CN106479889B - A kind of cell culture circulatory system - Google Patents
A kind of cell culture circulatory system Download PDFInfo
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- CN106479889B CN106479889B CN201610800906.0A CN201610800906A CN106479889B CN 106479889 B CN106479889 B CN 106479889B CN 201610800906 A CN201610800906 A CN 201610800906A CN 106479889 B CN106479889 B CN 106479889B
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
- C12M41/26—Means for regulation, monitoring, measurement or control, e.g. flow regulation of pH
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M29/00—Means for introduction, extraction or recirculation of materials, e.g. pumps
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M29/00—Means for introduction, extraction or recirculation of materials, e.g. pumps
- C12M29/18—External loop; Means for reintroduction of fermented biomass or liquid percolate
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
- C12M41/30—Means for regulation, monitoring, measurement or control, e.g. flow regulation of concentration
- C12M41/34—Means for regulation, monitoring, measurement or control, e.g. flow regulation of concentration of gas
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
- C12M41/40—Means for regulation, monitoring, measurement or control, e.g. flow regulation of pressure
Abstract
The present invention relates to technical field of cell culture more particularly to a kind of cell culture circulatory systems.It can be passed through gas as needed, increase the contact area of gas and culture solution, improve meltage, can satisfy the culture and industrialization production of cell.A kind of cell culture circulatory system, comprising: the culture solution conveying device and hollow fiber reactor, the hollow fiber reactor being connected to by the circulation conduit of culture solution include culture solution channel and cell growth chamber；The culture solution conveying device includes gas dissolver, the gas dissolver is internally provided with mixing chamber, the air inlet, inlet and liquid outlet being connected to the mixing chamber are offered on the gas dissolver, the gas dissolver is connected to by the inlet and the liquid outlet with the culture solution channel cycle.
Description
Technical field
The present invention relates to technical field of cell culture more particularly to a kind of cell culture circulatory systems.
Background technique
T cell has multiple biological function, and such as direct killing target cell, auxiliary or inhibition B cell generate antibody, to spy
The responsing reaction of Specific Antigen and mitogenesis original and generate cell factor etc., mature T cell is through blood distribution to outer
The thymus dependent area of all immune organs is settled down, and can be recycled through lymphatic vessel, peripheral blood and tissue fluid etc., is played cell and is exempted from
The functions such as epidemic disease and immunological regulation.Successful incubation T cell, and this cell is largely injected into patient's body, to enhance immune system
As a kind of possibility.
T cell cultivate mainly using two methods in the prior art, one kind is to use Tissue Culture Dish, high-grade
Laminar flow hood and carbon dioxide incubator cultivated, this method efficiency is lower, is not able to satisfy clinical demand；Another kind is logical
It crosses hollow fiber reactor to cultivate the cells, one of culture apparatus is sequentially connected referring specifically to Fig. 1 by diversion pipe
Main circulation pump 1, gas exchanges pipe 2, culture tube 3 and culture solution master library 4, be provided on the culture solution master library 4 with it is extraneous even
Logical gas vent；Wherein, the culture tube 3 is hollow fiber reactor, and the diversion pipe includes connecting 1 He of main circulation pump
First diversion pipe 11 of the gas exchanges pipe 2, the connection gas exchanges pipe 2 and the culture tube 3 the second diversion pipe 12,
It connects the third diversion pipe 13 of the culture tube 3 and the culture solution master library 4 and connects the culture solution master library 4 and the master
4th diversion pipe 14 of circulating pump 1, the third diversion pipe 13 are connected to by the 5th diversion pipe 15 with waste tank 5, wherein institute
Stating hollow fiber reactor 3 includes the culture solution channel 31 for flowing through culture solution and the cell growth chamber for inoculating cell
32, the culture solution that culture solution channel 31 flows through can be entered in the cell growth chamber by hollow fiber conduit to be provided for the cell
Nutrition cultivates the cells, and the cell growth chamber 32 is connected to the 5th diversion pipe 15 by the 6th diversion pipe 16, carefully
Born of the same parents cultivate caused by waste liquid can be drained into waste tank 5 through the 6th diversion pipe 16, in this incubation, extraneous oxygen and
Carbon dioxide can be dissolved in the culture solution for flowing through the gas exchanges pipe 2, and required carbon dioxide is provided for cell culture
With the gases such as oxygen, still, for different cells, the concentration of the gases such as required carbon dioxide and oxygen is different, uses
The gas exchanger 2, the gases such as carbon dioxide and oxygen dissolved in culture solution are limited, limit the culture and industry of cell
Metaplasia produces.
