TWM625568U - cell culture system - Google Patents

Abstract

The present invention provides a cell culture system, which includes a culture part and a circulation part. This new type of The culture part includes at least two reaction parts connected in parallel with each other as the culture site, which avoids the risk of contamination in the process of cell transfer, and is conducive to realizing large-scale cell culture by adjusting the number of the reaction parts; the circulation part and each The reaction parts are connected in parallel, so that different circulation control passages are formed between the circulation part and each of the reaction parts, so that the flow medium of different reaction parts is collected in the circulation part and then divided into each of the reaction parts, so that The seed cells in each of the reaction parts can be cultured under the same culture conditions, thereby ensuring the uniformity of the state of the target cells obtained in each of the reaction parts.

Description

cell culture system

The present invention relates to the field of biotechnology, in particular to a cell culture system.

Compared with static cell culture, in the process of dynamic cell culture, since the nutrient solution can continuously supply and recover metabolites, it avoids that the cells cannot obtain favorable growth space and obtain sufficient substances due to local cell density during the dynamic culture process. The problem of easy death due to exchange improves the utilization rate of the nutrient solution, enables the cells to be cultured in space for a long time, and is beneficial to improve the activity and function of the cells.

At present, various types of cells, such as normal hepatocytes for dialysis exchange, are in great demand for clinical applications, so it is necessary to carry out cell culture on a large scale, while improving the state uniformity of the harvested target cells to ensure the effect of treatment .

Patent Application Publication No. WO2020094809A1 discloses a method for culturing cells on a large scale. By setting cell culture chambers of different volumes, cells are gradually transferred and cultured from a small-volume culture chamber to a large-volume culture chamber. However, this culture method is cumbersome to operate, and because of the multiple cell transfer processes, it is very easy to contact with the external environment to contaminate the cell culture.

Therefore, it is necessary to develop a new cell culture system to solve the above problems existing in the prior art.

The purpose of the present invention is to provide a cell culture system that facilitates large-scale cell culture and avoids the risk of contamination due to cell transfer, while improving the state uniformity of the harvested target cells.

In order to achieve the above-mentioned purpose, the cell culture system of the present invention comprises at least two reaction parts connected in parallel with each other, so as to provide a culture place required for seed cells to carry out cell culture; the circulation part is connected in parallel with each of the reaction parts, so that the circulation part is Different circulation control passages are formed between the reaction part and each of the reaction parts, so that the flow medium of different reaction parts is collected in the circulation part and then divided into each of the reaction parts.

The beneficial effect of the cell culture system of the present invention is that: the cell culture system includes at least two reaction parts connected in parallel with each other as the culture site, which avoids the risk of contamination in the process of cell transfer, and facilitates adjusting the number of reaction parts by adjusting the number of reaction parts. Realize large-scale cell culture; further, the circulation part is connected in parallel with each of the reaction parts, so that different circulation control paths are formed between the circulation part and each of the reaction parts, so as to facilitate the flow medium of different reaction parts After being collected in the circulation part and then distributed to each reaction part, the seed cells in each reaction part can be cultured under the same culture conditions, thus ensuring the state uniformity of the target cells obtained by each reaction part.

Preferably, the circulation part is provided with a stirring part to drive the flowing medium in the circulation part to mix uniformly. The beneficial effect is that the seed cells in each reaction part can be cultured under the same culture condition.

Further preferably, it also includes a parameter monitoring part arranged in the circulation part, so as to obtain the reaction state parameters of the reaction part through the circulation part. The beneficial effect is that it is beneficial to monitor the cultivation situation online without disturbing the cultivation state of the reaction part.

Further preferably, the reaction state parameters include at least one of temperature data, pressure data, flow rate data, pH value data, liquid level metadata, metabolite content data and dissolved oxygen data.

Further preferably, it also includes a cell detection part arranged in at least one of the reaction parts to acquire cell state parameters. The beneficial effect is that it is beneficial to determine the time when the cell culture ends by the state of the cells in the reaction part.

