WO2024041442A1 - Dispositif, système et procédé de culture cellulaire - Google Patents

Dispositif, système et procédé de culture cellulaire Download PDF

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Publication number
WO2024041442A1
WO2024041442A1 PCT/CN2023/113494 CN2023113494W WO2024041442A1 WO 2024041442 A1 WO2024041442 A1 WO 2024041442A1 CN 2023113494 W CN2023113494 W CN 2023113494W WO 2024041442 A1 WO2024041442 A1 WO 2024041442A1
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WO
WIPO (PCT)
Prior art keywords
cell culture
culture device
gas
operating frame
chamber
Prior art date
Application number
PCT/CN2023/113494
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English (en)
Chinese (zh)
Inventor
刘景�
王高
刘雳宇
戴陆如
Original Assignee
国科温州研究院(温州生物材料与工程研究所)
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from CN202222208024.9U external-priority patent/CN218202863U/zh
Priority claimed from CN202222208046.5U external-priority patent/CN217948154U/zh
Priority claimed from CN202211006229.7A external-priority patent/CN117660178A/zh
Application filed by 国科温州研究院(温州生物材料与工程研究所) filed Critical 国科温州研究院(温州生物材料与工程研究所)
Publication of WO2024041442A1 publication Critical patent/WO2024041442A1/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M3/00—Tissue, human, animal or plant cell, or virus culture apparatus
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M1/00—Apparatus for enzymology or microbiology
    • C12M1/04—Apparatus for enzymology or microbiology with gas introduction means
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M1/00—Apparatus for enzymology or microbiology
    • C12M1/36—Apparatus for enzymology or microbiology including condition or time responsive control, e.g. automatically controlled fermentors
    • C12M1/38—Temperature-responsive control

Definitions

  • the present invention relates to the field of cell culture technology, and specifically to a cell culture device, system and method.
  • Cell culture is basic work in life science and medical related fields, and it is necessary to keep the cell culture dishes under suitable conditions, such as a temperature of 37 degrees Celsius, a carbon dioxide gas with a concentration of 5%, and a high humidity environment.
  • Current cell culture devices generally adopt a box-type structure and are used by multiple people, which can easily lead to bacterial infections caused by mixing or misuse. Since the internal environment of the incubator is a physiological environment, it is conducive to bacterial growth and can easily lead to bacterial infections.
  • Cell culture incubators are usually used by multiple people in the laboratory.
  • a first aspect of the present invention proposes a cell culture device that can be removably loaded into and removed from an operating frame.
  • the operating frame is configured to provide a centralized location for one or more cell culture devices.
  • Placement and culture system, the mobile cell culture device includes:
  • a maintenance system used to maintain a desired culture environment inside the culture chamber the maintenance system being configured to independently maintain the gas content inside the cell culture device after the cell culture device is removed from the operating frame, Temperature maintenance and humidity maintenance, the maintenance system provides gas and power supply respectively from the gas source and power supply built in the cell culture device;
  • a controller used to control the operation of the maintenance system
  • the cell culture device is provided with a connection interface along the direction in which the operating frame is installed to communicate with the operating frame.
  • a device connected to the gas supply interface and/or the power supply interface of the operating frame, so that after the cell culture device is installed in the operating frame, it is controlled to switch from the gas supply interface of the operating frame to the cell culture device.
  • a gas supply is provided, and the control is switched to charging the power supply of the cell culture device through the power supply interface of the operating frame.
  • the maintenance system includes a gas supply device controlled by the controller, the gas supply device being configured to supply gas to the interior of the cell culture device according to internal environmental data of the culture chamber.
  • the gas supply device includes at least one gas bottle placed inside the cell culture device, and the at least one gas bottle is configured to controllably supply gas to the culture chamber through a gas pipeline.
  • the at least one gas bottle is removably mounted inside the cell culture device.
  • the gas supply device includes a control valve located at a pipeline line position of the gas pipeline and/or a gas bottle outlet position, and when the cell culture device is moved out of the operating frame, the controller controls all The opening and closing of the control valve.
  • the maintenance system includes a temperature maintenance device controlled by the controller, the temperature maintenance device being configured to maintain the temperature inside the culture chamber within a predetermined range based on internal environmental data.
  • the temperature maintenance device includes at least one electric heater located inside the cell culture device for heating the culture chamber.
  • the maintenance system includes a humidity maintenance device configured to maintain the humidity inside the culture chamber within a predetermined range.
  • the humidity maintaining device is an open vessel containing water located inside the culture chamber, and the humidity is maintained through natural evaporation.
  • the power source built into the cell culture device includes at least one rechargeable battery pack.
  • the cell culture device is equipped with an external charging interface, and the external charging interface is used to receive external power input and charge the battery pack.
  • the cell culture device further includes a display screen module for displaying status parameters of the cell culture device.
  • the cell culture device further includes a user setting module for setting operating parameters of the cell culture device.
  • the cell culture device further includes a communication module for data exchange with the operating frame or external devices.
  • the cell culture device includes an acceleration sensor coupled to the controller.
  • a second aspect of the present invention proposes a cell culture system, including:
  • An operating frame configured with multiple physically independent holding chambers
  • One or more cell culture devices as described above can be moved out and installed into the accommodation cavity of the operating frame.
