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CN215162828U - Cell culture system - Google Patents

Cell culture system Download PDF

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Publication number
CN215162828U
CN215162828U CN202120460108.4U CN202120460108U CN215162828U CN 215162828 U CN215162828 U CN 215162828U CN 202120460108 U CN202120460108 U CN 202120460108U CN 215162828 U CN215162828 U CN 215162828U
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reaction
cell culture
circulation
culture system
circulating
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CN202120460108.4U
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孙亚珠
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Shanghai Celliver Biotechnology Co Ltd
Shanghai Cryowise Medical Technology Co Ltd
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Shanghai Celliver Biotechnology Co Ltd
Shanghai Cryowise Medical Technology Co Ltd
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Priority to CN202120460108.4U priority Critical patent/CN215162828U/en
Priority to TW110214171U priority patent/TWM625568U/en
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Abstract

The utility model provides a cell culture system, which comprises a culture part and a circulating part. The culture part of the utility model comprises at least two reaction parts which are connected in parallel as the culture place, thereby avoiding the pollution risk in the cell transfer process and being beneficial to realizing large-scale cell culture by adjusting the number of the reaction parts; the circulating part is connected with each reaction part in parallel, so that different circulating control passages are formed between the circulating part and each reaction part, flowing media of different reaction parts are collected in the circulating part and then flow to each reaction part, seed cells in each reaction part can be cultured under the same culture condition, and the state uniformity of target cells obtained by each reaction part is ensured.

Description

Cell culture system
Technical Field
The utility model relates to the field of biotechnology, especially, relate to cell culture system.
Background
Compared with static cell culture, in the process of dynamic cell culture, as the nutrient solution can be continuously supplied and the metabolites can be recovered, the problems that cells cannot obtain favorable growth space and obtain sufficient substance exchange and are easy to die due to local cell density in the dynamic culture process are solved, the utilization rate of the nutrient solution is improved, the cells can be cultured in space for a long time, and the improvement of the activity and the function of the cells is facilitated.
The current clinical application requires a large amount of various types of cells, such as normal hepatocytes for dialysis exchange, and therefore it is necessary to perform cell culture on a large scale while improving the uniformity of the state of the harvested target cells to ensure the therapeutic effect.
Patent application publication No. WO2020094809a1 discloses a method for culturing cells on a large scale by providing cell culture chambers of different volumes, and transferring cells from a small-volume culture chamber to a large-volume culture chamber step by step to culture the cells. However, this method is cumbersome and is very likely to contaminate the cell culture by contacting with the external environment due to the presence of multiple cell transfer processes.
Therefore, there is a need to develop a new cell culture system to solve the above problems in the prior art.
SUMMERY OF THE UTILITY MODEL
An object of the utility model is to provide a cell culture system to do benefit to and carry out cell culture on a large scale and avoid because the cell shifts the pollution risk that causes, improve the state homogeneity of the target cell of results simultaneously.
In order to achieve the above object, the cell culture system of the present invention comprises at least two reaction parts connected in parallel to each other to provide a culture place for the seed cells to be cultured; the circulating part is connected with each reaction part in parallel, so that different circulating control paths are formed between the circulating part and each reaction part, and flowing media of different reaction parts are collected in the circulating part and then flow to each reaction part.
The cell culture system of the utility model has the advantages that: the cell culture system comprises at least two reaction parts which are connected in parallel and are used as the culture place, so that the pollution risk in the cell transfer process is avoided, and the large-scale cell culture can be realized by adjusting the number of the reaction parts; furthermore, the circulating part is connected with each reaction part in parallel, so that different circulating control paths are formed between the circulating part and each reaction part, flowing media of different reaction parts are collected in the circulating part and then flow to each reaction part, seed cells in each reaction part can be cultured under the same culture condition, and the state uniformity of target cells obtained by each reaction part is ensured.
Preferably, the circulating part is provided with a stirring part to drive the flowing medium in the circulating part to be uniformly mixed. The beneficial effects are that: it is advantageous that the seed cells in each of the reaction parts can be cultured under the same culture conditions.
