TW202144561A - Automatic cell culture device - Google Patents

Abstract

The present invention reveals an automatic cell culture device, including a main body. The main body has a cultivating room and an infusion hole communicating between the cultivating room and the outer space. Users can put a cell cultivating bag in the cultivating room, connecting an infusion tube connected to the cell cultivating bag to an liquid source which provides the liquid for cell cultivation. The liquid source is deployed apart from the main body. Therefore, the structure and composition of the automatic cell culture device is simplified. Miniaturization and modularity may be applied to the cell culture device for location shifting, rapid deployment, cost management, and replication.

Description

Automated cell culture device

This creation is about a cell culture device.

In recent years, affected 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, and cell therapy.

Existing cell culture devices, for example, can refer to the description of the patent No. TWI670370, which is mainly a large-scale incubator with a thermal insulation wall. The medium is maintained at 4°C, the culture tank is maintained at 37°C for cell culture, and multiple culture containers are stored in a multi-layered shelf, and the measurement unit such as a camera is guided by a column to move and observe the cells in each culture container. Cultivate the situation to achieve automation and large-scale production.

Although the cell culture device of the aforementioned TWI670370 patent can provide large-scale production, however, the cell culture device is large in scale, and the left and right separated cold storage tanks and culture tanks need to be maintained at different temperatures, and further refrigeration equipment needs to be installed. It will make the overall equipment of the cell culture device larger, which cannot be purchased by non-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 in the culture tank, users need to pay more attention to whether the culture containers interfere with and contaminate each other when culturing cells. The constant internal environment of the culture tank, and whether the scaffolding will hinder the disinfection and maintenance of the sterile environment, are inconvenient in actual operation and use.

In contrast to this, another cell incubator described in Patent No. TWI567190 is a cell incubator with a thermal insulation wall that separates a refrigerator room, a culture room and a pump room, and places a culture medium, a culture bag and a peristaltic aid respectively. The Pu module integrates the main equipment required for cell culture into a single box-shaped device, featuring miniaturization, rapid configuration and easy movement. However, the cell incubator described in Patent No. TWI567190 also has both a cold room and a culture room, and needs to maintain different temperatures in the box. Even if a vacuum insulation panel is installed, it is still affected by the natural flow of heat and consumes energy. To maintain the low temperature of the cold room, the cell incubator still needs to be equipped with refrigeration equipment, so that the volume of the cell incubator is not easy to be further reduced, which is not conducive to the replication and stacking mass production, and it is difficult to improve the space utilization rate.

In view of this, one of the objectives of the present invention is to provide a cell culture device, in which the components in the device are modularized and miniaturized, so as to improve the space utilization during cell culture.

This creation provides an automated cell culture device for inserting a cell culture bag and performing cell culture. The automated cell culture device includes a body, the body has a culture chamber and an infusion hole, and the infusion hole is connected to the culture chamber and the external space for cell culture. When the bag is placed in the culture room, the infusion tube can be connected between the infusion source outside the body and the cell culture bag in the culture room through the infusion hole.

The above-mentioned automated cell culture device can further include a base, the base 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 placed on the cell culture bag.

In the above-mentioned automated cell culture device, the carrier can include a plate body and a partition, the plate body is used for holding water, the partition plate is used for holding cell culture bags, and the partition frame is placed on the plate body to separate the water contained in the plate body. As with the cell culture bag, the separator has several openings for the water contained in the tray to evaporate and spread in the culture chamber.

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

The above-mentioned automated cell culture device can further include a carbon dioxide module, the carbon dioxide module includes a carbon dioxide sensor, the carbon dioxide sensor is located in the culture chamber, the body has a second connector and a gas transmission hole, and the carbon dioxide sensor is electrically connected to the second. the connector, the second connector is exposed from the surface of the main body, and the gas transmission hole is connected with the culture chamber and the external space, so as to connect the carbon dioxide supply source outside the main body.

In the above-mentioned automated cell culture device, the main body can further have a plug seat, the plug seat 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 arranged in the plug seat. seat.

