Powder supply device

The powder supply device addresses the instability in powder supply for long-term bioprocess solutions by using a dual-container system to ensure continuous and stable delivery of powder medium to the mixing container, supporting consistent bioprocess conditions.

WO2025070314A1PCT designated stage expired Publication Date: 2025-04-03FUJIFILM CORP
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Patent Information

Application Number
PCT/JP2024/033735
Authority / Receiving Office
WO · WO
Patent Type
Applications
Current Assignee / Owner
Priority Date
2023-09-28
Filing Date
2024-09-20
Publication Date
2025-04-03

AI Technical Summary

Technical Problem

Existing bioprocess solutions for continuous preparation of bioprocess solutions over long periods, such as one month, lack a stable supply of powder to the mixing container, which is essential for maintaining consistent bioprocess conditions.

Method used

A powder supply device comprising a first container for storing powder, connected to a mixing container via a feeder, and a second container for storing powder, connected to the first container to supply powder, ensuring a stable and continuous supply of powder medium to the mixing container.

Benefits of technology

The powder supply device enables a stable supply of powder to the mixing container, facilitating continuous preparation of bioprocess solutions over extended periods without interruptions or fluctuations in powder availability.

✦ Generated by Eureka AI based on patent content.

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Abstract

This powder supply device continuously supplies powder to a mixing vessel in order to continuously prepare, in the mixing vessel, a bioprocess solution having a set concentration. The powder supply device comprises: a first vessel that stores the powder, is connected to the mixing vessel via a feeder, and supplies the powder to the feeder; and a second vessel that stores the powder, is connected to the first vessel, and supplies the powder to the first vessel.
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Description

Powder feeding device

[0001] The technology of the present disclosure relates to a powder supplying device.

[0002] Bioprocesses, such as culturing Chinese hamster ovary cells incorporating antibody genes to obtain antibody pharmaceuticals, require various bioprocess solutions. International Publication No. 2021 / 123248 describes a method for continuously preparing a bioprocess solution at a set concentration by continuously supplying a solvent and a powder to a mixing vessel and mixing the solvent and powder in the mixing vessel. The mixing vessel is connected to a bioprocess vessel, and the bioprocess solution is continuously supplied from the mixing vessel to the bioprocess vessel. The solvent is, for example, purified water, such as pure water, the powder is, for example, a powder culture medium, and the bioprocess solution is, for example, a culture medium (culture solution). The bioprocess vessel is, for example, a culture tank.

[0003] For continuous preparation of a bioprocess solution over a long period of time, such as one month, a stable supply of powder to the mixing vessel is essential. However, WO 2021 / 123248 does not provide any measures for the stable supply of powder to the mixing vessel.

[0004] One embodiment of the technique of the present disclosure provides a powder supplying device that can contribute to the stable supply of powder to a mixing container.

[0005] The powder supplying device of the present disclosure is a powder supplying device that continuously supplies powder to a mixing container to continuously prepare a bioprocess solution of a set concentration in the mixing container, and includes: a first container that stores powder, the first container being connected to the mixing container via a feeder, and supplying the powder to the feeder; and a second container that stores powder, the second container being connected to the first container, and supplying the powder to the first container.

[0006] Preferably, the second container is interchangeably connected to the first container.

[0007] Preferably, the first container expands and contracts.

[0008] The first container is preferably sealed.

[0009] It is preferred that a portion of the first container expands and contracts.

[0010] Preferably, the second container expands and contracts.

[0011] The second container is preferably sealed.

[0012] It is preferable that a portion of the second container expands and contracts.

[0013] The first container preferably has a first vent.

[0014] It is preferable that humidity-conditioned air by a humidity-conditioning mechanism is supplied into the first container through the first ventilation port.

[0015] Preferably, the first container does not expand or contract.

[0016] The second container preferably has a second vent.

[0017] Preferably, the second container does not expand or contract.

[0018] Preferably, the first container and the second container are expandable and contractible.

[0019] Preferably, the first container is expandable and contractible and the second container has a second vent.

[0020] It is preferable that the first container has a first vent, the second container expands and contracts, and humidity-conditioned air is supplied from the first vent into the first container by a humidity-conditioning mechanism.

[0021] It is preferable that the first container has a first vent port, the second container has a second vent port, and humidity-conditioned air by a humidity-conditioning mechanism is supplied into the first container through the first vent port.

[0022] Preferably, the solvent mixed with the powder in the mixing vessel is purified water, the powder is a powder medium, and the bioprocess solution is a medium.

[0023] Preferably, the medium is continuously fed from the mixing vessel to the culture tank.

[0024] The first and second containers are preferably disposable after one use.

[0025] According to the technique of the present disclosure, it is possible to provide a powder supplying device that can contribute to the stable supply of powder to a mixing container.

[0026] 1 is a diagram showing a culture medium preparation apparatus and a culture tank; FIG. 2 is a diagram showing a powdered culture medium supplying apparatus; FIG. 3 is a diagram showing a processing procedure of the powdered culture medium supplying apparatus; FIG. 4 is a diagram showing a first container and a second container that are partially expanded and contracted; FIG. 5 is a diagram showing another example of a first container that is partially expanded and contracted; FIG. 6 is a diagram showing a powdered culture medium supplying apparatus of a second embodiment; FIG. 7 is a diagram showing a powdered culture medium supplying apparatus of a third embodiment; FIG. 8 is a diagram showing another example of a humidity control mechanism; FIG. 9 is a diagram showing yet another example of a humidity control mechanism; FIG. 10 is a diagram showing a powdered culture medium supplying apparatus of a fourth embodiment;

[0027] [First embodiment] As an example, as shown in Figure 1, a culture medium preparation apparatus 10 prepares a culture medium CM. The culture medium preparation apparatus 10 is connected to a culture tank 11 and continuously supplies the prepared culture medium CM to the culture tank 11. The culture medium CM is an example of a "bioprocess solution" according to the technology of the present disclosure. Note that, although Figure 1 shows an example in which the culture medium preparation apparatus 10 is directly connected to the culture tank 11, this is not limiting. A tank for temporarily storing the culture medium CM may be provided between the culture medium preparation apparatus 10 and the culture tank 11.

[0028] Culture tank 11 is seeded with, for example, Chinese hamster ovary cells into which an antibody gene has been incorporated. In culture tank 11, the Chinese hamster ovary cells are cultured in culture medium CM. As described above, culture medium CM is continuously supplied to culture tank 11 from culture medium preparation device 10, and therefore the culture of Chinese hamster ovary cells carried out in culture tank 11 is perfusion culture. Culture tank 11 is connected to a purification device (not shown). The purification device purifies the antibodies produced by the Chinese hamster ovary cells during the culture process and uses them as active pharmaceutical ingredients for antibody pharmaceuticals.

[0029] The culture medium preparation device 10 includes a pure water storage tank 15, a mixing container 16, a powder culture medium supply device 17, a waste liquid recovery tank 18, a control unit 19, an operation unit 20, and the like.

[0030] The pure water storage tank 15 stores pure water PW. The pure water PW is an example of the "solvent" and "purified water" according to the technology of the present disclosure.