  • the one or more cell culture devices are provided with a cell culture environment and a culture dish placed therein. cultivation warehouse;
  • the operating frame has a first system for supplying gas to each accommodation cavity and a second system for supplying power to each accommodation cavity;
  • the cell culture device has a maintenance system that maintains a desired culture environment inside the cell culture device according to the internal environment data of the cell culture device.
  • the maintenance system is configured to be able to maintain the cell culture device after the cell culture device is removed from the accommodation chamber of the operating frame.
  • the gas content maintenance, temperature maintenance and humidity maintenance are independently realized internally, and the maintenance system provides gas and power supply respectively from the gas source and power supply built into the cell culture device; and
  • the cell culture device also has a controller, the controller is configured to control switching to provide gas supply to the cell culture device from the first system of the operating frame when the cell culture device is loaded into its corresponding receiving chamber, and Control is switched to charging the power source of the cell culture device from the second system of the operating frame.
  • the maintenance system includes a gas supply device controlled by the controller, the gas supply device being configured to supply gas, such as carbon dioxide gas, to the interior of the cell culture device based on internal environmental data.
  • gas such as carbon dioxide gas
  • the maintenance system includes a temperature maintenance device controlled by the controller, the temperature maintenance device being configured to maintain the temperature inside the culture chamber within a predetermined range based on internal environmental data.
  • the maintenance system includes a humidity maintenance device configured to maintain the humidity inside the culture chamber within a predetermined range.
  • the built-in power supply of the cell culture device includes at least one rechargeable battery pack, especially detachably installed inside the cell culture device as a built-in power supply.
  • the internal environment data includes at least one of carbon dioxide content, temperature and humidity inside the cell culture device, which can be detected in real time based on a carbon dioxide gas sensor, a temperature sensor and a humidity sensor, for example.
  • a method of operating a cell culture device on an operating frame equipped with a plurality of cell culture devices is also proposed.
  • the cell culture devices are accommodated in an independent accommodation cavity of the operating frame.
  • the method includes :
  • the cell culture device When the cell culture device is taken out from the accommodation cavity of the operating frame and used independently, the cell culture device performs system adjustment according to the internal environment data of its culture chamber to maintain the expected culture environment; the system adjustment includes independently adjusting the cell culture device inside the cell culture device.
  • the gas content maintenance, temperature maintenance and humidity maintenance can be adjusted accurately, and the gas and power supply are respectively provided by the built-in gas source and power supply of the cell culture device;
  • the cell culture device When the cell culture device is installed into the accommodation cavity of the operation frame, the cell culture device establishes a communication connection with the operation frame, and the control is switched to the operation frame for supplying each accommodation cavity.
  • a first system of gases provides gas supply to the cell culture device, and control is switched to a second system of the operating frame for supplying power to each holding chamber. The system charges the cell culture device's power source.
  • the method further includes:
  • the operating frame receives user input information to verify the user's permission to operate the cell culture device;
  • the operation of the cell culture device is allowed, otherwise the operation of the cell culture device is prohibited.
  • Figure 1 is a schematic diagram of a cell culture device according to an embodiment of the present invention.
  • Figure 2 is a schematic diagram of the internal structure of a cell culture device according to an embodiment of the present invention.
  • Figure 3 is a schematic structural diagram of the rear panel of the cell culture device according to the embodiment of the present invention.
  • Figure 4 is a schematic diagram of the gas path structure of the cell culture device according to the embodiment of the present invention.
  • FIG. 5 is a schematic diagram of a housing with a buffer mechanism of a cell culture device according to an embodiment of the present invention.
  • Figure 6 is a schematic diagram of a cell culture system according to an embodiment of the present invention.
  • Figure 7 is a schematic diagram of the interface at the bottom of the accommodation chamber in the insertion direction of the cell culture system according to the embodiment of the present invention.
  • Figure 8 is a schematic structural diagram of the air path of the cell culture system according to the embodiment of the present invention.
  • Figure 9 is a schematic diagram of the electrical path structure of the cell culture system according to the embodiment of the present invention.
  • the reference signs are: 100-Cell culture device, 100A-outer box, 100B-inner box, 100C-buffer material, 100D-partition plate, 101-culture chamber, 102-culture dish, 103-gas cylinder, 103A-flow valve, 104- Gas pipeline, 105-battery pack, 106-controller, 107-fan assembly, 108-electric heater, 109A-gas sensor, 109B-temperature sensor, 109C-humidity sensor, 110-gas outlet, 111-humidification device, 112 -Second air interface, 113-electrical contact, 114-power switch, 115-external charging interface, 116-communication programming interface, 117-solenoid valve, 120-display, 130-handle, 140-user identity authentication module ,150-control button, 1000-operating frame, 1100-operating frame gas inlet, 1200-gas channel, 1201-branch pipeline, 1202-first gas line connection Port, 1300-electrical entrance of the operating frame
  • the example cell culture device 100 shown in Figure 1 adopts a design with built-in power supply and air source, and automatically and continuously monitors the environmental parameters of the culture chamber inside the cell culture device, including temperature, humidity and carbon dioxide content, and communicates with the preset environment Compare with the control standards, control the automatic replenishment of carbon dioxide gas through the built-in gas source, and control the automatic temperature rise process, so as to maintain an ideal physiological environment conducive to cell growth in the culture chamber.