Summary of the invention
The embodiment of the present invention provides a kind of cell culture circulatory system, can be passed through gas as needed, increases gas
With the contact area of culture solution, meltage is improved, can satisfy the culture and industrialization production of cell.
In order to achieve the above objectives, the embodiment of the present invention adopts the following technical scheme that
The embodiment of the present invention provides a kind of cell culture circulatory system, comprising:
The culture solution conveying device and hollow fiber reactor being connected to by the circulation conduit of culture solution, the hollow fibre
Tieing up reactor includes culture solution channel and cell growth chamber；
The culture solution conveying device includes gas dissolver, and the gas dissolver is internally provided with mixing chamber, institute
The air inlet, inlet and liquid outlet for offering on gas dissolver and being connected to the mixing chamber are stated, the gas dissolver is logical
The inlet and the liquid outlet is crossed to be connected to the culture solution channel cycle.
Preferably, hollow fiber conduit is provided in the mixing chamber, the mixing chamber is divided by the hollow fiber conduit
Culture solution flows through side and gas flow side, and the gas flow side is in communication with the outside by the air inlet.
Preferably, the cell culture circulatory system further includes that carbon dioxide provides device and oxygen offer device, described
The outlet that carbon dioxide provides the outlet of device and the oxygen provides device is connected to the air inlet of the gas flow side,
The carbon dioxide provides and is provided with the first valve between device and the gas flow side, the oxygen provide device with it is described
The second valve is provided between gas flow side.
Optionally, the cell culture circulatory system further includes pH sensor and dissolved oxygen quantity sensor, the pH sensor
The culture solution is arranged in the dissolved oxygen quantity sensor to flow through on the circulation conduit that side is connected to the culture solution channel, it is described
For detecting to the pH value of the culture solution in the circulation conduit, the dissolved oxygen quantity sensor is used for described pH sensor
The dissolved oxygen amount of culture solution in circulation conduit is detected.
Further, the cell culture circulatory system further includes controller, and the controller is sensed with the pH respectively
Device, the first valve, dissolved oxygen quantity sensor and the electrical connection of the second valve, what the controller was used to be sent according to the pH sensor
First valve opening is adjusted in pH signal, so that the pH value of the culture solution in the circulation conduit is maintained at first in advance
If in range, second valve opening is adjusted according to the dissolved oxygen amount signal that the dissolved oxygen quantity sensor is sent, so that
The dissolved oxygen amount of culture solution in the circulation conduit is maintained in the second preset range.
Preferably, the culture solution conveying device further includes circulating pump, the output end of the circulating pump and the culture solution
Flow through the inlet connection of side, the outlet of input terminal and the culture solution channel, the circulating pump and controller electricity
Connection；
The cell culture circulatory system further includes pressure extension box；Filled with gas, the pressure in the pressure extension box
The bottom of power extension box is connected to the culture solution channel or the cell growth chamber, and the controller is also used to control described
Circulating pump conveys culture solution to the culture solution channel in the form of impulse wave, so that the culture solution channel and the cell are raw
The pressure difference of long chamber is positive and negative alternately to be changed, and the pressure extension box is used for the variation by gas volume so that the culture solution is logical
The pressure balance in road and the cell growth chamber.
Further, the cell growth chamber is provided with first pressure sensor, the liquid outlet of the gas dissolver with
It is provided with second pressure sensor on the circulation conduit of the culture solution channel connection, the controller is pressed with described first respectively
Force snesor, second pressure sensor and circulating pump electrical connection, the controller are used to be sensed according to the first pressure
The pressure that device and the second pressure sensor are sent is controlled the circulating pump and is handed over the first pre-set velocity and the second pre-set velocity
Culture solution is conveyed for the culture solution channel.
Preferably, the cell culture circulatory system further includes sealant supplement cylinder and culture solution delivery pump, and the sealant supplement cylinder goes out
Mouthful be connected to the input terminal of the culture solution delivery pump, the output end of the culture solution delivery pump and the cell growth chamber into
Mouth connection, the controller are electrically connected with the culture solution delivery pump, are also used to control the culture solution delivery pump and are opened, pass through
The sealant supplement cylinder directly conveys culture solution to the cell growth chamber.