Further preferably, the reaction device further comprises a parameter monitoring part arranged in the circulating part, so as to obtain the reaction state parameters of the reaction part through the circulating part. The beneficial effects are that: the culture condition can be monitored on line under the condition that the culture state of the reaction part is not disturbed.
Further preferably, the reaction state parameter includes at least one of temperature data, pressure data, flow rate data, pH data, liquid level data, metabolite content data, and dissolved oxygen data.
Further preferably, the apparatus further comprises a cell detection unit provided in at least one of the reaction units, so as to obtain a cell state parameter. The beneficial effects are that: it is advantageous to determine the time at which the cell culture is completed from the state of the cells in the reaction part.
Further preferably, the culture part includes a liquid supply part connecting at least one of the circulation part and each of the reaction parts to supply a liquid nutrient. The beneficial effects are that: compared with the liquid nutrient substance which directly enters each reaction part from the liquid supply part, the liquid nutrient substance enters different reaction parts through the circulation part and different circulation control passages, and the uniform mixing of the liquid nutrient substance is further ensured.
Further preferably, the culture part includes a gas supply part connecting each of the reaction parts to supply gaseous nutrients. The beneficial effects are that: the cells in the different reaction parts are provided with the nutrients necessary for the exchange of gaseous substances.
Preferably, each reaction part comprises an elastic cavity, and the culture part further comprises a lifting driving part acting on each elastic cavity to drive the flowing medium in each elastic cavity to move up and down. The beneficial effects are that: the good mass transfer process in the reaction part is controlled by adjusting the exchange time of the cells with the liquid nutrient and the gaseous nutrient, which is beneficial to improving the activity and the function of the harvested target cells.
Further preferably, the culture part includes a waste liquid collecting part connecting at least one of the circulation part and each of the reaction parts.
Further preferably, the reaction device further comprises a temperature adjusting part which is covered on at least one of the circulating part and each reaction part to adjust the reaction temperature.
Preferably, the apparatus further comprises a control unit connected to at least one of the circulation control path, the stirring unit, the parameter monitoring unit, the cell detecting unit, the liquid supply unit, the gas supply unit, the elevation driving unit, the waste liquid collecting unit, and the temperature adjusting unit, so as to perform corresponding mode control according to at least one of the reaction state parameter and the cell state parameter. The beneficial effects are that: is favorable for realizing the automatic control of cell culture.
More preferably, the culture apparatus further includes a storage unit connected to the control unit, and the storage unit stores culture mode information for the control unit to call and automatically perform the corresponding mode control.
Preferably, the culture part includes a measurement display part provided in the circulation part to assist confirmation of the amount of the fluid medium in the circulation part. The beneficial effects are that: is favorable for distributing flowing media to different reaction parts according to the culture requirement.
Drawings
FIG. 1 is a schematic structural view of a cell culture system according to example 1 of the present invention;
FIG. 2 is a schematic structural view of a cell culture system according to example 2 of the present invention;
fig. 3 is a schematic view of an assembly structure of a reaction driving part and a plurality of reaction main bodies according to embodiment 3 of the present invention;
FIG. 4 is a schematic structural view of a cell culture system according to example 4 of the present invention;
FIG. 5 is a schematic structural view of a cell culture system according to example 5 of the present invention.
Detailed Description
In order to make the objects, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below, and it is obvious that the described embodiments are some, but not all embodiments of the present invention. Based on the embodiments in the present invention, all other embodiments obtained by a person skilled in the art without creative efforts belong to the protection scope of the present invention. Unless defined otherwise, technical or scientific terms used herein shall have the ordinary meaning as understood by one of ordinary skill in the art to which this invention belongs. As used herein, the word "comprising" and similar words are intended to mean that the element or item listed before the word covers the element or item listed after the word and its equivalents, but does not exclude other elements or items.
To the problem that prior art exists, the embodiment of the utility model provides a cell culture system including reaction portion and circulation portion to do benefit to and realize extensive cell culture, guarantee each simultaneously the state homogeneity of the target cell that reaction portion obtained.
