, and a plurality of valves in the tubes, to automatically prepare the liquid bioprocess solution from the dry components. Controlling the automated system can include performing a series of successive mixing steps that cause the preparation of the liquid bioprocess solution. The method can further include obtaining one or more measurements during the preparation of the liquid bioprocess solution, each step being triggered by at least one of the measurements being below, equal to, or exceeding a measurement threshold. Each step can also include opening and closing at least one of the plurality of valves to control the flow of fluid in the automated 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 automated method. The automated method includes providing dry components to be reconstituted into a liquid bioprocess solution, and providing an automated system including at least one mixing chamber, a plurality of tubes for fluid flow in the system, a plurality of valves in the tubes, and one or more inlets to the tubes. The automated method also includes connecting a purified water source to one of the one or more inlets. The automated method further includes controlling the automated system with a processing circuit to prepare a liquid bioprocess solution from the dry components by performing a series of successive mixing steps, each step including opening and closing at least one of the plurality of valves to control the flow of fluid in the automated system, and obtaining one or more measurements during the preparation of the liquid bioprocess solution, each step being triggered by at least one of the measurements falling below, equaling, or exceeding a measurement threshold. The bioprocess solution can be a cell culture medium or a buffer solution.

[0016] A third embodiment of the present technology relates to an automated apparatus for preparing a liquid bioprocess solution from dry components. The automated apparatus includes at least one mixing chamber, a plurality of tubes, a plurality of valves disposed in the tubes, and a mixing controller. The mixing controller includes at least a processor and a memory having instructions stored therein, the mixing controller configured to control the plurality of valves to prepare the liquid bioprocess solution from the dry components. The automated apparatus may also include one or more sensors configured to obtain one or more measurements during preparation of the liquid bioprocess solution, the mixing controller configured to control the plurality of valves in response to at least one of the measurements being below, equal to, or exceeding a measurement threshold. The bioprocess solution may be a cell culture medium or a buffer solution.

[0017] A fourth embodiment of the present technology relates to an automated method, comprising 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 fluid flow in the system, and a plurality of valves in the tubes, to automatically prepare a liquid bioprocess buffer from the bioprocess buffer in the dry form. Controlling the automated system can include performing a series of successive mixing steps by the processing circuit, the series of successive mixing steps causing the preparation of a liquid bioprocess buffer. The method can further include obtaining one or more measurements during the preparation of the liquid bioprocess buffer, each step being caused by at least one of the measurements being below, equal to, or exceeding a 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 in the automated system. [Brief description of the drawings]

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

[0019] [Figure 1A] FIG. 1 is a schematic diagram of a mixing device used in the automated reconstitution method of a bioprocess solution. [Figure 1B] FIG. 1 is a schematic diagram of a mixing device used in the automated reconstitution method of a bioprocess solution.

[0020] [Diagram 2] FIG. 2 is a schematic diagram of a mixing control device for use with the mixing device of FIGS. 1A and 1B.

[0021] [Diagram 3] 1 is a flow chart illustrating an automated method for reconstituting powdered cell media.

[0022] [Figure 4A] FIG. 4 is a schematic diagram of the mixing device of FIGS. 1A and 1B illustrating the steps of the automated method of FIG. 3. [Figure 4B] FIG. 4 is a schematic diagram of the mixing device of FIGS. 1A and 1B illustrating the steps of the automated method of FIG. 3. [Figure 4C] FIG. 4 is a schematic diagram of the mixing device of FIGS. 1A and 1B illustrating the steps of the automated method of FIG. 3. [Figure 4D] FIG. 4 is a schematic diagram of the mixing device of FIGS. 1A and 1B illustrating the steps of the automated method of FIG. 3. [Figure 4E] FIG. 4 is a schematic diagram of the mixing device of FIGS. 1A and 1B illustrating the steps of the automated method of FIG. 3. [Figure 4F] FIG. 4 is a schematic diagram of the mixing device of FIGS. 1A and 1B illustrating the steps of the automated method of FIG. 3. [Figure 4G] FIG. 4 is a schematic diagram of the mixing device of FIGS. 1A and 1B illustrating the steps of the automated method of FIG. 3. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0023] In the following detailed description, reference is made to the accompanying drawings, which form a part of this disclosure. In the drawings, like numerals typically identify like components unless otherwise indicated by context. The exemplary embodiments described in the detailed description, drawings, and claims are not intended to be limiting. The detailed description is intended as an illustration of exemplary embodiments, and is not intended to represent the only embodiments that may be practiced. The term "exemplary" as used herein means "serving as an example, instance, or illustration," and should not necessarily be construed as preferred or advantageous over other embodiments. Other embodiments may be utilized, and other changes may 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, as generally described herein and illustrated in the drawings, can be arranged, substituted, combined, and designed in a wide variety of different configurations. All of these configurations are expressly contemplated and form a part of the present disclosure.