Preferably, it is additionally provided on the circulation conduit that the liquid outlet of the gas dissolver is connected to the culture solution channel
First temperature sensor, first temperature sensor are used to detect the temperature in the culture solution channel, and the sealant supplement cylinder goes out
Heater, the controller and first temperature are additionally provided on the pipeline that mouth is connected to the input terminal of the culture solution delivery pump
Sensor and heater electrical connection are spent, the controller is also used to the temperature signal sent according to first temperature sensor,
The open and close of the second culture solution delivery pump and the heater are controlled, so that the temperature in the culture solution channel
Degree is maintained in third preset range.
Preferably, second is additionally provided on the pipeline of the culture solution delivery pump and the inlet communication of the cell growth chamber
Temperature sensor, the controller are electrically connected with the second temperature sensor, and the controller is also used to according to described second
Temperature sensor send temperature signal the heating temperature of the heater is adjusted so that the culture solution delivery pump and
The temperature for the culture solution that the pipeline of the inlet communication of the cell growth chamber flows through is maintained in the 4th preset range.
A kind of cell culture circulatory system provided in an embodiment of the present invention, gas dissolver includes mixing in the circulatory system
Chamber, when culture solution flows through the gas dissolver by the inlet and the liquid outlet, Xiang Suoshu air inlet is passed through gas
Body, gas can contact in the mixing chamber with liquid, and be dissolved in liquid, so as to be passed through gas as needed,
The meltage of gas is controlled, the culture and industrialization production of cell are met.
Detailed description of the invention
Fig. 1 is a kind of structural schematic diagram for cell culture system that the prior art provides；
Fig. 2 is a kind of structural schematic diagram of cell cycle culture systems provided in an embodiment of the present invention；
Fig. 3 is the structural schematic diagram of another cell cycle culture systems provided in an embodiment of the present invention；
Fig. 4 is the structural schematic diagram of another cell cycle culture systems provided in an embodiment of the present invention；
Fig. 5 is the structural schematic diagram of another cell cycle culture systems provided in an embodiment of the present invention；
Fig. 6 is the structural schematic diagram of another cell cycle culture systems provided in an embodiment of the present invention；
Fig. 7 is the structural schematic diagram of another cell cycle culture systems provided in an embodiment of the present invention.
Specific embodiment
A kind of cell culture circulatory system provided in an embodiment of the present invention is described in detail with reference to the accompanying drawing.
In the description of the present invention, it is to be understood that, term " center ", "upper", "lower", "front", "rear", " left side ",
The orientation or positional relationship of the instructions such as " right side ", "vertical", "horizontal", "top", "bottom", "inner", "outside" is based on the figure
Orientation or positional relationship is merely for convenience of description of the present invention and simplification of the description, rather than the device of indication or suggestion meaning or
Element must have a particular orientation, be constructed and operated in a specific orientation, therefore be not considered as limiting the invention.
Term " first ", " second " be used for descriptive purposes only and cannot be understood as indicating or suggesting relative importance or
Implicitly indicate the quantity of indicated technical characteristic." first " is defined as a result, the feature of " second " can be expressed or imply
Ground includes one or more of the features.
It should be noted that the cell culture circulatory system provided in an embodiment of the present invention is suitable for the culture of various cells,
According to the different only by environmental parameter needed for changing various cell growths of cell category, for example, respectively being sought in culture solution
Support the concentration parameter of substance, carbon dioxide concentration parameter and oxygen concentration parameter etc.；The embodiment of the present invention is particularly suitable for suspending
The culture of cell and attached cell.
The embodiment of the present invention provides a kind of cell culture circulatory system, referring to fig. 2, comprising:
The culture solution conveying device (not shown) and doughnut reaction being connected to by the circulation conduit of culture solution
Device 3, the hollow fiber reactor 3 include culture solution channel 31 and cell growth chamber 32；
The culture solution conveying device includes gas dissolver 2, and the gas dissolver 2 is internally provided with mixing chamber,
The air inlet, inlet and liquid outlet being connected to the mixing chamber, the gas dissolver are offered on the gas dissolver 2
2 are connected to by the inlet and the liquid outlet with the culture solution channel 31 circulation.