Further preferably, the culturing part includes a liquid supply part, and the liquid supply part is connected with the circulation part and at least one of each of the reaction parts to provide liquid nutrients. The beneficial effect is: compared with the liquid nutrients directly entering each reaction part from the liquid supply part, the liquid nutrients can pass through the circulation part and then enter different reaction parts through different circulation control passages, which is beneficial to further ensure the liquid nutrients of mixing evenly.

Further preferably, the culturing part includes an air supply part, and the air supply part is connected to each of the reaction parts to provide gaseous nutrients. The beneficial effect of the invention lies in: providing the necessary nutrients for the exchange of gaseous substances for cells in different reaction parts.

Further preferably, each of the reaction parts includes an elastic cavity, and the culture part further includes a lift drive part acting on each of the elastic cavity to drive the flowing medium in each of the elastic cavity to move up and down. The beneficial effects of the invention are as follows: by regulating the exchange time between cells and liquid nutrients and gaseous nutrients, a good mass transfer process in the reaction part is controlled, which helps to improve the activity and function of the harvested target cells.

Further preferably, the culture part includes a waste liquid collection part, and the waste liquid collection part is connected to the circulation part and at least one of each of the reaction parts.

Further preferably, it also includes a temperature adjustment part, the temperature adjustment part covering at least one of the circulation part and each of the reaction parts to adjust the reaction temperature.

Preferably, it also includes a control part, which is connected to the circulation control passage, the stirring part, the parameter monitoring part, the cell detection part, the liquid supply part, the gas supply part, the lift drive part, and the waste liquid collection part. at least one of the part and the temperature regulation part, so as to according to the reaction state parameter and the cell state parameter At least one of them performs corresponding mode control. The beneficial effect is that it is beneficial to realize the automatic control of cell culture.

Further preferably, it also includes a storage unit connected to the control unit, and the storage unit stores cultivation mode information for the control unit to call and automatically perform the corresponding mode control.

Preferably, the culture part includes a metering display part arranged in the circulation part to assist in confirming the amount of the flowing medium in the circulation part. The beneficial effect is that it is beneficial to distribute the flow medium to different reaction parts according to the culture requirement.

13: Parameter Monitoring Department

14: Cell Detection Department

15: Measurement display part

110: Loop body

111: Main circulation outlet channel

112: Main circulation confluence path

113: Confluence Control Department

120: React Body

121: Sub liquid inlet channel

122: Sub-exit channel

123: Sub liquid inlet switch

124: Sub-inlet control department

21: Stirring part

22: Reaction Drive

31: storage cavity

32: Elastic cavity

410: Liquid supply body

411: Liquid supply channel

412: Liquid supply switch

413: Liquid Supply Control Department

420: Air supply main body

421: Air Supply Control Department

422: Air supply switch part

423: Air supply path

510: Waste liquid collection body

511: Waste liquid collection path

512: Waste liquid collection switch

Figure 1 is a schematic diagram of the structure of the cell culture system of the novel embodiment 1; Figure 2 is a schematic diagram of the structure of the cell culture system of the novel embodiment 2; Figure 3 is the assembly of the reaction driving part and several reaction bodies of the novel embodiment 3 Schematic diagram of the structure; FIG. 4 is a schematic diagram of the structure of the cell culture system of the novel embodiment 4; FIG. 5 is a schematic diagram of the structure of the cell culture system of the novel embodiment 5.

In order to make the purpose, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are part of the embodiments of the present invention, not all of them. example. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative work fall within the protection scope of the present invention. Unless otherwise defined, technical or scientific terms used herein shall have the ordinary meaning as understood by one of ordinary skill in the art to which this new invention belongs. The "packages" used in this article "Bracket" and similar words mean that the elements or things appearing before the word encompass the elements or things listed after the word and their equivalents, but do not exclude other elements or things.

Aiming at the problems existing in the prior art, the novel embodiment provides a cell culture system including a reaction part and a circulation part, so as to facilitate the realization of large-scale cell culture and ensure the uniformity of the state of the target cells obtained by each reaction part.

The cell culture system will be described in detail below through specific examples.

Example 1:

FIG. 1 is a schematic structural diagram of the cell culture system of the novel example 1. FIG.

In Embodiment 1 of the present invention, the culturing part is composed of at least two reaction parts connected in parallel with each other, so as to provide a culturing place for seed cells to carry out cell culture.

