Culture control system, culture control method, culture system, and culture method

Abstract

To reduce the time and effort for a user to monitor the culture state when controlling culture of cells or the like.SOLUTION: In a culture control system 20 for controlling culture of a culture vessel 30 housing a culture object, when conditions for transitioning to the next step have been established within a predetermined step among various steps created by dividing culture into a plurality of steps, control is exerted to automatically transition to the next step when the setting to automatically transition to the next step is performed, and to continue the predetermined step when the setting to automatically transition to the next step is not performed.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present disclosure relates to a technique for controlling the operation of a culture vessel. [Background technology]

[0002] BACKGROUND ART Mass culture of culture targets such as microorganisms, insect cells, plant cells, and animal cells is widely used for producing various substances useful as pharmaceuticals, foods, cosmetics, or raw materials for these.

[0003] Conventionally, a culture vessel has been proposed that accommodates a culture bag containing a liquid (culture medium) containing a culture target and a gas, and performs culture by adjusting the temperature, adjusting the gas flow rate, and shaking (see Patent Document 1). Furthermore, culture involves multiple steps, and when proceeding to the next step among the multiple steps, the user checks the temperature inside the culture vessel and the measured values ​​obtained by a flow rate sensor, and visually checks the culture state inside the culture vessel. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Japanese Patent Application Publication No. 2018-126172 Summary of the Invention [Problem to be solved by the invention]

[0005] However, among the multiple steps, there are some steps in which, as long as certain conditions are met, such as the temperature inside the culture vessel, the user can proceed to the next step without bothering to visually check the culture state inside the culture vessel. Conventionally, even in such cases, the user had to wait near the culture vessel to monitor the culture state, which was time-consuming.

[0006] The present disclosure has been made in consideration of the above-mentioned problems, and aims to reduce the effort required for a user to monitor the culture state when controlling the culture of cells or the like. [Means for solving the problem]

[0007] The present disclosure relates to a culture control system that controls the culture of a culture vessel containing a culture object, and has a control unit that controls the culture to automatically transition to the next step if a setting has been made to automatically transition to the next step when a condition for transitioning to the next step is met within a predetermined step among the steps into which the culture is divided into multiple processes, or to continue the predetermined step if a setting has not been made to automatically transition to the next step. [Effects of the Invention]

[0008] As described above, the present disclosure has the effect of reducing the effort required by the user to monitor the culture state when controlling the culture of cells or the like. [Brief explanation of the drawings]

[0009] [Figure 1] FIG. 1 is an overall configuration diagram of a culture system. [Figure 2] FIG. 2 is a diagram showing the electrical hardware configuration of the culture control device. [Figure 3] FIG. 2 is a diagram illustrating an electrical hardware configuration of a communication terminal. [Figure 4] FIG. 2 is a functional configuration diagram of the culture system. [Figure 5] FIG. 2 is a sequence diagram showing the processing of the culture system. [Figure 6] FIG. 10 is a diagram showing a setting screen for culture step control information displayed by the communication terminal. [Figure 7] FIG. 10 is a diagram showing a display screen of a driving situation displayed by a communication terminal. [Figure 8] FIG. 10 is a sequence diagram showing a process of displaying a screen showing whether a transition condition is satisfied. [Figure 9] FIG. 10 is a diagram showing a display screen showing whether a transition condition is satisfied. [Figure 10] 1 is a flowchart showing the control of each step in culture. DETAILED DESCRIPTION OF THE INVENTION

[0010] Hereinafter, a culture system 10 according to an embodiment will be described with reference to the drawings.

[0011] [Overall configuration of the culture system] First, the overall configuration of a culture system 10 will be described with reference to Fig. 1. Fig. 1 is a diagram showing the overall configuration of the culture system.

[0012] As shown in FIG. 1, a culture system 10 is constructed by a culture vessel 30, a culture control device 50, and a communication terminal 70. The culture control device 50 and the communication terminal 70 can communicate with each other via a communication network such as the Internet, a LAN (Local Area Network), or a cable. The communication may be wired or wireless. The communication terminal 70 may be attached to the culture control device 50. The culture control device 50 and the communication terminal 70 constitute a culture control system 20. This culture control system 20 controls the culture process of the culture vessel 30 in which the culture object is accommodated.

[0013] <Culture container> The culture vessel 30 is mainly composed of a vessel body 31 and a drive mechanism 35 for driving the vessel body 31. Inside the vessel body 31, a culture bag 40 is housed.

[0014] The culture bag 40 is made of a soft packaging material such as a thermoplastic resin such as polystyrene, polyamide, polyester, or polyolefin, or a film of a laminate of these. Therefore, the material of the culture vessel 30 is a composite material such as a metal such as stainless steel, resin, wood, laminated wood, or fiber-reinforced plastic, and has hardness (rigidity) sufficient to protect the culture bag 40.

[0015] The capacity (size) of the culture bag 40 is not particularly limited, but may be, for example, 0.1 L to 5000 L, and preferably 1 to 2000 L. The culture bag 40 may be single-use (disposable). Therefore, a culture vessel 30 that matches the size of the culture bag 40 is used.

[0016] The lower part of the culture bag 40 contains a liquid (culture medium), and the upper part of the culture bag 40 contains a gas. The volume ratio of the gas to the liquid (gas-liquid volume ratio) is not particularly limited, and the liquid may be more than the gas, the gas may be more than the liquid, or it may be about half and half. The gas-liquid volume ratio is preferably in the range of, for example, 1:9 to 9:1.