The cell culture system is described in detail below with specific examples.
Example 1:
FIG. 1 is a schematic structural view of a cell culture system according to example 1 of the present invention.
In embodiment 1 of the present invention, the culture part comprises at least two reaction parts connected in parallel to each other to provide a culture place for the seed cells to perform cell culture.
Specifically, the reaction part comprises a reaction main body and a sub regulation part which are connected in series by a sub passage, and the sub regulation part controls the flow or flow speed of the flowing medium entering the reaction main body.
More specifically, referring to FIG. 1, the culture part (not shown) is composed of 4 reaction parts (not shown) connected in parallel with each other. The sub liquid inlet switch portion 123 and the sub liquid inlet regulation portion 124 constitute a sub regulation portion. The sub liquid inlet passage 121 and the sub liquid outlet passage 122 constitute a sub passage. The liquid inlet switch part 123 and the liquid inlet regulation part 124 are disposed on the sub liquid inlet path 121, one end of the reaction body 120 is connected to the sub liquid inlet path 121, and the other end is connected to the sub liquid outlet path 122.
The reaction body 120 can contain seed cells and nutrients for cell culture of the seed cells. In some embodiments of the present invention, the reaction body 120 is a cell culture flask.
In some embodiments of the present invention, the seed cells are loaded on the carrier and then contained 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 directly loaded on the bottom of the reaction body 120 or the inner sidewall near the bottom.
In some embodiments of the present invention, the cell type of the seed cell is a hepatocyte or a stem cell.
The sub inlet switch portion 123 controls the conduction state of the sub inlet passage 121. In some specific embodiments of the present invention, the sub liquid inlet switch portion 123 is any one of a stop valve and a switch valve.
The sub-inlet regulation part 124 controls the flow rate or flow rate of the flowing medium into the reaction body 120. In some embodiments, the sub-liquid inlet control unit 124 is any one of a peristaltic pump and a metering pump.
In embodiment 1 of the present invention, the circulation unit is connected in parallel to each of the reaction units, which is advantageous for realizing large-scale cell culture by adjusting the number of the reaction units; in addition, different circulation control channels are formed between the circulation part and each reaction part, so that flowing media of different reaction parts are collected in the circulation part and then flow to each reaction part, the seed cells in each reaction part can be cultured under the same culture condition, and the state uniformity of the target cells obtained by each reaction part is ensured.
Specifically, the circulation part comprises a main circulation passage, a circulation main body and a confluence regulation part, wherein the circulation main body and the confluence regulation part are arranged in the main circulation passage in series. One part of the main circulation path is connected with one end of each of the sub regulation parts, and the other part of the main circulation path is connected with the other end of each of the sub regulation parts, so that the parallel connection is realized.
More specifically, referring to fig. 1, the main circulation liquid outlet passage 111 and the main circulation confluence passage 112 constitute a main circulation passage. The confluence control part 113 is arranged on the main circulation confluence passage 112, one end of the circulation main body 110 is connected with the main circulation liquid outlet passage 111, and is respectively connected with each of the sub liquid inlet passages 121 through the main circulation liquid outlet passage 111, the other end of the circulation main body is connected with the main circulation confluence passage 112, and is respectively connected with each of the sub liquid outlet passages 122 through the main circulation confluence passage 112, so as to realize the parallel connection.
The confluence controlling part 113 controls the flow rate or flow velocity of the flowing medium entering the circulation main body 110. In some specific embodiments, the confluence controlling part 113 is any one of a stop valve and an on-off valve.
The culture process using the cell culture system shown in FIG. 1 includes: the circulating control channel is used for controlling the flowing media in different reaction parts to converge in the circulating part so as to finish the converging treatment, and the circulating control channel is used for controlling the flowing media in the circulating part to be shunted to different reaction parts so as to finish the shunting treatment.
