Cell Culture Systems

The cell culture system addresses the challenge of balancing flow rate and preparation time by using a dual-mode operation, ensuring efficient and safe cell culture processes.

JP7666933B2Active Publication Date: 2025-04-22CKD CORP
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Patent Information

Application Number
JP2021003758
Authority / Receiving Office
JP · JP
Patent Type
Patents
Current Assignee / Owner
Filing Date
2021-01-13
Publication Date
2025-04-22
Estimated Expiration
2041-01-13

AI Technical Summary

Technical Problem

Existing cell culture systems struggle to balance the flow rate of culture medium to prevent cell tissue damage while also minimizing the preparation time before starting cell culture.

Method used

A cell culture system that employs a dual-mode operation, initially supplying culture medium at a high flow rate to expedite preparation and then switching to a lower flow rate once cell tissue is stored, ensuring minimal damage and efficient preparation.

Benefits of technology

This approach reduces the time required for preparation while effectively preventing cell tissue damage from medium flow, thus enhancing the efficiency and safety of cell culture processes.

✦ Generated by Eureka AI based on patent content.

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Patent Text Reader

Abstract

To provide a cell culture system that can shorten time required for a preparation process until cell culture begins while suppressing breaking of a cellular tissue by a flow of culture solution.SOLUTION: A cell culture system (10) comprises: a culture tank (50) which houses culture solution (L); a supply piping (42B) which supplies culture solution from the inside to the outside of the culture tank; a flow rate adjusting part (20) which adjusts the flow rate of culture solution flowing through the supply piping; pressure sensors (84, 86) which detect the pressure of culture solution supplied to the culture tank through the supply piping; and a control part (45) which executes a first mode of controlling the flow rate adjusting part in order to supply culture solution to the culture tank at a first flow rate through the supply piping, and a second mode of controlling the flow rate adjusting part in order to make a pressure detected by the pressure sensor after the first mode ended become lower than a predetermined breaking pressure at which a predetermined cellular tissue (B) begins to break and supply culture solution to the culture tank at a second flow rate smaller than the first flow rate through the supply piping.SELECTED DRAWING: Figure 1
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Description

[Technical field]

[0001] The present invention relates to a system for culturing cells. [Background technology]

[0002] Conventionally, there is a cell culture system that controls the concentration of a target gas in a culture solution based on the dissolved gas concentration detected by a dissolved gas sensor, and controls the culture solution delivery rate by a delivery pump based on the flow rate of the culture solution measured by a flow rate sensor (see Patent Document 1). The cell culture system described in Patent Document 1 is said to be able to further improve the accuracy of control of the dissolved gas concentration. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] JP 2020-89304 A Summary of the Invention [Problem to be solved by the invention]

[0004] Incidentally, the cell culture system described in Patent Document 1 takes into consideration the accuracy of control of the dissolved gas concentration, but does not consider the possibility that the flow of the culture solution may damage the cell tissue. In response to this, it is possible to reduce the flow rate of the culture solution to prevent cell damage, but if the flow rate of the culture solution is excessively reduced, it will take a long time for the preparation process before starting cell culture.

[0005] The present invention has been made to solve the above-mentioned problems, and its main objective is to provide a cell culture system that can reduce the time required for the preparation process before starting cell culture while suppressing damage to cell tissue due to the flow of culture medium. [Means for solving the problem]

[0006] A first means for solving the above problem is a cell culture system, A culture tank for storing a culture solution; A supply pipe for supplying the culture solution from the outside to the inside of the culture tank; A flow rate adjusting unit that adjusts the flow rate of the culture solution flowing through the supply pipe; A pressure sensor for detecting a pressure of the culture solution supplied to the culture tank through the supply pipe; A control unit that executes a first mode in which the flow rate adjustment unit is controlled to supply the culture solution to the culture tank through the supply pipe at a first flow rate, and a second mode in which the flow rate adjustment unit is controlled to lower the pressure detected by the pressure sensor after the end of the first mode below a predetermined damage pressure at which a predetermined cell tissue begins to be damaged and to supply the culture solution to the culture tank through the supply pipe at a second flow rate smaller than the first flow rate; Equipped with.

[0007] According to the above configuration, the culture tank stores a culture solution. A supply pipe supplies the culture solution from the outside to the inside of the culture tank. A flow rate regulator regulates the flow rate of the culture solution flowing through the supply pipe. A pressure sensor detects the pressure of the culture solution supplied to the culture tank through the supply pipe. Therefore, when culture solution is supplied to the inside of the culture tank through the supply pipe, the flow rate of the culture solution flowing through the supply pipe can be adjusted by the flow rate regulator while the pressure sensor detects the pressure of the culture solution supplied to the culture tank.

[0008] Here, the control unit executes a first mode in which the flow rate regulator is controlled to supply the culture solution to the culture tank at a first flow rate through the supply pipe. Therefore, the first mode is executed before the cell tissue is stored in the culture tank, i.e., in a state where there is no risk of damaging the cell tissue, and the culture solution can be supplied to the culture tank at a first flow rate through the supply pipe. Therefore, the time required for a preparation process before starting cell culture (for example, a process of storing the culture solution in the culture tank with the adjusted dissolved gas concentration) can be shortened.

[0009] Then, the control unit executes a second mode in which the pressure detected by the pressure sensor after the end of the first mode is lowered below a predetermined damage pressure at which the predetermined cell tissue begins to be damaged, and the flow rate regulator is controlled to supply the culture solution to the culture tank through the supply pipe at a second flow rate lower than the first flow rate. Therefore, the second mode is executed after the cell tissue is stored in the culture tank, the pressure of the culture solution supplied to the culture tank through the supply pipe is detected by the pressure sensor, and the pressure of the culture solution is lowered below the damage pressure and the flow rate of the culture solution is set to a second flow rate lower than the first flow rate, thereby preventing damage to the predetermined cell tissue due to the flow of the culture solution. Moreover, by executing the second mode after the first mode, the preparation process and the cell culture process before starting the cell culture can be easily executed, and the user's effort in performing the cell tissue culture can be reduced.

[0010] The second means includes a cell storage section for storing the cell tissue, the cell storage section being stored inside the culture tank, and the supply piping being inserted from the outside to the inside of the culture tank and connected to the cell storage section.

[0011] According to the above configuration, the cell storage unit stores the cellular tissue. The cell storage unit is stored inside the culture tank. Therefore, by placing the cell storage unit storing the predetermined cellular tissue in the culture tank, the cellular tissue can be easily placed in the culture tank.

[0012] Here, the supply pipe is inserted from the outside to the inside of the culture tank and connected to the cell storage section. This allows the culture medium to be directly supplied to the inside of the cell storage section, making it easier to generate a flow of culture medium inside the cellular tissue stored in the cell storage section. This makes it easier to culture the cellular tissue in an appropriate environment where a flow of culture medium is generated inside the cellular tissue, and the cultivation of the cellular tissue can be promoted. Moreover, since the pressure detected by the pressure sensor is lower than a predetermined damage pressure at which a predetermined cellular tissue begins to be damaged, damage to the cellular tissue due to the flow of culture medium can be suppressed.