The embodiment of the present invention provides a kind of cell culture circulatory system, and gas dissolver 2 includes mixing in the circulatory system
Chamber, when culture solution flows through the gas dissolver by the inlet and the liquid outlet, Xiang Suoshu air inlet is passed through gas
Body, gas can contact in the mixing chamber with liquid, and be dissolved in liquid, so as to be passed through gas as needed,
The meltage of gas is controlled, the culture and industrialization production of cell are met.
In one embodiment of the invention, referring to Fig. 3, hollow fiber conduit 21, the hollow fibre are provided in the mixing chamber
The mixing chamber is divided into culture solution and flows through side 22 and gas flow side 23 by dimension pipe 21, and the gas flow side 23 passes through described
Air inlet is in communication with the outside.
By the way that hollow fiber conduit 21 is arranged, it is capable of increasing the contact area of the gas Yu the culture solution, increases gas
Dissolved efficiency.
In one embodiment of the invention, referring to Fig. 3, the cell culture circulatory system further includes that carbon dioxide provides device
01 and oxygen device 02 is provided, the carbon dioxide provide device 01 outlet and oxygen offer device 02 outlet with
The air inlet of the gas flow side 23 is connected to, and the carbon dioxide provides the pipe that device 01 is connected to the gas flow side 23
It is provided with the first valve a on road, the oxygen, which provides, is provided with the on the pipeline that device 02 is connected to the gas flow side 23
Two valve b.
In embodiments of the present invention, it by opening and closing the first valve a and the second valve b, can control described
Carbon dioxide provide device 01 and the oxygen provide device 02 to the gas flow side convey a certain amount of carbon dioxide and
Oxygen controls so as to flow through the meltage of carbon dioxide and oxygen of culture solution of side to the culture solution.
In another embodiment of the present invention, referring to Fig. 3, the cell culture circulatory system further includes pH sensor 03 and molten
The culture solution of the gas dissolver 2 is arranged in oxygen amount sensor 04, the pH sensor 03 and the dissolved oxygen quantity sensor 04
It flows through on the circulation conduit that side 22 is connected to the culture solution channel 31 of the hollow fiber reactor 3, the pH sensor 03 is used
It is detected in the pH value to the culture solution in the circulation conduit, the dissolved oxygen quantity sensor 04 is used for the circulation conduit
Dissolved oxygen amount in interior culture solution is detected.
It is detected by pH value of the pH sensor 03 to the culture solution in the circulation conduit, it can be according to testing result
The flow for being passed through carbon dioxide is adjusted, by dissolved oxygen quantity sensor 04 to the dissolved oxygen of the culture solution in the circulation conduit
Amount is detected, can the flow according to testing result to the oxygen being passed through be adjusted, enable cell in suitable acid
Alkalinity and dissolved oxygen amount are cultivated.
In one embodiment of the invention, the cell culture circulatory system further includes controller (not shown), described
Controller is electrically connected with the pH sensor 03, the first valve a, dissolved oxygen quantity sensor 04 and the second valve b respectively, the control
The first valve a aperture is adjusted in the pH signal that device is used to be sent according to the pH sensor 03, so that the circulation
The pH value of culture solution in conduit is maintained in the first preset range, the oxygen concentration sent according to the dissolved oxygen quantity sensor 04
The second valve b aperture is adjusted in signal, so that the oxygen concentration of the culture solution in the circulation conduit is maintained at
In two preset ranges.
By the way that controller is arranged, the pH value and dissolved oxygen amount can be carried out automating accurate control.
In another embodiment of the present invention, referring to fig. 4, the culture solution conveying device further includes circulating pump 1, the circulation
The output end of pump 1 is connected to the inlet that the culture solution flows through side 22, and the outlet in input terminal and the culture solution channel 31 connects
Logical, the circulating pump 1 is electrically connected with the controller；
The cell culture circulatory system further includes pressure extension box 6；It is described filled with gas in the pressure extension box 6
The bottom of pressure extension box 6 is connected to the culture solution channel 31 or the cell growth chamber 32, and the controller is also used to
It controls the circulating pump 1 and conveys culture solution to the culture solution channel 31 in the form of impulse wave, so that the culture solution channel
11 and the cell growth chamber 32 pressure difference it is positive and negative when alternately changing, the pressure extension box is used for through the change of gas volume
Change the pressure balance so that the culture solution channel 31 and the cell growth chamber 32.