The above-mentioned automated cell culture device can further include a control module, the first connector is electrically connected to the control module, and the control module detects the temperature of the culture chamber through a temperature sensor, and controls the opening and closing of the heater to make the temperature of the culture chamber. The temperature approached 37°C. Secondly, the second connector is electrically connected to the control module, the control module detects the carbon dioxide concentration in the cultivation chamber through the carbon dioxide module, and controls the carbon dioxide supply source to supply carbon dioxide to the cultivation chamber through the gas transmission hole, so that the carbon dioxide in the cultivation chamber is The carbon dioxide volume concentration approaches 5%.

Using the above device, the automated cell culture device can be placed in a cell culture bag for cell culture, and can receive external supply for the culture medium. The thermal insulation environment and refrigeration equipment required for storing the culture medium do not need to be attached to the culture chamber of the automated cell culture device. It can avoid the mutual interference between the low temperature required for storing the culture solution and the high temperature of the culture room, and maintain the constant cell culture environment. Move, configure quickly, reduce setup costs and improve space utilization.

Please refer to FIG. 1. This creation provides an automated cell culture device, which can be inserted 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, Infusion source and control module 70 .

The main body 10 is a box or box-shaped container, including a bottom wall 11, a side wall 12 and a top cover 13. The side wall 12 extends upward from the periphery of the bottom wall 11, and the top cover 13 can be pivotally opened and closed on the side wall 12. A culture chamber 14 is formed between the wall 11, the side wall 12 and the top cover 13, which can be put into the cell culture bag 90 for cell culture. The bottom wall 11, the side wall 12 and the top cover 13 each have a thermal insulation interlayer. The bottom wall 11, the side wall 12 and the top cover 13 are, for example, a multi-layer structure with an inner layer of stainless steel plate, an outer layer of stainless steel plate, and an insulating foam interlayer or a vacuum interlayer between the inner layer and the outer layer, so that the culture chamber has thermal insulation, In terms of thermal insulation capability, preferably, the thermal insulation interlayers in the bottom wall 11 and the side wall 12 are connected to each other as a whole, which can have better thermal insulation and thermal insulation capabilities. The main body 10 also has an observation plate 15. The observation plate 15 is, for example, a transparent plate such as glass or acrylic, which can be pivotally opened and closed on the side wall 12, and is located under the top cover 13, and can be kept when the user opens the top cover 13. The cover is closed on the cultivation chamber 14 for the user to observe the situation in the cultivation chamber 14 and keep the environment in the cultivation chamber 14 stable. The above-mentioned bottom wall 11, side wall 12, top cover 13 and observation plate 15 are the specific implementations of the upper opening and closing. It is also possible to open or close the side of the door format, and change the observation plate 15 to the inside of the side wall.

The body also has an infusion hole 16, the infusion hole 16 is communicated with the culture chamber 14 and the external space, and the infusion tube 61 for conveying the culture fluid can penetrate the culture chamber 14 through the infusion hole 16 and be connected to the culture chamber 14. The culture medium is supplied to the cell culture bag 90. Specifically, please refer to Fig. 1 and Fig. 2. The main body additionally has a plug seat 17, and the top edge of the side wall 12 has a notch penetrating the inner and outer surfaces. The plug seat 17 is arranged in the recess. 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, so that the infusion tube 61 can pass into the culture chamber 14 through the infusion hole 16. Preferably, the plug seat 17 can be partially or completely made of soft plastic or rubber and has elasticity, and a number of slits 161 are arranged around the infusion hole 16, so that the plug seat 17 can be squeezed and deformed in a small amount to wrap the infusion hole 16. The plug base 17 can also have a cutout 171, which extends from the infusion hole 16 to the top edge of the plug base 17 for the user to pass the infusion tube 61 through the infusion hole 16. , the infusion tube 61 can be pressed into the infusion hole 16 through the incision 171 to facilitate 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 , a gas delivery hole 175 and a vent valve 176 , the first connector 172 , the second connector 173 and the third connector 174 Pass through the plug base 17 and extend to the culture chamber 14 and the external space, respectively, and the gas transmission hole 175 passes through the plug base 17. Preferably, the gas transmission hole 175 has a joint to facilitate the connection of the pipe body and allow the external gas to pass through the pipe body. The gas flows into the culture chamber through the air supply hole, and the air vent valve 176 is connected to the culture chamber 14 and the external space, and can vent air to the external space when the air pressure in the culture chamber 14 rises to discharge excess gas. The above-mentioned positions of the plug seat 17 and the infusion hole 16, as well as the positions of the first connector 172, the second connector 173, the third connector 174, the air infusion hole 175 and the air release valve 176 are only one of the specific embodiments of the present creation. If the plug seat 17 is changed to 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, the infusion hole 16, the first connector 172, the second It is feasible that the connector 173 , the third connector 174 , the air delivery hole 175 and the air release valve 176 are directly formed on the bottom wall 11 , the side wall 12 or the top cover 13 .