  • the cell culture device 100 of the illustrated exemplary embodiment includes a box that provides a carrier and support for constructing a cell culture environment.
  • the box includes an outer box 100A, an inner box 100B, and a buffer material 100C disposed in the interlayer space between the outer box 100A and the inner box 100B, as shown in FIG. 5 .
  • the outer box 100A and the inner box 100B can be made of plastic or metal and made into a certain shape, especially a regular shape, such as the square shape of the illustrated embodiment, thereby facilitating independent use and transfer. Put it into a protective box during the process, which is easy to achieve combination, stacking or other temporary storage and protection.
  • At least one side or bottom surface of the outer box 100A can form a structure that facilitates stacking or arranging multiple cell culture devices side by side while maintaining a certain stability, including but not limited to, such as slide rails, card slots or cards. Button fit construction.
  • the aforementioned cushioning material 100C can be, for example, a spring, a foam material, an inflatable bag, etc., and is installed in the interlayer between the outer box 100A and the inner box 100B in an advantageous manner.
  • a spring is taken as an example.
  • Multiple springs are respectively arranged in the interlayer between the outer box 100A and the inner box 100B, and the two ends of each spring are respectively fixed to the outer box 100A and the inner box 100B.
  • the buffer material 100C can also be made of foam material and fixed into the interlayer through glue layers, so that the outer box 100A, the inner box 100B and the buffer material 100C form a whole.
  • the impact of vibration on the cell culture device 100 during movement is reduced, the thermal insulation effect is improved, temperature compensation is reduced, and the system endurance is extended.
  • Figures 1 and 2 schematically illustrate the design of a cell culture device.
  • the cell culture device 100 has a maintenance system that maintains a desired culture environment inside the cell culture device 100 based on the internal environment data of the cell culture device 100 .
  • the maintenance system is configured to independently maintain the gas content, temperature and humidity inside the cell culture device 100 after the cell culture device 100 is removed from the accommodation chamber of the operating frame 1000.
  • the maintenance system is provided by a gas source built into the cell culture device 100. and power supplies provide gas and electricity supplies respectively.
  • At least one culture chamber 101 is provided in the box, located in the internal cavity defined by the inner box 100B.
  • the internal cavity defined by the inner box 100B is divided into an upper cavity and a lower cavity by a partition 100D, and the aforementioned culture chamber 101 is located in the upper cavity.
  • the culture chamber 101 builds a physiological environment that is conducive to cell growth, such as a certain temperature and humidity environment and a gas environment.
  • a typical environment is such as 37 degrees Celsius, carbon dioxide gas with a concentration of 5%, and a relative saturated humidity of more than 95%. In some embodiments, the relative saturation humidity can reach 100%.
  • a culture dish 102 for cell culture is stored inside the culture chamber 101, as shown in Figure 2.
  • the aforementioned internal environment data includes at least one of carbon dioxide content, temperature and humidity inside the culture chamber 101 of the cell culture device 100, which can be detected in real time based on the carbon dioxide gas sensor, temperature sensor and humidity sensor.
  • the cell culture device 100 is provided with a sensor component for monitoring the internal environment data of the culture chamber 101 , including a gas sensor 109A for monitoring the carbon dioxide content, a temperature sensor for monitoring the temperature inside the culture chamber.
  • the sensor 109B and the humidity sensor 109C used to monitor the humidity in the cultivation chamber monitor and provide feedback on the environmental parameters inside the cultivation chamber 101 at a set period.
  • the maintenance system includes a gas supply device controlled by the controller 106, the gas supply device being configured to supply carbon dioxide gas to the interior of the cell culture device 100 based on internal environmental data.
  • the gas supply device includes at least one gas bottle 103 placed inside the cell culture device 100 .
  • the at least one gas bottle 103 is configured to supply gas to the culture chamber 101 through a gas pipeline 104 in a controlled manner.
  • Carbon dioxide gas is stored in the gas cylinder 103
  • At least one gas bottle 103 is detachably mounted inside the cell culture device 100 .
  • the gas supply device includes a control valve located at the pipeline line position of the gas pipeline 104 and/or at the outlet position of the gas bottle 103.
  • the controller 106 operates the control valve. of opening and closing.
  • the cell culture device 100 has a built-in gas cylinder 103 for storing carbon dioxide gas.
  • a flow valve 103A is provided at the gas outlet position. The outlet of the flow valve 103A is connected to the interior of the culture chamber 101 through the gas pipe 104, so that carbon dioxide gas can be replenished into the culture chamber through the gas bottle 103.
  • a pressure reducing valve is provided in the pipeline of the gas pipeline 104 .
  • the first end of the gas pipeline 104 may be provided with a quick-change connector, such as a check quick connector, to quickly connect with the outlet end of the flow valve 103A.
  • the second end of the gas pipeline 104 is connected to and installed in the side wall of the culture chamber 101, and communicates with the interior of the culture chamber 101.
  • the gas cylinder 103 adopts a replaceable design.
  • the quick replacement can be achieved through the quick-release joint and the first end of the gas pipeline 104 .
  • the flow valve 103A is opened to connect the gas cylinder 103 to the gas pipeline 104 .
  • the flow valve 103A may be an electrically driven flow valve controlled by the aforementioned controller 106 .
  • the quick-change joint at the first end of the gas pipeline 104 and the joint at the outlet end of the flow valve 103A adopt a male-female quick-change joint design.