[0017] The liquid in the culture bag 40 contains a living organism to be cultured, such as a microorganism, insect cell, plant cell, animal cell, tissue, cell sheet, or cell mass. The gas in the culture bag 40 may be an aerobic atmosphere containing air (or an oxygen-containing gas), or an anaerobic atmosphere with a low oxygen concentration. The composition of this gas is not particularly limited, but a mixture of two or more gases is common. Examples of components of this gas include oxidizing gases such as oxygen (O2), inert gases such as nitrogen (N2) and argon (Ar), acidic gases such as carbon dioxide (CO2), basic gases such as ammonia (NH3), and reducing gases such as hydrogen sulfide (HS).

[0018] An inlet of an alkali tube 41 is connected to the upper side of the culture vessel 30, for supplying an alkaline solution from the culture control device 50 into the culture bag 40. Similarly, an air inlet of an upper aeration tube 42 is connected to the upper side of the culture vessel 30, for supplying at least one gas such as air and carbon dioxide from the culture control device 50 to the gas portion in the culture bag 40. Furthermore, an air inlet of a lower aeration tube 43 is connected to the lower side of the culture vessel 30, for supplying at least one gas such as nitrogen, air, and oxygen from the culture control device 50 to the liquid portion in the culture bag 40.

[0019] The culture vessel 30 is provided with a drive mechanism 35 for shaking the main body of the culture vessel 30 including the culture bag 40, and a temperature adjustment mechanism 36 for adjusting the temperature of the culture bag 40 and its contents (culture medium). A control cord 45 for communicating control signals from the culture control device 50 is connected to the drive mechanism 35 and the temperature adjustment mechanism 36.

[0020] The drive mechanism 35 is controlled by the culture control device 50 to repeatedly rotate and stop the container body 31 including the culture bag 40. This allows the contents in the culture bag 40 to be cultured while being stirred and mixed. The drive mechanism 35 can detect the weight of the container body 31 including the culture bag 40.

[0021] The culture vessel 30 is provided with a temperature control mechanism 36, which may include, but is not limited to, a jacket structure that allows a heat medium such as circulating water to pass through, a heating device such as a rubber heater, etc. The culture temperature depends on the type of organism being cultured, but for example, in the case of microorganisms, a temperature of 4 to 40°C is preferred, and 25 to 37°C is particularly preferred. When the culture vessel 30 is not used for culture but is instead used as an agitator for culture medium or the like, it may be cooled (for example, to 4 to 20°C).

[0022] The culture bag 40 is also provided with a sensor group 37, including a sensor for measuring DO (dissolved oxygen concentration), a sensor for measuring pH (hydrogen ion exponent) of the contents, and a sensor for measuring temperature. Measurement values ​​of the sensor group 37 are transmitted to the culture control device 50 via a sensor group code 47, and are used from the culture control device 50 for feedback control of the supply of gases and the like via the tubes 41, 42, and 43, as well as for feedback control of the drive mechanism 35 and the temperature adjustment mechanism 36 via a control code 45.

[0023] For example, for DO, the air ventilation rate is measured, and oxygen is supplied into the culture bag 40 from the culture control device 50 via the tube 43 through feedback control. In this case, the oxygen is preferably supplied from the tube 43 having an outlet in the liquid (below the liquid surface) so that oxygen is distributed evenly throughout the liquid in the culture bag 40.

[0024] The pH can be measured by inserting a pH electrode into the culture bag 40 or by attaching a chip that changes color depending on the pH to the inside of the culture bag 40. For example, if it is desired to make the inside of the culture bag 40 acidic, the culture control device 50 can change the pH to the acidic side by supplying CO2 gas into the culture bag 40 via tube 42 or tube 43, or by dripping an acid solution into the culture bag 40. When the culture control device 50 supplies CO2 gas, it is preferable that the culture control device 50 introduces CO2 gas from the top of the culture bag 40 via tube 42 or supplies it intermittently from the bottom of the culture bag 40 via tube 43 to prevent the CO2 gas from dissolving in the solution more than necessary. If it is desired to make the inside of the culture bag 40 basic, the culture control device 50 can make the pH basic by supplying (adding) an alkaline solution from the top of the culture bag 40 via tube 41.

[0025] The culture vessel 30 can be used for both fed-batch culture (fed-batch method) and perfusion culture (perfusion method). There are no particular limitations on the organisms, cells, etc. to be cultured, and it can be used to culture fungi such as Escherichia coli, yeast, microorganisms, insect cells, plant cells, animal cells, CHO (Chinese Hamster Ovary) cells for biopharmaceutical production, HeLa cells, COS cells, iPS cells for regenerative medicine, stem cells such as mesenchymal stem cells, and animal cells such as differentiated tissue cells. It is particularly suitable for culturing CHO cells.

[0026] The culture vessel 30 and the culture method using the same are particularly suitable for large-scale culture. It is preferable that the culture vessel 30 is equipped with a counterbalance, especially in the case of large-scale culture. Equipping the culture vessel 30 with a counterbalance allows the device to operate stably even when a culture bag 40 containing a large volume of culture medium is used. Two or more culture bags 40 may be installed in one culture vessel 30, so that they function as counterbalances to each other.

[0027] <Cultivation control device> The culture control device 50 executes each culture step (hereinafter referred to as "step"), which is a plurality of processes that divide the culture process (also simply referred to as "culture"). In each step, the culture control device 50 performs feedback control of the supply of gas and the like via the tubes 41, 42, and 43, and feedback control of the drive mechanism 35 and the temperature adjustment mechanism 36 via the control code 45, based on sensor signals received from the sensor group 37 of the culture vessel 30 via the sensor group code 47. The steps in the culture include, for example, a culture bag installation step, a culture solution conditioning step, a culture step, a sampling step, and a recovery step.