[0013] In the third aspect, the pressure sensor detects the pressure of the culture medium supplied to the culture tank through the supply pipe inside the cellular tissue. With this configuration, the pressure sensor can detect the pressure of the culture medium inside the cellular tissue, which further prevents the cellular tissue from being damaged by the flow of the culture medium. In addition, the pressure of the culture medium inside the cellular tissue as the environment in which the cellular tissue is cultured can be more accurately grasped.

[0014] The fourth means includes a pressure receiving unit that receives input of a set pressure, and the control unit executes, as the second mode, a pressure control mode in which the flow rate adjustment unit is controlled to make the pressure detected by the pressure sensor the set pressure received by the pressure receiving unit.

[0015] According to the above configuration, the pressure receiving unit receives an input of a set pressure. Therefore, the pressure of the culture fluid in the cell culture process can be set arbitrarily. However, the set pressure needs to be set lower than the damage pressure and the flow rate of the culture fluid needs to be set to a second flow rate lower than the first flow rate. Then, the control unit executes, as the second mode, a pressure control mode in which the flow rate regulator is controlled so that the pressure detected by the pressure sensor becomes the set pressure received by the pressure receiving unit. Therefore, the pressure control mode is executed as the second mode, and cell culture can be performed in a state in which the pressure detected by the pressure sensor is maintained at the set pressure.

[0016] The fifth means includes a flow rate receiving unit that receives input of a set flow rate, and a flow rate sensor that detects the flow rate of the culture medium supplied to the culture tank through the supply piping, and the control unit executes, as the second mode, a flow rate control mode in which the control unit controls the flow rate adjustment unit to make the flow rate detected by the flow rate sensor equal to the set flow rate received by the flow rate receiving unit.

[0017] According to the above configuration, the flow rate receiving unit receives an input of a set flow rate. Therefore, the flow rate of the culture solution in the cell culture process can be set arbitrarily. However, the set flow rate needs to be set smaller than the first flow rate. Then, the control unit executes a flow rate control mode as the second mode in which the flow rate detected by the flow rate sensor is controlled to the set flow rate received by the flow rate receiving unit. Therefore, the flow rate control mode is executed as the second mode, and cell culture can be performed in a state in which the flow rate detected by the flow rate sensor is maintained at the set flow rate.

[0018] The sixth means includes a pressure receiving unit that receives input of a set pressure, a flow rate receiving unit that receives input of a set flow rate, and a flow rate sensor that detects the flow rate of the culture medium supplied to the culture tank through the supply piping, and the control unit selectively executes, as the second mode, a pressure control mode in which the flow rate adjustment unit is controlled to make the pressure detected by the pressure sensor the set pressure received by the pressure receiving unit, and a flow rate control mode in which the flow rate adjustment unit is controlled to make the flow rate detected by the flow sensor the set flow rate received by the flow rate receiving unit.

[0019] According to the above configuration, the control unit can selectively execute the pressure control mode of the fourth means and the flow rate control mode of the fifth means. Therefore, it is possible to select and execute a mode suitable for culture depending on the purpose and the type of cell tissue.

[0020] In a seventh aspect, the first flow rate is greater than five times the second flow rate. Therefore, the first flow rate of the culture solution in the first mode can be greater than five times the second flow rate of the culture solution in the second mode, and the time required for the preparation step can be significantly shortened.

[0021] The first mode is basically performed before the cell tissue is placed in the culture tank, i.e., when there is no risk of damaging the cell tissue. However, if the pressure of the culture medium in the first mode is higher than the damage pressure, there is a risk that the culture medium at a pressure higher than the damage pressure will temporarily flow into the cell tissue when switching to the second mode.

[0022] In this regard, in the eighth aspect, the control unit makes the pressure detected by the pressure sensor lower than the damage pressure in the first mode, and therefore, when switching from the first mode to the second mode, it is possible to prevent the culture medium with a pressure higher than the damage pressure from temporarily flowing into the cell tissue.

[0023] The ninth means includes a status sensor that detects the state of the culture medium, a status adjustment unit that adjusts the state of the culture medium, and a display unit that displays an image, and in the first mode, the control unit controls the status adjustment unit to make the status detected by the status sensor a target status, and, on condition that the status detected by the status sensor becomes the target status, causes the display unit to display an image indicating that the preparation process has been completed.

[0024] According to the above configuration, the state sensor detects the state of the culture solution. As the state of the culture solution, for example, at least one of the pH, dissolved oxygen concentration DO, temperature T, etc. of the culture solution can be adopted. The state adjustment unit adjusts the state of the culture solution. For example, the state adjustment unit can adjust the pH by dissolving carbon dioxide in the culture solution, adjust the dissolved oxygen concentration DO by dissolving oxygen in the culture solution, and adjust the temperature T by heating the culture solution with a heater. The display unit displays an image.

[0025] In the first mode, the control unit controls the condition adjustment unit to make the state detected by the state sensor a target state. Therefore, by executing the first mode, the actual state of the culture solution can be made into the target state. Then, the control unit causes the display unit to display an image indicating that the preparation process is complete, on condition that the state detected by the state sensor has become the target state. Therefore, the user can easily know that the preparation process is complete by confirming that the display unit has displayed an image indicating that the preparation process is complete. In addition, the user can easily know that the preparation process is not complete by confirming that the display unit has not displayed an image indicating that the preparation process is complete.

[0026] The tenth means includes a confirmation receiving unit that receives an operation that confirms that the preparation process has been completed, and when the control unit receives the operation by the confirmation receiving unit, it stops the supply of the culture medium to the culture tank through the supply piping.

[0027] According to the above configuration, the confirmation receiving unit receives an operation that confirms that the preparation step has been completed. Then, when the control unit receives the operation from the confirmation receiving unit, the control unit stops the supply of the culture medium to the culture tank through the supply pipe. Therefore, when a user performs an operation that confirms that the preparation step has been completed, the supply of the culture medium to the culture tank can be stopped, and the process can be safely moved to the step of storing cell tissue in the culture tank.

[0028] In an eleventh aspect, the control unit controls the condition adjustment unit to maintain the state detected by the state sensor at a target state until the confirmation receiving unit receives the operation after displaying an image indicating that the preparation process has been completed on the display unit. With this configuration, the state of the culture solution can be maintained at the target state until the user performs an operation that confirms that the preparation process has been completed after the preparation process is completed. Therefore, the user can start cell culture at a time desired by performing the operation that confirms that the preparation process has been completed.

[0029] In a twelfth aspect, the state of the culture solution includes the pH, dissolved oxygen concentration, and temperature of the culture solution. With this configuration, the pH, dissolved oxygen concentration DO, and temperature T of the culture solution can be set to the target pH, target dissolved oxygen concentration, and target temperature, respectively, while the first mode is being performed. Therefore, the process can be quickly shifted to the cell culture process after the first mode is completed, reducing the user's efforts.

[0030] In a thirteenth aspect, the control unit stops the flow rate adjusting unit when the flow rate detected by the flow rate sensor is an abnormal flow rate. With this configuration, the flow of the culture medium can be stopped when the culture medium cannot be normally circulated. Therefore, the burden on the user to monitor the cell culture system during the first and second modes can be reduced.

