Automated cell culture device

Abstract

The present invention provides an automated cell culture device, which has a main body. The main body has a culture chamber and an infusion hole communicating the culture chamber with the external space. A user can place a cell culture bag in the culture chamber, and arrange an infusion tube for supplying a culture solution to the cell culture bag to pass through the infusion hole and connect to an infusion source outside the main body. In this way, the structure of the automated cell culture device is simplified, and characteristics such as miniaturization and modularization can be achieved, which is beneficial for movement, rapid configuration, cost reduction, and replication and stacking.

Description

Technical Field

[0001] The present invention relates to a cell culture device. Background Art

[0002] In recent years, influenced by the progress of medical technology, a large number of cells need to be cultured in the fields of drug R & D and production, gene therapy, immunotherapy, cell therapy, etc.

[0003] For existing cell culture devices, reference can be made to, for example, the description of Taiwan, China Patent No. TWI670370. Mainly, a large incubator with a heat-insulating wall is used. After connecting the culture medium and the culture container, they are respectively placed in a cold storage tank and a culture tank separated left and right. The cold storage tank is maintained at 4°C to store the culture medium, the culture tank is maintained at 37°C to carry out cell culture, and multiple culture containers are stored on a multi-layered shelf. Then, a measuring unit such as a camera is guided by a pillar to move and observe the cell culture situation of each culture container, achieving automated and large-scale production.

[0004] Although the cell culture device of the aforementioned Taiwan, China Patent No. TWI670370 can provide large-scale production, however, its cell culture device is large in scale, and the cold storage tank and the culture tank separated left and right each need to be maintained at different high and low temperatures, and further refrigeration equipment needs to be installed, which will make the overall equipment of the cell culture device even more bulky, and it can only be purchased by large laboratories or large medical institutions. In addition, there is a shelf in the culture tank. Although multiple groups of culture containers can be placed, when the user conducts cell culture, it is necessary to further pay attention to whether the culture containers interfere with and contaminate each other, whether the internal environment of the culture tank is affected when taking out or putting in the culture containers, and whether the shelf will hinder disinfection and maintenance of a sterile environment, which is inconvenient in actual operation and use.

[0005] In contrast, there is also a cell culture incubator described in Taiwan, China Patent No. TWI567190, which partitions a cold storage room, a culture room and a pump room in a cell culture incubator with the same heat-insulating wall, and places the culture solution, the culture bag and the peristaltic pump module respectively, integrating the main equipment required for cell culture in a single box-type device, featuring miniaturization, rapid configuration and easy movement. However, the cell culture incubator described in Taiwan, China Patent No. TWI567190 also has a cold storage room and a culture room, and different high and low temperatures need to be maintained inside the box. Even if a vacuum insulation board is set, it is still inevitably affected by the natural flow of heat and consumes energy. Secondly, in order to maintain the low temperature of the cold storage room, the cell culture incubator still needs to install refrigeration equipment, making it difficult to further reduce the volume of the cell culture incubator, not conducive to replication and stacking for mass production, and difficult to improve space utilization. Summary of the Invention

[0006] In view of this, one of the objectives of the present invention is to provide a cell culture device that modularizes and miniaturizes the components in the device, with the expectation of improving the space utilization rate during cell culture.

[0007] The present invention provides an automated cell culture device for placing a cell culture bag and performing cell culture. The automated cell culture device includes a main body that has a culture chamber and an infusion hole. The infusion hole communicates between the culture chamber and the external space, so that when the cell culture bag is placed in the culture chamber, an infusion tube can be connected between an infusion source outside the main body and the cell culture bag in the culture chamber via the infusion hole.

[0008] The above-mentioned automated cell culture device can further include a base that is accommodated in the culture chamber. The base includes a shaking seat and a carrier. The shaking seat can drive the carrier to shake, and the carrier is for placing the cell culture bag thereon.