[0028] The culture control device 50 controls the culture container 30 based on a request sent from the communication terminal 70. The culture control device 50 also sends various screen data to the communication terminal 70. Outside the culture control device 50, a plurality of display units 507a, 507b in a display unit group 507 and an alkali control device 512a, which is one of a meter group 512 and automatically controls the supply amount of alkaline solution, are provided.

[0029] The culture control device 50 controls the pH of the contents of the culture bag 40 to increase by supplying an alkaline solution through the tube 41. In contrast, the culture control device 50 controls the pH of the contents of the culture bag 40 to decrease by supplying carbon dioxide through the tube 42. By controlling the increase and decrease in these amounts, the pH can be controlled.

[0030] Furthermore, the culture control device 50 can control the dissolved oxygen concentration (DO) of the contents of the culture bag 40 by supplying nitrogen and oxygen through the tube 43. The culture control device 50 can adjust the air pressure inside the culture bag 40 by supplying air through the tubes 42 and 43, thereby restoring the deflated culture bag 40 to its original state.

[0031] Here, the electrical hardware configuration of the culture control device 50 will be described with reference to Fig. 2. Fig. 2 is a diagram showing the electrical hardware configuration of the culture control device.

[0032] (Hardware configuration) As shown in Figure 2, the culture control device 50 is a computer and includes a CPU (Central Processing Unit) 501, a ROM (Read Only Memory) 502, a RAM (Random Access Memory) 503, an SSD (Solid State Drive) 504, an external device connection I / F (Interface) 505, a network I / F 506, a display group 507, an operation unit 508, a media I / F 509, a bus line 510, a pump group 511, and an instrument group 512.

[0033] Of these, the CPU 501 controls the overall operation of the culture control device 50. The ROM 502 stores programs such as an IPL (Initial Program Loader) used to drive the CPU 501. The RAM 503 is used as a work area for the CPU 501.

[0034] The SSD 504 reads or writes various data under the control of the CPU 501. Instead of the SSD 504, a hard disk drive (HDD) may be provided.

[0035] The external device connection I / F 505 is an interface for connecting various external devices. In this case, the external devices include the culture vessel 30, a display, a speaker, a keyboard, a mouse, a USB (Universal Serial Bus) memory, a printer, etc.

[0036] The network I / F 506 is an interface for performing data communication with the communication terminal 70 and the like via the communication network 100 .

[0037] The display group 507 is a type of display means such as a liquid crystal display or an organic EL (Electro Luminescence) display that displays various images.

[0038] An operation unit 508 is an input means for selecting and executing various instructions such as various operation buttons, a power switch, a shutter button, and a touch panel, selecting a processing target, moving a cursor, and the like.

[0039] The media I / F 509 controls reading and writing (storing) of data from and to a recording medium 509m such as a flash memory, etc. The recording medium 509m includes a DVD (Digital Versatile Disc) and a Blu-ray Disc (registered trademark).

[0040] The pump group 511 includes, for example, a pump for supplying an alkaline solution from the culture control device 50 to the culture bag 40 of the culture container 30 via the alkali tube 41. The pump group 511 also includes, for example, a pump for supplying various gases from the culture control device 50 to the culture bag 40 of the culture container 30 via the upper aeration tube 42 or the lower aeration tube 43.

[0041] The meter group 512 includes a measuring instrument that measures the rotation speed when a specific pump in the pump group 511 supplies the alkaline solution. The meter group 512 also includes measuring instruments that measure the total upper airflow rate, the total lower airflow rate, etc.

[0042] The bus line 510 is an address bus, a data bus, or the like for electrically connecting the components such as the CPU 501 shown in FIG.

[0043] <Communication terminal> The communication terminal 70 is a desktop, notebook, or tablet PC (Personal Computer), a smartphone, etc. The communication terminal 70 transmits various requests to the culture control device 50. The communication terminal 70 also receives various image data transmitted by the culture control device 50.

[0044] Here, the electrical hardware configuration of the communication terminal 70 will be described with reference to Fig. 3. Fig. 3 is a diagram showing the electrical hardware configuration of the communication terminal 70.

[0045] (Hardware configuration) As shown in FIG. 3, the communication terminal 70 is a computer and includes a CPU 701, a ROM (Read Only Memory) 702, a RAM 703, an SSD 704, an external device connection I / F 705, a network I / F 706, a display unit 707, an operation unit 708, a media I / F 709, and a bus line 710.

[0046] Of these, the CPU 701 controls the overall operation of the communication terminal 70. The ROM 702 stores programs such as IPL used to drive the CPU 701. The RAM 703 is used as a work area for the CPU 701.

[0047] The SSD 704 reads or writes various data under the control of the CPU 701. The SSD 704 may not be provided, or an HDD may be provided instead of the SSD 704.

[0048] The external device connection I / F 705 is an interface for connecting various external devices, such as a display, a speaker, a keyboard, a mouse, a USB memory, and a printer.

[0049] The network I / F 706 is an interface for performing data communication with the culture control device 50 and the like via the communication network 100.

[0050] The display unit 707 is a type of display means such as a liquid crystal display or organic EL (Electro Luminescence) display that displays various images.