[0031] One end of a pure water supply line 21 is connected to the pure water storage tank 15. The other end of the pure water supply line 21 is connected to the mixing container 16. A pure water supply pump 22 and a pure water flow meter 23 are provided in the pure water supply line 21. The pure water supply pump 22 is driven and controlled by the control unit 19. When the pure water supply pump 22 is driven, the pure water PW in the pure water storage tank 15 is supplied to the mixing container 16 through the pure water supply line 21. The pure water flow meter 23 is disposed downstream of the pure water supply pump 22 and measures the flow rate of the pure water PW passing through the pure water supply line 21. The pure water flow meter 23 outputs the measured flow rate to the control unit 19. The control unit 19 controls the drive of the pure water supply pump 22 so that the flow rate of the pure water flow meter 23 becomes a set amount.

[0032] The mixing container 16 has, for example, a wide cylindrical shape and is a container for mixing pure water PW and powdered culture medium PM to produce a culture medium CM of a set concentration. The top of the mixing container 16 is sealed with a lid 25. A through-hole 26 is formed in the center of the lid 25. An outlet 27 for the powdered culture medium PM of the powdered culture medium supply device 17 is aseptically connected to the upper end of the through-hole 26. This aseptically connects the mixing container 16 and the powdered culture medium supply device 17. The powdered culture medium PM discharged from the outlet 27 is supplied to the mixing container 16 through the through-hole 26. The powdered culture medium PM is an example of a "powder" according to the technology of the present disclosure.

[0033] The powdered culture medium supplying device 17 continuously discharges a set amount of powdered culture medium PM from the discharge port 27 under the drive control of the control unit 19. The powdered culture medium supplying device 17 is an example of a “powder supplying device” according to the technology of the present disclosure.

[0034] The mixing container 16 is placed on the agitator 32. A stirrer 33 is placed in the mixing container 16. The stirrer 33 has a long, thin, cocoon-like shape with both ends rounded and a slightly bulging center. A magnet is built into the stirrer 33. The agitator 32 is driven and controlled by the control unit 19. The agitator 32 generates a magnetic force to rotate the stirrer 33. The agitator 32 rotates the stirrer 33 at a set rotation speed, thereby mixing the pure water PW and the powdered medium PM to produce the medium CM.

[0035] One end of a medium supply path 35 is connected to the mixing vessel 16. The other end of the medium supply path 35 is connected to the culture tank 11. A medium supply pump 36 and a medium flow meter 37 are provided in the medium supply path 35. The medium supply pump 36 is driven and controlled by the control unit 19. When the medium supply pump 36 is driven, the medium CM in the mixing vessel 16 is supplied to the culture tank 11 through the medium supply path 35. The medium flow meter 37 is disposed downstream of the medium supply pump 36 and measures the flow rate of the medium CM passing through the medium supply path 35. The medium flow meter 37 outputs the measured flow rate to the control unit 19. The control unit 19 controls the drive of the medium supply pump 36 so that the flow rate of the medium flow meter 37 becomes a set amount.

[0036] The flow rates of the pure water PW and the culture medium CM are set to values ​​that will keep the amount of liquid in the mixing container 16 constant from start to finish. More specifically, the flow rate of the culture medium CM is set according to the combined flow rate of the pure water PW and the supply amount of the powder culture medium PM. In practice, the weight of the mixing container 16 is measured with a weighing scale, and the flow rates of the pure water PW and the culture medium CM are set so that the measured weight remains constant.

[0037] A filter 38 is disposed upstream of the culture medium supply pump 36 in the culture medium supply path 35. The filter 38 removes unwanted matter from the culture medium CM. The unwanted matter is, for example, undissolved powder culture medium PM.

[0038] A conductivity meter 39 and a hydrogen ion index meter 40 are disposed downstream of the medium flow meter 37 in the medium supply path 35. A waste liquid path 42 is connected to the medium supply path 35 downstream of the hydrogen ion index meter 40 via a three-way valve 41. The three-way valve 41 is driven and controlled by the control unit 19. A waste liquid recovery tank 18 is connected to the waste liquid path 42. The waste liquid recovery tank 18 recovers waste liquid WL, which is medium CM that does not have the set concentration or medium CM with an abnormal hydrogen ion index.

[0039] The conductivity meter 39 measures the conductivity (unit: mS / cm) of the medium CM passing through the medium supply path 35. The conductivity meter 39 outputs the measured conductivity to the control unit 19. The control unit 19 derives the concentration of the medium CM based on the conductivity from the conductivity meter 39 and determines whether the derived concentration is the set concentration. If the control unit 19 determines that the medium CM is not at the set concentration, the control unit 19 switches the flow path of the three-way valve 41 to the waste flow path 42 and discharges the waste liquid WL, which is medium CM not at the set concentration, into the waste liquid recovery tank 18. On the other hand, if the control unit 19 determines that the medium CM is at the set concentration, the control unit 19 switches the flow path of the three-way valve 41 to the culture tank 11 and introduces medium CM at the set concentration into the culture tank 11. In this way, only medium CM at the set concentration is supplied to the culture tank 11. This prevents problems such as failure to culture Chinese hamster ovary cells due to medium CM not at the set concentration being supplied to the culture tank 11.

[0040] The hydrogen ion exponent meter 40 measures the hydrogen ion exponent of the culture medium CM passing through the culture medium supply path 35. The hydrogen ion exponent meter 40 outputs the measured hydrogen ion exponent to the control unit 19. If the hydrogen ion exponent value from the hydrogen ion exponent meter 40 is an abnormal value, the control unit 19 switches the flow path of the three-way valve 41 to the waste liquid path 42 side, and discharges the waste liquid WL, which is the culture medium CM with an abnormal hydrogen ion exponent, into the waste liquid recovery tank 18.

[0041] The control unit 19 includes a processor such as a CPU (Central Processing Unit), memory, and storage, and comprehensively controls the operation of each part of the culture medium preparation apparatus 10. The processor of the control unit 19 may be a programmable logic device (PLD), such as a field programmable gate array (FPGA), whose circuit configuration can be changed after manufacture, or a dedicated electrical circuit, such as an application specific integrated circuit (ASIC), which is a processor having a circuit configuration designed specifically for executing specific processing.

[0042] The operation unit 20 is, for example, a touch panel, and receives various operation instructions from an operator of the culture medium preparation apparatus 10. The various operation instructions include an instruction to start the continuous supply of pure water PW and powdered culture medium PM to the mixing container 16, an instruction to forcibly stop the supply of culture medium CM from the mixing container 16 to the culture tank 11, etc.

[0043] The pure water storage tank 15, mixing container 16, and waste liquid recovery tank 18 are so-called single-use devices that are disposed of after one use. The pure water supply line 21, culture medium supply line 35, filter 38, three-way valve 41, and waste liquid line 42 are also single-use devices.

[0044] The flow paths from the pure water storage tank 15 through the pure water supply path 21, the mixing container 16, and the culture medium supply path 35 to the culture tank 11 are all connected in a sterile manner. The culture medium supply path 35, the three-way valve 41, and the waste liquid path 42 are also connected in a sterile manner.

[0045] 2, the powdered culture medium supplying device 17 includes a first container 50, a second container 51, and a feeder 52. Both the first container 50 and the second container 51 store powdered culture medium PM. The capacities of the first container 50 and the second container 51, i.e., the amount of powdered culture medium PM stored in the first container 50 and the second container 51, are approximately the same. The first container 50 and the second container 51 are used by hanging them from a hook or the like.