In embodiments of the present invention, it by the way that pressure extension box 6 is arranged, is grown in the culture solution channel 31 and the cell
The pressure difference of chamber 32 is timing, and the culture solution in culture solution channel 31 enters the cell growth chamber 32, the pressure extension box 6
Gas volume is compressed into the pressure balance in the culture solution channel 31 and the cell growth chamber 32, it is logical in the culture solution
When the pressure difference of road 31 and the cell growth chamber 32 is negative, the waste liquid of the cell growth chamber 32 enters the culture solution channel
11, the gas volume of the pressure extension box 6 increases the pressure until the culture solution channel 31 and the cell growth chamber 32
Balance, can be realized the exchange to culture solution in cell cultivation process and waste liquid, to reduce the consumption of culture solution, also, also
The loss that the substance for being conducive to cell growth in the waste liquid generated in cell cultivation process can be reduced, simulates In vivo culture ring
Cell culture effect is improved in border.
It should also be noted that, it is raw suspension cell directly can be inoculated in cell when cultivating suspension cell
In long chamber 32, cell is in suspended state, and when cultivating attached cell, it needs to carry out the surface of cell growth chamber 32
Pretreatment, for example, when the inside of the hollow fiber conduit is cell growth chamber 32, then on the inner wall of the hollow fiber conduit
It is laid with one layer of albumen, the inner wall for enabling cell to be attached to the hollow fiber conduit carries out adhere-wall culture.Vice versa.
For different cell categories, the exchange capacity of culture solution and waste liquid is also different, and is applied to the training
Pressure difference between nutrient solution channel 31 and the cell growth chamber 32 would also vary from, for example, the attached cell with it is described
Suspension cell is compared, and is attached on the tube wall of the hollow fiber conduit due to attached cell, to culture solution and can more or less be given up
The exchange of liquid generates blocking, therefore, when usual attached cell is cultivated the culture solution channel 31 and the cell growth chamber 32 it
Between pressure difference be slightly larger than suspension cell culture when pressure difference.
In one embodiment of the invention, the cell growth chamber 32 is provided with first pressure sensor 05, the culture solution
It flows through and is provided with second pressure sensor 06 on the circulation conduit that the liquid outlet of side 22 is connected to the culture solution channel 31, it is described
Controller is electrically connected with the first pressure sensor 05, second pressure sensor 06 and the circulating pump 1 respectively, the control
Device is used to follow according to the pressure signal control that the first pressure sensor 05 and the second pressure sensor 06 are sent
Ring pump 1 alternately conveys culture solution to the culture solution channel 31 with the first pre-set velocity and the second pre-set velocity.
In embodiments of the present invention, it is sensed by controller according to the first pressure sensor 05 and the second pressure
The pressure signal for the cell growth chamber 32 that device 06 is sent is controlled the circulating pump 1 and is handed over the first pre-set velocity and the second pre-set velocity
Culture solution is conveyed for circulation conduit, culture solution is conveyed to the culture solution channel 31 in the form of rectangular wave, so that the training
The pressure in nutrient solution channel 31 is fluctuated, so that the pressure difference of the culture solution channel 31 and the cell growth chamber 32 is just
It is negative alternately to change.
In one embodiment of the invention, referring to Fig. 5, the top of the pressure extension box 6 is provided with the pipe being in communication with the outside
Road 61 is provided with valve c on the pipeline 61, and 6 outside of pressure extension box is from top to bottom respectively in the first height and second
The first liquid level sensor 07 and the second liquid level sensor 08 are provided at height, the controller is passed with first liquid level respectively
Sensor 07, the second liquid level sensor 08 and third valve c electrical connection, the controller are used in first liquid level sensor 07
Detect that the valve c is controlled when the liquid level of culture solution reaches the first height to be opened, and is filled in Xiang Suoshu pressure extension box 6
Gas controls the valve c when second liquid level sensor 08 detects liquid level the second height of arrival of culture solution
Open, the discharge section gas out of described pressure extension box 6 so that the liquid level of the culture solution be maintained at the first height and
Between second height.