[0051] The operation unit 708 is an input means for selecting and executing various instructions such as various operation buttons, a power switch, a shutter button, and a touch panel, selecting a processing target, moving a cursor, and the like.

[0052] The media I / F 709 controls reading and writing (storing) of data from and to a recording medium 709m such as a flash memory, etc. The recording medium 709m includes DVDs, Blu-ray Discs (registered trademarks), etc.

[0053] The bus line 710 is an address bus, a data bus, or the like for electrically connecting the components such as the CPU 701 shown in FIG.

[0054] [Functional configuration of the culture system] Next, the functional configuration of the culture control device 50 and the communication terminal 70 of the culture system will be described with reference to Fig. 4. Fig. 4 is a diagram showing the functional configuration of the culture system.

[0055] <Functions of the culture control device> As shown in Fig. 4, the culture control device 50 has a communication unit 51, a reception unit 52, a determination unit 53, a display control unit 54, a control unit 55, an actual measurement value acquisition unit 56, and a creation unit 57. Each of these units is a function or means realized when any of the components shown in Fig. 2 operates in response to an instruction from the CPU 501 in accordance with a program loaded from the SSD 504 onto the RAM 503. The culture control device 50 also has a storage unit 60 constructed by the ROM 502, RAM 503, or SSD 504 shown in Fig. 2. A recipe management DB 61 that manages culture recipe data is constructed in the storage unit 60.

[0056] The communication unit 51 controls transmission of various data (or information) from the network I / F 506 to the communication terminal 70 etc. via the communication network 100, and reception of various data (or information) from the communication terminal 70 etc. via the communication network 100 at the network I / F 506. The communication unit 51 is an example of a transmitting unit and a receiving unit.

[0057] The reception unit 52 receives various selections or inputs from the operation unit 508 or a keyboard, mouse, or the like connected to the external device connection I / F 505, and recognizes the contents of the selections or inputs.

[0058] The determination unit 53 performs various determinations (S101 to S104, S107) to be described later.

[0059] The display control unit 54 causes the display units 507a and 507b to display various images and information.

[0060] The control unit 55 mainly realizes processing by the CPU 501, and controls the drive mechanism 35 and the temperature adjustment mechanism 36 of the culture vessel 30 by transmitting control signals to the drive mechanism 35 and the temperature adjustment mechanism 36 via the control code 45. The control unit 55 also controls the driving of the pump group 511 and the instrument group 512.

[0061] The actual measurement value acquiring unit 56 acquires a signal indicating an actual measurement value, which is a measurement value, from the sensor group 37 of the incubation container 30 via the sensor group code 47. Note that wireless communication may be performed in addition to wired communication via the sensor group code 47.

[0062] The creation unit 57 creates various screen data that the communication unit 51 transmits to the communication terminal 70. It should be noted that the culture control device 50 does not necessarily have to include the creation unit 57.

[0063] <Functions of communication terminal> As shown in Fig. 4, the communication terminal 70 has a communication unit 71, a reception unit 72, and a display control unit 54. Each of these units is a function or means realized by any of the components shown in Fig. 3 operating in response to an instruction from the CPU 701 in accordance with a program loaded from the SSD 704 onto the RAM 703. The communication terminal 70 also has a storage unit 80 constructed by the ROM 702, RAM 703, or SSD 704 shown in Fig. 3.

[0064] The communication unit 71 controls the transmission of various data (or information) from the network I / F 706 to the culture control device 50, etc. via the communication network 100, and the reception of various data (or information) from the culture control device 50, etc. via the communication network 100 at the network I / F 706.

[0065] The reception unit 72 receives various selections or inputs from the operation unit 708 or a keyboard, mouse, or the like connected to the external device connection I / F 705, and recognizes the contents of the selections or inputs.

[0066] The display control unit 74 displays various images and information on the display unit 707. If the culture control device 50 does not have the creation unit 57, the communication unit 51 may transmit parameters and the like for creating a screen such as that shown in Fig. 7 or 8 to the communication terminal 70, and the display control unit 74 on the communication terminal 70 side may create a screen such as that shown in Fig. 7 or 8 using the parameters and the like received by the communication unit 71 and display it on the display unit 707.

[0067] [Processing or Operation of This Embodiment] Next, the processing or operation of this embodiment will be described with reference to Figures 5 to 9. Figure 5 is a sequence diagram showing the processing of the culture system.

[0068] <Display process of the setting screen> S11: First, in order to perform various settings for each step in the culture before the culture, the reception unit 72 of the communication terminal 70 receives a user operation, and the display control unit 74 causes the display unit 707 to display a culture step control information setting screen 720, as shown in Fig. 6. Here, the culture step control information setting screen will be described with reference to Fig. 6.

[0069] (Culture step control information setting screen) FIG. 6 is a diagram showing a setting screen for culture step control information displayed by the communication terminal.

[0070] The display control unit 74 creates a setting screen as shown in Fig. 6 and displays it on the display unit 707. Fig. 6 is a diagram showing a setting screen for culture step control information.

[0071] 6, the setting screen 720 includes a recipe selection area 711 for a predetermined culture, a step selection area 712, a setting area 713 for selected step information, a setting area 714 for each transition condition, and a setting area 517 for control parameters. Furthermore, the setting screen 720 includes a "Register" button 718 and a "CSV output" button 719.

[0072] Current recipes Selection area 711 is an area for selecting a recipe for culturing predetermined cells, etc. In Fig. 6, "Recipe 2" is selected.