[0046] Both the first container 50 and the second container 51 are sterile sealed bags made of a soft resin conforming to USP (United States Pharmacopeia) Class 6, such as polyethylene, polyvinyl chloride, or ethylene-vinyl acetate copolymer. That is, both the first container 50 and the second container 51 are expandable and contractible and are sealed. Furthermore, like the mixing container 16, the first container 50 and the second container 51 are single-use containers that are disposed of after one use. Note that "expandable and contractible" means that they are flexible and deform in response to changes in pressure inside the container.

[0047] The first container 50 is funnel-shaped, and a feeder 52 is attached to the narrowed lower portion of the funnel. The feeder 52 is connected to an outlet 27 for discharging the powdered medium PM into the mixing container 16. Therefore, it can be said that the first container 50 is connected to the mixing container 16 via the feeder 52. The feeder 52 may be attached to the first container 50 in a detachable or non-detachable manner.

[0048] The first container 50 supplies the powdered medium PM to the feeder 52. In other words, the first container 50 functions as a hopper. Under the control of the control unit 19, the feeder 52 continuously discharges the powdered medium PM from the first container 50 through the outlet 27 into the mixing container 16. The feeder 52 is, for example, a screw feeder (also called an auger feeder) that continuously discharges a set amount of powdered medium PM from the outlet 27 by rotating a spiral screw using a motor. The feeder 52 is not limited to the illustrated screw feeder, but may also be a table feeder (also called a circle feeder), rotary feeder, belt feeder, vibratory feeder, etc. An agitator may be installed inside the first container 50 to break down ratholes that occur during long-term use. The inner surfaces of the first container 50 and the second container 51 may be slip-processed to improve the dischargeability of the powdered medium PM.

[0049] A first connection part 53 is provided on the upper part of the first container 50 opposite the lower part to which the feeder 52 is attached. A second connection part 54 corresponding to the first connection part 53 is provided on the lower part of the second container 51. The second container 51 is exchangeably connected to the first container 50 by the first connection part 53 and the second connection part 54.

[0050] The second connection part 54 opens when connected to the first connection part 53, and functions as a supply port for supplying the powdered medium PM in the second container 51 to the first container 50. For example, a seal is attached to the second connection part 54, and when this seal is broken by a blade formed on the first connection part 53, the second connection part 54 opens.

[0051] A valve 55 is provided at the first connection part 53. The control part 19 opens and closes the valve 55 in response to an operation instruction from the operator inputted via the operation part 20. By opening and closing this valve 55, the powder medium PM in the second container 51 is supplied to the first container 50 or the supply is stopped.

[0052] As an example, as shown in FIG. 3A, when the amount of powdered medium PM stored in the first container 50 falls below a set amount and the operator inputs an instruction to open the valve 55 into the operation unit 20, the valve 55 is opened under the control of the control unit 19. As a result, the powdered medium PM is supplied from the second container 51 to the first container 50 via the first connection unit 53 and the second connection unit 54. The amount of powdered medium PM supplied per unit time from the second container 51 to the first container 50 exceeds the amount of powdered medium PM supplied per unit time from the first container 50 to the mixing container 16. Therefore, there is no risk of the supply of powdered medium PM from the second container 51 to the first container 50 not keeping up and the powdered medium PM in the first container 50 running out.

[0053] As the powdered medium PM is supplied from the second container 51 to the first container 50, back pressure is generated in the first container 50, creating a negative pressure in the second container 51. Therefore, if this continues, the supply of powdered medium PM from the second container 51 to the first container 50 will be delayed. However, since the first container 50 and the second container 51 expand and contract, the first container 50 expands to relieve the back pressure, and the second container 51 contracts to relieve the negative pressure. Therefore, there is no risk of the supply of powdered medium PM from the second container 51 to the first container 50 being delayed due to the back pressure in the first container 50 and the negative pressure in the second container 51.

[0054] Furthermore, as shown in (2), when the supply of powdered medium PM from the second container 51 to the first container 50 is almost complete, negative pressure develops within the first container 50 as the powdered medium PM is supplied from the first container 50 to the mixing container 16 via the feeder 52. Therefore, if this continues, the supply of powdered medium PM from the first container 50 to the mixing container 16 will be delayed. However, since the first container 50 expands and contracts, the first container 50 contracts to eliminate the negative pressure. Therefore, there is no risk of the supply of powdered medium PM from the first container 50 to the mixing container 16 being delayed due to the negative pressure within the first container 50.

[0055] As shown in (3), when the supply of powdered medium PM from second container 51 to first container 50 is completed, the operator inputs an operation instruction to close valve 55 to operation unit 20, and valve 55 is closed under the control of control unit 19. Then, the operator removes the empty second container 51 from first container 50 and attaches a new second container 51 filled with powdered medium PM to first container 50 instead. In other words, second container 51 is replaced.

[0056] The powdered medium PM has the property of coagulating due to moisture absorption. If the powdered medium PM in the first container 50 coagulates due to moisture absorption, the supply of the powdered medium PM from the first container 50 to the mixing container 16 will be delayed. However, because the first container 50 is sealed, there is no risk of the powdered medium PM in the first container 50 coagulating due to moisture absorption. Therefore, there is no risk of the supply of the powdered medium PM from the first container 50 to the mixing container 16 being delayed due to coagulation caused by moisture absorption of the powdered medium PM.

[0057] The processes shown in (1) to (3) are repeated as long as the culture in the culture tank 11 continues, without stopping the entire operation of the culture medium preparation apparatus 10, including the supply of the powdered medium PM to the mixing container 16 by the feeder 52. The replacement of the second container 51 shown in (3) may be performed at any timing between the end of the supply of the powdered medium PM from the second container 51 to the first container 50 and the time when the amount of powdered medium PM stored in the first container 50 becomes equal to or less than the set amount.

[0058] As described above, the powdered medium supplying device 17 is a device that continuously supplies powdered medium PM to the mixing container 16 in order to continuously prepare medium CM at a set concentration in the mixing container 16, and includes a first container 50 and a second container 51. Both the first container 50 and the second container 51 store powdered medium PM. The first container 50 is connected to the mixing container 16 via a feeder 52 and supplies powdered medium PM to the feeder 52. The second container 51 is connected to the first container 50 and supplies powdered medium PM to the first container 50. The addition of the second container 51 contributes to a more stable supply of powdered medium PM to the mixing container 16 than when only the first container 50 is used.

[0059] As shown in (3) of Figure 3, the second container 51 is replaceably connected to the first container 50. This significantly contributes to the stable supply of powdered medium PM to the mixing container 16. As a result, the medium CM can be continuously prepared over a long period of time, such as one month. Compared to increasing the capacity of the first container 50 by, for example, setting the capacity of the first container 50 to 50 times the capacity of the second container 51, the powdered medium supplying device 17 can be made smaller. Furthermore, compared to increasing the capacity of the first container 50, the powdered medium supplying device 17 can be made easier to handle.

[0060] Supply of the powdered culture medium PM from the second container 51 to the first container 50 can be completed simply by replacing the second container 51 and opening the valve 55. This allows the powdered culture medium PM to be easily supplied from the second container 51 to the first container 50. Since there is no risk of the powdered culture medium PM being scattered, the environment surrounding the powdered culture medium supply device 17 can be kept clean.

[0061] 2, the first container 50 and the second container 51 expand and contract. Therefore, the powdered medium PM can be smoothly supplied from the second container 51 to the first container 50 without being hindered by the back pressure in the first container 50 or the negative pressure in the second container 51. Furthermore, the powdered medium PM can be smoothly supplied from the first container 50 to the mixing container 16 without being hindered by the negative pressure in the first container 50.