With the progress of cell culture, the gas in pressure extension box 6 is possible to occur slowly to leak, and leads to pressure
Gas in extension box 6 is reduced, alternatively, can generate exhaust gas in cell cultivation process, a part of exhaust gas can enter the pressure
In extension box, the gas in pressure extension box 6 is caused to increase, increases the pressure in the pressure extension box 6, pressure extension box 6
Interior gas reduces or increases and can all have an impact to the exchange capacity of culture solution and waste liquid, therefore, passes through the first liquid level sensor
07 and second liquid level sensor 08 liquid level of culture solution is detected, and controlled by the controller to the pressure
It is filled with gas in extension box 6 or releases gas out of described pressure extension box 6, is able to maintain in the pressure extension box 6
Gas flow, convenient for controlling the exchange capacity of culture solution and waste liquid.
In one embodiment of the invention, referring to Fig. 5, the culture solution conveying device further includes culture liquid storage tank 4, the training
The outlet of nutrient solution storage tank 4 is connected to the input terminal of the circulating pump 1, the outlet of import and the culture solution channel 31, institute
Stating the cell culture circulatory system further includes waste tank 5 and waste liquid delivery pump 51, the input terminal of the waste liquid delivery pump with it is described
Pipeline connection between nutrient solution storage tank 4 and the culture solution channel 31, output end are connected to the waste tank 5, the control
Device is electrically connected with the waste liquid delivery pump 51, and the controller is also used to control the waste liquid delivery pump 51 every preset time and open
It opens, the culture solution in the circulation conduit is drained into the waste tank 5.
With the culture of cell, the waste liquid that cell generates is more and more, at this moment can be rule of thumb when by certain
Between after, by the controller control waste liquid delivery pump 51 open, by the culture solution in the circulation conduit drain into waste liquid storage
In tank 5, culture solution update can be carried out to cell culture in time.
It is, of course, also possible to detection is sampled to the culture solution flowed through in the circulation conduit in cell cultivation process,
When testing result is not suitable for cell culture, then the waste liquid delivery pump 52 is controlled by the controller and opened, followed described
Culture solution in ring conduit drains into waste tank 5.
In another embodiment of the present invention, referring to Fig. 6, the cell culture circulatory system further includes sealant supplement cylinder 7 and culture
The outlet of liquid delivery pump 71, the sealant supplement cylinder 7 is connected to the input terminal of the culture solution delivery pump 71, the culture solution delivery pump
71 output end and the inlet communication of cell growth chamber 32, the controller are also electrically connected with the culture solution delivery pump 71, also
It is opened for controlling the culture solution delivery pump 71, is directly conveyed and cultivated to the cell growth chamber 32 by the sealant supplement cylinder 7
Liquid.
By the way that culture solution delivery pump 71 is arranged, the training can be opened when the waste liquid of cell growth chamber has little time exchange
Nutrient solution delivery pump 71 directly conveys culture solution to the cell growth chamber 32 by the sealant supplement cylinder 7, additionally it is possible to need to increase
When the pressure of the cell growth chamber 32 makes the pressure difference of culture solution channel 31 and the cell growth chamber 32 change, open
The culture solution delivery pump 71 is opened, culture solution is directly conveyed to the cell growth chamber 32 by the sealant supplement cylinder 7, promotes culture
The exchange of liquid and waste liquid.
In another embodiment of the present invention, referring to Fig. 7, the liquid outlet of the gas dissolver 2 and the culture solution channel
Be additionally provided with the first temperature sensor 09 on the circulation conduits of 31 connections, the sealant supplement cylinder and the culture solution delivery pump 71 it is defeated
Enter upper setting having heaters 8, the controller on the pipeline between end to be electrically connected with first temperature sensor 09 and heater 8
It connects, the controller is also used to the temperature signal sent according to first temperature sensor 09, to the culture solution delivery pump
71 and the open and close of the heater 8 controlled so as to be maintained at third default for the temperature in the culture solution channel 31
In range.
In embodiments of the present invention, the temperature signal sent according to first temperature sensor 09, controls the culture
The open and close of liquid delivery pump 71 and the heater are controlled, the culture solution that can be conveyed to the culture solution delivery pump
Temperature controlled, can be to described to be exchanged by heat between the culture solution and the culture solution channel 31
The temperature in culture solution channel 31 is adjusted.