[0073] Step selection Selection area 712 is an area for selecting the name of a step (step name) for which a condition for transitioning to the next step can be set in setting areas 713 and 714 in the recipe selected in selection area 711. This step name is set or changed in setting area 713 for selected step information, which will be described later. FIG. 6 shows that 10 steps are performed in recipe 2. Furthermore, a condition for transitioning to the next step can be set for each step in setting areas 713 and 714. In other words, when the selected step is changed, the display contents of setting areas 713 and 714 are also changed. Furthermore, the display area of ​​setting area 715 is also changed.

[0074] Selection step information The setting area 713 displays the name of the step selected in the selection area 712, whether user confirmation is required before proceeding to the next step, the step time, and the message content.

[0075] The “step name” input field is a field for the user to input the name of the step selected in the selection area 712 .

[0076] The "Step transition" selection field is a field for selecting "Confirmation required" or "Confirmation not required" as the necessity of confirmation before transitioning to the next step. When "Confirmation required" is selected, the culture control device 50 will not automatically transition the culture vessel 30 to the next step unless the user confirms the progress of the culture in the culture vessel 30 at the step to be set. In this case, the user checks the progress and, if there are no problems, presses a predetermined start button or the like to instruct manual transition to the next step.

[0077] On the other hand, even if the progress of the culture in the step to be set is not confirmed by the user, if the condition of reaching the step time is met (the condition is satisfied) and all the conditions of each item in the setting area 714 are met (satisfied), the culture control device 50 automatically transitions to the next step (automatic transition) without user intervention for the culture container 30. In Fig. 6, since "Confirmation required" is selected, a transition condition is set such that the culture container 30 will not proceed to the next step named "STEP002" unless the progress is confirmed by the user in the step named "STEP001".

[0078] The "step time" input field is one of the transition conditions to the next step, and is a field for inputting the time to wait before proceeding to the next step. In other words, when a step time is set, even if all of the transition conditions for each item in the setting area 714 are met in the step to be set, the control unit 55 of the culture control device 50 will not cause the culture vessel 30 to proceed to the next step until a predetermined time (step time) has elapsed since the start of this step. On the other hand, if a step time is not set, the control unit 55 of the culture control device 50 will cause the culture vessel 30 to proceed to the next step once all of the transition conditions for each item in the setting area 714 are met. In FIG. 6, the step time is set to "1 day, 2 hours, 3 minutes, and 4 seconds," and unless this time has elapsed, the culture vessel 30 will not proceed to the next step, even if, for example, other transition conditions are met.

[0079] The "Message Content" input field is a field where the user can input information for reference, such as a method for the user to check the culture state in the culture vessel 30.

[0080] Transition conditions The setting area 714 displays the name (item name) of each transition condition item for transitioning to the next step in the step to be set. This item name is the same for each step and is set in advance. There are three types of selections for each transition condition, (1) to (3), as follows, and any one of them can be selected. Note that the following (1) and (2) indicate the relationship between the measured value of a predetermined situation in the culture vessel 30 and the preset setting value. (1) Invalidation of transition conditions (2) Measured value (PV: Process Value) ≥ Set value (SV: Setting Value) (3) Actual measurement value (measured value) ≦ set value The user selects the desired transition condition from these three types for each transition condition item, and if they do not select invalid, they input the set value SV. For example, in Figure 6, for DO (dissolved oxygen concentration) in Workflow 1, the transition condition for the air volume item "WF1 DO (Air)" is "PV≧SV", and the SV is set to "1.00" L / min.

[0081] (1) The culture control device 50 does not use the transition conditions of the items for which invalid is selected when determining whether to proceed to the next step. Also, if transition conditions (2) and (3) are selected for multiple transition condition items, the culture control device 50 will not proceed to the next step unless all of these selected transition conditions are met.

[0082] Control parameters In the setting area 715, it is possible to select whether or not to use feedback control by a PID (Proportional-Integral-Differential Controller) for each instrument such as a thermometer. When the automatic (AOTO) mode is selected, the input field for the set value (SV) becomes active, allowing the setting of the PID set value. On the other hand, when the manual (MANUAL) mode is selected, the input field for the manipulated value (MV: Manipulated Value) becomes active, allowing the setting of the manipulated value of the output instrument.

[0083] The "Register" button 718 is a button for registering the contents set on the setting screen 720. The "CSV Output" button 719 is a button for outputting the contents set on the setting screen 720 to the outside of the culture control device 50 as a CSV (Comma-Separated Values) file.

[0084] <Display of driving status> S12: Next, returning to FIG. 5, the reception unit 62 receives a setting operation of selection or input by the user on the setting screen 720.

[0085] S13: When the reception unit 62 receives a user pressing the "Register" button 718, the communication unit 71 transmits culture step control information indicating the settings made by the user to the culture control device 50. As a result, the communication unit 51 of the culture control device 50 receives the culture step control information.

[0086] S14: In the culture control device 50, the communication unit 51 stores the culture step control information received in step S13 in the recipe management DB 61 of the storage unit 60.

[0087] S15: Thereafter, in the communication terminal 70, the reception unit 72 receives a command to start culture through a user operation.

[0088] S16: Based on the reception of the culture start in step S15, the communication unit 71 transmits a culture start request by a log-on operation or the like to the culture control device 50. As a result, the culture control device 50 receives the start request.

[0089] S17: The culture control device 50 controls each step in the culture based on the start request received in step S16. The contents of this control will be explained in detail later.

[0090] S18: Depending on the content of process S17, the communication unit 51 of the culture control device 50 transmits, during process S17, to the communication terminal 70, each parameter and the like for creating the display screen of the operating status shown in Fig. 7. As a result, the communication unit 71 of the communication terminal 70 receives each parameter.