[0024] The embodiments described herein generally relate to devices / apparatus, systems, and methods for preparing solutions from dry components, such as cell culture media from dry powdered cell culture media or buffer solutions from dry buffer powders. One or more of the provided embodiments may overcome one or more shortcomings, limitations, or deficiencies that exist in the art with respect to reconstituting solutions, particularly with respect to reconstituting cell culture media in dry form, including dry powdered media. For example, in some embodiments described herein, automated methods and apparatus mix dry components into a liquid bioprocess solution such that the mixing process is easy to use, can be used to reconstitute relatively large volumes of solution, and can result in a thoroughly mixed, non-agglomerated solution.

[0025] The present disclosure refers to the systems and methods described herein in the context of preparing liquid cell culture media from powdered cell culture media. However, it is understood that the systems and methods described herein can be adapted to prepare 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 materials. As another example, the systems and methods described herein can be used to prepare various "bioprocess solutions," or solutions used in processes that use living cells or components thereof to obtain a desired product. Additionally, it is believed that the systems and methods described herein can be adapted to many broader commercial or industrial applications. By way of example, many liquid pharmaceuticals are prepared in hospital pharmacies with a certain frequency and volume. Saline solutions, nutritional formulations, imaging reagents, dyes, sterilizing liquids, and anesthetics are reconstituted as liquids. Additional alternative applications include, but are not limited to, the preparation of pesticides, fertilizers, and various beverages (e.g., milk, iced tea, etc.) that are typically prepared from powders, all of which could be reconstituted using embodiments of the systems and methods described herein. In this regard, dry components that may be reconstituted using the present systems and methods can include, but are not limited to powdered cell culture media, dry powdered media, dry buffer powders, granular media, dry salts, dry chemicals, dry components, dry materials, and non-hydrated components.

[0026] FIG. 1A is an overall system diagram of one embodiment of the mixing device 10. Preferably, the mixing device 10 is made of materials suitable for a cell culture environment, such as non-toxic medical grade plastics or other non-toxic materials that will 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, which are connected to each other by various lengths of tubing (e.g., flexible hoses). As described in more detail below, the tubing further includes various valves disposed therein to selectively allow (e.g., when the valves are in an open position) and stop (e.g., when the valves are in a closed position) the flow of fluids through the valves. In an exemplary embodiment, the valves are pinch valves, but in other embodiments, the valves can be or include other types of valves, such as ball valves. In various embodiments, the mixing device 10 is designed to reconstitute powdered cell culture media into liquid media. For example, the mixing device 10 can be a single-use device pre-packaged with the necessary media components (e.g., powdered cell culture media, sodium bicarbonate, etc.). However, one of ordinary skill in the art will understand that the mixing device 10 can be used to reconstitute other forms of undissolved cell culture media (e.g., granular cell culture media), prepare bioprocess buffers from dried forms, or more generally reconstitute liquids from powders.

[0027] First, in various embodiments, the first mixing chamber 12 contains a dry powdered medium to be reconstituted into a liquid medium. It is contemplated that the first mixing chamber 12 is provided with a pre-measured amount of the dry powdered medium. In some embodiments, the first mixing chamber 12 can be pre-packaged with a pre-measured amount of the dry powdered medium therein. Furthermore, in various embodiments, the first mixing chamber 12 is designed to facilitate mixing of the medium with other powders or liquids, such as purified water and / or dissolved sodium bicarbonate or supplementary substances. For example, the first mixing chamber 12 can include an upper cone and / or a lower cone coupled to the upper and / or lower ends, respectively, of the first mixing chamber 12 to facilitate the creation of a swirling vortex motion when the fluid enters the first mixing chamber 12. The swirling vortex motion facilitates mixing of the dry powdered medium, purified water, dissolved sodium bicarbonate, supplementary substances, etc. Various configurations and embodiments of the first mixing chamber 12 are described in U.S. patent application Ser. No. 15 / 087,826, entitled "Medium Mixing Chamber," filed Mar. 31, 2016, which is incorporated herein in its entirety.

[0028] The first mixing chamber 12 includes three ports by which fluid can enter and exit the first mixing chamber 12: a top port 20, an upper port 22, and a lower port 24. In an exemplary embodiment, the ports 22 and 24 are positioned in the first mixing chamber 12 such that fluid enters the first mixing chamber 12 through the ports 22 and 24 at a substantially tangential angle to the inner wall of the first mixing chamber 12, which may further facilitate mixing of the various media components within the first mixing chamber 12.

[0029] A top inlet / outlet tube 30 is connected to the first mixing chamber 12 at the top port 20. As shown in FIG. 1A, the top inlet / outlet tube 30 connects the first mixing chamber 12 to a common inlet tube 32 and an upper filter inlet tube 34. Similarly, the common inlet tube 32 connects to a supplement inlet tube 36 and a compressed air inlet tube 38. The supplement inlet tube 36 is configured to connect to a supplement source (not shown) at a supplement inlet 40. The supplement source can include any type of supplement used in cell culture media, such as amino acid supplements, cholesterol supplements, lipid supplements, etc. The compressed air inlet tube 38 is configured to connect to a compressed air source (not shown) at a compressed air inlet 42. Thus, when a fluid (e.g., medium supplements, compressed air) is introduced into the device 10 via the supplement inlet tube 36 and the compressed air inlet tube 38, the fluid flows to the common inlet tube 32. The fluid then flows to the top inlet / outlet pipe 30 and enters the first mixing chamber 12 through the top port 20 .