Specifically, the reaction part includes a reaction main body and a sub-regulation part connected in series by a sub-channel, and the sub-regulation part controls the flow rate or flow rate of the flowing medium entering the reaction main body.

More specifically, referring to FIG. 1 , the culture part (not shown in the figure) is composed of four reaction parts (not shown in the figure) connected in parallel with each other. The sub-liquid inlet switch part 123 and the sub-liquid inlet control part 124 constitute the sub-control part. The sub liquid inlet channel 121 and the sub liquid outlet channel 122 constitute a sub channel. The sub-liquid inlet switch part 123 and the sub-liquid inlet control part 124 are disposed in the sub-liquid inlet passage 121 , one end of the reaction main body 120 is connected to the sub-liquid inlet passage 121 , and the other end is connected to the sub-liquid outlet passage 122 .

The reaction body 120 can accommodate seed cells and nutrients for cell culture of the seed cells. In some specific embodiments of the present invention, the reaction main body 120 is a cell culture flask.

In some embodiments of the present invention, after the seed cells are loaded on the carrier, they are accommodated in the reaction body 120 . Specifically, the carrier is a slide. The seed cells are primary cells.

In some embodiments of the present invention, the seed cells are adherent cells, and are directly loaded on the bottom of the reaction body 120 or the inner wall near the bottom.

In some embodiments of the present invention, the cell type of the seed cells is hepatocytes or stem cells.

The sub-liquid inlet switch part 123 controls the conduction state of the sub-liquid inlet passage 121 . In some specific embodiments of the present invention, the sub-liquid inlet switch portion 123 is any one of a shut-off valve and an on-off valve.

The sub-feed control part 124 controls the flow rate or flow rate of the flow medium entering the reaction main body 120 . In some specific embodiments of the present invention, the sub-liquid inlet control part 124 is any one of a peristaltic pump and a metering pump.

In the first embodiment of the present invention, the circulation part is connected in parallel with each of the reaction parts. On the one hand, it is beneficial to realize large-scale cell culture by adjusting the number of reaction parts; Different circulation control channels are formed between the different reaction parts, so that the flow medium of different reaction parts can be collected in the circulation part and then shunted to each reaction part, so that the seed cells in each reaction part can be cultured under the same culture conditions. , thereby ensuring the uniformity of the state of the target cells obtained by each reaction part.

Specifically, the circulation portion includes a main circulation passage, a circulation main body and a confluence regulation portion arranged in series on the main circulation passage. A part of the main circulation path is connected to one end of each of the sub-regulation parts, and the other part is connected to the other end of each of the sub-regulation parts, so as to realize the parallel connection.

More specifically, referring to FIG. 1 , the main circulation liquid outlet passage 111 and the main circulation confluence passage 112 constitute the main circulation passage. The confluence control part 113 is arranged in the main circulation confluence passage 112 , one end of the circulation main body 110 is connected to the main circulation liquid outlet passage 111 , and is respectively connected to each of the sub liquid inlet passages 121 through the main circulation liquid outlet passage 111 , and the other end is connected to the main circulation liquid outlet passage 111 . The main circulation confluence passage 112 is connected to each of the sub-liquid outlet passages 122 respectively through the main circulation confluence passage 112 to realize the parallel connection.

The confluence regulating part 113 controls the flow rate or flow rate of the flowing medium entering the circulation body 110 . In some specific embodiments of the present invention, the confluence regulating portion 113 is any one of a shut-off valve and an on-off valve.

The culturing process using the cell culture system shown in FIG. 1 includes: controlling the flow medium in different reaction parts to flow into the circulation part through the circulation control passage, so as to complete the confluence process, so as to and controlling the flow medium in the circulation part to be divided into different reaction parts through the circulation control passage, so as to complete the division treatment.