  • the aforementioned maintenance system includes a temperature maintenance device controlled by the controller 106, and the temperature maintenance device is configured to maintain the temperature inside the culture chamber 101 within a predetermined range according to internal environmental data.
  • the temperature maintenance device includes at least one electric heater 108 located inside the cell culture device 100 for heating the culture chamber.
  • the electric heater 108 is provided in the form of a heating plate and is installed inside the culture chamber 101, for example, at the inner bottom surface of the culture chamber 101, so that uniform heating can be performed by the air flow inside the culture chamber.
  • the maintenance system includes a humidity maintenance device, and the humidity maintenance device is configured to maintain the humidity inside the culture chamber 101 within a predetermined range, such as maintaining a humidity level of 100%.
  • the humidity maintenance device includes a humidification device 111 located inside the culture chamber 101 .
  • the humidification device 111 provided inside the culture chamber 101 can be a horizontally placed open container filled with water, which can be humidified through natural evaporation to maintain the humidity level inside the culture chamber 101. 100%.
  • the humidity sensor 109C when the humidity sensor 109C detects a decrease in humidity, it indicates that the humidification device 111 is in a water shortage state and the humidity level cannot be maintained through evaporation, and water needs to be replenished.
  • the controller 106 can control the alarm reminder through the alarm device.
  • a fan assembly 107 is also provided inside the culture chamber 101 , and its operation is controlled by the controller 106 , thereby maintaining a uniform gas, temperature, and humidity in the culture chamber 101 through air flow.
  • At least one gas outlet 110 is provided on the side wall of the culture chamber 101 for balancing the internal and external pressures of the culture chamber 101 .
  • the cell culture device 100 is configured to monitor the interior of the culture chamber 101
  • the environmental data sensor components are all arranged inside the cultivation chamber 101 to realize direct detection of carbon dioxide gas content, temperature and humidity.
  • the electric heater 108 and the fan assembly 107 for realizing gas circulation in the culture chamber are both located inside the culture chamber 101 .
  • a second chamber body is also formed inside the inner box 100B of the cell culture device 100, forming an independent space relative to the culture chamber 101.
  • a cavity of appropriate shape and size located on the outer side of the culture chamber 101 is convenient for installing the aforementioned electric heater 108, the fan assembly 107 for realizing gas circulation in the culture chamber, and the sensor assembly.
  • the second chamber body is independent. in the culture chamber 101 and maintain the communication state with the culture chamber 101.
  • the cavity of the second compartment is designed in a long strip shape, and the two ends of the cavity are respectively connected to the two ends of the channel culture compartment.
  • the fan assembly 107 is arranged in the second compartment.
  • the gas is realized The circulation within the second chamber body and the culture chamber 101. Moreover, when the electric heater 108 is running to raise the temperature, uniform heating and temperature rise are achieved through the circulation of hot air in the second chamber body and the culture chamber 101 .
  • the fan assembly 107, the electric heater 108 and the gas sensor 109A may be disposed within the second chamber body.
  • the built-in power supply of the cell culture device 100 includes at least one rechargeable battery pack 105 .
  • the battery pack 105 provides power supply to various electrical devices through a power circuit not shown in the figure, such as the controller 106, the fan assembly 107, the electric heater 108, the gas sensor 109A, the temperature sensor 109B, the humidity sensor 109C, and the humidifier.
  • Device 111 and other devices provide power.
  • the power circuit can adopt an existing power supply circuit design, such as a circuit including one or more DC-DC modules, to achieve the output of different voltages, thereby realizing power supply to different devices.
  • the battery pack 105 is preferably formed of a plurality of rechargeable battery cells (Cell) connected in series and/or in parallel, in which a battery management unit (BMS) is configured to charge and discharge the battery. Management and battery status detection.
  • the aforementioned rechargeable battery unit (Cell) may be a lithium matrix battery or a nickel-metal hydride battery.
  • the battery pack 105 is detachably installed inside the cell culture device 100.
  • the battery pack 105 adopts a replaceable design. When the power of the battery pack is insufficient, the battery pack can be quickly replaced by replacing the battery, thereby facilitating the operation. When the cell culture device 100 is used alone, the battery pack can be easily replaced, enabling long-term independent use.
  • the cell culture device 100 is configured with at least two battery packs 105 to achieve a redundant power supply design.
  • the cell culture device 100 is also equipped with a charging circuit, which is connected to the aforementioned controller 106 and charges the battery pack 105 by connecting to an external power source, especially a DC power source.
  • a battery pack can be charged via a portable power bank.
  • the charging circuit is correspondingly configured with an external charging interface 115 , and the external charging interface 115 is used to receive external power input and charge the battery pack 105 .
  • the external charging interface 115 can adopt a round port, a square port, a Type-C interface, a USB-A interface, etc., to receive external power supply input.
  • the external charging interface 115 is connected to a charging circuit provided in the culture chamber, and is used to receive external power input and charge the battery pack 105 .
  • a round port charging interface is used as an example for explanation.
  • the controller 106 can use an embedded processor with low power consumption to control the cell culture device 100 .
  • the fan assembly 107, the electric heater 108 of the cell culture device 100, and the aforementioned gas sensor 109A, temperature sensor 109B, and humidity sensor 109C are all electrically connected to the aforementioned controller 106, and are controlled and operated by the controller 106.