Specifically, referring to fig. 1, in an initial state, a plurality of flowing media are accommodated in the circulation body 110, and each reaction body 120 accommodates adherent cells loaded on an inner wall of each reaction body 120 and an initial amount of the flowing media therein. The confluence control portion 113 and each of the sub liquid inlet switch portions 123 are adjusted to enable each circulation control passage (not shown) to be in a conducting state, and then each of the sub liquid inlet control portions 124 controls the flowing medium in the circulation main body 110 to enter each of the reaction main bodies 120 at a certain flow rate or flow velocity to complete the confluence process, and each of the reaction main bodies 120 is controlled to confluence the circulation main body 110 at a certain flow rate or flow velocity to complete the split process.
The embodiment 1 of the utility model provides an in, circulation control cultivates and still includes: and controlling the confluence processing and the diversion processing to be continuously performed through the circulation control path.
Specifically, referring to fig. 1, the flowing medium of each circulation control path is continuously flowed by controlling the confluence controlling part 113 and each of the sub liquid inlet controlling parts 124.
The embodiment of the utility model provides an in 1, converge handle with the reposition of redundant personnel is handled the in-process that goes on, through circulation control access control is different the volume of flow medium is unanimous with the initial volume that corresponds in the reaction portion, is favorable to in same batch.
Specifically, the flowing medium is continuously flowed by controlling the confluence controlling part 113 and each of the sub liquid inlet controlling parts 124, so that the flow rate of the flowing medium branched into the single reaction part is identical to the flow rate of the flowing medium flowing out from the single reaction part, and the amount of the flowing medium in each of the reaction bodies 120 is identical to the corresponding initial amount. The amount of the flowing medium refers to any one of the mass and the volume of the flowing medium.
In some embodiments of the present invention, each of the reaction bodies 120 has the same volume, and the mass of the seed cells contained in each of the reaction bodies 120 is the same, and the volume or the mass of the flowing medium in each of the reaction bodies 120 is the same while the flowing medium is continuously flowed by controlling each of the seed feed liquid regulating parts 124.
In some embodiments of the present invention, the flowing medium is a liquid nutrient required for cell culture of the seed cells. Specifically, the cell culture includes primary culture, amplification culture or differentiation culture, and the corresponding liquid nutrient is common knowledge of those skilled in the art.
The embodiment of the utility model provides an in 1, circulation portion is provided with parameter monitoring portion, with pass through circulation portion acquires the reaction state parameter of reaction portion.
Specifically, referring to fig. 1, the parameter monitoring unit 13 is disposed on the circulation body 110, specifically, on a side wall of the circulation body 110.
In the cell culture process using the cell culture system shown in fig. 1, when each circulation control path (not shown) is in a conducting state and the flow medium is controlled to be in a continuous flow state in each circulation control path (not shown), the flow medium state in the circulation main body 110 is consistent with the flow medium state in each reaction main body 120, so that the culture condition can be monitored on line without disturbing the culture condition in each reaction main body 120.
In some embodiments, the reaction state parameter includes at least one of temperature data, pressure data, flow rate data, pH data, liquid level data, metabolite content data, and dissolved oxygen data.
In some embodiments of the present invention, the parameter monitoring unit 13 comprises a temperature sensing unit, a pressure sensing unit, a pH monitoring unit, a nutrient content monitoring unit, and a dissolved oxygen monitoring unit.
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 the content of glucose and the content of lactic acid; the dissolved oxygen monitoring part is an online dissolved oxygen analyzer.
The embodiment 1 of the present invention provides the cell culture system further comprising a cell detecting unit disposed in at least one of the reaction units to obtain cell state parameters.
Specifically, referring to fig. 1, one reaction body 120 is provided with a cell detecting part 14, and the cell detecting part 14 is specifically provided on a side wall of the reaction body 120.
In the process of the culture process using the cell culture system shown in fig. 1, when each circulation control path (not shown) is in a conducting state and the flowing medium is controlled to be in a continuous flowing state in each circulation control path (not shown), since the number and the state of the seed cells in each reaction body 120 are controlled to be consistent and the content of the flowing medium in each reaction body 120 is controlled to be consistent, it can be determined that the state of the cells in any one reaction body 120 represents the state of the cells in each reaction body 120.