[0031] In a fourteenth aspect, the control unit stops the condition adjustment unit when the condition detected by the condition sensor is an abnormal condition. With this configuration, the adjustment of the culture solution condition can be stopped when the culture solution condition cannot be adjusted to normal. Therefore, the burden on the user to monitor the cell culture system during the first and second modes can be reduced. [Brief description of the drawings]

[0032] [Figure 1] FIG. 1 is a schematic diagram showing a cell culture system. [Diagram 2] 11 is a flowchart showing a procedure in a standby mode. [Diagram 3] 11 is a flow chart showing the procedure of a culture mode. [Figure 4] 11 is a flowchart showing a procedure for liquid transfer control. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0033] Hereinafter, an embodiment of a cell culture system for culturing cells will be described with reference to the drawings.

[0034] As shown in FIG. 1, the cell culture system 10 includes a pressure control liquid delivery unit 20, a cell culture vessel 50, a mixer 60, mass flow controllers (MFCs) 61 to 63, a control unit 45, a display unit 70, a pump 90, and the like.

[0035] The pressure control liquid delivery section 20 (flow rate adjustment section) includes an air supply source 21, a flow rate proportional valve 24, a throttle valve 27, a sterilizing filter 31, a tank 34, a pressure sensor 37, a liquid level sensor 41, a flow rate sensor 85, and the like.

[0036] Air supply source 21 (gas supply source) supplies air (gas) at a predetermined pressure. Air supply source 21 is connected to tank 34 via pipes 22 and 23. Pipe 22 is provided with flow proportional valve 24. Flow proportional valve 24 can adjust its opening in proportion to an input signal, and adjusts the flow rate of air supplied from air supply source 21. Flow proportional valve 24 is controlled by control unit 45.

[0037] Pipe 22 and pipe 23 are connected at connection part 25. Pipe 23 is provided with a sterilizing filter 31. Sterilizing filter 31 sterilizes the air flowing through pipe 23 to tank 34. Tank 34 is formed in a cylindrical shape with a bottom, is airtight, and stores (contains) culture solution L. Pipe 23 is connected to the upper part of tank 34. In other words, pipe 23 is connected to a position in tank 34 that is higher than the liquid level of culture solution L, and is not in contact with culture solution L. Pipes 22 and 23 form a first pipe. The shape of tank 34 is not limited to a cylindrical shape with a bottom, and may be any shape.

[0038] The culture solution L is supplemented with a reagent, such as bicarbonate, which is free to have a pH buffer function in the range of pH 6 to 8. As the bicarbonate, sodium bicarbonate (sodium hydrogen carbonate), potassium hydrogen carbonate, calcium hydrogen carbonate, etc. can be used. In addition, serum, amino acids, vitamins, sugars, etc. are added to the culture solution L as nutrients necessary for the activity of the cellular tissue B (cells) having blood vessels. An indicator such as phenol red is added to the culture solution L to visually check the pH.

[0039] The pressure sensor 37 detects the pressure P1 of the culture solution L at the bottom of the tank . The liquid level sensor 41 detects the position of the liquid level of the culture solution L in the tank .

[0040] A pipe 26 is connected to the connection part 25. The connection part 25 is connected to an air discharge part 28 by the pipe 26. A throttle valve 27 is provided in the pipe 26. The throttle valve 27 (throttle part) is, for example, a needle valve that adjusts a minute flow rate, and limits (adjusts) the flow rate of air discharged to the discharge part 28. The opening degree of the throttle valve 27 is set to a predetermined opening degree so that the pressure of the air in the tank 34 (the pressure in the tank 34) becomes a target pressure. The opening degree of the throttle valve 27 may be changed according to the target pressure of the air in the tank 34. The air that flows to the discharge part 28 is discharged to the outside (atmosphere) of the pressure control liquid delivery part 20. The pipes 23 and 26 form a second pipe.

[0041] The cell culture vessel 50 (culture vessel) is formed in a hollow rectangular parallelepiped shape, and stores (contains) therein a culture solution L. The shape of the cell culture vessel 50 is not limited to a hollow rectangular parallelepiped shape, and may be a hollow cylindrical shape, etc.

[0042] A cell storage section 51 is placed (stored) inside the cell culture tank 50. The cell storage section 51 is formed in a hollow rectangular parallelepiped shape without an upper base. The above-mentioned cell tissue B is stored inside the cell storage section 51. Note that the shape of the cell storage section 51 is not limited to a hollow rectangular parallelepiped shape without an upper base, and may be a hollow cylindrical shape without an upper base, etc.

[0043] The liquid supply pipes 42A and 42B (supply pipes) connect the inside of the culture solution L stored in the tank 34 to the cell storage section 51 (cell culture tank 50). That is, the liquid supply pipes 42A and 42B supply the culture solution L from the outside to the inside of the cell culture tank 50. The liquid supply pipe 42A is inserted into the culture solution L stored in the tank 34, and the lower end of the liquid supply pipe 42 is located at a position lower than the liquid level of the culture solution L in the tank 34.

[0044] The liquid supply pipes 42A and 42B are provided with an electromagnetic valve 46, a check valve 47, a flow rate sensor 85, and the like. The electromagnetic valve 46 opens and closes the liquid supply pipe 42A. The electromagnetic valve 46 is controlled by the control unit 45. The check valve 47 (check valve) allows the culture solution L to flow from the electromagnetic valve 46 (tank 34) to the cell storage unit 51 (cell culture tank 50) and prohibits the culture solution L from flowing from the cell storage unit 51 (cell culture tank 50) to the electromagnetic valve 46 (tank 34). The flow rate sensor 85 detects the flow rate of the culture solution L flowing through the liquid supply pipe 42A, i.e., the flow rate of the culture solution L supplied to the cell culture tank 50 by the liquid supply pipes 42A and 42B.

[0045] Culture solution L is delivered (supplied) to the cell culture tank 50 from the tank 34 via the delivery pipes 42A and 42B. More specifically, the culture solution L is delivered directly to the cell storage unit 51 via the delivery pipe 42B. As a result, a flow path Bp for the culture solution L is formed in the cell tissue B, and a flow of the culture solution L occurs in the cell tissue B. The culture solution L that has flowed in the flow path Bp flows out to the outside of the cell storage unit 51 as shown by the dashed arrow. The cell tissue B is, for example, an animal cell tissue having blood vessels. The cell tissue B is cultured in the culture solution L and develops a predetermined biological function. During this process, the dissolved oxygen concentration DO and pH of the culture solution L in the cell culture tank 50 change due to the activity of the cells.

[0046] During the cultivation of the cell tissue B, the culture fluid L is fed to the cell storage section 51 of the cell culture tank 50 at a pressure (pressurization) lower than the damage pressure Pd [mmHg] so as not to damage the blood vessels of the cell tissue B. The damage pressure Pd is a predetermined pressure (for example, 5 to 10 [mmHg]) at which the cell tissue B starts to be damaged, and varies depending on the type of the cell tissue B. In addition, in order for the cell tissue B to exhibit a predetermined biological function, it is preferable to use pressure-controlled feeding, which feeds the culture fluid L at a target pressure, rather than flow-rate-controlled feeding, which feeds the culture fluid L at a target flow rate. This is because in the animal cell tissue of an actual animal, blood is fed by the heart, which is closer to pressure-controlled feeding than flow-rate-controlled feeding. In addition, in order for the cell tissue B to exhibit a predetermined biological function, it is preferable that the pressure acting on the cell tissue B is stable. When the culture fluid L is fed to the cell storage section 51 at a pressure (pressurization) lower than the damage pressure Pd [mmHg], the flow rate of the culture fluid L is smaller than the culture flow rate Fg [mL / min]. The culture flow rate Fg (second flow rate) is a flow rate suitable for culturing the cell tissue B, and is, for example, 1 to 3 [mL / min].