[0030] As shown in FIG. 1A, the compressed air inlet conduit 38 also includes a compressed air valve 44. When in the open position, the compressed air valve 44 allows compressed air to flow from the compressed air source through the compressed air valve 44 to the first mixing chamber 12, as described. 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 inlet conduit 36 ​​does not include a valve. Thus, unlike compressed air, the auxiliary substance can flow to the first mixing chamber 12 whenever the auxiliary substance is introduced into the apparatus 10 by the auxiliary substance inlet conduit 36.

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

[0032] 1A, the water inlet tube 48 further connects to a lower flow tube 54, a second chamber tube 56, and a lower filter tube 58. The lower flow tube 54 is connected to the first mixing chamber 12 by the lower port 24, and a second chamber outlet tube 60 branches off from the lower flow tube 54 midway through its length. The lower flow tube 54 further includes a lower port valve 62 proximate the tube section where the water inlet tube 48, the lower flow tube 54, the second chamber tube 56, and the lower filter tube 58 connect. Thus, when the lower port valve 62 is in an open position, fluid can flow into and out of the first mixing chamber 12 through the lower flow tube 54 and the lower port 24, but when the lower port valve 62 is in a closed position, fluid cannot flow through the valve 62.

[0033] The second mixing chamber 14 contains an additive 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 mixing of the sodium bicarbonate with purified water. Additionally, the second mixing chamber 14 can be prepackaged 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., includes upper and / or lower cones coupled to the upper and / or lower ends, respectively, of the second mixing chamber 14 to facilitate the creation of a swirling vortex motion as fluid enters the second mixing chamber 14). In other embodiments, the second mixing chamber 14 is configured differently than the first mixing chamber 12. Various configurations and embodiments of the second mixing chamber 14 are described in U.S. Patent Application Serial No. 15 / 087,826, entitled "Medium Mixing Chamber," filed March 31, 2016, which is hereby incorporated in its entirety as above.

[0034] The second mixing chamber 14 includes two ports by which fluid may enter and exit the second mixing chamber 14, a second chamber top port 64 and a second chamber bottom port 66. In an exemplary embodiment, the port 66 is positioned such that the fluid enters the second mixing chamber 14 through the port 66 at a substantially tangential angle to the inner wall of the second mixing chamber 14, which may further facilitate mixing of the sodium bicarbonate and the sodium bicarbonate within the second mixing chamber 14.

[0035] As shown in FIG. 1A, the second chamber outlet conduit 60 is connected to the second mixing chamber 14 at the second chamber top port 64. The second chamber outlet conduit 60 also includes a second chamber outlet valve 68 proximate where the second chamber outlet conduit 60 branches off from the lower flow conduit 54. Additionally, as shown in FIG. 1A, the second chamber conduit 56 is connected to the second mixing chamber 14 at the second chamber bottom port 66. The second chamber inlet conduit 56 further includes a second chamber inlet valve 70 proximate the portion of the conduit where the water inlet conduit 48, the lower flow conduit 54, the second chamber conduit 56, and the lower filter conduit 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 inlet valve 70 and the second chamber outlet valve 68 are in the open position. When the second chamber inlet valve 70 and the second chamber outlet valve 68 are in the closed position, fluid cannot flow into or out of the second mixing chamber 14 .

[0036] The lower filter tube 58 connects the tubing section where the water inlet tube 48, the lower flow tube 54, the second chamber tube 56, and the lower filter tube 58 converge to the upper filter inlet tube 34 at the location where the lower filter tube 58 and the upper filter inlet tube 34 join. The combined lower filter tube 58 and upper filter inlet tube 34 then connect to the filter unit 16. As shown in FIG. 1A, the filter unit 16 includes a filter tubing section 72 that connects to the lower filter tube 58 and the upper filter inlet tube 34 whereby the filter unit 16 joins. The filter tubing section 72 is also connected to an outlet 74 that terminates at an apparatus outlet 76. The apparatus outlet 76 is configured to connect to a collection vessel that collects the media solution mixed and discharged by the apparatus 10. In various embodiments, the collection vessel can be made of glass, plastic, or metal and can be preformed or flexible.

[0037] Filter 16 is configured to filter the solution entering the filter via filtration tubing 72. For example, filter 16 can remove undissolved powdered medium from the solution via a membrane within filter 16. Filter 16 can further be configured to sterilize the solution entering the filter before the solution exits the device via outlet 74. In addition, filter 16 can further include a top segment with a hydrophobic vent that allows air to escape filter 16, since air will not pass through the membrane of filter 16 when filter 16 is wet. This vent prevents air from becoming trapped in filter 16 and interfering with the filtration process.

[0038] Filters of the type contemplated by the present technology can be purchased from a number of suppliers. For example, filter 16 can include nylon or cellulose acetate. In addition, for media products, filter 16 is typically a 0.2μ filter, although it is contemplated that other filter sizes can be selected for specific functions. For example, preparation of electrophoresis buffer requires a contaminated, but not necessarily sterile, solution, and a 0.45μ filter is sufficient. Similarly, preparation of more viscous solutions may require a wider pore size. In short, filter 16 can be of any desired size, volume, pore size, etc. Additionally, for other applications of the technology disclosed herein, additional filtration devices may not be necessary. The liquid then travels directly through outlet 74 to a collection vessel. Instead, in some embodiments, a hydrophobic vent filter is used somewhere before filter 16 to allow air entrained in the dissolved media to exit without filling filter 16.