In one embodiment of the invention, the import of the output end of the culture solution delivery pump 71 and the cell growth chamber 32
Second temperature sensor 010 is additionally provided on the pipeline of connection, the control system is electrically connected with the second temperature sensor 010
It connects, the control system is also used to add the heater according to the temperature signal that the second temperature sensor 010 is sent
Hot temperature is adjusted, so that the pipe of the output end of the culture solution delivery pump 71 and the inlet communication of the cell growth chamber 32
The temperature for the culture solution that road flows through is in the 4th preset range.
By the way that second temperature sensor 010 is arranged, the heating temperature of the heater 8 can be controlled, avoid temperature
The high or too low activity to cell is spent to impact.
In another embodiment of the present invention, the inlet communication of the culture solution delivery pump 71 and the cell growth chamber 32
Third pressure sensor 011 is additionally provided on pipeline, the control system is electrically connected with the third pressure sensor 011, institute
It is defeated to the culture solution delivery pump 71 to state the pressure signal that control system is also used to send according to the third pressure sensor 011
The speed of culture solution is sent to be controlled, so that the speed of the culture solution delivery pump 71 conveying culture solution is maintained at the 5th default model
In enclosing.
It can be defeated to the culture solution delivery pump 71 by the pressure signal sent according to the third pressure sensor 011
It send the speed of culture solution to be controlled, is controlled so as to the flow to the culture solution delivery pump 71 conveying culture solution,
The heat exchange capacity of itself and the culture solution in the culture solution channel 31 is controlled, and then the culture solution can be accurately controlled
The temperature in channel 31, so that it is maintained in third preset range.
The above description is merely a specific embodiment, but scope of protection of the present invention is not limited thereto, any
Those familiar with the art in the technical scope disclosed by the present invention, can easily think of the change or the replacement, and should all contain
Lid is within protection scope of the present invention.Therefore, protection scope of the present invention should be based on the protection scope of the described claims.
Claims (10)
1. a kind of cell culture circulatory system characterized by comprising
The culture solution conveying device and hollow fiber reactor, the doughnut being connected to by the circulation conduit of culture solution are anti-
Answering device includes culture solution channel and cell growth chamber；
The culture solution conveying device includes gas dissolver, and the gas dissolver is internally provided with mixing chamber, the gas
The air inlet, inlet and liquid outlet being connected to the mixing chamber are offered on body dissolvers, the gas dissolver passes through institute
Inlet and the liquid outlet is stated to be connected to the culture solution channel cycle；
The cell culture circulatory system further includes pressure extension box；Filled with gas in the pressure extension box, the pressure expands
The bottom of exhibition case is connected to the culture solution channel or the cell growth chamber, and the pressure extension box is used in the culture
When the positive and negative alternating of the pressure difference of liquid channel and the cell growth chamber changes, by the variation of gas volume so that the culture solution
The pressure balance in channel and the cell growth chamber.
2. the cell culture circulatory system according to claim 1, which is characterized in that
Hollow fiber conduit is provided in the mixing chamber, the mixing chamber is divided into culture solution and flows through side by the hollow fiber conduit
With gas flow side, the gas flow side is in communication with the outside by the air inlet.
3. the cell culture circulatory system according to claim 1, which is characterized in that
The cell culture circulatory system further includes that carbon dioxide provides device and oxygen offer device, and the carbon dioxide provides
The outlet that the outlet of device and the oxygen provide device is connected to the air inlet of the gas flow side, the carbon dioxide
There is provided and be provided with the first valve between device and the gas flow side, the oxygen provide device and the gas flow side it
Between be provided with the second valve.
4. the cell culture circulatory system according to claim 1 or 3, which is characterized in that
The cell culture circulatory system further includes pH sensor and dissolved oxygen quantity sensor, the pH sensor and the dissolved oxygen amount
Sensor is arranged in the culture solution and flows through on the circulation conduit that side is connected to the culture solution channel, and the pH sensor is used for
The pH value of culture solution in the circulation conduit is detected, the dissolved oxygen quantity sensor is used for in the circulation conduit
The dissolved oxygen amount of culture solution is detected.