Specifically, referring to FIG. 1 , in the initial state, the circulation body 110 contains several flow media, and each reaction body 120 contains adherent cells and an initial amount of flow media, and the adherent cells are loaded in each The inner wall of the reaction body 120 . Adjust the confluence control part 113 and each of the sub-liquid inlet switch parts 123 to make each circulation control passage (not marked in the figure) in a conducting state, and then control the circulation in the circulation main body 110 through each of the sub-liquid inlet control parts 124. The flowing medium enters each of the reaction bodies 120 at a certain flow rate or flow rate to complete the confluence process, and controls each of the reaction bodies 120 to flow into the circulation body 110 at a certain flow rate or flow rate to complete the split flow process.

In Embodiment 1 of the present invention, the circulation-controlled culture further includes: controlling the confluence processing and the shunt processing to be performed continuously through the circulation control passage.

Specifically, referring to FIG. 1 , the flow medium of each of the circulation control passages continuously flows through the control of the confluence regulation portion 113 and each of the sub-liquid inlet regulation portions 124 .

In the first embodiment of the present invention, in the process of the confluence treatment and the split treatment, the amount of the flowing medium in the different reaction parts is controlled by the circulation control channel to be consistent with the corresponding initial amount, which is beneficial to the same batch.

Specifically, the continuous flow of the flow medium is carried out through the control of the confluence control part 113 and each of the sub-feed control parts 124, so that the flow rate of the flow medium shunted into the single reaction part is the same as the flow rate of the flow medium flowing out from the single reaction part. The flow rate of the flow medium is consistent, and the amount of the flow medium in each reaction body 120 is consistent with the corresponding initial amount. The amount of the flow medium refers to either the quality or the volume of the flow medium.

In some embodiments of the present invention, each of the reaction bodies 120 has the same volume, and the quality of the seed cells contained in each of the reaction bodies 120 is the same. While the continuous flow of the flow medium is controlled by the control method, the volume or quality of the flow medium in each of the reaction bodies 120 is the same.

In some embodiments of the present invention, the flow medium is a liquid nutrient required for cell culture of the seed cells. Specifically, the cell culture includes primary culture, expansion culture or differentiation culture, and the corresponding liquid nutrients are the common knowledge of those skilled in the art.

In the first embodiment of the present invention, the circulation part is provided with a parameter monitoring part, so as to obtain the reaction state parameters of the reaction part through the circulation part.

Specifically, referring to FIG. 1 , the parameter monitoring unit 13 is arranged on the circulation body 110 , and is specifically arranged on the side wall of the circulation body 110 .

During the cell culture process using the cell culture system shown in Figure 1, when each circulation control channel (not shown in the figure) is in a conducting state and the flow medium is controlled to be in each circulation control channel (not shown in the figure) In the continuous flow state, the state of the flow medium in the circulation body 110 is consistent with the state of the flow medium in each of the reaction bodies 120 , so it is beneficial to avoid disturbing the culture state in each of the reaction bodies 120. Ability to monitor the cultivation situation online.

In some embodiments of the present invention, the reaction state parameters include at least one of temperature data, pressure data, flow rate data, pH value data, liquid level metadata, metabolite content data, and dissolved oxygen data.

In some embodiments of the present invention, the parameter monitoring part 13 is composed of a temperature sensing part, the pressure sensing part, the pH monitoring part, the nutrient content monitoring part and the dissolved oxygen monitoring part.

Specifically, the temperature sensing part is a temperature sensor; the pressure sensing part is a pressure sensor, and the pH monitoring part is a pH electrode; the substance content monitoring part is a bioanalyzer capable of detecting glucose content and lactic acid content ; The dissolved oxygen monitoring unit is an online dissolved oxygen analyzer.

In Embodiment 1 of the present invention, the cell culture system further includes a cell detection part disposed in at least one of the reaction parts to obtain cell state parameters.

Specifically, referring to FIG. 1 , a reaction main body 120 is provided with a cell detection part 14 , and the cell detection part 14 is specifically arranged on the side wall of the reaction main body 120 .

During the culture process using the cell culture system shown in Figure 1, when each circulation control channel (not marked in the figure) is in a conducting state and the flow medium is controlled to be in each circulation control channel (not marked in the figure) In the continuous flow state, since the consistency of the number and state of seed cells in each reaction body 120 and the consistency of the flow medium content in each reaction body 120 are controlled, it can be determined that any reaction body 120 The cell states represent the cell states within each of the reaction bodies 120 .