[0039] As shown in FIG. 1A, the lower filter tube 58 further includes a water bypass valve 78 proximate the tube section where the water inlet tube 48, the lower flow tube 54, the second chamber tube 56, and the lower filter tube 58 connect. Thus, when the water bypass valve 78 is in an open position and the water source is open, fluid flows from the fluid 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 via the filter tube section 72. In this manner, 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 relieve back pressure on the filter 16). When the water bypass valve 78 is in a closed position, the water bypass valve 78 prevents fluid (e.g., water from the water source, bicarbonate solution mixed by the second mixing chamber 14) from bypassing the first mixing chamber 12 and flowing directly to the filter 16.

[0040] As also 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 an open position, the upper filter inlet tube 34 allows fluid to flow through the upper filter inlet tube 34 to the filter 16. More specifically, when the first mixing chamber 12 is filled with a solution (e.g., a solution of purified water, powdered medium, bicarbonate, and / or supplementary substances), the solution exits the first mixing chamber 12 through the top port 20 and enters the top inlet outlet 30. The solution then enters the upper filter inlet tube 34 and enters the filter 16 through the filter tube section 72 when the upper filter inlet valve 80 is in an open position. On the other hand, when the upper filter inlet valve 80 is in a closed position, fluid cannot flow through the upper filter inlet tube 34 to the filter 16.

[0041] Additionally, in various embodiments, the mixing device 10 can include various sensors for obtaining measurements within the mixing device 10. These sensors can include, for example, pressure sensors (e.g., for detecting water pressure within the device 10), conductivity sensors (e.g., for detecting the conductivity and therefore the concentration of the solution within the device 10), volume sensors such as rotary flow meters (e.g., for detecting the volume and flow rate of the fluid consumed in the mixing process), pH sensors (e.g., for detecting the pH of the solution within the device 10), viscometers (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 tube 34, a conductivity sensor 92 located in the combined upper filter inlet tube 34 and lower filter tube 58, and a volume sensor 94 located in the water inlet tube 48. The pressure sensor 90 is configured to measure the pressure of the fluid entering the filter 16 (e.g., to prevent the back pressure of the filter 16 from becoming too high). Conductivity sensor 92 is configured to measure the conductivity of the solution flowing into filter 16, thereby indirectly measuring the concentration of the solution flowing into filter 16 and ultimately out of device 10. Finally, volume sensor 94 is configured to measure the volume and flow rate of water consumed during the mixing process.

[0042] In various embodiments, as described in further detail below, the powdered medium is mixed into the liquid medium in the mixing device 10 in an automated manner. Preparing liquid medium from dry powdered medium in an automated manner using the mixing device 10 is an improvement over the current art because it allows for easy and efficient preparation of liquid medium. Furthermore, having programming logic that controls the automated method (e.g., implemented by processing circuitry executing instructions stored on a non-transitory machine-readable medium as part of a computing system) makes the preparation of liquid medium from dry powdered medium reproducible and consistent.

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

[0044] Accordingly, FIG. 2 illustrates a computing system configured to control the mixing device 10 according to an automated method, which is embodied as a mixing controller 100. As shown in FIG. 2, the mixing controller 100 includes a communication interface 102 and a processing circuit 104. The communication interface 102 is configured to facilitate communication between the mixing controller 100 and an external system or device. Thus, as shown in FIG. 2, the communication interface 102 can receive data related to the mixing process from 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. Additionally, the communication interface 102 can receive commands from a user via the user device 170. For example, the communication interface 102 can receive commands from a user via the user device 170 to initiate execution of an automated mixing method.

[0045] 2, the communications interface 102 can send commands to one or more of the valves 152, such as the valves 44, 52, 62, 68, 70, 78, and 80 discussed above. Similarly, the communications interface 102 can send instructions or commands to the component sources 154, such as the water source 160 (e.g., coupled to the water inlet 50), the auxiliary material source 162 (e.g., coupled to the auxiliary material inlet 40), the compressed air source 164 (e.g., coupled to the compressed air inlet 42), etc. For example, the communications interface 102 can send instructions to open or close any valve in the valves 152 or any component source in the component sources 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 communicating data with an external system or device. In various embodiments, the communication can be direct (e.g., local wired or wireless communication) or over a communication network (e.g., a WAN, the Internet, a cellular network, etc.). For example, the communication interface 102 can include an Ethernet card and port for transmitting and receiving data over an Ethernet-based communication link or network. In another example, the communication interface 102 can include a WiFi transceiver for communicating over 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), 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., CD-ROM, network storage, remote server, etc.).