[0009] In the above-mentioned automated cell culture device, the carrier may include a disk body and a partition. The disk body is for holding water, and the partition is for holding the cell culture bag. The partition is placed on the disk body to separate the water held in the disk body from the cell culture bag. The partition has a number of openings for the water held in the disk body to evaporate and disperse in the culture chamber.

[0010] The above-mentioned automated cell culture device can further include a temperature control module that includes a heater and a temperature sensor. The temperature control module can sense the temperature of the culture chamber and selectively heat the culture chamber. The main body has a first connector, and the heater and the temperature sensor are electrically connected to the first connector, and the first connector is exposed outside the main body surface.

[0011] The above-mentioned automated cell culture device can further include a carbon dioxide module that includes a carbon dioxide sensor. The carbon dioxide sensor is located in the culture chamber. The main body has a second connector and an air inlet hole. The carbon dioxide sensor is electrically connected to the second connector, and the second connector is exposed outside the main body surface. The air inlet hole communicates between the culture chamber and the external space for connecting a carbon dioxide supply source outside the main body.

[0012] In the above-mentioned automated cell culture device, the main body can further have a plug seat that extends from the culture chamber to the external space. The infusion hole penetrates and is formed in the plug seat, and the first connector and / or the second connector can be disposed on the plug seat.

[0013] The above-mentioned automated cell culture device can further include a control module. The first connector is electrically connected to the control module. The control module measures the temperature of the culture chamber via a temperature sensor and controls the heater to turn on and off so that the temperature of the culture chamber approaches 37°C. Secondly, the second connector is electrically connected to the control module. The control module measures the carbon dioxide concentration in the culture chamber via a carbon dioxide module and controls the carbon dioxide supply source to supply carbon dioxide to the culture chamber through an air inlet hole so that the volume concentration of carbon dioxide in the culture chamber approaches 5%.

[0014] Using the above device, the automated cell culture device can be placed into a cell culture bag for cell culture and receive externally supplied culture medium. The heat insulation environment and refrigeration equipment required for storing the culture medium do not need to be attached beside the culture chamber of the automated cell culture device, which can avoid the mutual interference between the low temperature required for storing the culture medium and the high temperature of the culture chamber, maintain the constancy of the cell culture environment, and the structure of the culture chamber can be further streamlined, miniaturized, and each component can be modularized, which is beneficial for disinfection, movement, rapid configuration, reducing the setting cost, and improving the space utilization rate. Description of the Drawings

[0015] Figure 1 It is a schematic diagram of the automated cell culture device of the present invention.

[0016] Figure 2 It is a schematic diagram of the plug seat in the automated cell culture device of the present invention.

[0017] Figure 3 It is an exploded perspective view of the base in the automated cell culture device of the present invention.

[0018] Figure 4 It is a schematic diagram of another embodiment of the automated cell culture device of the present invention.

[0019] Description of the reference numerals: body 10; bottom wall 11; side wall 12; top cover 13; culture chamber 14; observation plate 15; infusion hole 16; plug seat 17; notch 171; first connector 172; second connector 173; third connector 174; air inlet hole 175; air release valve 176; base 20; rocking seat 21; base 211; drive rod 212; pedestal 213; disc body 221; partition 222; heater 31; temperature sensor 32; carbon dioxide sensor 41; gas cylinder connector 51; control valve 52; gas supply pipe 53; infusion pipe 61; storage tank 62; infusion pump 63; control module 70; cell culture bag 90; carbon dioxide high-pressure gas cylinder 91. Detailed Description of the Invention

[0020] Please refer to Figure 1, the present invention provides an automated cell culture device that can be placed into a cell culture bag 90 for cell culture. The automated cell culture device includes a main body 10, a base 20, a temperature control module, a carbon dioxide module, a carbon dioxide supply source, an infusion source, and a control module 70.