  • the aforementioned gas cylinder 103, flow valve 103A, battery pack 105, and controller 106 are all disposed in the lower cavity.
  • a window can be configured around the corresponding box part around the periphery of the lower cavity and closed with a cover plate.
  • the cover plate is tightly closed at the window position in the form of a buckle, which is beneficial to The cover plate at the window position is operated from the outside to quickly replace the battery pack 105 or the gas cylinder 103.
  • a solenoid valve 117 is provided on the pipeline extending from the outlet of the flow valve 103A to the aforementioned gas pipeline 104 of the culture chamber 101 and is connected to the aforementioned controller 106.
  • the controller 106 controls the switch of the solenoid valve 117. and/or opening size.
  • the solenoid valve 117 can be an electromagnetic flow valve or other electronically controlled flow valve, used to control the replenishment of carbon dioxide gas to the culture chamber.
  • the controller 106 controls the operation of the gas supply device and the temperature maintenance device and monitors the status of the humidity maintenance device according to the monitored temperature, humidity, and carbon dioxide content in the cultivation chamber 101, and regulates the environment in the cultivation chamber. To maintain an ideal cultivation environment.
  • the controller 106 controls the solenoid valve 117 to open, and the gas cylinder 103 flows to the culture chamber via the gas pipeline 104 101. Supplement carbon dioxide gas until the carbon dioxide concentration in the culture chamber reaches a predetermined level, and control to close the solenoid valve 117.
  • the controller 106 controls the heating plate to start working until the temperature rises to a predetermined level, such as 37 degrees Celsius, and then controls the heating plate to turn off.
  • the aforementioned fan assembly 107 is configured to be controlled by the controller 106 to maintain continuous operation, and through continuous gas circulation, the gas, temperature and humidity in the culture chamber are maintained in a uniform state.
  • a constant rotation speed or other appropriate control strategy can be used to control the operation of the fan assembly 107 .
  • the cell culture device 100 is also configured with a communication module, such as a wireless network transceiver module, for establishing a communication connection with user equipment.
  • the communication module can use a Wifi module based on the IEEE protocol, a wireless communication module based on a cellular network, or a Bluetooth module based on the Bluetooth protocol, etc., to be connected to the controller 106 and transmit through wireless
  • the protocol enables the cell culture device 100 to access the wireless LAN or the Internet, so that the user can establish a communication connection with the cell culture device 100 through his or her device (such as a handheld mobile communication device, a mobile tablet computer, etc.), thereby receiving the data sent by the cell culture device 100 Detection data, or send control instructions to the cell culture device 100, for example, send control instructions based on the monitored temperature, humidity, and carbon dioxide content in the culture chamber, which are executed by the above-mentioned controller to control the gas supply device, temperature maintenance device, and humidity maintenance device. of operation.
  • the wireless network transceiver module includes at least two of the above-mentioned IEEE protocol-based Wifi module, cellular network-based wireless communication module, and Bluetooth protocol-based Bluetooth module, which are advantageously integrated into one module. superior.
  • the cell culture device 100 is also equipped with an acceleration sensor connected to the above-mentioned controller 106 .
  • the tilted or inverted state of the cell culture device 100 is sensed by the acceleration sensor to avoid irreversible consequences to the cell culture in the culture dish.
  • a display screen 120 is provided on the front panel of the cell culture device 100 .
  • the display screen 120 can be an LCD display screen, an LED display screen, etc., is connected to the controller 106 , and can be powered by a battery.
  • the group 105 supplies power and displays the status information of the cell culture device 100 through the display screen 120, including but not limited to the temperature, humidity, carbon dioxide concentration, battery power, remaining gas volume of the gas cylinder and other information of the culture chamber.
  • the display screen 120 may be a touch-sensitive display screen.
  • At least one input device such as an operation panel type input device, may be provided on the front panel of the cell culture device 100 to provide an input interface interface for operating the cell culture device 100 . It is particularly preferred that the aforementioned touch-sensitive display screen constitutes an input device.
  • At least one control button 150 may be provided around the display screen 120 , which is connected to the controller 106 and serves as a control switch for controlling the lighting of the display screen 120 .
  • display 120 is illuminated and information is displayed in response to an external trigger control button.
  • the lighting mode of the display screen 120 is set to delayed extinguishing, for example, in response to an external trigger control button, the display screen 120 is lit and information is displayed, and after a delay of a predetermined time, the display screen 120 automatically goes out. , thereby saving power.
  • a handle 130 is also provided on the front panel of the cell culture device 100 for user operation.
  • the cell culture device 100 is provided with a compartment door that can be operated and opened. When the compartment door is locked, the cell culture device 100 remains in a sealed state. When the compartment door is operated and opened, the culture dishes 102 stored in the cell culture device 100 can be operated, picked up and placed.
  • the front panel of the cell culture device 100 is also provided with user identity authentication.
  • the module 140 is used to provide an interface or entrance for confirming the user's identity information, such as a password verification module, a biological information verification module, etc., is connected to the controller 106, and is used to confirm the user's identity information, thereby allowing the user to operate the cell culture device 100 , including but not limited to, in response to passing the identity verification, allowing the user to open the cell culture device 100 to operate the culture dish located in the culture chamber 101, regulate the environmental parameters in the culture chamber 101, etc.