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

[0049] The mixing controller 100 further includes a measurement controller 110 and a method execution controller 112. As shown in FIG. 2, the measurement controller 110 is configured to receive measurements from the sensor group 150 via the communication interface 102. In addition, in various embodiments, the measurement controller 110 is configured with an internal timer for tracking elapsed time during execution of the automated method. The measurement controller 110 provides one or more of the received measurements and / or the tracked elapsed time to the method execution controller 112 during execution of the automated method. In addition, the measurement controller 110 can receive data indicative of the progress of the automated method from the method execution controller 112 during execution of the automated method. For example, the measurement controller 110 can receive an indication from the method execution controller 112 that a certain step of the automated method is currently being executed.

[0050] The method execution controller 112 is configured to provide commands to one or more of the valves 152 and the component sources 154. In various embodiments, the method execution controller 112 provides commands in response to (a) instructions from a user received via the communication interface 102 and (b) data received from the measurement controller 110. In one example, the method execution controller 112 can open or close a particular valve of the valves 152 and / or a particular component source of the component sources 154 in response to a user command to initiate execution of an automated method. In a second example, the method execution controller 112 can open or close a particular valve of the valves 152 and / or a particular component source of the component sources 154 in response to a received measurement value being at a particular level. In a third example, the method execution controller 112 can open or close a particular valve of the valves 152 and / or a particular component source of the component sources 154 in response to a particular elapsed time. In addition, the method execution controller 112 can be further configured to provide feedback data to the measurement controller 110. For example, the method execution controller 112 may provide a notification to the measurement controller 110 indicating that a given step of the automated method has been performed.

[0051] FIG. 3 shows a flow chart illustrating one embodiment of an automated method 200 for mixing powdered medium into liquid medium using the mixing device 10. FIGS. 4A-4G show the flow of fluids through the mixing device 10 during the steps of the automated method 200. As described below, the sequence of steps shown in FIG. 3 and FIGS. 4A-4E show a strict protocol for successfully using the mixing device 10 to reconstitute powdered medium into liquid medium. The use of this strict protocol provides timing that is key to the success of the automated method 200. For example, in an exemplary embodiment, the mixing control device 100 uses the protocol of the automated method 200 to mix a powdered cell culture medium volume that is less than 50% of the volume of the first mixing chamber 12.

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

[0053] Initially, all valves (e.g., valves 44, 52, 62, 68, 70, 78, and 80) are closed (202) during transportation, installation, and setup of the mixing device 10. This helps prevent leakage and contamination during the setup process of the mixing device 10. For example, during setup, the first mixing chamber 12 and the second mixing chamber 14 are unpacked and set up as shown in FIG. 1A, with pre-measured amounts of powdered medium and sodium bicarbonate provided in the chambers 12 and 14, respectively. Alternatively, the first mixing chamber 12 and the second mixing chamber 14 are set up as shown in FIG. 1A, and aliquots of powdered medium and sodium bicarbonate are placed in the chambers 12 and 14. The first mixing chamber 12 and the second mixing chamber 14 are then configured with the filter 16 and tubing to produce the mixing device 10 as shown in FIG. 1A. Additionally, a source of compressed air is connected to the compressed air inlet 42, a purified water source containing a quantity of water is connected to the water inlet 50, and, if desired, a source of auxiliary substances is connected to the auxiliary substances inlet 40. A collection vessel is also connected to the device outlet 76.

[0054] The mixing controller 100 then opens (204) the water source, the lower port valve 62, and the upper filter inlet valve 80. As shown in FIG. 4A, with the water source and the lower port valve 62 open, water flows from the water source through the water inlet conduit 48 and the lower port valve 62 into the lower flow conduit 54. The water then flows from the lower flow conduit 54 through the lower port 24 and into the first mixing chamber 12, at which point the water begins to mix with the powdered media contained within the first mixing chamber 12.

[0055] Additionally, as the first mixing chamber 12 begins to fill with water from the bottom of the chamber 12 because the top filter inlet valve 80 is open, displaced air is exhausted from the top port 20 of the first mixing chamber 12, as shown in FIG. 4B. The exhausted air flows through the top inlet outlet 30 and the top filter inlet tube 34. The exhausted air exits the mixing device 10 by passing through the filter 16 and out of the outlet 74. Alternatively, if the filtration membrane of the filter 16 becomes wet, the membrane may prevent air from passing through the membrane and the filter 16. Therefore, instead, air can exit the mixing device 10 through a hydrophobic vent provided in the filter 16 (e.g., provided in the top segment of the filter 16). This is beneficial because it reduces the amount of air trapped within the first mixing chamber 12.

[0056] Finally, water fills the first mixing chamber 12, which flows into the first mixing chamber 12 through the bottom port 24 and mixes with the powdered medium to form the medium solution. In some embodiments, the first mixing chamber 12 is filled with the solution immediately after the mixing process begins (e.g., during step 204). In other embodiments, the first mixing chamber 12 is filled with the solution later in the mixing process (e.g., after step 204). Regardless, when this occurs, the solution follows the same path as the exhausted air, as shown in FIG. 4B. The solution exits the first mixing chamber 12 through the top port 20, and flows through the top inlet outlet 30 and the upper filter inlet tube 34 into the filter 16 through the filter tube section 72. After being filtered and sterilized by the filter 16, the solution flows into the outlet 74 and exits the mixing device 10 through the device outlet 76, where it is collected by a collection vessel. Although not shown in Figures 4C-4E, once solution begins to flow out of first mixing chamber 12 through top port 20, the solution will continue to flow out of first mixing chamber 12, through filter 16, and out of apparatus 10 through apparatus outlet 76 for as long as water continues to flow into first mixing chamber 12 (e.g., until step 216, described below).