[0021] The main body 10 is a container in the shape of a box or a case, including a bottom wall 11, side walls 12, and a top cover 13. The side walls 12 extend upward from the periphery of the bottom wall 11. The top cover 13 is pivotally arranged on the side walls 12 so as to be openable and closable. A culture chamber 14 is defined between the bottom wall 11, the side walls 12, and the top cover 13, into which the cell culture bag 90 can be placed for cell culture. The bottom wall 11, the side walls 12, and the top cover 13 each have a heat insulation layer. Specifically, the bottom wall 11, the side walls 12, and the top cover 13 are, for example, multi-layer structures having an inner stainless steel plate, an outer stainless steel plate, and a heat insulation foam layer or a vacuum layer between the inner and outer layers, so that the culture chamber has heat insulation and heat preservation capabilities. Preferably, the heat insulation layers in the bottom wall 11 and the side walls 12 are connected to each other as a whole, which can have better heat insulation and heat preservation capabilities. The main body 10 also has an observation panel 15. The observation panel 15 is, for example, a transparent plate such as glass or acrylic, and is pivotally arranged on the side walls 12 and is located below the top cover 13. When the user opens the top cover 13, it can remain closed on the culture chamber 14, allowing the user to observe the situation inside the culture chamber 14 and maintaining the stability of the environment inside the culture chamber 14. The above-described bottom wall 11, side walls 12, top cover 13, and observation panel 15 are specific implementation manners of opening and closing upwards. However, if the top cover, side walls, and bottom wall are made into one body, and instead, one side of the side wall is set to open upwards or in a side-opening door plate manner, and the observation panel 15 is set inside the side wall, it is also acceptable.

[0022] The main body also has an infusion hole 16 which communicates the culture chamber 14 with the external space. The infusion tube 61 for delivering the culture medium can penetrate into the culture chamber 14 through the infusion hole 16 and be connected to the cell culture bag 90 in the culture chamber 14 to supply the culture medium to the cell culture bag 90. Specifically, referring to FIGS. 1 and 2, the main body further has a plug seat 17. There is a notch penetrating the inner and outer surfaces at the top edge of the side wall 12. The plug seat 17 is arranged in the notch so that the plug seat 17 extends from the culture chamber 14 to the external space and penetrates the inner and outer surfaces of the side wall 12. The infusion hole 16 is formed in the plug seat 17 and penetrates the plug seat 17, allowing the infusion tube 61 to penetrate into the culture chamber 14 through the infusion hole 16. Preferably, the plug seat 17 can be made of soft plastic or rubber partially or entirely and has elasticity. Several slits 161 are distributed around the infusion hole 16, enabling the plug seat 17 to be slightly deformed under extrusion to wrap and adapt to infusion tubes 61 of different diameters. The plug seat 17 can also have a cut 171 extending from the infusion hole 16 to the top edge of the plug seat 17, allowing the user to press the infusion tube 61 into the infusion hole 16 through the cut 171 when passing the infusion tube 61 through the infusion hole 16, facilitating the installation of the infusion tube 61. The plug seat 17 also has a first connector 172, a second connector 173, a third connector 174, an air inlet hole 175 and a relief valve 176. The first connector 172, the second connector 173 and the third connector 174 respectively penetrate the plug seat 17 and extend to the culture chamber 14 and the external space. The air inlet hole 175 penetrates the plug seat 17. Preferably, the air inlet hole 175 has a connector for facilitating the connection of a pipe body, allowing external gas to flow into the culture chamber through the pipe body via the air inlet hole. The relief valve 176 is connected to the culture chamber 14 and the external space and can release air to the external space when the air pressure in the culture chamber 14 rises, discharging the excess gas. The positions of the above-mentioned plug seat 17 and infusion hole 16, as well as the positions of the first connector 172, the second connector 173, the third connector 174, the air inlet hole 175 and the relief valve 176 are only one of the specific embodiments of the present invention. If the plug seat 17 is arranged at any edge, middle or center of the bottom wall 11, the side wall 12 or the top cover 13, or the plug seat 17 is omitted and the infusion hole 16, the first connector 172, the second connector 173, the third connector 174, the air inlet hole 175 and the relief valve 176 are directly formed on the bottom wall 11, the side wall 12 or the top cover 13, it is all feasible.