  • the user identity authentication module 140 includes a recognizable mark, such as a QR code or a barcode, and the user can verify the identity by scanning the mark, and in response to the verification being passed, access to the cell culture device 100 is allowed. operation, otherwise the operation of the cell culture device 100 is prohibited.
  • a recognizable mark such as a QR code or a barcode
  • a second air path interface 112 and an electrical contact 113 are provided on the rear panel.
  • the second air path interface 112 preferably uses a non-return quick connector. Used to achieve quick docking.
  • the electrical contact 113 is preferably an electrical contact adapted to the POGO-PIN.
  • the rear panel of the cell culture device 100 is also provided with a power switch 114 for controlling turning on or off the cell culture device 100 when the cell culture device 100 is used independently or transferred as a mobile cell culture device.
  • the internal power supply allows the controller, various sensors and execution components to operate normally after being powered on.
  • the rear panel of the cell culture device 100 is also provided with a communication programming interface 116, which is used to establish a communication connection between the cell culture device 100 and the control device when the cell culture device 100 is used independently and during movement.
  • the cell culture device 100 is programmed and controlled.
  • a cell culture system includes an operating frame 1000 and a control system 2000 .
  • the control system 2000 can be implemented using a locally deployed computer system, a server, or a server deployed in the cloud, and is used to monitor and control the operation of the operation frame 1000 .
  • control system 2000 is configured to support remote access and control, for example, based on a certain protocol, interact with remote computer systems, smart terminals and other control devices, and send on-site monitoring data to the remote control device, and receiving operation instructions sent by the remote control device to realize operation control of the operation frame 1000.
  • the operating frame 1000 is configured with multiple physically independent accommodation chambers, and each accommodation chamber is used to provide an independent accommodation space for the cell culture device 100 .
  • One or more cell culture devices 100 can be removed and loaded into the accommodation cavity of the operating frame 1000 .
  • Each cell culture device 100 has a maintenance system that maintains a desired culture environment inside the cell culture device 100 based on the internal environment data of the cell culture device 100 .
  • the maintenance system is configured to independently maintain the gas content, temperature and humidity inside the cell culture device 100 after the cell culture device 100 is removed from the accommodation chamber of the operating frame 1000.
  • the maintenance system is provided by a gas source built into the cell culture device 100. and power supplies provide gas and electricity supplies respectively.
  • the aforementioned internal environment data includes at least one of carbon dioxide content, temperature and humidity inside the culture chamber 101 of the cell culture device 100, which can be detected in real time based on the carbon dioxide gas sensor, temperature sensor and humidity sensor.
  • the operating frame 1000 is configured to centrally supply air and power to the cell culture device 100 installed in the accommodation chamber.
  • the operating frame 1000 has a first system for supplying gas to each containment cavity and a second system for supplying power to each containment cavity.
  • each accommodation cavity when a cell culture device 100 is loaded into it and installed in place, a gas connection and an electrical connection with the installed cell culture device 100 are established in the accommodation cavity of the operating frame 1000 , to realize the takeover of the internal environment control of the installed cell culture device 100, including:
  • the first system of the operating frame 1000 is switched to provide gas supply to the cell culture device 100
  • the second system of the operating frame 1000 is switched to provide gas supply to the cell culture device 100.
  • the power supply is charged to realize switching from the internal air supply to the centralized air supply and power supply of the operating frame 1000.
  • a centralized gas source 3000 such as a gas supply steel tank loaded with compressed carbon dioxide gas, is connected to the operating frame 1000 through a pressure reducing valve 3001 and a pipeline.
  • the operating frame 1000 includes components for detecting the remaining capacity of the gas source 3000.
  • the first system of the operating frame 1000 includes at least one operating frame gas inlet 1100 for receiving external gas and a gas channel 1200 communicating with the operating frame gas inlet 1100 and used for applying gas to each accommodation cavity.
  • the gas channel 1200 includes a main pipeline extending from the gas inlet 1100 of the operating frame and branch pipelines 1201 extending from the main pipeline towards each accommodation chamber.
  • the end of each branch pipeline 1201 is provided with a cell culture device.
  • 100 forms a first gas path interface 1202 for gas path connection.
  • the aforementioned gas source 3000 for centralized gas supply is connected to the operating frame gas inlet 1100 through the pressure reducing valve 3001 and the pipeline, and is connected to the main pipeline.
  • the first gas path interface 1202 is configured to form a pair of male and female interface structures with the second gas path interface 112 of the cell culture device 100 installed in the accommodation chamber.
  • the second air path interface 112 provided on the rear panel of the cell culture device 100 installed therein forms a pair of male and female matching structures with the first air path interface 1202, where , the second gas circuit interface 112 and the first gas circuit interface 1202 both adopt a non-return quick connector design, which can realize quick connection and disconnection. After the connection is disconnected, the joints at both ends are automatically closed, and no gas leakage will occur. Highly stain-resistant and easy to clean.
  • the second system of the operation frame 1000 includes at least one operation frame electrical input for receiving external power input.
  • Port 1300 and an electrical channel electrically connected to the electrical inlet 1300 of the operating frame and used to apply power to each accommodation cavity.
  • the aforementioned external power input refers in particular to 220VAC, 110VAC and other mains inputs, which can be configured according to the area where the equipment is used.