[0057] After a predetermined elapsed time, the mixing controller 100 closes the lower port valve 62 and opens the upper inlet valve 52 (206). For example, in one embodiment, the mixing controller 100 waits one minute before closing the lower port valve 62 and opening the upper inlet valve 52. As shown in FIG. 4C, this causes water to stop flowing into the first mixing chamber 12 through the lower port 24. Instead, water flows from the water inlet tube 48 to the upper inlet 46. From the upper inlet 46, the water enters the first mixing chamber 12 through the upper port 22 and continues to mix with the powdered medium in the first mixing chamber 12. Switching the flow of water into the first mixing chamber 12 from the lower port 24 to the upper port 22 helps to maintain a uniform dissolution rate of the powdered medium in the chamber 12 without flooding the filter 16 with high concentrations of solutes, undissolved particles, and air that can occur when water enters the chamber 12 through the lower port 24. Additionally, switching the water flow can promote a desirable beneficial dissolution rate.

[0058] During the above-mentioned steps of the automated method 200, the mixing controller 100 continuously monitors (e.g., via pressure sensor 90) the pressure in the upper filter inlet line 34. When the pressure in the upper filter inlet line 34 reaches a predetermined level, the mixing controller 100 opens (208) the water bypass valve 78. For example, in one embodiment, when the pressure in the upper filter inlet line 34 reaches 20 psig (pounds per square inch gauge pressure), the mixing controller 100 opens the water bypass valve 78. When this occurs, as shown in FIG. 4D, 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 source through the water inlet line 48 into the lower filter line 58. From the lower filter line 58, the water mixes with the solution (not shown) exiting the first mixing chamber 12 where the upper filter inlet line 34 and the lower filter line 58 join. The solution then flows into the filter 16 through the filter line segment 72. After filtering, the water exits the device 10 through outlet 74 and into a collection vessel. Opening the water bypass valve 78 allows water to bypass the first and second mixing chambers 12, 14 and flow directly to the filter 16, helping to reduce backpressure within the filter 16 and helping to maintain the flow necessary for the first mixing chamber 12 to function properly.

[0059] The mixing controller 100 keeps the water bypass valve 78 open for a predetermined period of time, allowing water to flow directly to the filter 16. After the predetermined period of time has elapsed, the mixing controller 100 closes (210) the water bypass valve 78. For example, in one embodiment, the mixing controller 100 closes the water bypass valve 78 after two minutes. The direct flow of water to the filter 16 then stops, and the mixing device 10 is returned to the state of step 206, as shown in FIG. 4C. By closing the water bypass valve 78, the mixing controller 100 helps to avoid premature depletion of the volume of water (e.g., a volume of 1000 L of purified water) required for the automated method 200.

[0060] The mixing controller 100 also continuously monitors (e.g., via the conductivity sensor 92) the conductivity of the solution entering the filter. By monitoring the conductivity of the solution entering the filter, the mixing controller 100 can indirectly monitor the concentration of the solution leaving the first mixing chamber 12, since the solution is conductively related to its concentration (e.g., higher solution conductivity indicates higher solution concentration and vice versa). When the conductivity of the solution reaches a predetermined conductivity, the mixing controller 100 closes the upper inlet valve 52 and opens the lower port valve 62 (212). For example, in one embodiment, the mixing controller 100 closes the upper inlet valve 52 and opens the lower port valve 62 when the conductivity of the solution entering the filter is equal to or less than 6 mS / cm (millisiemens per centimeter). 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. Switching the water flow from upper port 22 to lower port 24 when the conductivity of the solution reaches 6 mS / cm helps ensure that a sufficient concentration of solute (e.g., powdered medium) in the solution being mixed in first mixing chamber 12 is maintained (e.g., so that a certain amount of water provided in the water source is not used up without being mixed into a sufficiently concentrated solution). 1.

[0061] In addition to monitoring the pressure in the upper filter inlet conduit 34 and the conductivity of the solution entering the filter 16, the mixing controller 100 also continuously monitors (e.g., via the volume sensor 94) the amount of water consumed during the execution of the automated method 200. Once a predetermined total amount of water has been consumed, the mixing controller 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 controller 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 is equal to or greater than 800 L. When this occurs, as shown in FIG. 4E, water flows from the water source through the water inlet conduit 48 into the second chamber conduit 56. From the second chamber conduit 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 in the second mixing chamber 14. As the second mixing chamber 14 fills with water, the water and bicarbonate solution is forced out the second chamber top port 64 and into the second chamber outlet 60. The bicarbonate solution then flows from the second chamber outlet 60 into the lower flow conduit 54 and finally into the first mixing chamber 12 by way of the lower port 24. As the bicarbonate solution enters the first mixing chamber 12, it mixes with the water and powdered media contained in the first mixing chamber 12. In this manner, the sodium bicarbonate powder (and / or other additives contained within the second mixing chamber 14) is dissolved separately before being added to the solution in the first mixing chamber 12.