Specifically, the circulation-controlled culture further comprises: obtaining a cell state parameter of cells in at least one of the reaction parts by the cell detection part, and judging whether to terminate the circulation control culture according to the cell state parameter.
In some embodiments of the invention, the cell state parameter comprises a number of viable cells.
The culture part of the embodiment 1 of the utility model also comprises a measuring display part arranged on the circulating part. Specifically, referring to fig. 1, the circulation body 110 is provided with a metering display part 15, and the metering display part 15 is specifically provided at the bottom of the circulation body 110 to assist in confirming the amount of the flowing medium in the circulation body 110.
Some embodiments of the utility model are before the cultivation technology that the cell culture system that the application is shown in fig. 1 goes on, flow medium earlier store in circulation main part 110, through it makes to converge regulation and control portion 113 the main cycle converges passageway 112 and is in the off-state, through every sub-feed liquor switch portion 123 makes every sub-feed liquor passageway 121 is in the on-state and through controlling every respectively sub-feed liquor regulation and control portion 124 provides flow medium to corresponding reaction main part 120 in, and combines measurement display portion 15 is supplementary to be confirmed every the quantity of flow medium that needs in the reaction main part 120 is favorable to distributing flow medium to different reaction main parts 120 according to the cultivation demand.
Example 2:
FIG. 2 is a schematic structural view of a cell culture system according to example 2 of the present invention.
In the embodiment 2 of the present invention, the circulation portion is provided with a stirring portion. Specifically, referring to fig. 1 and 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, and is particularly provided at the top of the stirring part 21. The utility model discloses embodiment 2's circulation control is cultivateed and is still included through stirring portion 21 drives flow medium homogeneous mixing in the circulation main part 110 makes follow-up reposition of redundant personnel to every the flow medium of reaction main part 120 has same constitution to be favorable to each the cell state uniformity in the reaction main part 120.
In some embodiments of the present invention, the stirring portion 21 is a stirring device disposed at the bottom or the side wall of the circulation main body 110, and the stirring device is specifically a magnetic stirring device.
In the embodiment of the present invention, the reaction portion is provided with a reaction driving portion. Specifically, referring to fig. 1 and 2, the cell culture system shown in fig. 2 is different from the cell culture system shown in fig. 1 in that: the reaction driving part 22 is an integrated stirring device, is provided at the bottom of each of the reaction bodies 120, and performs dynamic cell culture by disturbing a fluid medium in each of the reaction bodies 120, thereby improving the uniformity of the reaction.
The utility model discloses embodiment 2's circulation control cultivates still includes, through reaction drive portion 22 drives under same drive rate the mobile medium motion in two at least reaction portions to the supplementary dynamic cell culture that carries out.
In some embodiments, the reaction driving part 22 is disposed on each of the sidewalls of the reaction body 120.
In some embodiments of the present invention, the reaction driving part 22 is composed of a plurality of sub-stirring devices,
the plurality of sub-stirring devices are respectively disposed in each of the reaction bodies 120 in a one-to-one correspondence. Specifically, the sub-stirring devices are disposed at the bottom or the side wall of each of the reaction bodies 120.
In some embodiments of the present invention, the reaction driving part 22 is a magnetic stirring device.
In the cultivation process according to some embodiments of the present invention, the disturbance of the flowing medium in each of the reaction bodies 120 controlled by the reaction driving part 22 is the same or similar.
Example 3:
fig. 3 is a schematic view of an assembly structure of a reaction driving part and a plurality of reaction main bodies according to embodiment 3 of the present invention.
The embodiment of the utility model provides an in 3, every the reaction part includes the elasticity cavity, culture part is still including acting on every the lift drive division of elasticity cavity.