The base 20 is accommodated in the culture chamber 14 for containing the cell culture bag 90 and driving the cell culture bag 90 to shake. Specifically, please refer to FIG. 1 and FIG. 3, the base 20

The rocking base 21 includes a base 211, one to several driving rods 212 and a base 213. The bottom end of the driving rod 212 is set on the base 211, and the top is set on the base 213, and the base 211 can drive the Each driving rod 212 moves up and down, so that the pedestal 213 is partially lifted by the driving rod 212 to tilt and shake. The carrier includes a plate body 221 and a partition plate 222. The plate body 221 is arranged on the pedestal 213 and shakes together with the pedestal plate. The partition plate 222 has a plurality of openings, so that the accommodating space under the partition plate 222 is communicated with other spaces in the culture chamber 14 through the openings.

The temperature control module is at least partially located in the cultivation chamber 14, and can detect and control the temperature of the cultivation 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 The devices 32 are respectively disposed on the inner surface of the side wall 12, and are electrically connected to the first connector 172 for connection and control of the control module 70 located outside the cultivation chamber 14. The temperature sensor 32 senses the temperature of the cultivation chamber 14, The heater 31 can be driven to start heating or stop heating, so as to maintain the temperature of the culture chamber 14 close to a target temperature suitable for cell culture, such as 37°C. It should be mentioned that, since the target temperature suitable for cell culture is usually higher than 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 room, the temperature control module may also include a cooler alone or both a cooler and a heater.

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 concentration in the incubation chamber 14 and output an electrical signal.

The carbon dioxide supply source can be controlled to provide carbon dioxide to the culturing 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 the carbon dioxide high-pressure gas cylinder 91, and automatically The carbon dioxide high-pressure gas cylinder receives carbon dioxide, and the control valve 52 is connected to one end of the gas cylinder connector 51 and 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 is connected to the gas transmission hole 175 .

The infusion source can be controlled to provide culture liquid 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 through the infusion hole 16. 14 and connected to the cell culture bag 90, the other end is connected to the infusion pump 63, the infusion pump is connected to the preservation tank 62, can be controlled to open and close and adjust the liquid flow supplied from the preservation tank 62 to the infusion pipe 61, the preservation tank 62 For storing the culture medium used for cell culture, preferably, the storage tank 62 has an insulating foam interlayer or a vacuum interlayer, and the storage tank 62 has a refrigeration device, such as a refrigerant-phase change refrigeration device or a thermoelectric cooling chip A type of refrigeration equipment can be used to keep the temperature in the preservation tank 62 at a temperature suitable for preserving the culture solution, for example, 4°C.