[0062] 2, the first container 50 is sealed. Therefore, there is no risk of the powdered medium PM in the first container 50 coagulating due to moisture absorption. Therefore, the powdered medium PM can be smoothly supplied from the first container 50 to the mixing container 16 without being hindered by coagulation of the powdered medium PM in the first container 50.

[0063] 2, the second container 51 is also sealed. Therefore, there is no risk of the powdered medium PM in the second container 51 solidifying due to moisture absorption. Therefore, the powdered medium PM can be smoothly supplied from the second container 51 to the first container 50 without being hindered by solidification of the powdered medium PM in the second container 51.

[0064] 1, the solvent mixed with the powder medium PM in the mixing vessel 16 is pure water PW, the powder is the powder medium PM, and the bioprocess solution is the medium CM. Therefore, the medium CM, which is essential for cultivation, can be prepared stably for a relatively long period of time.

[0065] Furthermore, the medium CM is continuously supplied from the mixing vessel 16 to the culture tank 11. This allows for perfusion culture, enabling relatively long-term culture close to the living body environment.

[0066] 2, the first container 50 and the second container 51 are both disposable after one use, which prevents contamination due to repeated use.

[0067] (Modification of the First Embodiment) In Fig. 2, the first container 50 and the second container 51 are illustrated as expanding and contracting as a whole, but this is not limiting. As an example, as shown in Fig. 4, the first container 60 and the second container 61 may be partially expanding and contracting. Note that parts common to the first container 50 and the second container 51, such as the first connecting portion 53 and the second connecting portion 54, are denoted by the same reference numerals, and description thereof will be omitted. The same applies to Figs. 5 to 10 below.

[0068] The first container 60 is composed of an upper portion 62 to which the second container 61 is connected, a lower portion 63 with a narrower opening to which the feeder 52 is connected, and a central portion 65 which is integrated with the upper and lower portions 62, 63 by a sealing material 64. The upper and lower portions 62, 63 are both made of a hard resin conforming to USP Class 6, such as polyethylene, polypropylene, or polycarbonate. In contrast, the central portion 65 is made of a soft resin conforming to USP Class 6. In other words, the upper and lower portions 62, 63 do not expand or contract, but only the central portion 65 does.

[0069] The second container 61 is composed of an upper portion 66, a lower portion 67 connected to the first container 60, and a central portion 68 integrated with the upper and lower portions 66 and 67 by a sealing material 64. Like the upper and lower portions 62 and 63 of the first container 60, the upper and lower portions 66 and 67 are both formed of a hard resin conforming to USP Class 6. In contrast, like the central portion 65 of the first container 60, the central portion 68 is formed of a soft resin conforming to USP Class 6. In other words, the upper and lower portions 66 and 67 do not expand or contract; only the central portion 68 expands and contracts. This configuration also allows for smooth supply of powdered medium PM from the second container 61 to the first container 60 and from the first container 60 to the mixing container 16 without being hindered by the back pressure and negative pressure within the first container 60 and the negative pressure within the second container 61.

[0070] When the upper portion 62 to which the second container 61 is connected and the lower portion 63 to which the feeder 52 is attached do not expand or contract, as in the case of the first container 60, the stability of installation of the second container 61 on the first container 60 and the stability of installation of the first container 60 on the feeder 52 can be improved. Furthermore, when the lower portion 67 connected to the first container 60 does not expand or contract, as in the case of the second container 61, the stability of installation of the second container 61 on the first container 60 can be improved.

[0071] As an example, the configuration shown in FIG. 5 may be employed. In FIG. 5, the first container 70 is composed of a main body 71 and a balloon 72. The balloon 72 is attached to a first vent 73 located at the top of the main body 71, where the powdered medium PM is not stored, and is connected to the main body 71 through this first vent 73. The main body 71 is made of a hard resin conforming to USP Class 6. In contrast, the balloon 72 is made of a soft resin conforming to USP Class 6. In other words, the main body 71 does not expand or contract, and only the balloon 72 expands and contracts. Even with this configuration, the powdered medium PM can be smoothly supplied from the second container 51 to the first container 70, and from the first container 70 to the mixing container 16, without being hindered by back pressure or negative pressure within the first container 70. Note that while FIG. 5 illustrates the first container 70, a similar configuration may also be employed for the second container.

[0072] [Second Embodiment] In the first embodiment, the first container 50 and the second container 51 both expand and contract, but this is not limiting. As an example, as in the powdered culture medium supplying device 80 shown in Figure 6, the first container 81 may be made of a soft resin conforming to USP Class 6 and expand and contract, and the second container 82 may be made of a hard resin conforming to USP Class 6 and not expand and contract.

[0073] The second container 82 has a second vent 83 at its upper portion where the powdered culture medium PM is not stored. The second vent 83 functions as an air intake port that introduces outside air into the second container 82 to eliminate negative pressure inside the second container 82 that occurs when the powdered culture medium PM is supplied from the second container 82 to the first container 81.

[0074] A seal is attached to the second vent port 83. The seal is removed by the operator when starting the supply of the powder medium PM from the second container 82 to the first container 81. A filter may be attached to the second vent port 83. For example, an Aervent-50 hydrophobic disposable filter manufactured by Merck can be used as the filter.

[0075] As described above, in the second embodiment, the first container 81 expands and contracts, and the second container 82 has the second vent port 83. Even with this configuration, the powdered culture medium PM can be smoothly supplied from the second container 82 to the first container 81, and from the first container 81 to the mixing container 16, without being hindered by the back pressure and negative pressure in the first container 81 and the negative pressure in the second container 82. However, since it is necessary to provide the second vent port 83 in the second container 82, the powdered culture medium supplying device 80 of the second embodiment has a more complex configuration than the powdered culture medium supplying device 17 of the first embodiment.

[0076] The second container 82 does not expand or contract. Therefore, the second container 82 can be fixed in a shape that is easy for an operator to handle. Furthermore, the stability of the installation of the second container 82 on the first container 81 can be improved. Note that the first container 60 shown in FIG. 4 or the first container 70 shown in FIG. 5 may be used instead of the first container 81.

[0077] [Third embodiment] The opposite of the second embodiment may also be used. That is, as an example, as in the powder culture medium supplying device 90 shown in Figure 7, the first container 91 may be made of a hard resin conforming to USP Class 6 and does not expand or contract, and the second container 92 may be made of a soft resin conforming to USP Class 6 and does expand or contract.

[0078] The first container 91 has a first vent 93 at its top where the powdered culture medium PM is not stored. The first vent 93 functions as an exhaust port that discharges air from the first container 91 to the outside in order to eliminate back pressure within the first container 91 that occurs when the powdered culture medium PM is supplied from the second container 92 to the first container 91. The first vent 93 also functions as an intake port that introduces outside air into the first container 91 in order to eliminate negative pressure within the first container 91 that occurs when the powdered culture medium PM is supplied from the first container 91 to the mixing container 16. As with the second vent 83, the first vent 93 may be fitted with a filter such as an Aervent-50 hydrophobic disposable filter manufactured by Merck.