[0047] An oxygen concentration sensor 81, a pH sensor 82, and a temperature sensor 83 are inserted into the culture solution L stored in the cell culture tank 50. The oxygen concentration sensor 81 (status sensor) detects the dissolved oxygen concentration DO (status) of the culture solution L in the cell culture tank 50. The pH sensor 82 (status sensor) detects the pH (status) of the culture solution L in the cell culture tank 50. When detecting the pH of the culture solution L by the pH sensor 82, a small amount of reference liquid (internal liquid) may leak from the pH sensor 82 into the culture solution L. The temperature sensor 83 (status sensor) detects the temperature (status) of the culture solution L in the cell culture tank 50. In addition, a pressure sensor 84 is inserted into the flow path Bp (cell tissue B) of the cell tissue B. The pressure sensor 84 detects the pressure of the culture solution L in the flow path Bp, that is, the pressure of the culture solution L supplied to the cell storage section 51 (cell culture tank 50) by the liquid supply pipe 42B.

[0048] The cell culture tank 50 is provided with a heater 52. The heater 52 (condition adjustment unit) heats the culture solution L stored in the cell culture tank 50. The heater 52 is controlled by the control unit 45. The culture solution L inside the cell culture tank 50 is stirred by a stirrer (not shown).

[0049] The cell culture tank 50 is connected to the tank 34 by a liquid return pipe 43. A pump 90 and a check valve 92 are provided in the liquid return pipe 43. The pump 90 pumps the culture liquid L when the liquid level detected by the liquid level sensor 41 falls below a predetermined position (liquid level sensor 41: OFF). The pump 90 stops pumping the culture liquid L when the liquid level detected by the liquid level sensor 41 rises above the predetermined position (liquid level sensor 41: ON). The check valve 92 (non-return valve) allows the culture liquid L to flow from the pump 90 to the tank 34 and prohibits the culture liquid L from flowing from the tank 34 to the pump 90. The liquid return pipe 43 is connected to a position lower than the liquid level of the culture liquid L in the tank 34 and higher than the lower end of the liquid delivery pipe 42A.

[0050] The control unit 45 is a microcomputer equipped with a CPU, a ROM, a RAM, an input / output interface, etc. The control unit 45 controls the flow rate proportional valve 24 to send the culture solution L to the cell culture tank 50 at a target pressure. That is, the pressure control solution sending unit 20 adjusts the flow rate of the culture solution L flowing through the solution sending pipes 42A and 42B.

[0051] The control unit 45 controls the pressure control liquid delivery unit 20 to deliver the culture liquid L from the tank 34 to the cell culture tank 50 via the liquid delivery pipes 42A and 42B, and controls the flow proportional valve 24 so that air is supplied at a target flow rate calculated based on predetermined conditions. The control unit 45 maintains the state for a predetermined time (e.g., 3 [S]) of 5 [S] or less until the pressure Pv in the tank 34 is equilibrated. In this embodiment, the pressure Pv is equilibrated in approximately 1 [S]. As a result, the culture liquid L is delivered to the cell culture tank 50 at the target pressure.

[0052] The time from when air starts to be supplied from the air supply source 21 until the pressure Pv inside the tank 34 is equilibrated becomes longer as the volume of the tank 34 becomes larger, the effective cross-sectional area S of the throttle valve 27 becomes larger, and the target pressure inside the tank 34 becomes higher. In this regard, in culturing the cell tissue B having blood vessels, since it is necessary to send the culture solution L to the cell culture tank 50 at a minute pressure lower than the damage pressure Pd [mmHg], the target pressure inside the tank 34 is set very low. Therefore, the time until the pressure Pv is equilibrated becomes very short.

[0053] When the culture solution L is fed from the tank 34 to the cell culture tank 50 through the liquid feeding pipes 42A and 42B, the control unit 45 balances the pressure inside the tank 34 in a state where the flow rate proportional valve 24 is controlled so that air is supplied at a target flow rate corresponding to the target pressure inside the tank 34 based on a predetermined correlation between the flow rate of air supplied from the air supply source 21 in a state where the pressure inside the tank 34 is equilibrated and the pressure inside the tank 34. In other words, the control unit 45 balances the pressure inside the tank 34 in a state where the flow rate proportional valve 24 is controlled so that air is supplied at a target flow rate corresponding to the target pressure inside the tank 34 based on a predetermined correlation between the flow rate of air supplied from the air supply source 21 in a state where the pressure inside the tank 34 is equilibrated and feeds the culture solution L from the tank 34 to the cell culture tank 50 through the liquid feeding pipes 42A and 42B.

[0054] Oxygen, carbon dioxide, and nitrogen supplied from an oxygen cylinder (not shown), a carbon dioxide cylinder (not shown), and a nitrogen cylinder (not shown) are supplied to the mixer 60 via MFCs 61-63, respectively. The MFCs 61-63 (condition adjustment units) adjust the flow rates of oxygen, carbon dioxide, and nitrogen, respectively. The MFCs 61-63 are controlled by the control unit 45. The mixer 60 mixes these gases. The mixer 60 is connected to the cell culture tank 50. The oxygen, carbon dioxide, and nitrogen mixed in the mixer 60 are supplied to the cell culture tank 50 via a gas pipe 65. The gas supplied to the cell culture tank 50 is discharged to the outside of the cell culture tank 50 from a gas outlet or gap of the cell culture tank 50.

[0055] The display unit 70 is composed of a touch panel (liquid crystal panel + touch pad). The display unit 70 (pressure receiving unit, flow rate receiving unit, confirmation receiving unit) displays images and receives touch operations by the user. Touch operations include operations of pressing displayed buttons (icons), inputting numerical values, etc.

[0056] In the cell culture system 10 described above, a preparation step must be performed before starting the culture step of the cell tissue B. In the preparation step, for example, a culture solution L with an adjusted dissolved gas concentration and temperature T is stored in the cell culture tank 50. The cell culture system 10 performs the preparation step in a standby mode, and performs the culture step in a culture mode.

[0057] In the standby mode (first mode), the control unit 45 controls the pressure-controlled liquid delivery unit 20 to supply the culture fluid L to the cell culture tank 50 at a first flow rate F1 through the liquid delivery pipes 42A and 42B. In detail, the user operates an image displayed in advance by the display unit 70 to input a set pressure P1s, which is a target value of the pressure P1 detected by the pressure sensor 37 in the standby mode. The set pressure P1s is a pressure lower than the above-mentioned damage pressure Pd and is a pressure at which the culture fluid L can be delivered quickly to the cell culture tank 50. In addition, the display unit 70 accepts an operation to start the standby mode by the user. The display unit 70 displays a "standby" button that instructs the start of the standby mode. The control unit 45 starts the standby mode when the "standby" button is pressed.