Specifically, referring to fig. 3, taking the reaction body 120 as an example, the reaction body 120 is composed of an object placing cavity 31 and an elastic cavity 32 which are connected and communicated with each other, the object placing cavity 31 can accommodate the seed cells or the slide glass loading the seed cells, and the elastic cavity 32 can accommodate the flowing medium. The reaction driving part 22 is specifically a lifting driving part, and is disposed at the bottom of each reaction main body 120 to drive the elastic cavity 32 to move up and down along the arrow direction shown in fig. 3, so that the flowing medium enters the placing cavity 31 to contact the seed cells or the slide loaded with the seed cells and then flows back into the elastic cavity 32, thereby controlling a good mass transfer process in each reaction main body 120 by adjusting the exchange time of the cells with liquid and gaseous nutrients, and contributing to improving the activity and function of the harvested target cells.
The utility model discloses in the circulation control culture process of embodiment 3, through the drive of reaction drive portion the mobile medium in two at least reaction portions carries out elevating movement in step with the speed that does not exceed 15 millimeters/second, so that the difference reaction portion realizes synchronous dynamic cell culture.
Further, the circulation control channel controls the circulation outflow rate of the flowing media in different reaction parts to converge on the circulation part not to exceed the driving rate, so as to avoid generating obvious shearing force to damage cells.
In the same way, the circulating inflow rate of the flowing medium in the circulating part which is divided to different reaction parts is controlled by the circulating control passage not to exceed the driving rate.
In the cultivation process according to some embodiments of the present invention, at least one of the rising rate and the falling rate of the fluid medium in each of the reaction bodies 120 is controlled to be uniform by the reaction driving part 22.
In some embodiments of the present invention, the circulation-controlled cultivation further comprises: and acquiring a reaction state parameter of the circulation control culture through the parameter monitoring part, and carrying out rate control on the reaction driving part according to the reaction state parameter.
Example 4:
FIG. 4 is a schematic structural view of a cell culture system according to example 4 of the present invention.
The embodiment 4 of the utility model provides an in, culture part includes liquid supply portion and air feed portion, the liquid supply portion is connected circulation portion is in order to provide liquid nutrient substance. The gas supply part is connected with each reaction part to supply gaseous nutrient substances.
In some embodiments of the present invention, the gaseous nutrient is a mixture of carbon dioxide and oxygen.
Specifically, the cell culture system shown in FIG. 4 differs from the cell culture system shown in FIG. 1 in that:
in the cell culture system shown in FIG. 4, the liquid supply part is constituted by a liquid supply main body 410, a liquid supply passage 411, and a liquid supply switch part 412 and a liquid supply control part 413 provided in the liquid supply passage 411; the air supply main body 420, the air supply path 423, and the air supply switch portion 422 and the air supply regulation portion 421 provided in the air supply path 423 constitute the air supply portion.
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 nutrient substance to each reaction main body 120 through the circulation main body 110, compared with the way of directly feeding the liquid nutrient substance from the liquid supply main body 410 to each reaction main body 120, the transport mode ensures that the liquid nutrient substance is uniformly mixed in the circulation main body 110 and then enters each reaction main body 120, which is beneficial to the state consistency of the target cells obtained by each reaction main body 120.
Further, the gas supply main body 420 communicates with the different reaction main bodies 120 through the gas supply path 423 to communicate the interiors of the different reaction main bodies 120, so as to maximally ensure the consistency of gas phase material exchange conditions in each of the reaction main bodies 120.
The liquid supply body 410 stores the liquid nutrient; the gas supply body 420 stores the gaseous nutrients. In some 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 412 and the gas supply switch 422 control the conduction states of the liquid supply passage 411 and the gas supply passage 423, respectively. In some embodiments, the liquid supply switch portion 412 and the gas supply switch portion 422 are any one of a stop valve and a switch valve.
The liquid supply control part 413 controls the flow rate or flow rate of the liquid nutrient substance into the circulation main body 110. In some embodiments of the present invention, the liquid supply control part 413 is any one of a peristaltic pump and a metering pump.
The gas supply controlling part 421 controls the flow rate or the flow rate of the gaseous nutrient substance into each of the reaction bodies 120. In some specific embodiments of the present invention, the air supply regulation and control portion 421 is a flow valve.