[0091] S19: In the communication terminal 70, the display control unit 74 uses the parameters and the like to create a driving situation display screen 730 as shown in Fig. 7, and displays it on the display unit 707. Note that processes S18 to S20 are repeated while process S17 is being performed. Here, the driving situation display screen displayed by the communication terminal 70 will be described with reference to Fig. 7.

[0092] (Operating status display screen) FIG. 7 is a diagram showing a display screen of the driving situation displayed by the communication terminal.

[0093] A display screen 730 shown in FIG. 7 displays parameters indicating the operating status of the culture vessel 30. As shown in FIG. 7, the display screen 730 displays a schematic diagram 30p of the culture vessel 30 in the center, and similarly to FIG. 1, displays schematic diagrams 41p, 42p, and 43p of the tubes 41, 42, and 43 corresponding to the culture vessel 30, as well as a display field 741 displaying actual measured values ​​(PV) and set values ​​(SV) of meters described below. Note that a schematic diagram 511p of an alkali pump, which is one of the pump group 511 in the culture control device 50, and a setting icon 512ap of the alkali control device 512a are linked to the schematic diagram 41p of the tube 41. Since the set value (SV) is set for each step in the culture, as shown in FIG. 6, when the process proceeds to the next step, the display control unit 74 switches the display of the parameters on the display screen 730 to display parameters such as actual measured values ​​(PV) and set values ​​(SV) for the next step.

[0094] When all of the set transition conditions are met, the "Confirm" button 731 becomes operable (active) by the display control unit 74, and the display mode is changed. When the user checks the inside of the incubation vessel 30 and determines that the progress of the solvent is proceeding as planned, for example, and presses the "Confirm" button 731, the control unit 55 controls the incubation vessel 30 to transition to the next step. The "Confirm" button 731 is an example of a first display portion. In this case, the change in the display mode is a change in the shape, pattern, color, text, or symbol of the "Confirm" button 731.

[0095] The "forced transition" button 732 is a button that can be pressed by the user to forcibly transition to the next step even when all of the set transition conditions are not met. For example, even when the transition conditions are not met because the actual measured value (PV) by the device is not equal to or greater than the set value (SV), the button can be pressed when the user visually checks the culture state in the culture vessel 30 and determines that it is OK to transition to the next step. The "forced transition" button 732 is an example of a second display portion.

[0096] The "Display transition conditions" button 733 is a button for displaying a display screen 770 showing whether the transition conditions at each step are met, as shown in FIG. 9, which will be described later.

[0097] The display field 734 displays the message entered in the "Message Content" input field of the setting area 713 shown in FIG.

[0098] Display field 735 displays the step elapsed time (individual step), step elapsed time (total), and the name of the currently running step. The step elapsed time (individual step) indicates the elapsed time of the currently running step, and is reset to zero when proceeding to the next step. The step elapsed time (total) indicates the total time since the start of the batch operation.

[0099] The display field 736 shows the measured value (PV) and set value (SV) of the pH in the culture bag 40. As described above, the measured value (PV) of pH increases with the supply of alkaline solution and decreases with the supply of carbon dioxide.

[0100] The display field 737 shows the measured value (PV) and set value (SV) of the dissolved oxygen concentration (DO) of the contents of the culture bag 40. As described above, the measured value (PV) of the dissolved oxygen concentration (DO) is changed by controlling the supply amounts of nitrogen and oxygen.

[0101] Display fields 741 to 751 show the control parameters and setting status of each instrument such as a thermometer, etc. Display fields 741 to 743 and 746 to 751 show whether the setting area 715 in Fig. 6 is set to AUTO mode (A) or MANUAL mode (M), and also show PV and SV values.

[0102] Also, a display field 744 indicates whether the setting area 715 in FIG. 6 is set to AUTO mode (A) or MANUAL mode (M), and indicates the jacket temperature and bag temperature for each PV and SV.

[0103] Furthermore, a display field 745 indicates whether the setting area 715 in FIG. 6 is set to AUTO mode (A) or MANUAL mode (M), and indicates the weight of the container body 31 for each PV and SV.

[0104] Furthermore, display field 747 indicates the total aeration volume of gas (at least one of air and carbon dioxide) supplied from the culture control device 50 to the culture bag 40 via the upper aeration tube 42. In FIG. 7, the total of the flow rates measured by the MFC (flow control device) for "MF1 upper Air" and the MFC for "MF2 upper CO2" is shown. In addition, display field 751 indicates the total aeration volume of gas (at least one of nitrogen, oxygen, and carbon dioxide) supplied from the culture control device 50 to the culture bag 40 via the lower aeration tube 43. In FIG. 7, the total of the flow rates measured by the MFC for "MF5 submerged (lower) N2", the MFC for "MF3 submerged (lower) Air", and the MFC for "MF4 submerged (lower) O2" is shown.

[0105] When the setting icon 512ap is pressed by the user, a screen for setting the drive control (ON / OFF) of the alkali supply pump, the rotation direction of the pump, and the rotation speed is displayed, allowing the user to make settings.

[0106] S20: Next, returning to Fig. 5, in the communication terminal 70, if the reception unit 72 receives various operations from the user during processing S17, the communication unit 71 transmits instructions corresponding to the operations to the culture control device 50. These instructions are reflected in processing S17.