[0058] In the culture mode (second mode), the control unit 45 controls the pressure control liquid delivery unit 20 so that the pressure P2 detected by the pressure sensor 84 is lower than the damage pressure Pd after the standby mode ends and the culture liquid L is supplied to the cell culture tank 50 through the liquid delivery pipes 42A and 42B at a second flow rate F2 lower than the first flow rate F1. In detail, the first flow rate F1 is greater than five times the second flow rate F2 (the first flow rate F1 is an order of magnitude greater than the second flow rate F2). When the standby (preparation step) is completed, the control unit 45 causes the display unit 70 to pop up a "standby completed" and "confirm" button. When the "confirm" button is pressed and held (operated) by the user (the display unit 70 receives an operation confirming that the standby is completed), the control unit 45 determines that the user has confirmed that the standby is completed. The control unit 45 executes the culture mode on the condition that it is determined that the user has confirmed that the standby is completed.

[0059] The control unit 45 selectively executes a pressure control mode and a flow control mode as the culture mode. The display unit 70 displays a "pressure control mode" button and a "flow control mode" button. The user presses (operates) the "pressure control mode" button or the "flow control mode" button in advance to select the pressure control mode or the flow control mode.

[0060] In the pressure control mode, the user operates the image displayed in advance by the display unit 70 to input a set pressure P2s which is a target value of the pressure P2 detected by the pressure sensor 84. The set pressure P2s is a pressure lower than the above-mentioned damage pressure Pd and is a pressure suitable for culturing the cell tissue B. In the pressure control mode (cultivation mode, second mode), the control unit 45 controls the pressure control liquid delivery unit 20 so that the pressure P2 detected by the pressure sensor 84 becomes the set pressure P2s.

[0061] In the flow rate control mode, the user operates the image displayed in advance on the display unit 70 to input a set flow rate Fs, which is a target value of the flow rate F detected by the flow rate sensor 85. The set flow rate Fs is a flow rate suitable for culturing the cell tissue B. In the flow rate control mode (culture mode, second mode), the control unit 45 controls the pressure-control liquid delivery unit 20 so that the flow rate F detected by the flow rate sensor 85 becomes the set flow rate Fs.

[0062] 2 is a flowchart showing the procedure of the standby mode. This series of processes is executed by the control unit 45 when a user operates the display unit 70 to start the standby mode.

[0063] First, it is determined whether the liquid level sensor 41 is ON and whether the pressure P1 is less than the threshold pressure P1r (S10). That is, it is determined whether the liquid level detected by the liquid level sensor 41 is higher than a predetermined position and whether the pressure P1 of the culture solution L at the bottom of the tank 34 detected by the pressure sensor 37 (hereinafter referred to as "pressure P1 inside the tank 34") is lower than the threshold pressure P1r. The threshold pressure P1r is a pressure that is lower than the above-mentioned damage pressure Pd and does not prevent the culture solution L from being quickly sent to the cell culture tank 50. In this determination, if it is determined that the liquid level sensor 41 is not ON or that the pressure P1 is not less than the threshold pressure P1r (S10: NO), the determination of S10 is executed again.

[0064] On the other hand, if it is determined that the liquid level sensor 41 is ON and the pressure P1 is less than the threshold pressure P1r (S10: YES), the solenoid valve 46 is opened to allow the culture liquid L to be sent from the tank 34 to the cell culture tank 50 (S11).

[0065] Next, it is determined whether pressure P2<threshold pressure P2r (S12). That is, it is determined whether pressure P2 inside the cell tissue B detected by the pressure sensor 84 is lower than threshold pressure P2r. Threshold pressure P2r is a pressure that is lower than the damage pressure Pd and does not prevent the culture fluid L from being promptly sent to the cell culture tank 50. Note that threshold pressure P1r and threshold pressure P2r may be the same or different. In this determination, if it is determined that pressure P2<threshold pressure P2r is not satisfied (S12: NO), the pressure control fluid sending unit 20 is controlled to reduce the pressure inside the tank 34 (S13). Thereafter, the process is executed again from the determination in S12.

[0066] On the other hand, if it is determined that the pressure P2 is less than the threshold pressure P2r (S12: YES), it is determined whether or not the pressure P1 is approximately equal to the set pressure P1s (S14). That is, it is determined whether or not the pressure P1 inside the tank 34 detected by the pressure sensor 37 is approximately equal to the set pressure P1s. If the pressure P1 is approximately equal to the set pressure P1s, the culture fluid L is supplied to the cell culture tank 50 at the first flow rate F1 through the fluid supply pipes 42A and 42B. If it is determined that the pressure P1 is not approximately equal to the set pressure P1s in this determination (S14: NO), the pressure control fluid supply unit 20 is controlled so that the pressure inside the tank 34 approaches the set pressure P1s (S15). Then, the process is executed again from the determination in S12.

[0067] On the other hand, if it is determined in S14 that the pressure P1 is approximately equal to the set pressure P1s (S14: YES), the pressure control liquid delivery unit 20 is controlled so as to maintain the pressure inside the tank 34 at the set pressure P1s (S16).

[0068] Next, it is determined whether or not the dissolved oxygen concentration DO is approximately equal to the target dissolved oxygen concentration, pH is approximately equal to the target pH, and temperature T is approximately equal to the target temperature (S17). Note that in a culture solution conditioning control different from the flowchart in Fig. 2, the control unit 45 controls the MFCs 61-63 and the heater 52 so that the dissolved oxygen concentration DO is approximately equal to the target dissolved oxygen concentration, pH is approximately equal to the target pH, and temperature T is approximately equal to the target temperature. In this determination, if it is determined that any of the pH, the dissolved oxygen concentration DO, and the temperature T is not approximately equal to the target value (S17: NO), the process is executed again from S12.

[0069] On the other hand, when it is determined that the dissolved oxygen concentration DO is approximately equal to the target dissolved oxygen concentration, the pH is approximately equal to the target pH, and the temperature T is approximately equal to the target temperature (S17: YES), the display unit 70 pops up a "Standby Completed" and "Confirm" button (S18). That is, in the standby mode, the MFCs 61-63 and the heater 52 are controlled so that the state of the culture solution L detected by the sensors 81-83 becomes the target state, and an image indicating that the standby is completed is displayed on the display unit 70, provided that the state of the culture solution L detected by the sensors 81-83 becomes the target state.

[0070] Next, it is determined whether or not the user has confirmed that the standby has been completed (S19). In this determination, if it is determined that the user has not confirmed that the standby has been completed (S19: NO), the process is executed again from S12. That is, after an image indicating that the standby has been completed is displayed on the display unit 70, the MFCs 61-63 and the heater 52 are controlled so as to maintain the state of the culture solution L detected by the sensors 81-83 at the target state until the display unit 70 receives an operation to confirm that the standby has been completed.