[0023] The base 20 is accommodated in the culture chamber 14 for holding the cell culture bag 90 and driving the cell culture bag 90 to shake. Specifically, referring to FIGS. 1 and 3, the base 20

[0024] It includes a shaking base 21 and a stage. The shaking base 21 has a base 211, one or more driving rods 212 and a pedestal 213. The bottom ends of the driving rods 212 are arranged on the base 211, and the top ends are arranged on the pedestal 213. Moreover, the base 211 can drive each driving rod 212 to move up and down respectively, so that the pedestal 213 is partially jacked up by the driving rods 212 and tilts and shakes. The stage includes a disk body 221 and a partition 222. The disk body 221 is arranged on the pedestal 213 and shakes together with the pedestal. The partition 222 is placed on the disk body 221, so that there is a containing space between the partition 222 and the disk body 221. The partition 222 has a plurality of openings, so that the containing space below the partition 222 communicates with other spaces in the culture chamber 14 through the openings.

[0025] The temperature control module is at least partially located in the culture chamber 14 and can detect and control the temperature of the culture chamber 14. Specifically, the temperature control module includes a plurality of heaters 31 and a plurality of temperature sensors 32. The heaters 31 and the temperature sensors 32 are respectively arranged on the inner surface of the side wall 12 and are electrically connected to the first connector 172 for the control module 70 located outside the culture chamber 14 to connect and control. The temperature sensors 32 sense the temperature of the culture chamber 14, and the heaters 31 can be driven to turn on for heating or stop heating to maintain the temperature of the culture chamber 14 close to the target temperature suitable for cell culture, for example, 37°C. It should be mentioned that since the target temperature suitable for cell culture is usually higher than the room temperature, the temperature control module usually only needs to be controlled to turn on or stop heating the culture chamber 14 to achieve the purpose of controlling the temperature of the culture chamber 14. However, depending on the temperature requirements of the culture chamber, the temperature control module may also separately include a cooler or include both a cooler and a heater at the same time.

[0026] The carbon dioxide module includes a plurality of carbon dioxide sensors 41, which are arranged on the inner surface of the side wall 12 and are electrically connected to the second connector 173. The carbon dioxide sensors are, for example, infrared spectroscopy carbon dioxide sensors, which can sense the surrounding environment, that is, the carbon dioxide concentration in the culture chamber 14 and output an electrical signal.

[0027] The carbon dioxide supply source can be controlled to supply carbon dioxide to the culture chamber 14. Specifically, the carbon dioxide supply source includes a gas cylinder connector 51, a control valve 52 and a gas supply pipe 53. The gas cylinder connector 51 can be connected to a carbon dioxide high-pressure gas cylinder 91 to receive carbon dioxide from the carbon dioxide high-pressure gas cylinder. The control valve 52 is connected to the gas cylinder connector 51 and one end of the gas supply pipe 53, and can be controlled to open and close and adjust the gas flow rate supplied from the gas cylinder connector 51 to the gas supply pipe 53. The other end of the gas supply pipe 53 is connected to the air inlet hole 175.

[0028] The infusion source can be controlled to supply the culture solution to the cell culture bag in the culture chamber 14. Specifically, the infusion source includes an infusion tube 61, a storage tank 62, and an infusion pump 63. One end of the infusion tube 61 extends into the culture chamber 14 through the infusion hole 16 and is connected to the cell culture bag 90, and the other end is connected to the infusion pump 63. The infusion pump is connected to the storage tank 62 and can be controlled to open and close and adjust the liquid flow rate supplied from the storage tank 62 to the infusion tube 61. The storage tank 62 is for storing the culture solution used for cell culture. Preferably, the storage tank 62 has a heat-insulating foam sandwich or a vacuum sandwich, and a refrigeration device is provided in the storage tank 62, such as a refrigerant-phase change refrigeration device or a thermoelectric refrigeration chip device, so that the temperature suitable for storing the culture solution can be maintained in the storage tank 62, such as 4°C.