5. the cell culture circulatory system according to claim 4, which is characterized in that
The cell culture circulatory system further includes controller, the controller respectively with the pH sensor, the first valve, molten
Oxygen amount sensor and the electrical connection of the second valve, the pH signal that the controller is used to be sent according to the pH sensor is to described the
One valve opening is adjusted, so that the pH value of the culture solution in the circulation conduit is maintained in the first preset range, according to
Second valve opening is adjusted in the dissolved oxygen amount signal that the dissolved oxygen quantity sensor is sent, so that in the circulation conduit
The dissolved oxygen amount of culture solution be maintained in the second preset range.
6. the cell culture circulatory system according to claim 5, which is characterized in that
The culture solution conveying device further includes circulating pump, and the output end of the circulating pump flows through the feed liquor of side with the culture solution
Mouth connection, the outlet of input terminal and the culture solution channel, the circulating pump are electrically connected with the controller, the circulation
Pump is for conveying culture solution to the culture solution channel in the form of impulse wave under the control of the controller, so that the training
The pressure difference of nutrient solution channel and the cell growth chamber is positive and negative alternately to be changed.
7. the cell culture circulatory system according to claim 6, which is characterized in that
The cell growth chamber is provided with first pressure sensor, and the culture solution flows through the liquid outlet of side and the culture solution leads to
Be provided with second pressure sensor on the circulation conduit of road connection, the controller respectively with the first pressure sensor, the
Two pressure sensors and circulating pump electrical connection, the controller are used for according to the first pressure sensor and described second
The pressure that pressure sensor is sent controls the circulating pump with the first pre-set velocity and the second pre-set velocity alternately to the culture
Liquid channel conveys culture solution.
8. the cell culture circulatory system according to claim 5, which is characterized in that
The cell culture circulatory system further includes sealant supplement cylinder and culture solution delivery pump, and the sealant supplement cylinder and the culture solution convey
The input terminal of pump is connected to, the inlet communication of the output end of the culture solution delivery pump and the cell growth chamber, the controller
Be electrically connected with the culture solution delivery pump, be also used to control the culture solution delivery pump and open, by the sealant supplement cylinder directly to
The cell growth chamber conveys culture solution.
9. the cell culture circulatory system according to claim 8, which is characterized in that
The first temperature is additionally provided on the circulation conduit that the liquid outlet that the culture solution flows through side is connected to the culture solution channel
Sensor, first temperature sensor are used to detect the temperature in the culture solution channel, the sealant supplement cylinder and the culture solution
Heater, the controller and first temperature sensor and heating are additionally provided on pipeline between the input terminal of delivery pump
Device electrical connection, the controller is also used to the temperature signal sent according to first temperature sensor, defeated to the culture solution
The open and close of pump and the heater are sent to be controlled, so that the temperature in the culture solution channel is maintained at third and presets model
In enclosing.
10. the cell culture circulatory system according to claim 9, which is characterized in that
It is additionally provided with second temperature sensor on the pipeline of the culture solution delivery pump and the inlet communication of the cell growth chamber,
The controller is electrically connected with the second temperature sensor, and the controller is also used to be sent out according to the second temperature sensor
The heating temperature of the heater is adjusted in the temperature signal sent, so that the culture solution delivery pump and cell growth
The temperature for the culture solution that the pipeline of the inlet communication of chamber flows through is maintained in the 4th preset range.
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| CN107043734B (en) * | 2017-05-26 | 2020-12-25 | 奥凯（苏州）生物技术有限公司 | Automatic cell collection method of cell amplification system |
| CN107189975B (en) * | 2017-05-26 | 2020-12-25 | 奥凯（苏州）生物技术有限公司 | Cell collection method of closed cell amplification system |
| CN107523497A (en) * | 2017-08-25 | 2017-12-29 | 江阴瑞康健生物医学科技有限公司 | A kind of gas-liquid exchange device |
| CN110055173A (en) * | 2019-03-13 | 2019-07-26 | 浙江大学 | A kind of ferment fermentor |
| CN110106084A (en) * | 2019-05-17 | 2019-08-09 | 西南交通大学 | Cell culture apparatus and the method for making culture medium hydrogen-rich |
| CN111197006B (en) * | 2020-01-16 | 2023-09-12 | 杭州键一生物科技有限公司 | CAR-T cell expander |
| CN112940934B (en) * | 2021-01-29 | 2023-11-07 | 上海睿钰生物科技有限公司 | In-vitro life support perfusion culture system and control method thereof |
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