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

[0063] Finally, when the mixing controller 100 determines (e.g., via the volume sensor 94) that the total amount of water consumed has reached a predetermined total amount, the mixing controller 100 closes the water source and top filter inlet valve 80. The mixing controller 100 also opens (218) the compressed air valve 44 and the water bypass valve 78. For example, in one embodiment, the mixing controller 100 closes the water source and top filter inlet valve 80 and opens the compressed air valve 44 and the water bypass valve 78 when 1,000 L of water has been consumed during the mixing process. When this occurs, compressed air flows from the compressed air source into the compressed air inlet 38 via the compressed air inlet 42. From the compressed air inlet 38, the compressed air flows into the common inlet 32 ​​and into the first mixing chamber 12 through the top port 20 via the top inlet outlet 30. The compressed air flowing into the first mixing chamber 12 expels any solution remaining in the chamber 12 from the chamber 12 through the bottom port 24 into the bottom flow conduit 54. The discharged solution then flows through lower flow conduit 54 into lower filter tube 58 and into filter 16 by filter tubing section 72. After being filtered, the solution flows through outlet 74 into a collection vessel connected to device outlet 76. In this manner, compressed air can be used to evacuate remaining solution in first mixing chamber 12 from device 10 into a collection vessel to obtain a targeted volumetric 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 illustrates the flow of a given auxiliary substance into the first mixing chamber 12. The auxiliary substance enters the auxiliary substance inlet 36 of the device 10 via the auxiliary substance inlet 40 and follows the auxiliary substance inlet 36 tube 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 enters the top inlet outlet 30 from the common inlet 32 ​​and enters the first mixing chamber 12 via the top port 20. If the solution being mixed in the first mixing chamber 12 fills the chamber 12 and is exiting the top port 20, the auxiliary substance mixes with the solution exiting the chamber 12 in the top filter inlet tube 34.

[0065] However, while the automated method 200 described above relates to the reconstitution of powdered cell culture media, it is understood that the mixing device 10 embodiments can be used with automated method embodiments to reconstitute various dry components into liquids, such as various bioprocess powders into bioprocess solutions. Additionally, it is contemplated that the liquid solvent used can be water, alcohol, or other organic. The solubility characteristics, the solvent used, the amount required, and the chemical interactions of the solvent with the reconstituted chemicals serve to provide guidelines for the automated method embodiments used to reconstitute powders and the configuration of the mixing device used in a given automated method embodiment. Additionally, while the preferred embodiments described herein add liquid to dry components for the purpose of reconstituting these dry components, it is contemplated that the mixing device is similarly effective for the reconstitution of concentrated liquids or a range of combinations of liquids and powders.

[0066] Various modified versions 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 solids 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., to separately mix additional secondary additives).

[0067] The above description details certain embodiments of the systems, devices, and methods disclosed herein. However, it should be understood that no matter how detailed the above is in text, the devices and methods can be implemented in various ways. Also, as mentioned above, it should be noted that the use of a particular term in describing a particular feature or aspect of a technology does not mean that the term is redefined herein to be limited to include the particular characteristics of the feature or aspect of the technology with which the term is associated. Therefore, the scope of the present disclosure should be interpreted according to the appended claims and their equivalents.

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

[0069] The embodiments herein have been described with reference to the drawings, which show certain details of particular embodiments implementing the systems and methods described herein, however, describing the embodiments with the drawings should not be construed as imposing limitations on the present disclosure that may be present in the drawings.

[0070] With respect to the use of plural and / or singular terms herein, those of skill in the art may translate from the plural to the singular and / or from the singular to the plural as appropriate to the context and / or application. The various singular / plural permutations may be expressly set forth herein for clarity.

[0071] In general, those skilled in the art will understand that the terms used in this specification, and in particular in the appended claims, are generally intended as "open" terms (e.g., the term "including" should be interpreted as "including, but not limited to," the terms "comprising" and "having" should be interpreted as "including at least" and "having at least," respectively, the term "includes" should be interpreted as "including, but not limited to," etc.). Furthermore, where a specific number of introduced claim recitations is intended, such intent is expressly set forth in the claim, and in the absence of such recitation, those skilled in the art will understand that no such intent exists. For example, as an aid to understanding, the following appended claims may include the use of the introductory phrases "at least one" and "one or more" to introduce the claim recitations. However, the use of such phrases should not be construed as implying that introducing a claim recitation with the indefinite article "a" or "an" limits a particular claim that includes such a claim recitation to embodiments that contain only one such recitation, even if the same claim includes the introductory phrases "one or more" or "at least one" and an indefinite article such as "a" or "an." In general, "a" and / or "an" should be construed to mean "at least one" or "one or more," and the same applies to the use of definite articles used to introduce claim recitations.