[0029] The control module 70 is, for example, a programmable system-on-chip, which can be pre-programmed to perform the following control independently, or can be connected to a computer to obtain instructions and then further perform the control. The control module 70 is connected to the first connector 172 and can measure the temperature of the culture chamber 14 via the first connector 172 and the temperature sensor 32, so as to control the opening and closing of the heater 31 via the first connector 172, making the temperature of the culture chamber 14 approach the target temperature suitable for cell culture, such as 37°C. The control module 70 is connected to the second connector 173 and the control valve 52, and can measure the carbon dioxide concentration in the culture chamber 14 via the second connector 173 and the carbon dioxide sensor 41, so as to control the carbon dioxide flow rate flowing into the culture chamber 14 from the gas supply pipe 53 and the gas injection hole 175 via the control valve 52, making the carbon dioxide concentration in the culture chamber 14 approach the carbon dioxide concentration suitable for cell culture, such as a volume concentration of 5%. The control module 70 is connected to the infusion pump 63 and can control the flow rate of the culture solution supplied to the infusion tube 61 and the cell culture bag 90 via the infusion pump 63. The supply flow rate can be set by a program, such as supplying a fixed amount at a fixed time or giving a specified flow rate according to the time elapsed after the start of cell culture. The control module 70 can be further connected to the third connector 174, and the third connector 174 is connected to the base 20 to supply power to the shaking seat 21 and control the opening and closing, shaking frequency, and shaking amplitude of the shaking seat 21. However, if the third connector is omitted and the shaking seat 21 is driven by a built-in battery, it is also acceptable.

[0030] When using the above-mentioned automated cell culture device, when the user wants to perform cell culture, the components can be pre-configured. First, store the culture solution in the storage tank 62, connect the gas cylinder connector 51 to the carbon dioxide high-pressure gas cylinder 91, and pour water into the disk body of the base. The cell culture bag 90 to be used for cell culture can be connected to the infusion tube 61 and then placed into the culture chamber 14, and the cell culture bag 90 is placed on the partition plate. The partition plate can separate the cell culture bag 90 above from the water below. The infusion tube 61 can be pressed into the infusion hole through the notch of the plug seat 17, and then the observation plate 15 and the top cover 13 can be covered to complete the installation.

[0031] During the process of performing cell culture, the control module can control the flow rate of the culture medium and the flow rate of carbon dioxide. The water in the base disk can evaporate and be dispersed into the culture chamber through the openings in the partition, so as to keep the temperature, humidity and carbon dioxide concentration in the culture chamber constant. Among them, in order to avoid the phenomenon of local non-uniformity of temperature, humidity and carbon dioxide concentration in the culture chamber, a fan can also be added in the culture chamber to make the environment in the culture chamber uniform; and in order to record the environmental conditions during the cell culture process, a humidity sensor can also be set in the culture chamber and electrically connected to the control device 70 through a connector for the control device to detect the humidity value in the culture chamber.

[0032] When setting up the above-mentioned automated cell culture device, since the main body, the carbon dioxide supply source and the infusion source are separately set, the user can also use the storage tank of the same infusion source and the same carbon dioxide high-pressure gas cylinder to add multiple sets of infusion pumps, infusion tubes, control valves and gas supply tubes, connect multiple sets of main bodies for use, modularize the configuration of the main bodies, stack and store them, which has the characteristics of simple structure, low setting cost and high space utilization rate.