In some embodiments, the liquid supply part is connected with each reaction part, and the liquid nutrient substance is directly provided to the circulating part and each reaction part respectively.
In some embodiments of the present invention, the circulation-controlled cultivation further comprises, through the gas supply portion to each the reaction portion synchronously provides gaseous nutrients.
Example 5:
FIG. 5 is a schematic structural view of a cell culture system according to example 5 of the present invention.
In the embodiment 5 of the present invention, the culture part includes a drainage part and is connected to the circulation part and each of the reaction parts.
The cell culture system shown in FIG. 5 differs from the cell culture system shown in FIG. 4 in that: the waste liquid collecting body 510, the waste liquid collecting passage 511, and the waste liquid collecting switch section 512 constitute the waste liquid collecting section.
Further, both ends of the waste liquid collecting passage 511 are respectively communicated with the waste liquid collecting body 510 and the side wall of the circulation body 110, and the waste liquid collecting switch part 512 is disposed in the waste liquid collecting passage 511.
After the flow dividing treatment and the confluence treatment are stopped through the circulation control passage, the flowing medium in the circulating part is discharged out of the circulating part through the liquid discharging part, and then liquid nutrient substances are supplied to the circulating part through the liquid supplying part, so that the liquid changing treatment is completed.
Specifically, the waste liquid collecting switch 512 is controlled to make part of the flowing medium in the circulation body 110 enter the waste liquid collecting body 510 through the waste liquid collecting passage 511 to be recovered, while maintaining the moving state of the flowing medium in each circulation control passage (not shown), so as to complete the liquid changing process.
And after the liquid changing treatment is finished, performing the circulation control culture through the circulation control passage. Specifically, after recovering a part of the flowing medium, the waste liquid collecting switch 512 is closed, and liquid nutrients are supplemented to the circulating body 110 through the liquid supply body 410, and the supplemented liquid nutrients are mixed with the flowing medium in the circulating body 110 and then enter each of the circulation control passages (not shown).
The liquid changing treatment and the circulation control culture are alternately carried out, so that the liquid nutrient substance can be changed while the cell culture process is not influenced.
In some embodiments of the present invention, the recycling amount of the flowing medium in the circulation main body 110 is controlled by referring to the metering display unit 15 to be equal to the amount of the liquid nutrient supplemented to the circulation main body 110, and the liquid changing process is completed for several times to change the flowing medium in the reaction main body 120.
In some embodiments, the recovery amount of the fluid medium in the circulation main body 110 is controlled to be greater than or less than the amount of the liquid nutrient to be supplied to the circulation main body 110 with reference to the metering display part 15.
In some embodiments, the two ends of the waste liquid collecting passage 511 are respectively communicated with the waste liquid collecting body 510 and the main circulation converging passage 112.
In some embodiments of the present invention, the cell culture system further comprises a temperature adjusting part covering the circulation part and each of the reaction parts to adjust the reaction temperature.
Specifically, the temperature adjustment unit is a closed cover body provided with a temperature adjustment device, and the circulation body 110, all the reaction bodies 120 and a passage connecting the circulation body 110 and the reaction bodies 120 are accommodated in the closed cover body, so that the temperature for performing the cell culture is controlled by the temperature adjustment device.
The utility model discloses some embodiments, the cell culture system still includes the control part, the control part is connected the circulation control route the stirring portion the parameter monitoring portion the cell detection portion the liquid supply portion the gas supply portion the lift drive portion the waste liquid collection portion with at least one of the portion that adjusts the temperature, with the basis reaction state parameter with at least one of cell state parameter carries out corresponding mode control to realize corresponding function regulation and control and store corresponding control data.
The utility model discloses some concrete embodiments, refer to fig. 1 to 5, every is connected to the control part electricity sub-feed liquor switch portion 123, every sub-feed liquor regulation and control portion 124, parameter monitoring portion 13, cell detection portion 14 converge regulation and control portion 113, measurement display portion 15 stirring portion 21 reaction drive portion 22, supply liquid switch portion 412 and supply liquid regulation and control portion 413, air feed switch portion 422, air feed regulation and control portion 421, waste liquid collection route 511 and waste liquid collection switch portion 512 at least one.