  • the electrical channel includes a power management module 1301 electrically connected to the electrical inlet 1300 of the operating frame and a line 1302 introduced from the output end of the power management module 1301 to each accommodation cavity.
  • An electrical connector 1303 is provided at the end of the line 1302.
  • the electrical connector 1303 The electrical contacts 113 are configured to come into contact with the cell culture device 100 installed in the accommodation chamber to form electrical communication between the accommodation chamber and the cell culture device 100 installed in the accommodation chamber.
  • the electrical connector 1303 adopts a spring-type probe (POGO PIN), which is arranged toward the entrance of the accommodation cavity.
  • POGO PIN spring-type probe
  • the operation rack 1000 is provided with a user identity authentication module, which provides an interface or entrance for confirming user identity information, and is used to authorize operation permission of the cell culture device 100 .
  • the user identity authentication module sets the user identity authentication QR code 140 on the front panel of the cell culture device 100 as an interface or entrance to confirm the user's identity information, and determines based on the verification result that the user's access to the cell culture device 100 is from the operation frame 1000 If the operation authority is verified, for example, the cell culture device 100 is allowed to be extracted from the operation rack 1000; otherwise, the cell culture device 100 is prohibited from being withdrawn from the operation rack 1000, thereby realizing the operation authorization of the cell culture device 100.
  • the user identity authentication module can also be configured to implement identity authentication in other ways, including but not limited to password verification, fingerprint and other biometric information verification, etc.
  • each accommodation cavity of the operating frame 1000 is provided with at least one guide mechanism, such as a guide rail or a guide groove, for providing a guide for loading/unloading the cell culture device 100 .
  • the combination position of the cell culture device 100 and the operating frame 1000 can also be provided with an anti-detachment mechanism, including but not limited to an anti-detachment structure based on electronics, electromagnetic, mechanical design or a combination thereof. To prevent the cell culture device 100 from being accidentally pulled out, slid out or detached.
  • an anti-detachment mechanism including but not limited to an anti-detachment structure based on electronics, electromagnetic, mechanical design or a combination thereof.
  • the control system 2000 corresponding to the operating frame 1000 communicates with the cell culture device 100 and controls the charging of the battery pack 105 of the cell culture device 100 to replenish the power.
  • the control system 2000 correspondingly configured on the operating frame 1000 executes the control of the cell culture device 100, including based on Carbon dioxide concentration, temperature and humidity are monitored and controlled.
  • control system 2000 controls to close the flow valve 103A corresponding to the cell culture device 100 and cut off the air supply channel from the gas cylinder 103 to the culture chamber 101 .
  • Each cell culture device 100 is configured to send its feedback to the control system 2000 in real time or according to a preset cycle.
  • Status information including but not limited to one or more of temperature, humidity, carbon dioxide concentration, battery power, and remaining gas volume in the cylinder.
  • the control system 2000 controls the execution devices in the corresponding cell culture device 100, such as the operation of the heating plate, and reminds to replace or replenish the humidification device. Until the temperature and humidity in the culture chamber 101 reach the preset level.
  • the control system 2000 is also configured to control the opening of the solenoid valve 117 and release the carbon dioxide gas provided by the gas source 3000 based on the carbon dioxide content in the culture chamber 101 of a certain cell culture device 100 being lower than a preset level, for example, lower than 5%.
  • the branch pipeline 1201 enters the accommodation chamber where the cell culture device 100 is located through the gas channel 1200, thereby replenishing the carbon dioxide into the culture chamber 101 of the cell culture device 100 until the carbon dioxide content in the culture chamber 101 reaches a preset level.
  • the controller 106 of the cell culture device 100 can control the built-in circuit of the cell culture device 100.
  • the gas source and power supply respectively provide gas and power supply, cut off the gas supply channel of the first system to the cell culture device 100, and cut off the power charging channel of the second system to the cell culture device 100.
  • the cell culture device 100 itself can provide air and power supply.
  • the first system is in an open circuit state (for example, the main pipeline or branch pipeline has an open circuit failure, resulting in the inability to successfully transport carbon dioxide gas), the secondary system is in an open circuit state (for example, there is no external AC input or a circuit failure caused by a line failure, which prevents the smooth charging of the battery pack).
  • a preset threshold such as 5%
  • the controller 106 controls the switching to the air supply from the gas bottle inside the cell culture device 100 and the power supply from the internal battery pack to ensure that the cell culture device 100 can still be independent when it is installed in the operating frame 100 when the operating frame cannot provide centralized air supply and power supply. to operate normally.
  • each accommodation chamber serves as an independent compartment and can accommodate an independent cell culture device 100.
  • Each cell culture device 100 can be extracted from the operating frame 1000. Based on the quick plug-in combination structure, in the identity Under the premise that the verification is passed, it can be connected and removed at any time, so that the cell culture device 100 can be freely operated and moved, and has mobility to meet the mobile needs of the cell culture device 100 in multiple scenarios; on the other hand, when After the cell culture device 100 is removed from the operating frame 1000, it can be used as an independent culture device. Gas and power supplies are provided through the internal gas bottles and battery packs, so that each sensor and actuator can operate normally and maintain the interior of the cell culture device 100.