[0033] Secondly, the main body structure of the automated cell culture device of the present invention is simple, which is convenient for installation and setting, and at the same time is easy to be repeatedly disinfected and used, and has the characteristics of easy operation.

[0034] In the above embodiment, the control device has a separate housing, which can facilitate the control of multiple sets of infusion pumps, control valves and the main body by a single controller. Please refer to Figure 4. In another embodiment of the present invention, the control device 70 can also be combined and fixed to the main body 10, and a control device 70 is used in cooperation with a main body 10, or a control device 70 is used in cooperation with its main body 10 and other main bodies without a control device, and it still has the above similar usage modes and characteristics.

[0035] In summary, the automated cell culture device of the present invention modularizes each component and simplifies the structure, making the automated cell culture device easy to use, move, quickly configure, reduce costs, and further reduce costs by stacking and storing, which can improve the space utilization rate.

Claims

1. An automated cell culture device for placing a cell culture bag and performing cell culture, characterized in that, Comprising: A main body having a culture chamber and an infusion hole. The infusion hole communicates with the culture chamber and the external space. When the cell culture bag is placed in the culture chamber, an infusion tube can be connected between an infusion source outside the main body and the cell culture bag in the culture chamber via the infusion hole; and A temperature control module including a heater and a temperature sensor. The temperature control module can sense the temperature of the culture chamber and selectively heat the culture chamber. The main body has a first connector, and the heater and the temperature sensor are electrically connected to the first connector, and the first connector is exposed outside from the surface of the main body; Wherein, the main body has a plug seat extending from the culture chamber to the external space, the infusion hole penetrates and is formed in the plug seat, and the first connector is arranged on the plug seat; Wherein, at the top edge of the side wall of the main body, there is a notch penetrating the inner and outer surfaces. The plug seat is arranged in the notch, so that the plug seat extends from the culture chamber to the external space and penetrates the inner and outer surfaces of the side wall. The infusion hole is formed in the plug seat and penetrates the plug seat. The plug seat can also have a cut extending from the infusion hole to the top edge of the plug seat. The plug seat also has a first connector, a second connector, a third connector, an air inlet hole and a relief valve. The first connector, the second connector and the third connector respectively pass through the plug seat and extend to the culture chamber and the external space, and the air inlet hole passes through the plug seat.

2. The automated cell culture device according to claim 1, wherein: It further comprises a base accommodated in the culture chamber. The base includes a shaking seat and a carrier. The shaking seat can drive the carrier to shake, and the cell culture bag can be placed on the carrier.

3. The automated cell culture device according to claim 2, characterized in that: The carrier includes a disc body and a partition. The disc body is for holding water, and the partition is for holding the cell culture bag. The partition is placed on the disc body to separate the water held in the disc body from the cell culture bag. The partition has a plurality of openings for the water held in the disc body to evaporate and disperse into the culture chamber.

4. The automated cell culture device according to any one of claims 1 to 3, characterized in that: It further comprises a carbon dioxide module including a carbon dioxide sensor located in the culture chamber. The carbon dioxide sensor is electrically connected to the second connector, and the second connector is exposed outside from the surface of the main body. The air inlet hole communicates with the culture chamber and the external space for connecting a carbon dioxide supply source outside the main body.

5. The automated cell culture device according to any one of claims 1 to 3, characterized in that: It further comprises a control module. The first connector is electrically connected to the control module. The control module measures the temperature of the culture chamber through the temperature sensor, and the control module controls the opening and closing of the heater so that the temperature of the culture chamber approaches 37 °C.

6. The automated cell culture device according to claim 4, wherein: It further comprises a control module. The second connector is electrically connected to the control module. The control module measures the carbon dioxide concentration in the culture chamber through the carbon dioxide module, and the control module controls the carbon dioxide supply source to supply carbon dioxide to the culture chamber through the air inlet hole, so that the volume concentration of carbon dioxide in the culture chamber approaches 5%.

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