[0072] Also, in instances where a conventional expression similar to "at least one of A, B, and C, etc." is used, such syntax is generally intended in the sense that one of ordinary skill in the art would understand the conventional expression (e.g., "a system having at least one of A, B, and C" includes, but is not limited to, systems 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, etc.). In instances where a conventional expression similar to "at least one of A, B, or C, etc." is used, such syntax is generally intended in the sense that one of ordinary skill in the art would understand the conventional expression (e.g., "a system having at least one of A, B, or C" includes, but is not limited to, systems 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, etc.). Those skilled in the art will further appreciate that virtually any disjunction and / or phrase presenting two or more alternative terms, whether in the specification, claims, or drawings, should be understood to contemplate the possibility of including one of the terms, either 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 purposes of this disclosure, the term "connected" means that two members are directly or indirectly joined to one another. Such joining may be fixed or movable. Such joining may be achieved by the two members or the two members and an additional intermediate member being integrally formed with one another as a single unitary body, or by the two members or the two members and an additional intermediate member being attached to one another. Such joining may be permanent in nature, or removable or releasable in nature.

[0074] The technology described herein has many applications, and while 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. Therefore, the foregoing description should be considered illustrative rather than limiting, and the true scope of the invention is defined in the appended claims.

Claims

1. 1. An automated bioprocess solution preparation apparatus comprising: a first mixing chamber containing a component of a bioprocessing solution, the first mixing chamber including top and bottom ports for fluid to enter the first mixing chamber and a top port for a liquid bioprocessing solution prepared from the component to exit the first mixing chamber; a plurality of tubes for fluid flow within the device; a conductivity sensor positioned to measure the conductivity of the liquid bioprocessing solution exiting the first mixing chamber; a first valve configured to control flow to the top port; a second valve configured to control flow to the lower port; and Including, If the conductivity meets or exceeds a threshold value, the apparatus: closing the first valve to prevent the fluid from entering the first mixing chamber through the top port; opening the second valve to allow the fluid to enter the first mixing chamber through the lower port; 3. An automated device operable to:

2. 10. The automated apparatus of claim 1, further comprising a filter and a bypass valve, the bypass valve configured to control the flow of the fluid to the filter.

3. further comprising a pressure sensor configured to measure a pressure of a fluid flowing into the filter; 3. The automated apparatus of claim 2, wherein if the pressure meets or exceeds a threshold value, the apparatus is further operable to open the bypass valve to supply the fluid to the filter, bypassing the first mixing chamber.

4. 3. The automated apparatus of claim 2, further comprising a compressed air inlet valve configured to control air flow to the top port.

5. The method of claim 1, further comprising: providing a mixing device for mixing a fluid with a mixing volume of the fluid; If the volume meets or exceeds a threshold, the device further: opening the compressed air inlet valve to allow air to enter the first mixing chamber through the top port; opening the bypass valve to supply fluid to the filter; 5. The automated device of claim 4, operable to:

6. 2. The automated apparatus of claim 1, wherein the top port is located above the first mixing chamber.

7. The automated device of claim 1 , wherein the fluid is water.

8. 10. The automated apparatus of claim 1 further comprising a second mixing chamber containing an additive.

9. 9. The automated apparatus of claim 8, wherein the second mixing chamber is connected to a top port of the first mixing chamber by the plurality of tubes.

10. The apparatus according to claim 1, further comprising a volume sensor configured to measure a volume of fluid consumed during a mixing process in the apparatus; The second mixing chamber comprises: a second chamber inlet valve associated with the second chamber inlet; a second chamber outlet valve associated with the second chamber outlet; Including, If the volume meets or exceeds a first threshold, the device: closing the second valve to allow fluid to enter the first mixing chamber through the lower port; opening the second chamber inlet valve to supply fluid to the second mixing chamber; opening the second chamber outlet valve to supply fluid to the first mixing chamber; 10. The automated apparatus of claim 9, operable to:

11. 11. The automated apparatus of claim 10, further comprising a filter and a bypass valve, the bypass valve configured to control the flow of the fluid to the filter.

12. 12. The automated apparatus of claim 11, wherein if the volume meets or exceeds a second threshold, the apparatus is further operable to open the bypass valve to supply the fluid to the filter by bypassing each of the first and second mixing chambers.

13. The automated device of claim 10, wherein the fluid is water.

14. The plurality of tubes are an upper filter inlet pipe fluidly coupled to the first mixing chamber and the filter, the upper filter inlet pipe including an upper inlet valve; a lower filter inlet line fluidly coupled to a fluid source and to the filter, the lower filter inlet line including a bypass valve; The automated device of claim 3 , comprising:

15. 15. The automated apparatus of claim 14, further comprising a compressed air inlet valve configured to control air flow to the first mixing chamber.

16. The apparatus according to claim 1, further comprising a volume sensor configured to measure a volume of fluid consumed during a mixing process in the apparatus; If the volume meets or exceeds a threshold, the device further: closing the upper inlet valve to prevent the bioprocess solution from flowing through the upper filter inlet line to the filter; opening the compressed air inlet valve to supply air to the first mixing chamber; opening the bypass valve to allow the bioprocess solution to flow out of the first mixing chamber through the lower filter inlet line to the filter; 16. The automated device of claim 15, operable to:

17. 15. The automated device of claim 14, wherein the device is configured to close the bypass valve after a predetermined period of time.

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