[0071] On the other hand, when it is determined in the judgment of S19 that the user has confirmed that the standby has been completed (S19: YES), the solenoid valve 46 is closed, the supply of oxygen, carbon dioxide, and nitrogen to the mixer 60 is stopped, and the pressure control inside the tank 34 by the pressure control liquid delivery unit 20 is stopped (S20). That is, when an operation confirming that the standby has been completed is received by the display unit 70, the supply of the culture liquid L to the cell culture tank 50 through the liquid delivery pipes 42A and 42B and the supply of gas to the cell culture tank 50 through the gas pipe 65 are stopped. After that, this series of processes is ended (END), and the user puts the cell tissue B into the cell culture tank 50 to make it ready for culture. In detail, the cell storage unit 51 in which the cell tissue B is stored is installed inside the cell culture tank 50, and the liquid delivery pipe 42B is connected to the cell storage unit 51.

[0072] 3 is a flow chart showing the procedure of the culture mode. This series of processes is executed when a user operates the display unit 70 to start the culture mode.

[0073] First, the pump 90 executes tank liquid level control (S30). In detail, when the liquid level detected by the liquid level sensor 41 falls below a predetermined level (liquid level sensor 41: OFF), the pump 90 pumps the culture solution L. Then, when the liquid level detected by the liquid level sensor 41 rises above the predetermined level (liquid level sensor 41: ON), the pump 90 stops pumping the culture solution L.

[0074] Next, the control unit 45 executes culture solution conditioning control (S31). Specifically, the control unit 45 controls the MFCs 61-63 and the heater 52 so that the dissolved oxygen concentration DO is approximately equal to the target dissolved oxygen concentration, the pH is approximately equal to the target pH, and the temperature T is approximately equal to the target temperature.

[0075] Next, the control unit 45 executes the liquid delivery control (S32). Fig. 4 is a flowchart showing the procedure of the liquid delivery control.

[0076] As shown in the figure, it is determined whether or not pressure P2<threshold pressure P2r (S321). That is, it is determined whether or not the pressure P2 inside the cellular tissue B detected by the pressure sensor 84 is lower than the threshold pressure P2r. In this determination, if it is determined that pressure P2<threshold pressure P2r is not satisfied (S321: NO), the pressure control liquid delivery unit 20 is controlled to lower the pressure inside the tank 34 (S322). After that, the process returns to the next process of S32 in FIG. 3 (RET).

[0077] On the other hand, if it is determined that the pressure P2 is less than the threshold pressure P2r (S321: YES), it is determined whether the pressure P2 is approximately equal to the set pressure P2s or the flow rate F is approximately equal to the set flow rate Fs (S323). That is, if the pressure control mode is being executed, it is determined whether the pressure P2 inside the cell tissue B detected by the pressure sensor 84 is approximately equal to the set pressure P2s. If it is determined that the pressure P2 is not approximately equal to the set pressure P2s (S323: NO), the pressure control liquid delivery unit 20 is controlled so as to bring the pressure P2 closer to the set pressure P2s (S324). Also, if the flow control mode is being executed, it is determined whether the flow rate of the culture liquid L detected by the flow sensor 85 is approximately equal to the set flow rate Fs. If it is determined that the flow rate F is not approximately equal to the set flow rate Fs (S323: NO), the pressure control liquid delivery unit 20 is controlled so as to bring the flow rate F closer to the set flow rate Fs (S324). Thereafter, the process returns to the next process of S32 in FIG.

[0078] On the other hand, if it is determined in S323 that the pressure P2 is approximately equal to the set pressure P2s or the flow rate F is approximately equal to the set flow rate Fs (S323: YES), the pressure control liquid delivery unit 20 is controlled so as to maintain the pressure inside the tank 34 at the current pressure (S325). Then, the process returns to the next process of S32 in FIG. 3 (RET).

[0079] Returning to FIG. 3, in the process of S33, the control unit 45 determines whether or not a culture stop operation has been performed by the user (S33). More specifically, it determines whether or not a culture mode stop operation has been performed by the user on the display unit 70. If it is determined in this determination that a culture stop operation has not been performed by the user (S33: NO), the process is executed again from S30. On the other hand, if it is determined in this determination that a culture stop operation has been performed by the user (S33: YES), this series of processes is terminated (END).

[0080] The present embodiment described above in detail has the following advantages.

[0081] The control unit 45 executes a standby mode in which the pressure-controlled liquid delivery unit 20 is controlled to supply the culture solution L at a first flow rate F1 to the cell culture tank 50 through the liquid delivery pipes 42A, 42B. Therefore, the standby mode is executed before the cell tissue B is stored in the cell culture tank 50, that is, when there is no risk of damaging the cell tissue B, and the culture solution L can be supplied at the first flow rate F1 to the cell culture tank 50 through the liquid delivery pipes 42A, 42B. Therefore, the time required for the preparation process before starting cell culture (for example, the process of storing the culture solution L with an adjusted dissolved gas concentration in the cell culture tank 50) can be shortened.

[0082] Then, the control unit 45 executes a culture mode in which the pressure P2 detected by the pressure sensor 84 after the standby mode is terminated is made lower than the predetermined damage pressure Pd at which the predetermined cell tissue B begins to be damaged, and the pressure control liquid delivery unit 20 is controlled so as to supply the culture liquid L to the cell culture tank 50 through the liquid delivery pipes 42A and 42B at a second flow rate F2 smaller than the first flow rate F1. Therefore, the culture mode is executed after the cell tissue B is stored in the cell culture tank 50, and the pressure P2 of the culture liquid L supplied to the cell culture tank 50 through the liquid delivery pipes 42A and 42B is detected by the pressure sensor 84, and the pressure P2 of the culture liquid L is made lower than the damage pressure Pd and the flow rate F of the culture liquid L is set to the second flow rate F2 smaller than the first flow rate F1, thereby preventing the predetermined cell tissue B from being damaged by the flow of the culture liquid L. Moreover, by executing the culture mode after the standby mode, the preparation process (standby) and the cell culture process before the start of cell culture can be easily executed, and the user's effort in executing the cell tissue B culture can be reduced.

[0083] The cell storage section 51 stores the cellular tissue B. The cell storage section 51 is stored inside the cell culture tank 50. Therefore, by placing the cell storage section 51 storing the desired cellular tissue B in the cell culture tank 50, the cellular tissue B can be easily placed in the cell culture tank 50.

[0084] The liquid supply pipe 42B is inserted from the outside to the inside of the cell culture tank 50 and is connected to the cell storage section 51. This allows the culture solution L to be directly supplied to the inside of the cell storage section 51, making it easier to generate a flow of the culture solution L inside the cellular tissue B stored in the cell storage section 51. This makes it easier to culture the cellular tissue B in an appropriate environment where a flow of the culture solution L is generated inside the cellular tissue B, and promotes the culture of the cellular tissue B. Moreover, since the pressure P2 detected by the pressure sensor 84 is set lower than a predetermined damage pressure Pd at which the predetermined cellular tissue B begins to be damaged, damage to the cellular tissue B due to the flow of the culture solution L can be suppressed.

[0085] The pressure sensor 84 detects, inside the cellular tissue B, the pressure P2 of the culture solution L supplied to the cell culture tank 50 through the liquid supply pipe 42B. With this configuration, the pressure sensor 84 can detect the pressure P2 of the culture solution L inside the cellular tissue B, which further prevents the cellular tissue B from being damaged by the flow of the culture solution L. In addition, the pressure P2 of the culture solution L inside the cellular tissue B, which serves as the environment in which the cellular tissue B is cultured, can be more accurately grasped.