Specifically, the cycle-controlled culture further includes: acquiring at least one cell state parameter of the cells in the reaction part through the cell detection part, and judging whether to terminate the cycle-controlled culture according to the cell state parameter.

In some embodiments of the present invention, the cell state parameter includes the number of viable cells.

The culture part of the first embodiment of the present invention further includes a metering display part provided in the circulation part. Specifically, referring to FIG. 1 , the circulation main body 110 is provided with a metering display part 15 , and the metering display part 15 is specifically arranged at the bottom of the circulation main body 110 to assist in confirming the amount of the flowing medium in the circulation main body 110 .

In some embodiments of the present invention, before applying the culture process of the cell culture system shown in FIG. 1 , the flow medium is first stored in the circulation main body 110 , and the main circulation confluence channel 112 is closed by the confluence regulation part 113 , Each of the sub-liquid inlet switch parts 123 keeps each of the sub-liquid inlet passages 121 in a conducting state and provides a flow medium to the corresponding reaction main body 120 by controlling each of the sub-liquid inlet control parts 124 respectively, and combined with the metering display Section 15 assists in determining the amount of flow medium required in each of the reaction bodies 120, facilitating the distribution of flow medium to different reaction bodies 120 according to culture requirements.

Example 2:

FIG. 2 is a schematic structural diagram of the cell culture system of the novel example 2. FIG.

In the second embodiment of the present invention, the circulation part is provided with a stirring part. Specifically, referring to FIG. 1 and FIG. 2 , one of the differences between the cell culture system shown in FIG. 2 and the cell culture system shown in FIG. 1 is that the circulation body 110 is provided with a stirring part 21 , which is specifically provided in the stirring part 21 top of.

The cycle-controlled culture in the second embodiment of the present invention further includes driving the flow medium in the circulation main body 110 to mix uniformly through the stirring part 21, so that the flow medium distributed to each of the reaction main bodies 120 has the same composition, which is beneficial to the Consistency of the cell state within the reaction body 120 .

In some embodiments of the present invention, the stirring part 21 is a stirring device disposed at the bottom or side wall of the circulation main body 110 , and the stirring device is specifically a magnetic stirring device.

In the second embodiment of the present invention, the reaction part is provided with a reaction driving part. Specifically, referring to FIG. 1 and FIG. 2 , the second difference between the cell culture system shown in FIG. 2 and the cell culture system shown in FIG. 1 is that the reaction driving part 22 is an integrated stirring device, which is arranged in each reaction main body. At the bottom of 120, dynamic cell culture is performed by disturbing the flow medium in each reaction body 120 to improve the uniformity of the reaction.

The cycle-controlled culture in the novel embodiment 2 further includes that the reaction driving part 22 drives the movement of the flow medium in the at least two reaction parts at the same driving speed, so as to assist in the dynamic cell culture.

In some embodiments of the present invention, the reaction driving part 22 is disposed on the sidewall of each reaction body 120 .

In some embodiments of the present invention, the reaction driving part 22 is composed of a plurality of sub-stirring devices, and the plurality of sub-stirring devices are respectively disposed on each of the reaction main bodies 120 in a one-to-one correspondence. Specifically, the sub-stirring device is disposed at the bottom or side wall of each of the reaction bodies 120 .

In some embodiments of the present invention, the reaction driving part 22 is specifically a magnetic stirring device.

In the culture process of some embodiments of the present invention, the reaction driving part 22 controls the disturbance of the flow medium in each of the reaction bodies 120 to be the same or similar.

Example 3:

FIG. 3 is a schematic diagram of the assembly structure of the reaction driving part and several reaction main bodies according to the third embodiment of the novel.

In the third embodiment of the present invention, each of the reaction parts includes an elastic cavity, and the culture part further includes a lift drive part acting on each of the elastic cavity.