  • the cultivation environment maintains the ideal physiological environment required for cell growth and reduces the negative impact on cell growth when moved. At the same time, when it is installed in the operating frame, it can provide centralized air and power supply to achieve unified management and operation. And the status information and growth process of each cell culture device 100 can be extracted, analyzed and stored to achieve the purpose of scientific research.

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Abstract

L'invention concerne un dispositif, un système et un procédé de culture cellulaire. Le système comprend : un cadre de fonctionnement pourvu de cavités de réception physiquement indépendantes ; et des dispositifs de culture cellulaire chargés de façon mobile dans le cadre de fonctionnement et déplacés hors du cadre de fonctionnement et pourvus chacun d'un bac de culture pour construire un environnement de culture cellulaire et contenant une boîte de culture. Le cadre de fonctionnement présente un premier système d'alimentation en gaz de chaque cavité de logement et un deuxième système d'alimentation en énergie. Le dispositif de culture cellulaire est pourvu d'un système de maintenance qui permet à l'intérieur du dispositif de culture cellulaire de maintenir un environnement de culture attendu selon des données d'environnement interne du dispositif de culture cellulaire, et le gaz et la puissance sont fournis par une source de gaz intégrée et une alimentation électrique, respectivement. Lorsqu'un dispositif de culture cellulaire est chargé dans la cavité de réception correspondante de celui-ci, une commutation est effectuée pour utiliser le premier système et le deuxième système pour fournir une alimentation en gaz pour le dispositif de culture cellulaire et charger l'alimentation électrique du dispositif de culture cellulaire, respectivement. Par conséquent, un fonctionnement et un mouvement libres du dispositif de culture cellulaire peuvent être réalisés, et une alimentation en gaz et une alimentation électrique centralisées peuvent également être réalisées lorsque le dispositif de culture cellulaire est chargé dans le cadre d'opération, ce qui permet d'obtenir une gestion et un fonctionnement unifiés.
PCT/CN2023/113494 2022-08-22 2023-08-17 Dispositif, système et procédé de culture cellulaire WO2024041442A1 (fr)

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Application Number Priority Date Filing Date Title
CN202211006229.7 2022-08-22
CN202222208024.9U CN218202863U (zh) 2022-08-22 2022-08-22 细胞培养系统
CN202222208024.9 2022-08-22
CN202222208046.5 2022-08-22
CN202222208046.5U CN217948154U (zh) 2022-08-22 2022-08-22 移动式细胞培养装置
CN202211006229.7A CN117660178A (zh) 2022-08-22 2022-08-22 细胞培养系统及方法

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Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2006149232A (ja) * 2004-11-25 2006-06-15 Astec:Kk 培養装置
US20170073628A1 (en) * 2014-05-15 2017-03-16 Ert Optik Dr. Thiel Gmbh Modular Incubator System
CN208055361U (zh) * 2018-01-24 2018-11-06 四川理工学院 一种多功能细胞培养箱
CN209368302U (zh) * 2018-12-28 2019-09-10 江苏省人民医院（南京医科大学第一附属医院） 一种多功能自动化独立/联合共培养装置
CN211921589U (zh) * 2019-12-31 2020-11-13 秦皇岛照见生物科技有限公司 一种大型定制化细胞培养仓
US20210032587A1 (en) * 2018-02-05 2021-02-04 Xcell Biosciences, Inc. Multiple incubator cell culture system with atmospheric regulation operated by an integrated control system
CN113088451A (zh) * 2021-04-21 2021-07-09 云南中医药大学 一种实验用生物培养箱
CN216786146U (zh) * 2021-12-06 2022-06-21 武汉普诺赛生命科技有限公司 一种多功能集群化智能管理细胞培养箱
CN217948154U (zh) * 2022-08-22 2022-12-02 国科温州研究院(温州生物材料与工程研究所) 移动式细胞培养装置
CN218202863U (zh) * 2022-08-22 2023-01-03 国科温州研究院(温州生物材料与工程研究所) 细胞培养系统

Patent Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2006149232A (ja) * 2004-11-25 2006-06-15 Astec:Kk 培養装置
US20170073628A1 (en) * 2014-05-15 2017-03-16 Ert Optik Dr. Thiel Gmbh Modular Incubator System
CN208055361U (zh) * 2018-01-24 2018-11-06 四川理工学院 一种多功能细胞培养箱
US20210032587A1 (en) * 2018-02-05 2021-02-04 Xcell Biosciences, Inc. Multiple incubator cell culture system with atmospheric regulation operated by an integrated control system
CN209368302U (zh) * 2018-12-28 2019-09-10 江苏省人民医院（南京医科大学第一附属医院） 一种多功能自动化独立/联合共培养装置
CN211921589U (zh) * 2019-12-31 2020-11-13 秦皇岛照见生物科技有限公司 一种大型定制化细胞培养仓
CN113088451A (zh) * 2021-04-21 2021-07-09 云南中医药大学 一种实验用生物培养箱
CN216786146U (zh) * 2021-12-06 2022-06-21 武汉普诺赛生命科技有限公司 一种多功能集群化智能管理细胞培养箱
CN217948154U (zh) * 2022-08-22 2022-12-02 国科温州研究院(温州生物材料与工程研究所) 移动式细胞培养装置
CN218202863U (zh) * 2022-08-22 2023-01-03 国科温州研究院(温州生物材料与工程研究所) 细胞培养系统

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