The control module 70 is, for example, a programmable system-on-chip, which can be pre-set with a program to independently execute the control described later, or can be connected to a computer to obtain instructions to further execute the control. The control module 70 is connected to the first connector 172 , and can detect the temperature of the culture chamber 14 through the first connector 172 and the temperature sensor 32 , so as to control the opening and closing of the heater 31 through the first connector 172 to make the culture chamber The temperature of 14 approaches the target temperature suitable for cell culture, eg 37°C. The control module 70 is connected to the second connector 173 and the control valve 52 , and can detect the carbon dioxide concentration in the culture chamber 14 through the second connector 173 and the carbon dioxide sensor 41 , so as to control the flow from the gas supply pipe 53 to the control valve 52 through the control valve 52 . The gas supply hole 175 flows into the carbon dioxide flow in the culture chamber 14, so that the carbon dioxide concentration in the culture chamber 14 is close to the carbon dioxide concentration suitable for cell culture, eg, 5% by volume. The control module 70 is connected to the infusion pump 63, and can control the flow rate of the culture liquid supplied to the infusion tube 61 and the cell culture bag 90 through the infusion pump 63, and can set the supply flow rate through a program, such as regular quantitative supply or according to the start of cell culture. The length of time elapsed to give the specified flow. 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 rocking base 21 and control the opening and closing of the rocking base 21 as well as the shaking frequency and the shaking amplitude, unless the third connector 174 is omitted. Connector, it is also possible to change the shaking seat 21 to be driven by a built-in battery.

Using the above-mentioned automated cell culture apparatus, when the user wants to perform cell culture, he can pre-arrange various components, 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 connect it to the tray of the base. The body is poured into water, the cell culture bag 90 to be cultured can be connected to the infusion tube 61 and placed in the culture chamber 14, and the cell culture bag 90 can be placed on the partition plate, which can connect the cell culture bag 90 above with the cell culture bag 90. The water below is separated, and the infusion tube 61 can be pressed into the infusion hole through the incision of the plug base 17, and the observation plate 15 and the top cover 13 can be covered to complete the installation.

During the process of cell culture, the flow rate of culture fluid and carbon dioxide can be controlled by the control module, and the water in the base plate can evaporate and spread into the culture room through the openings of the partition, so that the temperature, humidity and The carbon dioxide concentration remains constant. Among them, in order to avoid the phenomenon of local uneven temperature, humidity and carbon dioxide concentration in the culture room, a fan can also be added in the culture room to promote the uniformity of the environment in the culture room; and in order to record the environmental conditions during the cell culture process, also A humidity sensor can be arranged in the culture chamber, and is further electrically connected to the control device 70 through a connector, so that the control device can measure the humidity value in the culture chamber.

When the above automatic cell culture device is set up, since the body, carbon dioxide supply source and infusion source are set separately, the user can also add multiple sets of infusion pumps, infusion tubes, and control valves using the same infusion source storage tank and the same carbon dioxide high-pressure gas cylinder. And the air supply pipe, connected to multiple groups of bodies for use, the body is modularly configured, stacked and stored, which has the characteristics of simplified structure, low installation cost and high space utilization.

Secondly, the main body structure of the automatic cell culture device of this creation is simple, which is convenient for installation and setting, and is also easy to be repeatedly sterilized and used, and has the characteristics of easy operation.

In the above-mentioned embodiment, the control device has a separate casing, which can facilitate the use of a single controller to control multiple sets of infusion pumps, control valves and main bodies. Please refer to FIG. 4. In another embodiment of the present invention, it is also possible to use Instead, the control device 70 is combined and fixed to the main body 10, and a control device 70 is used in conjunction with a main body 10, or a control device 70 is used in conjunction with its main body 10 and other main bodies without a control device, and the above-mentioned similar usage methods and Features

To sum up, the automated cell culture device of this creation modulates each component and simplifies the structure, so that the automated cell culture device is easy to use, move, quickly configure, and reduce costs. Space utilization and further cost reduction are the expectations of medical research and medical-related industries. However, the above embodiments are only intended to illustrate and describe the technical content of this creation.