[0107] <Control processing of culture vessel> S21: Meanwhile, depending on the content of process S17, the control unit 55 of the culture control device 50 transmits a control signal for operation to the temperature adjustment mechanism 36 or the drive mechanism 35 of the culture container 30 via the control code 45 during process S17, as shown in FIG.

[0108] S22: During step S17, the sensor group 37 of the culture vessel 30 transmits the actual measurement value (PV) to the actual measurement value acquiring unit 56 of the culture control device 50 via the sensor group code 47, as shown in Fig. 1. This enables the culture control device 50 to perform feedback control in step S21. Note that steps S21 and S22 are repeatedly performed while step S17 is being performed.

[0109] <Displaying transition condition fulfillment status> Next, the process for displaying the display screen 770 showing the status of whether the transition condition is met will be described with reference to FIGS.

[0110] FIG. 8 is a sequence diagram showing a process of displaying a display screen showing whether the transition condition is satisfied.

[0111] S31: The reception unit 72 of the communication terminal 70 receives a press of the "display transition condition" button 733, thereby receiving a display of a display screen showing the status of fulfillment of the transition condition.

[0112] S32: The communication unit 71 transmits a request for the measured value (PV) and the set value (SV) regarding the transition condition to the culture control device 50. As a result, the communication unit 51 of the culture control device 50 receives this request.

[0113] S33: The communication unit 51 transmits each data of the transition conditions based on the actual measured values ​​(PV) acquired from the actual measured value acquisition unit 56 and the set values ​​(SV) acquired from the recipe management DB 61 to the communication terminal 70. As a result, the communication unit 71 of the communication terminal 70 receives each data of the transition conditions.

[0114] S34: In the communication terminal 70, the display control unit 74 creates a display screen 770 showing the fulfillment status of the transition condition as shown in Fig. 9 using the data received in process S33, and causes the display unit 707 to display the display screen 770. Here, the display screen 770 showing the fulfillment status of the transition condition will be described with reference to Fig. 9.

[0115] (Display screen of the establishment status) FIG. 9 is a diagram showing a display screen showing whether the transition conditions are met.

[0116] The display screen 770 displays the item name 771 of the transition condition set for a given step, the transition condition 772, the set value (SV) 773, and whether or not the condition is met. For example, FIG. 9 shows that the transition conditions for the MF1 DO (Air) and back (culture bag 40) pressure items are not met (not satisfied). However, if the user presses the "Forced Transition" button 732, the process will proceed to the next step even if the transition conditions for the MF1 DO (Air) and back (culture bag 40) pressure items are not met. This allows the user to understand the status of the transition conditions for moving to the next step at each step.

[0117] <Control of each culture step> Furthermore, step S17 will be described in detail with reference to Fig. 10. Fig. 10 is a flowchart showing the control of each step in the culture.

[0118] S101: At each step in the culture, the judgment unit 53 judges whether the communication unit 51 has received a forced transition instruction from the communication unit 71 when the reception unit 72 receives a press of the “forced transition” button 732 for a specified step.

[0119] S102: When the communication unit 51 receives a request for forced transition (S101; NO), the judgment unit 53 judges whether all transition conditions in the predetermined step are met. As described above, the judgment of whether the transition conditions are met is based on whether the step time set in the setting area 713 shown in FIG. 6 has elapsed, and whether the transition conditions of the items for which invalid has not been selected in the transition condition setting area 714 are met. If all transition conditions in the predetermined step are not met (S102; NO), the process returns to S101.

[0120] S103: On the other hand, if all transition conditions within the specified step are met (S102; YES), the judgment unit 53 refers to the recipe management DB 61 and determines whether automatic transition has been set by selecting "No confirmation required" in the setting area 713 of the selected step information on the setting screen 720 shown in FIG. 6.

[0121] S104: If automatic transition has been set (S103; YES), the judgment unit 53 judges whether all steps in the culture have been completed. If 10 steps have been set as shown in Fig. 6, it is judged whether all of these 10 steps have been completed. Then, if all steps have been completed (S104; YES), the control of each step in the culture shown in Fig. 10 is terminated.

[0122] S105: On the other hand, if all steps have not been completed (S104; NO), the control unit 55 controls the incubation container 30 to move to the next step, and then returns to the process S101.

[0123] S106: Furthermore, in process S103, if automatic transition has been set, that is, if manual transition has been set by selecting "Confirmation Required" in the setting area 713 of the selected step information on the setting screen 720 shown in FIG. 6 (S103; YES), the control unit 55 causes the culture vessel 30 to continue the predetermined step. For example, if the drive mechanism 35 is shaking the vessel body 31, it continues shaking it. Furthermore, the communication unit 51 transmits an instruction to the communication terminal 70 to change the display mode of the "Confirm" button 731 to activate it. As a result, the communication unit 71 of the communication terminal 70 receives the instruction to activate, and the display control unit 74 changes the display mode of the "Confirm" button 731 shown in FIG. 7 to activate it.

[0124] S107: Next, the determination unit 53 determines whether the communication unit 51 has received an instruction to transition to manual mode from the communication unit 71 when the reception unit 72 receives a request to press the "Confirm" button 731 shown in Fig. 7. Then, transition to the next step is put on hold until the "Confirm" button 731 is pressed (S107; NO). On the other hand, if the "Confirm" button 731 is pressed (S107; YES), the process proceeds to step S104.

[0125] This concludes the detailed description of process S17.