Specifically, referring to FIG. 3 , taking the reaction main body 120 as an example, the reaction main body 120 is composed of a storage cavity 31 and an elastic cavity 32 that are connected and communicated with each other, and the storage cavity 31 can accommodate the seed cells or load the A slide of seeded cells, the elastic cavity 32 can accommodate the flow medium. The reaction driving part 22 is a lift driving part, which is arranged at the bottom of each reaction body 120 to drive the elastic cavity 32 to move up and down in the direction of the arrow shown in FIG. 3 , so that the flowing medium enters the storage cavity 31 After contacting the seed cells or the carrier sheet loaded with the seed cells, it flows back into the elastic cavity 32, so as to control the exchange time between cells and liquid nutrients and gaseous nutrients to control each reaction body 120. Mass transfer process that helps to enhance the viability and function of the harvested target cells.

During the cycle-controlled cultivation process in Example 3 of the present novel, the reaction driving part drives the flow medium in the at least two reaction parts to synchronously ascend and descend at a rate of not more than 15 mm/s, so that the different reaction parts can achieve synchronous The dynamic cell culture.

Further, the circulating outflow rate of different flow media in the reaction portion confluent to the circulating portion is controlled by the circulating control path not to exceed the driving rate, so as to avoid the generation of obvious shear force and damage to the cells.

Similarly, the circulating inflow rate at which the flow medium in the circulating portion is controlled to be split to different reaction portions through the circulating control passage does not exceed the driving rate.

In the culture process of some embodiments of the present invention, at least one of the rising rate and the falling rate of the flowing medium in each reaction body 120 is controlled by the reaction driving part 22 to be consistent.

In some embodiments of the present invention, the cycle-controlled culture further includes: acquiring a reaction state parameter of the cycle-controlled culture through the parameter monitoring part, and performing rate control on the reaction driving part according to the reaction state parameter.

Example 4:

FIG. 4 is a schematic structural diagram of the cell culture system of the novel example 4. FIG.

In the fourth embodiment of the present invention, the culture part includes a liquid supply part and a gas supply part, and the liquid supply part is connected to the circulation part to provide liquid nutrients. The gas supply part is connected to each of the reaction parts to supply gaseous nutrients.

In some embodiments of the present invention, the gaseous nutrient is a mixture of carbon dioxide and oxygen.

Specifically, the difference between the cell culture system shown in Figure 4 and the cell culture system shown in Figure 1 is: In the cell culture system shown in FIG. 4 , the liquid supply main body 410 , the liquid supply passage 411 , the liquid supply switch part 412 and the liquid supply control part 413 provided in the liquid supply passage 411 constitute the liquid supply part; the gas supply main body 420 , the air supply passage 423 , the air supply switch part 422 and the air supply regulation part 421 arranged in the air supply passage 423 constitute the air supply part.

Further, one end of the liquid supply passage 411 is connected to the liquid supply main body 410, and the other end is connected to the circulation main body 110, so as to transport the liquid nutrients to each of the reaction main bodies 120 through the circulation main body 110. The liquid nutrients directly enter each of the reaction bodies 120 from the liquid supply body 410, which ensures that the liquid nutrients are evenly mixed in the circulation body 110 and then enters each of the reaction bodies 120, which is beneficial to each of the reaction bodies 120. Consistency of the state of target cells.

Further, the gas supply main body 420 communicates with the different reaction main bodies 120 through the gas supply passage 423 , so that the interiors of the different reaction main bodies 120 communicate with each other, so as to ensure the maximum exchange conditions of gas-phase substances in each of the reaction main bodies 120 . consistency.

The liquid supply body 410 stores the liquid nutrients; the gas supply body 420 stores the gaseous nutrients. In some specific embodiments of the present invention, the liquid supply body 410 is a sterile wide-mouth bottle, and the gas supply body 420 is a pressurized gas bottle.

The liquid supply switch part 412 and the air supply switch part 422 respectively control the conduction state of the liquid supply passage 411 and the air supply passage 423 . In some specific embodiments of the present invention, any one of the liquid supply switch portion 412 and the gas supply switch portion 422 is any one of a shut-off valve and an on-off valve.

The liquid supply control unit 413 controls the flow or flow rate of liquid nutrients entering the circulation body 110 . In some specific embodiments of the present invention, the liquid supply regulating part 413 is any one of a peristaltic pump and a metering pump.

The gas supply control unit 421 controls the flow rate or flow rate of the gaseous nutrients entering each of the reaction bodies 120 . In some specific embodiments of the present invention, the air supply control part 421 is a flow valve.