[0079] A replaceable desiccant cartridge 95 is connected to the first vent 93 as the humidity control mechanism 94. The desiccant cartridge 95 contains, for example, silica gel as a desiccant. The desiccant cartridge 95 dehumidifies the outside air introduced into the first container 91, and keeps the relative humidity of the outside air at a set humidity (for example, 60%) or less. For this reason, humidity-controlled air is supplied into the first container 91 through the first vent 93. The desiccant cartridge 95 is provided with an indicator that notifies the user when it is time to replace the desiccant cartridge 95. When the time for replacement has come, the desiccant cartridge 95 is replaced by the operator.

[0080] As described above, in the third embodiment, the first container 91 has a first vent 93, and the second container 92 expands and contracts. Humidity-controlled air is supplied from the first vent 93 to the first container 91 by a humidity control mechanism 94 (desiccant cartridge 95). Even with this configuration, the powdered medium PM can be smoothly supplied from the second container 92 to the first container 91 and from the first container 91 to the mixing container 16 without being hindered by the back pressure and negative pressure in the first container 91 and the negative pressure in the second container 92. Furthermore, since there is no risk of the powdered medium PM in the first container 91 coagulating due to moisture absorption, the powdered medium PM can be smoothly supplied from the first container 91 to the mixing container 16 without being hindered by the coagulation of the powdered medium PM in the first container 91. However, since it is necessary to provide a first air vent 93 in the first container 91 and also to provide a humidity control mechanism 94, the powdered culture medium supplying device 90 of the third embodiment has a more complex configuration than the powdered culture medium supplying device 17 of the first embodiment and the powdered culture medium supplying device 80 of the second embodiment.

[0081] The first container 91 does not expand or contract, which improves the stability of the installation of the first container 91 on the feeder 52 and the stability of the installation of the second container 92 on the first container 91.

[0082] In addition, in order to eliminate back pressure within the first container 91, a first air vent that functions as an exhaust port for discharging air within the first container 91 to the outside, and a first air vent that functions as an intake port for introducing outside air into the first container 91 in order to eliminate negative pressure within the first container 91 may be provided separately.

[0083] (Variation of the Third Embodiment) The humidity control mechanism is not limited to the illustrated desiccant cartridge 95. As an example, a humidity control mechanism 100 shown in FIG. 8 may be employed. The humidity control mechanism 100 is configured with a humidity control device 101, a chamber 102 connected to a first vent 93, and a supply path 103 and a return path 104 connecting the humidity control device 101 and the chamber 102. The humidity control device 101 is driven and controlled by a control unit 19. The humidity control device 101 takes in outside air. The humidity control device 101 also takes in air from the first container 91 through the first vent 93, the chamber 102, and the return path 104. The humidity control device 101 then dehumidifies the relative humidity of the taken-in outside air and the air from the first container 91 to a set humidity or lower. The humidity control device 101 supplies the outside air and air dehumidified to a set humidity or lower to the first container 91 through the supply path 103, the chamber 102, and the first vent 93.

[0084] A pressure gauge is provided in the chamber 102. Based on the pressure measured by this pressure gauge, the control unit 19 determines whether negative pressure or back pressure has occurred in the first container 91. If it is determined that negative pressure has occurred in the first container 91, the control unit 19 drives the humidity control device 101 to dehumidify the outside air and the air in the first container 91 to a set humidity or lower before supplying them to the first container 91. On the other hand, if it is determined that back pressure has occurred in the first container 91, the control unit 19 does not drive the humidity control device 101 and instead discharges the air in the first container 91 to the outside through the first air vent 93, the chamber 102, the return flow path 104, and the humidity control device 101. This configuration also eliminates the risk of the powdered medium PM in the first container 91 coagulating due to moisture absorption, allowing the powdered medium PM to be smoothly supplied from the first container 91 to the mixing container 16 without being hindered by the coagulation of the powdered medium PM in the first container 91.

[0085] As another example, a humidity control mechanism 110 shown in FIG. 9 may be employed. The humidity control mechanism 110 includes a humidity control chamber 111, an air handling unit (AHU) 112, and an exhaust fan 113. The humidity control chamber 111 airtightly encloses the entire culture medium preparation apparatus, including the mixing container 16 and the powdered culture medium supply device 90. The air conditioner 112 and the exhaust fan 113 are driven and controlled by a control unit 19. The air conditioner 112 takes in outside air and dehumidifies it to a set humidity or lower. The outside air dehumidified by the air conditioner 112 to a set humidity or lower is supplied to the humidity control chamber 111 through a supply path 114. The exhaust fan 113 exhausts the air in the humidity control chamber 111 to the outside through an exhaust path 115. Even with this configuration, there is no risk of the powdered medium PM in the first container 91 solidifying due to moisture absorption, so the powdered medium PM can be smoothly supplied from the first container 91 to the mixing container 16 without being hindered by solidification of the powdered medium PM in the first container 91. In this case, the operator performs work such as replacing the second container 92 inside the humidity-controlled chamber 111.

[0086] [Fourth embodiment] As an example, as shown in FIG. 10, a powder culture medium supplying device 120 may be used in which both a first container 121 and a second container 122 are made of a hard resin conforming to USP Class 6 and do not expand or contract.

[0087] The first container 121 has a first vent 123 at the top where the powder medium PM is not stored. The first vent 123 performs the same function as the first vent 93 of the third embodiment.

[0088] A desiccant cartridge 125 is replaceably connected to the first ventilation port 123 as a humidity control mechanism 124. The desiccant cartridge 125 performs the same function as the desiccant cartridge 95 of the third embodiment.

[0089] The second container 122 has a second vent 126 at the top where the powder medium PM is not stored. The second vent 126 performs the same function as the second vent 83 of the second embodiment.

[0090] As described above, in the fourth embodiment, the first container 121 has a first vent 123, and the second container 122 has a second vent 126. Humidified air is supplied from the humidity control mechanism 124 (desiccant cartridge 125) into the first container 121 through the first vent 123. Even with this configuration, the powdered medium PM can be smoothly supplied from the second container 122 to the first container 121 and from the first container 121 to the mixing container 16 without being hindered by the back pressure and negative pressure in the first container 121 and the negative pressure in the second container 122. Furthermore, since there is no risk of the powdered medium PM in the first container 121 coagulating due to moisture absorption, the powdered medium PM can be smoothly supplied from the first container 121 to the mixing container 16 without being hindered by the coagulation of the powdered medium PM in the first container 121. However, since it is necessary to provide a first air vent 123 in the first container 121, a second air vent 126 in the second container 122, and a humidity control mechanism 124, the powdered culture medium supplying device 120 of the fourth embodiment has a more complex configuration than the powdered culture medium supplying device 17 of the first embodiment, the powdered culture medium supplying device 80 of the second embodiment, and the powdered culture medium supplying device 90 of the third embodiment.

[0091] As the humidity control mechanism, instead of the humidity control mechanism 124 configured by the illustrated desiccant cartridge 125, the humidity control mechanism 100 shown in FIG. 8 or the humidity control mechanism 110 shown in FIG. 9 may be used.

[0092] When the second vent 83 or 126 is provided, as in the second container 82 of the second embodiment or the second container 122 of the fourth embodiment, a humidity control mechanism may be provided to dehumidify the air introduced into the second container 82 or 122 through the second vent 83 or 126 to a set humidity level or lower. By preventing moisture absorption by the powdered medium PM in the second container 82 or 122, the powdered medium PM can be smoothly supplied from the second container 82 or 122 to the first container 81 or 121. Furthermore, preventing moisture absorption by the powdered medium PM in the second container 82 or 122 effectively prevents solidification of the powdered medium PM supplied to the first container 81 or 121 due to moisture absorption. This is more preferable because it contributes to the smooth supply of the powdered medium PM from the first container 81 or 121 to the mixing container 16.