[0126] [Major Effects of the Embodiments] As described above, according to this embodiment, some steps in the culture may proceed automatically to the next step if the transition conditions are met. Therefore, by selecting "No confirmation required" in FIG. 6, the transition of such steps can be automated. Furthermore, there are some steps for which the user may proceed to the next step without actually checking the solvent state in the culture vessel 30, provided that the user knows that each transition condition is met (the transition conditions are met) by displaying the display screen 770 shown in FIG. 10. In such cases, the user can make a transition decision simply by looking at the display screen 770 shown in FIG. 10. On the other hand, even in cases where it is not desirable to proceed to the next step until the user actually checks the solvent state in the culture vessel 30, the user can use the display screen shown in FIG. 10 to help determine whether to proceed to the next step, provided that the user knows that each transition condition is met (the transition conditions are met).

[0127] This has the effect of saving the user the trouble of monitoring the culture state in the culture vessel 30 near the culture vessel 30. It also has the effect of preventing the occurrence of human error, such as the user mistakenly proceeding to the next step or not proceeding at all due to inexperience or the like.

[0128] 〔supplement〕 Although the embodiments have been described above, the present invention is not limited to the above-described embodiments, and various modifications and substitutions can be made without departing from the scope of the present invention.

[0129] (1) Each of the above-mentioned programs can be recorded on a (non-transitory) recording medium and distributed, or can be provided via a communication network such as the Internet.

[0130] (2) In the communication between the culture vessel 30 and the culture control device 50, other devices (servers, routers, etc.) may relay data, etc. For example, for the sake of simplicity, this specification describes that the culture vessel 30 receives data (information) from the culture control device 50 and that the culture vessel 30 transmits data (information) to the culture control device 50, but the intent is that each of these receiving and transmitting processes also includes cases where other devices relay data, etc.

[0131] (3) The CPUs 501 and 701 serving as processors may each be single or multiple.

[0132] (4) In the above embodiment, the culture control device 50 has the judgment unit 53 and has constructed the recipe management DB 61 in the storage unit 60, but this is not limited to this. For example, the communication terminal 70 may have a judgment unit equivalent to the judgment unit 53. Furthermore, the communication terminal 70 may construct the recipe management DB 61 in the storage unit 80. Furthermore, a server (database server) other than the communication terminal 70 may manage the recipe management DB 61, and the communication unit 51 may access the recipe management DB 61 to send and receive data. [Explanation of symbols]

[0133] 10. Culture System 20. Cultivation Control System 30 Culture vessel 50 Culture control device (also called "control device") 51 Communication unit (an example of a transmission unit, an example of a reception unit) 52 Reception 53 Judgment Department 54 Display control unit 55 Control Unit 56 Actual measurement value acquisition unit 57 Creation Department 60 Storage section 61 Recipe Management DB 70 Communication terminal (also called "display terminal") 71 Communication unit (an example of a terminal transmitting unit, an example of a terminal receiving unit) 72 Reception 74 Display control unit 507 Display group 707 Display section

Claims

1. A culture control system that controls the culture of a culture vessel in which a culture object is accommodated, A culture control system having a control unit that, when the conditions for transitioning to the next step are met within a specified step among the steps into which the culture is divided into multiple processes, automatically transitions to the next step if a setting for automatic transition to the next step has been made, or controls the specified step to continue if a setting for automatic transition to the next step has not been made.

2. The culture control system according to claim 1, A culture control system having a display control unit that displays parameters indicating the operating status of the culture vessel and, when moving to the next step, switches to displaying parameters indicating the operating status of the culture vessel in the next step.

3. The culture control system of claim 2, wherein if a setting to automatically transition to the next step has not been made, the display control unit changes the display format of the first display portion that is selected when transition to the next step is allowed.

4. The culture control system according to claim 3 , wherein when the display portion is selected, the control unit controls the culture vessel to transition to the next step.

5. The culture control system of claim 1, wherein when multiple transition conditions are set, the transition condition to the next step is met when all of the multiple transition conditions are met.

6. The culture control system according to claim 1 , wherein the transition condition is that a predetermined time has elapsed since the start of the predetermined step in the predetermined step.

7. The culture control system according to claim 1 , wherein the transition condition indicates a relationship between a measured value of a predetermined situation in the culture vessel and a preset set value in the predetermined step.

8. The culture control system according to claim 2 , wherein the display control unit displays a display screen showing a status of establishment of the transition condition in each step.

9. When the culture in the culture vessel is being controlled in the predetermined step, the display control unit displays a second display portion that is selected when forcibly transitioning to the next step, The control unit performs control to forcibly transition the incubation container to the next step based on the selection of the second display portion. The culture control system according to claim 2 .

10. A culture control method executed by a culture control system that controls the culture of a culture vessel in which a culture object is accommodated, comprising: A culture control method in which, when a condition for transitioning to the next step is met within a predetermined step among the steps into which the culture is divided into multiple processes, if a setting for automatic transition to the next step has been made, the culture is automatically transitioned to the next step, and if a setting for automatic transition to the next step has not been made, the culture is controlled to continue the predetermined step.

11. The culture control system according to any one of claims 1 to 8, The culture vessel; A culture system having:

12. A culture method carried out by a culture system having a culture vessel in which a culture object is accommodated and a culture control system that controls the culture of the culture vessel, The culture control system performs control such that, when a condition for transitioning to the next step is met within a predetermined step among the steps into which the culture is divided into a plurality of processes, the culture control system automatically transitions to the next step if a setting for automatic transition to the next step has been made, and continues the predetermined step if a setting for automatic transition to the next step has not been made, The culture vessel performs culture based on the control of the culture control system. Culture method.

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