In some embodiments of the present invention, the liquid supply part is also connected to each of the reaction parts, and the liquid nutrients are directly supplied to the circulation part and each of the reaction parts respectively.

In some embodiments of the present invention, the cycle-controlled culture further includes: synchronously supplying gaseous nutrients to each of the reaction parts through the gas supply part.

Example 5:

FIG. 5 is a schematic structural diagram of the cell culture system of the novel example 5. FIG.

In the fifth embodiment of the present invention, the culture part includes a drain part, and is connected to the circulation part and each of the reaction parts.

The difference between the cell culture system shown in FIG. 5 and the cell culture system shown in FIG. 4 is that the waste liquid collection body 510 , the waste liquid collection passage 511 and the waste liquid collection switch part 512 constitute the waste liquid collection part.

Further, both ends of the waste liquid collection passage 511 are respectively connected to the waste liquid collection main body 510 and the side wall of the circulation main body 110 , and the waste liquid collection switch portion 512 is disposed in the waste liquid collection passage 511 .

After stopping the shunting process and the confluence process through the circulation control passage, the flowing medium in the circulation part is discharged from the circulation part through the liquid discharge part, and then liquid nutrients are supplied to the circulation part through the liquid supply part to complete the exchange. liquid treatment.

Specifically, under the condition that the motion state of the flowing medium in each circulation control passage (not marked in the figure) remains unchanged, the waste liquid collection switch part 512 is controlled to make part of the flowing medium in the circulation main body 110 pass through the waste liquid The liquid collection passage 511 enters the waste liquid collection body 510 for recovery, so as to complete the liquid exchange process.

After the liquid exchange treatment is completed, the circulation control culture is performed through the circulation control passage. Specifically, after part of the flowing medium is recovered, the waste liquid collection switch 512 is closed, and the liquid supply body 410 supplements the circulation body 110 with liquid nutrients, and the supplemented liquid nutrients are combined with the circulation body 110 . After mixing, the flow medium enters each of the circulation control passages (not shown in the figure).

The medium exchange treatment and the cycle-controlled culture are alternately performed to complete the exchange of liquid nutrients without affecting the cell culture process.

In some embodiments of the present invention, referring to the metering display part 15 to control the recovery amount of the flowing medium in the circulation main body 110 to be equal to the amount of liquid nutrients supplemented to the circulation main body 110 , the liquid replacement process is completed for each Replacement of the flow medium in the reaction body 120 .

In some embodiments of the present invention, with reference to the metering display part 15 , the recovered amount of the flowing medium in the circulation main body 110 is controlled to be larger or smaller than the amount of liquid nutrients supplemented to the circulation main body 110 .

In some embodiments of the present invention, two ends of the waste liquid collection passage 511 are respectively connected to the waste liquid collection main body 510 and the main circulation confluence passage 112 .

In some embodiments of the present invention, the cell culture system further includes a temperature regulation part, the temperature regulation part is covered on at least one of the circulation part and each of the reaction parts to adjust the reaction temperature.

Specifically, the temperature adjustment part is a closed cover body with a temperature adjustment device installed, and the circulation main body 110, all the reaction main bodies 120 and the passage connecting the circulation main body 110 and the reaction main body 120 are accommodated in the closed cover body, The temperature at which the cell culture is carried out is controlled by the temperature regulating device.

In some embodiments of the present invention, the cell culture system further includes a control part, the control part is connected to the circulation control channel, the stirring part, the parameter monitoring part, the cell detection part, the liquid supply part, the gas supply part, the At least one of the elevating driving part, the waste liquid collecting part and the temperature regulating part is used to perform corresponding mode control according to at least one of the reaction state parameter and the cell state parameter, so as to realize corresponding function regulation and store corresponding control data .

In some specific embodiments of the present invention, referring to FIGS. 1 to 5 , the control unit is electrically connected to each of the sub-liquid inlet switch units 123 , each of the sub-liquid inlet control units 124 , the parameter monitoring unit 13 , and the cell detection unit 14 , the confluence control part 113, the metering display part 15, the stirring part 21, the reaction driving part 22, the liquid supply switch part 412, the liquid supply control part 413, the gas supply switch part 422, the gas supply control part 421, the waste liquid collection At least one of the passage 511 and the waste liquid collection switch 512 .