[0093] [Example] First, the equipment used in the example will be listed. A beaker (model number B-200 SCI, capacity 200 mL) manufactured by HARIO Corporation was used as the mixing container 16. A Micron Feeder (model number TF-70-CT (AD)) manufactured by Aisin Nano Technology Co., Ltd. was used as the feeder 52.

[0094] For each of the channels such as the pure water supply channel 21, the culture medium supply channel 35, and the waste channel 42, a lab silicone tube (product number 9-869-07, inner diameter x outer diameter = φ4 mm x φ6 mm) manufactured by AS ONE Corporation was used, cut appropriately.

[0095] A Masterflex pump (model number 07528-30) manufactured by Yamato Scientific Co., Ltd. was used as the drive unit for the pure water supply pump 22 and the culture medium supply pump 36. A Masterflex pump head (model number 77201-60) manufactured by Yamato Scientific Co., Ltd. was used as the pump head for the pure water supply pump 22 and the culture medium supply pump 36. The drive unit for the pure water supply pump 22 and the culture medium supply pump 36 was the same Masterflex pump described above, and two of the Masterflex pump heads described above were attached to one Masterflex pump.

[0096] The pure water flow meter 23 and the culture medium flow meter 37 were clamp-on flow sensors (model number FD-XA1) manufactured by Keyence Corporation.

[0097] An Ultra Stirrer (Model No. MSD-1) manufactured by AS ONE Corporation was used as the stirrer 32. A regular stirrer (Model No. C 8×30, diameter×length=φ8 mm×30 mm) manufactured by AS ONE Corporation was used as the stirrer 33.

[0098] The main body of the conductivity meter 39 and the hydrogen ion index meter 40 was a benchtop pH (Potential Hydrogen) / electrical conductivity meter (model number F-74) manufactured by Horiba, Ltd. The electrodes of the conductivity meter 39 were a general-purpose electrical conductivity cell (model number 3562-10D) manufactured by Horiba, Ltd. The electrodes of the hydrogen ion index meter 40 were a refill-free pH electrode (model number 9652-20D) manufactured by Horiba, Ltd. Both of these electrodes are capable of measuring conductivity and hydrogen ion index in-line. The flow cell installed together with these electrodes was a flow cell manufactured by Horiba, Ltd. (product number 3200844642).

[0099] Charge bags (model number PE-S) manufactured by ChargePoint were used for the first and second containers that expand and contract, such as first container 50, second container 51, first container 81, and second container 92. Furthermore, for the first and second containers that do not expand and contract, such as second container 82, first container 91, first container 121, and second container 122, the aforementioned hard resin processed into a cylindrical shape was used.

[0100] A single-use split butterfly valve passive (model number SUP) manufactured by ChargePoint was used as the valve 55. The humidity control mechanism employed was the humidity control mechanism 100 shown in Fig. 8. A humidity adjustment unit (model number STU-1) manufactured by AS ONE Corporation was used as the humidity control device 101.

[0101] As the powder medium PM, BalanCD® CHO Growth A manufactured by FUJIFILM Irvine Scientific, Inc. was used.

[0102] The experimental conditions for the example are listed below. The flow rate of the pure water PW supplied to the mixing vessel 16 is 80 mL / min. The amount of powder medium PM supplied to the mixing vessel 16 per unit time is 0.76 g / min. The screw rotation speed of the feeder 52 is 1 rpm (rotations per minute). The amount of liquid in the mixing vessel 16 is 100 mL. The rotation speed of the agitator 32 is 300 rpm. The measurement intervals of the conductivity meter 39 and the hydrogen ion exponent meter 40 are 10 seconds.

[0103] The flow rate of pure water PW was calculated from the amount of powder medium PM supplied, using a value that matched the "amount of water to be added per certain amount of powder" stated in the instruction manual for powder medium PM. The amount of powder medium PM supplied was determined by rotating the screw of feeder 52 at a set rotation speed to actually supply powder medium PM, and measuring the weight of powder medium PM supplied per unit time using an electronic balance. A compact balance (model number EW-150i) manufactured by A&D Co., Ltd. was used as the electronic balance.

[0104] As described above, the amount of liquid in the mixing container 16 remains constant from start to finish because the amount of pure water PW supplied to the mixing container 16 and the amount of medium CM discharged from the mixing container 16 are appropriately controlled. If the amount of liquid in the mixing container 16 (i.e., the initial solvent) before the continuous supply of pure water PW and powdered medium PM begins is too large, it may take longer for the medium CM concentration to reach the set concentration, or the concentration of medium CM in the mixing container 16 may be more likely to be unevenly distributed. On the other hand, if the amount of initial solvent in the mixing container 16 before the continuous supply of pure water PW and powdered medium PM begins is too small, the amount of powdered medium PM supplied will be too high relative to the amount of initial solvent, leading to accumulation of the powdered medium PM on the liquid surface and other problems that may result in poor dissolution. Taking these factors into consideration, the amount of liquid in the mixing container 16 was set to 100 mL, which is neither too large nor too small compared to the amount of powdered medium PM supplied.

[0105] Using the above equipment and conditions, the powdered medium PM was actually supplied from the second container to the first container for each of the possible combinations of the first to fourth embodiments, and the powdered medium PM was also supplied from the first container to the mixing container to evaluate whether or not the four issues described above were addressed. The evaluation results are shown in Tables 130 to 133 in Figures 11 to 14.

[0106] Here, the measures to address the four issues are measures to deal with negative pressure in the second container (hereinafter referred to as second container negative pressure measures), measures to deal with back pressure in the first container (hereinafter referred to as first container back pressure measures), measures to deal with negative pressure in the first container (hereinafter referred to as first container negative pressure measures), and measures to deal with solidification due to moisture absorption of the powder culture medium PM in the first container (hereinafter referred to as solidification measures).

[0107] In tables 130 to 133, a circle is marked if measures have been taken to address the issues and the issues have been overcome, and a triangle is marked if measures have not been taken to address the issues and the issues have not been overcome.The overall evaluation is marked with a circle if measures have been taken to address all four of the issues and all four issues have been overcome, and a triangle is marked if measures have not been taken to address any one of the four issues and any one of the four issues has not been overcome.

[0108] The second container negative pressure countermeasure is evaluated as ◯ when the powdered medium PM can be smoothly supplied from the second container to the first container without negative pressure occurring inside the second container. On the other hand, the second container negative pressure countermeasure is evaluated as △ when negative pressure occurs inside the second container and the supply of powdered medium PM from the second container to the first container is delayed.

[0109] Similarly, the first container backpressure countermeasure is evaluated as ◯ when no backpressure occurs in the first container and the powdered medium PM can be smoothly supplied from the second container to the first container. In contrast, the first container backpressure countermeasure is evaluated as △ when backpressure occurs in the first container and the supply of powdered medium PM from the second container to the first container is delayed.

[0110] Furthermore, the first container negative pressure countermeasure is evaluated as ◯ when the first container does not become negative pressure and the powdered medium PM can be smoothly supplied from the first container to the mixing container 16. In contrast, the first container negative pressure countermeasure is evaluated as △ when the first container becomes negative pressure and the supply of the powdered medium PM from the first container to the mixing container 16 is delayed.