[0086] The pressure receiving unit (display unit 70) receives the input of the set pressure P2s. Therefore, the pressure of the culture fluid L in the cell culture process can be set arbitrarily. However, the set pressure P2s must be set lower than the damage pressure Pd and the flow rate F of the culture fluid L must be set to a second flow rate F2 that is lower than the first flow rate F1. Then, the control unit 45 executes a pressure control mode as the culture mode, in which the pressure control fluid delivery unit 20 is controlled so that the pressure P2 detected by the pressure sensor 84 becomes the set pressure P2s received by the pressure receiving unit. Therefore, the pressure control mode is executed as the culture mode, and cell culture can be performed in a state in which the pressure P2 detected by the pressure sensor 84 is maintained at the set pressure P2s.

[0087] The flow rate receiving unit (display unit 70) receives an input of a set flow rate Fs. Therefore, the flow rate F of the culture fluid L in the cell culture process can be set arbitrarily. However, the set flow rate Fs needs to be set smaller than the first flow rate F1. Then, the control unit 45 executes a flow rate control mode as the culture mode, in which the pressure-controlled liquid delivery unit 20 is controlled so that the flow rate F detected by the flow rate sensor 85 becomes the set flow rate Fs received by the flow rate receiving unit. Therefore, the flow rate control mode is executed as the culture mode, and cell culture can be performed in a state in which the flow rate F detected by the flow rate sensor 85 is maintained at the set flow rate Fs.

[0088] The control unit 45 can selectively execute a pressure control mode and a flow rate control mode. Therefore, a mode suitable for culture can be selected and executed depending on the purpose and the type of cell tissue B.

[0089] The first flow rate F1 is greater than five times the second flow rate F2. Therefore, the first flow rate F1 of the culture solution L in the standby mode can be greater than five times the second flow rate F2 of the culture solution L in the culture mode, and the time required for the preparation process can be significantly shortened.

[0090] The standby mode is basically executed before the cell tissue B is stored in the cell culture tank 50, that is, in a state where there is no risk of damaging the cell tissue B. However, if the pressure of the culture solution L in the standby mode is higher than the damage pressure Pd, there is a risk that the culture solution L at a pressure higher than the damage pressure Pd will temporarily flow to the cell tissue B when switching to the culture mode. In this regard, the control unit 45 makes the pressure P1 detected by the pressure sensor 37 lower than the damage pressure Pd (threshold pressure P1r) in the standby mode. Therefore, it is possible to prevent the culture solution L at a pressure higher than the damage pressure Pd from temporarily flowing to the cell tissue B when switching from the standby mode to the culture mode.

[0091] The sensors 81-83 detect the state of the culture solution L. As the state of the culture solution L, the pH, the dissolved oxygen concentration DO, and the temperature T of the culture solution L are adopted. The MFCs 61-63 and the heater 52 adjust the state of the culture solution L. Specifically, the pH can be adjusted by dissolving carbon dioxide in the culture solution L, the dissolved oxygen concentration DO can be adjusted by dissolving oxygen in the culture solution L, and the temperature T can be adjusted by heating the culture solution L with the heater 52.

[0092] In the standby mode, the control unit 45 controls the MFCs 61-63 and the heater 52 so that the state detected by the sensors 81-83 becomes the target state. Therefore, by executing the standby mode, the actual state of the culture solution L can become the target state. Then, the control unit 45 causes the display unit 70 to display an image indicating that the preparation process is complete, on the condition that the state detected by the sensors 81-83 becomes the target state. Therefore, the user can easily know that the preparation process is complete by confirming that the image indicating that the preparation process is complete is displayed by the display unit 70. In addition, the user can easily know that the preparation process is not complete by confirming that the image indicating that the preparation process is complete is not displayed by the display unit 70.

[0093] The confirmation receiving unit (display unit 70) receives an operation that confirms that the preparation process has been completed. Then, when the confirmation receiving unit receives the operation, the control unit 45 stops the supply of the culture fluid L to the cell culture tank 50 through the liquid delivery pipes 42A, 42B. Therefore, when the user performs an operation that confirms that the preparation process has been completed, the supply of the culture fluid L to the cell culture tank 50 can be stopped, and the process of storing the cell tissue B in the cell culture tank 50 can be safely proceeded to.

[0094] After displaying an image indicating that the preparation process is completed on the display unit 70, the control unit 45 controls the MFCs 61-63 and the heater 52 to maintain the state detected by the sensors 81-83 in the target state until the confirmation receiving unit receives an operation. With this configuration, the state of the culture solution L can be maintained in the target state until the user performs an operation that confirms that the preparation process is completed after the preparation process is completed. Therefore, the user can perform the operation that confirms that the preparation process is completed at a time desired by the user to start cell culture. Furthermore, since the state detected by the sensors 81-83 is maintained in the target state until the confirmation receiving unit receives an operation, the conditions for starting cell culture can be made uniform, and the reproducibility of cell culture can be improved.

[0095] During standby mode, the pH, dissolved oxygen concentration (DO), and temperature (T) of the culture solution L can be set to the target pH, target dissolved oxygen concentration, and target temperature, respectively. Therefore, after the standby mode is completed, the process can be quickly started, reducing the user's efforts.

[0096] The above embodiment can be modified as follows: The same parts as those in the above embodiment are denoted by the same reference numerals and the description thereof will be omitted.

[0097] 2 and S322 and S324 in Fig. 4, the range in which the pressure inside the tank 34 is changed and the period in which the pressure is changed may be variably set. Also, the range in which the pressure P1 is considered to be approximately equal to P1s and the range in which the pressure P2 is considered to be approximately equal to P2s may be variably set.

[0098] The control unit 45 may stop the pressure-controlled liquid delivery unit 20 when the flow rate F detected by the flow rate sensor 85 is an abnormal flow rate. With this configuration, the flow of the culture solution L can be stopped when the culture solution L cannot be circulated normally. This reduces the burden on the user to monitor the cell culture system 10 during the standby mode and the culture mode. Furthermore, the control unit 45 may notify the user that the flow of the culture solution L is abnormal by using the display unit 70 or a warning light when the flow rate F detected by the flow rate sensor 85 is an abnormal flow rate.

[0099] The control unit 45 may stop the MFCs 61-63 and the heater 52 when the state detected by the sensors 81-83 is an abnormal state. With this configuration, it is possible to stop the adjustment of the state of the culture solution L when the state of the culture solution L cannot be adjusted normally. This reduces the burden on the user to monitor the cell culture system 10 during the standby mode and the culture mode. Furthermore, when the state detected by the sensors 81-83 is an abnormal state, the control unit 45 may notify the user that the state of the culture solution L is abnormal by the display unit 70 or a warning light.

[0100] After causing the display unit 70 to display an image indicating that the preparation process has been completed, the control unit 45 can also omit the control of maintaining the state detected by the sensors 81 to 83 at the target state until an operation is received by the confirmation receiving unit.