In some specific embodiments of the present invention, referring to FIGS. 1 to 5 , the control unit is electrically connected to each of the sub-liquid inlet switch units 123 , each of the sub-liquid inlet control units 124 , the parameter monitoring unit 13 , and the cell detection unit 14 , the confluence control part 113, the metering display part 15, the stirring part 21, the reaction driving part 22, the liquid supply switch part 412, the liquid supply control part 413, the gas supply switch part 422, the gas supply control part 421, the waste liquid collection The passage 511 and the waste liquid collection switch part 512 .

In some embodiments of the present invention, the cell culture system further includes a storage unit connected to the control unit, and the storage unit stores a number of culture mode information.

Specifically, the cell culture process further includes: calling the target culture mode information from the plurality of culture mode information through the control unit, and starting the cycle control culture according to the target culture mode information.

Although the embodiments of the present invention have been described in detail above, it will be apparent to those skilled in the art that various modifications and changes can be made to these embodiments. However, it should be understood that such modifications and changes fall within the scope and spirit of the present invention as set forth in the claims. Furthermore, the invention described herein is capable of other embodiments and of being practiced or carried out in various ways.

13: Parameter Monitoring Department

15: Measurement display part

110: Loop body

112: Main circulation confluence path

120: React Body

410: Liquid supply body

510: Waste liquid collection body

511: Waste liquid collection path

512: Waste liquid collection switch

Claims (13)

A cell culture system, comprising: a culture part, including at least two reaction parts connected in parallel with each other, to provide a culture place required for seed cells to carry out cell culture; and a circulation part, wherein the circulation part and each of the reaction parts The parts are connected in parallel, so that different circulation control passages are formed between the circulation part and each of the reaction parts, so that the flow media of different reaction parts are collected in the circulation part and then divided into each of the reaction parts. The cell culture system according to claim 1, wherein the circulation part is provided with a stirring part to drive the flowing medium in the circulation part to mix uniformly. The cell culture system according to claim 2, further comprising a parameter monitoring part disposed in the circulation part, so as to obtain a reaction state parameter of the reaction part through the circulation part. The cell culture system of claim 3, wherein the reaction state parameters include at least one of temperature data, pressure data, flow rate data, pH value data, liquid level data, metabolite content data, and dissolved oxygen data. The cell culture system according to claim 3, further comprising a cell detection part disposed in at least one of the reaction parts to acquire a cell state parameter. The cell culture system according to claim 5, wherein the culture part further comprises a liquid supply part, the liquid supply part is connected with the circulation part and at least one of each of the reaction parts to provide liquid nutrients. The cell culture system of claim 6, wherein the culture part further comprises an air supply part, and the air supply part is connected to each of the reaction parts to provide gaseous nutrients. The cell culture system according to claim 7, wherein each of the reaction parts further includes an elastic cavity, and the culture part further includes a lift driving part acting on each of the elastic cavity to drive each of the elastic cavity The flowing medium in the body moves up and down. The cell culture system according to claim 8, wherein the culture part further comprises a waste liquid collection part, and the waste liquid collection part is connected to the circulation part and at least one of each of the reaction parts. The cell culture system according to claim 9, further comprising a temperature regulation part, the temperature regulation part is covered on at least one of the circulation part and each of the reaction parts to adjust the reaction temperature. The cell culture system according to claim 10, further comprising a control part, the control part is connected to the circulation control channel, the stirring part, the parameter monitoring part, the cell detection part, the liquid supply part and the gas supply part , at least one of the elevating driving part, the waste liquid collecting part and the temperature adjusting part to perform corresponding mode control according to at least one of the reaction state parameter and the cell state parameter. The cell culture system according to claim 11, further comprising a storage unit connected to the control unit, the storage unit stores culture mode information for the control unit to call and automatically perform the corresponding mode control. The cell culture system according to claim 1, wherein the culture part further comprises a metering display part arranged in the circulation part to assist in confirming the amount of the flowing medium in the circulation part.

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