[0111] The coagulation countermeasure is evaluated as ◯ when the powdered medium PM in the first container does not coagulate due to moisture absorption and can be smoothly supplied from the first container to the mixing container 16. In contrast, the coagulation countermeasure is evaluated as △ when the powdered medium PM in the first container coagulates due to moisture absorption, causing a delay in the supply of powdered medium PM from the first container to the mixing container 16.

[0112] Table 130 shown in Figure 11 summarizes possible combinations of the first embodiment in which both the first container and the second container expand and contract, and their evaluations. No. 1_1 is the configuration shown in Figure 2, in which the first container and the second container are not provided with vents (the first container and the second container are sealed). In this case, all of the issues are overcome, so the overall evaluation is ○. No. 1_2 is a configuration in which the first container is sealed and the second container is provided with a second vent. In this case, all of the issues are overcome, so the overall evaluation is ○.

[0113] In No. 1_3, the first container is provided with a first vent hole and the second container is sealed, and in No. 1_4, the first container is provided with a first vent hole and the second container is provided with a second vent hole. In these cases, the overall evaluation is ◯, provided that measures to prevent solidification are taken using a humidity control mechanism.

[0114] Table 131 shown in Figure 12 summarizes possible combinations of the second embodiment in which the first container expands and contracts but the second container does not, along with their evaluations. No. 2_1 is a configuration in which the first container and the second container are not provided with vents (the first container and the second container are sealed). In this case, no measures are taken to prevent negative pressure in the second container, so the overall evaluation is △. No. 2_2 is the configuration shown in Figure 6 in which the first container is sealed and the second container is provided with a second vent. In this case, all of the issues are overcome, so the overall evaluation is ◯.

[0115] In No. 2_3, the first container has a first vent hole and the second container is sealed, while in No. 2_4, the first container has a first vent hole and the second container has a second vent hole. In the case of No. 2_3, as in the case of No. 2_1, no measures are taken to prevent negative pressure in the second container, so the overall rating is △. In the case of No. 2_4, the overall rating is ○, provided that measures to prevent solidification are taken using a humidity control mechanism.

[0116] Table 132 shown in Figure 13 summarizes possible combinations of the third embodiment in which the first container does not expand and contract, but the second container does, and their evaluations. No. 3_1 is a configuration in which the first container and the second container are not provided with vents (the first container and the second container are sealed). No. 3_2 is a configuration in which the first container is sealed, and the second container is provided with a second vent. In these cases, no measures are taken to prevent back pressure in the first container or negative pressure in the first container, so the overall evaluation is Fair for both.

[0117] No. 3_3 is the configuration shown in Fig. 7, in which the first container is provided with a first vent hole and the second container is sealed, and No. 3_4 is the configuration in which the first container is provided with a first vent hole and the second container is provided with a second vent hole. In these cases, the overall evaluation is ○, provided that measures to prevent solidification are taken using a humidity control mechanism.

[0118] Table 133 shown in Figure 14 summarizes possible combinations of the fourth embodiment in which neither the first nor the second container expands or contracts, along with their evaluations. No. 4_1 is a configuration in which the first and second containers are not provided with vents (the first and second containers are sealed). In this case, no measures are taken other than measures to prevent solidification, so the overall evaluation is Fair. No. 4_2 is a configuration in which the first container is sealed, and the second container is provided with a second vent. In this case, no measures are taken to prevent back pressure in the first container or negative pressure in the first container, so the overall evaluation is Fair.

[0119] No. 4_3 is a configuration in which a first vent is provided in the first container and the second container is sealed, while No. 4_4 is a configuration in which a first vent is provided in the first container and a second vent is provided in the second container, as shown in Figure 10. In the case of No. 4_3, no measures are taken to prevent negative pressure in the second container, so the overall rating is △. In the case of No. 4_4, the overall rating is ○, provided that measures to prevent solidification are taken using a humidity control mechanism.

[0120] From the above, it has been confirmed that the aspects shown in the first to fourth embodiments (No. 1_1 in FIG. 11, No. 2_2 in FIG. 12, No. 3_3 in FIG. 13, and No. 4_4 in FIG. 14) can overcome all of the challenges, although some of them require measures to prevent solidification using a humidity control mechanism.

[0121] Because the bulk density of the powder medium PM is relatively high and air is not easily transmitted through it, negative pressure and back pressure tend to occur in the first and / or second containers. Furthermore, the powder medium PM is relatively hygroscopic and easily solidifies. Therefore, when the powder medium PM is used as the powder, the effect of overcoming all of these issues is more pronounced.

[0122] A sensor may detect that the powdered medium PM in the first container has fallen below a set amount, and automatically open valve 55 without operator intervention. Similarly, a sensor may detect that the supply of powdered medium PM from the second container to the first container has ended, and automatically close valve 55 without operator intervention.

[0123] Instead of or in addition to measuring the weight of the mixing container 16 with a weighing scale, the weight of the first container may be measured with a weighing scale. The amount of powdered medium PM supplied from the first container to the mixing container 16 may then be controlled so that the decrease in measured weight per unit time is constant. In this case, it is preferable to temporarily suspend control while the second container is being replaced and / or while the powdered medium PM is being supplied from the second container to the first container. Alternatively, while the second container is being replaced and / or while the powdered medium PM is being supplied from the second container to the first container, control may be continued based on the weight measured immediately before the second container is replaced and / or immediately before the powdered medium PM is supplied from the second container to the first container. If control is continued based on the immediately preceding measured weight, after the second container is replaced and / or after the powdered medium PM is supplied from the second container to the first container, the previously measured weight is reset, a new weight is measured, and control is resumed based on the newly measured weight.

[0124] When the second container is connected to the first container, there is a concern that vibrations from the second container may be transmitted to the first container, causing instability in the measured weight of the first container. Therefore, it is preferable to connect the first container and the second container in a manner that prevents vibrations from the second container from being transmitted to the first container. Specifically, it is preferable that the first container and the second container are connected flexibly rather than rigidly. For example, it is preferable that a member (e.g., a hook) that supports the weight of the first container and a member (e.g., a hook) that supports the weight of the second container are independent of each other.

[0125] The conductivity measured by the conductivity meter 39 is a representative value obtained by adding up the conductivity of each component dissolved in the medium CM. Therefore, to more accurately determine whether the concentration of the medium CM has reached the set concentration, it is preferable to measure the concentration of each component of the medium CM. However, since it is not easy to measure the concentration of each component of the medium CM, the representative value of the conductivity of each component is measured instead.

[0126] If it is possible to measure the concentration of each component of the medium CM, it would be best to determine whether the concentration of the medium CM has reached the set concentration based on the results. However, if the concentration of each component of the medium CM is measured individually, the time it takes for each component to reach the set concentration may vary. For this reason, when it is determined that all components have reached the set concentration, it is necessary to stop the wastewater of the medium CM and start the supply to the culture tank 11.

[0127] The properties of the medium CM supplied to the culture tank 11 that are measured inline are not limited to the electrical conductivity and hydrogen ion exponent shown above. In addition to or instead of these, Raman spectrum, infrared absorption spectrum, near-infrared absorption spectrum, ultraviolet absorption spectrum, fluorescence spectrum, etc. may also be measured. The concentration of the medium CM may then be derived based on the measurement results of these spectra.