10: Ontology 11: Bottom wall 12: Sidewall 13: Top cover 14: Cultivation room 15: Observation board 16: Infusion hole 17: Plug seat 171: Cut 172: first connector 173: Second connector 174: Third connector 175: air hole 176: Bleed valve 20: base 21: Shake the seat 211: Pedestal 212: Drive rod 213: Pedestal 221: plate body 222: Separator 31: Heater 32: temperature sensor 41: Carbon dioxide sensor 51: Gas cylinder connector 52: Control valve 53: Air supply pipe 61: Infusion tube 62: Preservation Jar 63: Infusion pump 70: Control Module 90: Cell Culture Bag 91: Carbon dioxide high pressure cylinder

FIG. 1 is a schematic diagram of the creation of an automated cell culture device. FIG. 2 is a schematic diagram of a plug seat in the creation of an automated cell culture device. FIG. 3 is an exploded perspective view of a base in the creation of an automated cell culture device. FIG. 4 is a schematic diagram of another embodiment of creating an automated cell culture apparatus.

10: Ontology

11: Bottom wall

12: Sidewall

13: Top cover

14: Cultivation room

15: Observation board

16: Infusion hole

17: Plug seat

20: base

31: Heater

32: temperature sensor

41: Carbon dioxide sensor

51: Gas cylinder connector

52: Control valve

53: Air supply pipe

61: Infusion tube

62: Preservation Jar

63: Infusion pump

70: Control Module

90: cell culture bag

91: Carbon dioxide high pressure cylinder

Claims (10)

An automated cell culture device for placing in a cell culture bag and performing cell culture, comprising: a body, the body has a culture chamber and an infusion hole, the infusion hole communicates with 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 to the infusion hole through the infusion hole between an infusion source outside the body and the cell culture bag in the culture chamber. The automated cell culture device according to claim 1, further comprising a base, the base is accommodated in the culture chamber, the base comprises a shaking seat and a stage, the shaking seat can drive the stage to shake, the stage on which the cell culture bag is placed. The automated cell culture device according to claim 2, wherein the carrier comprises a tray and a partition, the tray is used for holding water, the partition is used for holding the cell culture bag, and the partition is placed on the The plate body is used to separate the water contained in the plate body from the cell culture bag, and the separator has a plurality of openings for the water contained in the plate body to evaporate and spread in the culture chamber. The automated cell culture device according to claim 1, further comprising a temperature control module, the temperature control module comprising a heater and a temperature sensor, the temperature control module can sense the temperature of the culture chamber and The culture chamber is selectively heated, the body has a first connector, the heater and the temperature sensor are electrically connected to the first connector, and the first connector is exposed from the surface of the body. The automated cell culture device according to claim 4, wherein the body has a plug seat, the plug seat extends from the culture chamber to an external space, the infusion hole penetrates and is formed in the plug seat, and the first connector is disposed on the the plug seat. The automated cell culture device according to any one of claims 1 to 4, further comprising a carbon dioxide module, the carbon dioxide module comprising a carbon dioxide sensor, the carbon dioxide sensor being located in the culture chamber, and the body having a first Two connectors and a gas delivery hole, the carbon dioxide sensor is electrically connected to the second connector, the second connector is exposed from the surface of the body, the gas delivery hole communicates with the culture chamber and the external space, so as to For connection to a carbon dioxide supply source outside the body. The automated cell culture device of claim 5, further comprising a carbon dioxide module, the carbon dioxide module comprising a carbon dioxide sensor, the carbon dioxide sensor being located in the culture chamber, the body having a second connector and an input a gas hole, the carbon dioxide sensor is electrically connected to the second connector, the second connector is exposed from the surface of the main body, and the gas transmission hole is communicated with the culture chamber and the external space for a Carbon dioxide supply source connection. The automated cell culture device according to claim 7, wherein the second connector is disposed on the plug seat. The automated cell culture device according to any one of claims 1 to 5, further comprising a control module, the first connector is electrically connected to the control module, and the control module is detected by the temperature sensor For the temperature of the culture chamber, the control module controls the heater to turn on and off so that the temperature of the culture chamber approaches 37°C. The automated cell culture device according to claim 7 or 8, further comprising a control module, the second connector is electrically connected to the control module, and the control module detects through the carbon dioxide module the amount of cells in the culture chamber For the carbon dioxide concentration, the control module controls the carbon dioxide supply source to supply carbon dioxide to the cultivation chamber through the gas supply hole, so that the volume concentration of carbon dioxide in the cultivation chamber is close to 5%.

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