The utility model discloses some concrete embodiments, refer to fig. 1 to 5, every is connected to the control part electricity sub-feed liquor switch portion 123, every sub-feed liquor regulation and control portion 124, parameter monitoring portion 13, cell detection portion 14 converge regulation and control portion 113, measurement display portion 15 stirring portion 21 reaction drive portion 22, supply liquid switch portion 412 and supply liquid regulation and control portion 413, air feed switch portion 422, air feed regulation and control portion 421, waste liquid collection route 511 and waste liquid collection switch portion 512.
In some embodiments of the present invention, the cell culture system further comprises a storage unit connected to the control unit, wherein the storage unit stores a plurality of culture mode information.
Specifically, the cell culture process further comprises: calling, by the control section, target culture mode information from the plurality of pieces of culture mode information, and starting the circulation control culture according to the target culture mode information.
Although the embodiments of the present invention have been described in detail hereinabove, it is apparent to those skilled in the art that various modifications and variations can be made to these embodiments. However, it is to be understood that such modifications and variations are within the scope and spirit of the present invention as set forth in the appended claims. Moreover, the invention as described herein is capable of other embodiments and of being practiced or of being carried out in various ways.

Claims (13)

1. A cell culture system comprising a culture section, characterized in that:
the cell culture system also comprises a circulating part, wherein the culture part comprises at least two reaction parts which are connected in parallel with each other so as to provide a culture place for culturing the seed cells;
the circulating part is connected with each reaction part in parallel, so that different circulating control paths are formed between the circulating part and each reaction part, and flowing media of different reaction parts are collected in the circulating part and then flow to each reaction part.
2. The cell culture system according to claim 1, wherein the circulating part is provided with a stirring part to drive the flowing medium in the circulating part to be uniformly mixed.
3. The cell culture system according to claim 2, further comprising a parameter monitoring section provided in the circulation section to acquire a reaction state parameter of the reaction section by the circulation section.
4. The cell culture system of claim 3, wherein the reaction state parameter comprises at least one of temperature data, pressure data, flow rate data, pH data, fluid level data, metabolite content data, and dissolved oxygen data.
5. The cell culture system according to claim 3, further comprising a cell detection section provided in at least one of the reaction sections to obtain a cell state parameter.
6. The cell culture system according to claim 5, wherein the culture part comprises a liquid supply part connecting at least one of the circulation part and each of the reaction parts to supply a liquid nutrient.
7. The cell culture system according to claim 6, wherein the culture part comprises a gas supply part which connects each of the reaction parts to supply a gaseous nutrient.
8. The cell culture system according to claim 7, wherein each of the reaction parts comprises an elastic cavity, and the culture part further comprises a lifting driving part acting on each of the elastic cavities to drive the flowing medium in each of the elastic cavities to perform lifting movement.
9. The cell culture system according to claim 8, wherein the culture part comprises a waste liquid collecting part that connects at least one of the circulation part and each of the reaction parts.
10. The cell culture system according to claim 9, further comprising a temperature adjusting part covering at least one of the circulation part and each of the reaction parts to adjust a reaction temperature.
11. The cell culture system according to claim 10, further comprising a control unit that is connected to at least one of the circulation control path, the stirring unit, the parameter monitoring unit, the cell detecting unit, the liquid supply unit, the gas supply unit, the elevation driving unit, the waste liquid collecting unit, and the temperature control unit to perform corresponding mode control based on at least one of the reaction state parameter and the cell state parameter.
12. The cell culture system according to claim 11, further comprising a storage unit connected to the control unit, wherein the storage unit stores culture mode information for the control unit to call and automatically perform the corresponding mode control.
13. The cell culture system according to claim 1, wherein the culture part comprises a metering display part provided in the circulation part to assist confirmation of the amount of the flowing medium in the circulation part.
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