[0101] When the confirmation receiving unit receives an operation confirming that the preparation process has been completed, the control unit 45 may omit the process of stopping the supply of the culture solution L to the cell culture tank 50 through the liquid supply pipes 42A and 42B. In addition, the supply of the culture solution L to the cell culture tank 50 through the liquid supply pipes 42A and 42B may be stopped manually.

[0102] The target state of the culture solution L can be preset by a program.

[0103] The adjustment of at least one of the pH, the dissolved oxygen concentration DO, and the temperature T of the culture solution L may be omitted or may be performed manually. Accordingly, the detection of at least one of the pH, the dissolved oxygen concentration DO, and the temperature T of the culture solution L may be omitted or may be performed manually.

[0104] In the standby mode, the control unit 45 does not necessarily have to make the pressure P1 detected by the pressure sensor 37 lower than the damaging pressure Pd.

[0105] The first flow rate F1 is not limited to being set to be greater than five times the second flow rate F2, and may be set to be greater than twice the second flow rate F2, or may be set to be greater than one time the second flow rate F2.

[0106] The set pressures P1s, P2s and set flow rate Fs of the culture solution L can also be preset by a program.

[0107] The control unit 45 may be configured to execute only one of the pressure control mode and the flow rate control mode.

[0108] A pressure sensor 84 for detecting the pressure inside the cell tissue B (flow path Bp) can be inserted from the liquid supply pipe 42B into the cell tissue B. In addition, as the pressure P2 of the culture solution L supplied to the cell culture tank 50 by the liquid supply pipes 42A and 42B, the pressure P2 of the culture solution L just before the cell culture tank 50 in the liquid supply pipe 42B may be detected by a pressure sensor 86, as shown by a dashed line in FIG.

[0109] Instead of the pressure-controlled liquid delivery unit 20, a variable-capacity precision pump can be used.

[0110] The cell culture system 10 may be provided with a storage device, and various parameters may be stored in the storage device at any time. Also, the cell culture system 10 may be configured to allow an external storage medium to be inserted, and various parameters may be stored in the external storage medium at any time. With these configurations, evidence of the test can be easily left behind. The time interval for storing various parameters may be variably set.

[0111] The cell culture system 10 may be capable of communicating with an external device, so that various data can be acquired and various settings can be executed by the external device. The cell culture system 10 may also be capable of storing various data in the cloud. Furthermore, the communication function allows users in remote locations to share data in real time and hold real time meetings. Furthermore, when it is difficult for a user to operate the display unit 70, the same operations can be executed by a tablet terminal or the like capable of communicating with the cell culture system 10. [Explanation of symbols]

[0112] 10...cell culture system, 20...pressure controlled liquid delivery section (flow rate adjustment section), 34...tank, 37...pressure sensor, 42A...liquid delivery piping (supply piping), 42B...liquid delivery piping (supply piping), 45...control section, 50...cell culture tank (culture tank), 51...cell storage section, 70...display section (pressure receiving section, flow rate receiving section, confirmation receiving section), 81...oxygen concentration sensor (status sensor), 82...pH sensor (status sensor), 83...temperature sensor (status sensor), 84...pressure sensor, 85...flow rate sensor, 86...pressure sensor.

Claims

1. A culture tank for storing a culture solution; A supply pipe for supplying the culture solution from the outside to the inside of the culture tank; A flow rate adjusting unit that adjusts the flow rate of the culture solution flowing through the supply pipe; A pressure sensor for detecting a pressure of the culture solution supplied to the culture tank through the supply pipe; A control unit that executes a first mode in which the flow rate adjustment unit is controlled to supply the culture solution to the culture tank at a first flow rate through the supply pipe before a predetermined cell tissue is stored in the culture tank, and a second mode in which the flow rate adjustment unit is controlled to lower the pressure detected by the pressure sensor after the first mode is completed below a predetermined damage pressure at which the cell tissue begins to be damaged and to supply the culture solution to the culture tank at a second flow rate lower than the first flow rate through the supply pipe; A cell culture system comprising:

2. A cell storage section for storing the cell tissue, The cell storage unit is stored inside the culture tank, The cell culture system according to claim 1 , wherein the supply pipe is inserted from the outside to the inside of the culture tank and connected to the cell storage unit.

3. The cell culture system according to claim 2 , wherein the pressure sensor detects, inside the cell tissue, a pressure of the culture medium supplied to the culture tank through the supply pipe.

4. A pressure receiving unit is provided for receiving an input of a set pressure, The cell culture system according to any one of claims 1 to 3, wherein the control unit executes a pressure control mode as the second mode in which the control unit controls the flow rate control unit so that the pressure detected by the pressure sensor becomes the set pressure received by the pressure receiving unit.

5. A flow rate receiving unit that receives an input of a set flow rate; A flow rate sensor for detecting a flow rate of the culture solution supplied to the culture tank through the supply piping; The control unit executes a flow control mode as the second mode in which the flow rate detected by the flow sensor is controlled to the set flow rate received by the flow rate receiving unit. The cell culture system according to any one of claims 1 to 4.

6. A pressure receiving unit that receives an input of a set pressure; A flow rate receiving unit that receives an input of a set flow rate; A flow rate sensor for detecting a flow rate of the culture solution supplied to the culture tank through the supply piping; The control unit selectively executes, as the second mode, a pressure control mode in which the flow rate adjustment unit is controlled so that the pressure detected by the pressure sensor becomes the set pressure received by the pressure receiving unit, and a flow rate control mode in which the flow rate adjustment unit is controlled so that the flow rate detected by the flow sensor becomes the set flow rate received by the flow rate receiving unit.The cell culture system described in any one of claims 1 to 3.

7. The cell culture system according to any one of claims 1 to 6, wherein the first flow rate is greater than five times the second flow rate.

8. The cell culture system according to any one of claims 1 to 7, wherein the control unit, in the first mode, sets the pressure detected by the pressure sensor to be lower than the damaging pressure.

9. A state sensor for detecting a state of the culture solution; A condition adjusting unit that adjusts the condition of the culture solution; A display unit that displays an image, The cell culture system according to any one of claims 1 to 8, wherein in the first mode, the control unit controls the condition adjustment unit to make the condition detected by the condition sensor a target state, and causes the display unit to display an image indicating that the preparation process has been completed, on condition that the condition detected by the condition sensor has become the target state.

10. a confirmation receiving unit that receives an operation that confirms that the preparation process has been completed, The cell culture system according to claim 9 , wherein the control unit stops the supply of the culture medium to the culture tank through the supply pipe when the operation is accepted by the confirmation accepting unit.

11. The cell culture system of claim 10, wherein the control unit controls the condition adjustment unit to maintain the condition detected by the condition sensor at a target state until the operation is accepted by the confirmation acceptance unit, after displaying an image indicating that the preparation process has been completed on the display unit.

12. The cell culture system according to any one of claims 9 to 11, wherein the state of the culture medium includes a pH, a dissolved oxygen concentration, and a temperature of the culture medium.

13. The cell culture system according to claim 5 or 6, wherein the control unit stops the flow rate regulator when the flow rate detected by the flow rate sensor is an abnormal flow rate.

14. The cell culture system according to any one of claims 9 to 12, wherein the control unit stops the condition adjustment unit when the condition detected by the condition sensor is an abnormal condition.

Citation Information

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