[0128] In the above embodiments, pure water PW is exemplified as the solvent and purified water, but this is not limiting. Distilled water, water for injection (WFI), or the like may also be used. Furthermore, in the above embodiments, culture medium CM is exemplified as the bioprocess solution, but this is not limiting. The bioprocess solution may also be a buffer solution. Therefore, the powder is not limited to the exemplified powder culture medium, and may also be a powder that constitutes the solid component of a buffer solution.

[0129] From the above description, the technology described in the following supplementary paragraphs can be understood.

[0130] [Supplementary Item 1] A powder supplying device that continuously supplies powder to a mixing container to continuously prepare a bioprocess solution of a set concentration in the mixing container, the powder supplying device comprising: a first container for storing the powder, the first container connected to the mixing container via a feeder, and supplying the powder to the feeder; and a second container for storing the powder, connected to the first container, and supplying the powder to the first container. [Supplementary Item 2] The powder supplying device according to Supplementary Item 1, wherein the second container is replaceably connected to the first container. [Supplementary Item 3] The powder supplying device according to Supplementary Item 1 or Supplementary Item 2, wherein the first container expands and contracts. [Supplementary Item 4] The powder supplying device according to Supplementary Item 3, wherein the first container is hermetically sealed. [Supplementary Item 5] The powder supplying device according to Supplementary Item 3 or Supplementary Item 4, wherein the first container is hermetically sealed. [Supplementary Item 5] The powder supplying device according to Supplementary Item 3 or Supplementary Item 4, wherein a portion of the first container expands and contracts. [Supplementary Item 6] The powder supplying device according to any one of Supplementary Items 1 to 5, wherein the second container expands and contracts. [Supplementary Item 7] The powder supplying device according to Supplementary Item 6, wherein the second container is sealed. [Supplementary Item 8] The powder supplying device according to Supplementary Item 6 or Supplementary Item 7, wherein a portion of the second container expands and contracts. [Supplementary Item 9] The powder supplying device according to any one of Supplementary Items 1 to 8, wherein the first container has a first vent port. [Supplementary Item 10] The powder supplying device according to Supplementary Item 9, wherein humidity-conditioned air by a humidity control mechanism is supplied into the first container through the first vent port. [Supplementary Item 11] The powder supplying device according to Supplementary Item 9 or Supplementary Item 10, wherein the first container does not expand and contract. [Supplementary Item 12] The powder supplying device according to any one of Supplementary Items 1 to 11, wherein the second container has a second vent port. [Supplementary Item 13] The powder supplying device according to Supplementary Item 12, wherein the second container does not expand or contract. [Supplementary Item 14] The powder supplying device according to any one of Supplementary Items 1 to 13, wherein the first container and the second container expand or contract. [Supplementary Item 15] The powder supplying device according to any one of Supplementary Items 1 to 13, wherein the first container expands and contracts, and the second container has a second vent hole.[Supplementary Item 16] The powder supplying device according to any one of Supplementary Items 1 to 13, wherein the first container has a first vent, the second container expands and contracts, and humidity-controlled air by a humidity control mechanism is supplied into the first container through the first vent. [Supplementary Item 17] The powder supplying device according to any one of Supplementary Items 1 to 13, wherein the first container has a first vent, the second container has a second vent, and humidity-controlled air by a humidity control mechanism is supplied into the first container through the first vent. [Supplementary Item 18] The powder supplying device according to any one of Supplementary Items 1 to 17, wherein the solvent mixed with the powder in the mixing container is purified water, the powder is a powdered culture medium, and the bioprocess solution is a culture medium. [Supplementary Item 19] The powder supplying device according to Supplementary Item 18, wherein the culture medium is continuously supplied from the mixing container to a culture tank. [Supplementary Item 20] The powder supplying device according to any one of Supplementary Items 1 to 19, wherein the first container and the second container are disposable after one use.

[0131] The technology of the present disclosure can be appropriately combined with the various embodiments and / or various modified examples described above. Furthermore, it is needless to say that the technology is not limited to the above-described embodiments, and various configurations can be adopted as long as they do not deviate from the gist of the present disclosure.

[0132] The above-described description and illustrations are a detailed explanation of the parts related to the technology of the present disclosure and are merely an example of the technology of the present disclosure. For example, the above description of the configuration, functions, actions, and effects is an explanation of an example of the configuration, functions, actions, and effects of the parts related to the technology of the present disclosure. Therefore, it goes without saying that unnecessary parts may be deleted, new elements may be added, or replacements may be made to the above-described description and illustrations within the scope of the gist of the technology of the present disclosure. Furthermore, to avoid confusion and facilitate understanding of the parts related to the technology of the present disclosure, the above-described description and illustrations omit explanations of common technical knowledge that do not require particular explanation to enable the implementation of the technology of the present disclosure.

[0133] In this specification, "A and / or B" is synonymous with "at least one of A and B." In other words, "A and / or B" means that it may be only A, only B, or a combination of A and B. In addition, in this specification, the same concept as "A and / or B" is also applied when three or more things are expressed by connecting them with "and / or."

[0134] All publications, patent applications, and technical standards mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent application, or technical standard was specifically and individually indicated to be incorporated by reference.

Claims

1. A powder supplying device that continuously supplies powder to a mixing vessel to continuously prepare a bioprocess solution of a set concentration in the mixing vessel, comprising: a first vessel that stores the powder, the first vessel being connected to the mixing vessel via a feeder and supplying the powder to the feeder; and a second vessel that stores the powder, the second vessel being connected to the first vessel and supplying the powder to the first vessel.

2. The powder supplying device according to claim 1, wherein the second container is replaceably connected to the first container.

3. The powder supplying device according to claim 1, wherein said first container expands and contracts.

4. The powder feeder of claim 3, wherein said first container is hermetically sealed.

5. The powder supplying device according to claim 3, wherein a portion of said first container expands and contracts.

6. The powder supplying device according to claim 1, wherein said second container expands and contracts.

7. The powder feeder of claim 6, wherein said second container is hermetically sealed.

8. The powder supplying device according to claim 6, wherein a portion of said second container expands and contracts.

9. The powder feeder of claim 1, wherein said first container has a first vent.

10. A powder supplying device as described in claim 9, wherein humidified air by a humidity control mechanism is supplied to the first container through the first air vent.

11. The powder supplying device according to claim 9, wherein the first container does not expand or contract.

12. The powder feeder of claim 1, wherein said second container has a second vent.

13. The powder supplying device of claim 12, wherein the second container does not expand or contract.

14. The powder supplying device of claim 1, wherein the first container and the second container expand and contract.

15. The powder feeder of claim 1, wherein said first container expands and contracts, and said second container has a second vent.

16. A powder supplying device as described in claim 1, wherein the first container has a first air vent, the second container expands and contracts, and humidity-conditioned air is supplied from the first air vent into the first container by a humidity control mechanism.

17. A powder supplying device as described in claim 1, wherein the first container has a first air vent, the second container has a second air vent, and humidified air is supplied from the first air vent into the first container by a humidity control mechanism.

18. The powder supplying device according to claim 1, wherein the solvent mixed with the powder in the mixing vessel is purified water, the powder is a powder culture medium, and the bioprocess solution is a culture medium.

19. The powder supplying device according to claim 18, wherein the medium is continuously supplied from the mixing vessel to the culture tank.

20. The powder supplying device according to claim 1, wherein the first container and the second container are disposable after one use.

Citation Information

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