CN108823094A - cell culture system and method - Google Patents
cell culture system and method Download PDFInfo
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- CN108823094A CN108823094A CN201810367505.XA CN201810367505A CN108823094A CN 108823094 A CN108823094 A CN 108823094A CN 201810367505 A CN201810367505 A CN 201810367505A CN 108823094 A CN108823094 A CN 108823094A
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- 238000004113 cell culture Methods 0.000 title claims abstract description 101
- 238000000034 method Methods 0.000 title abstract description 10
- 230000035699 permeability Effects 0.000 claims abstract description 76
- 239000007789 gas Substances 0.000 claims description 317
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 claims description 123
- 238000010438 heat treatment Methods 0.000 claims description 120
- 229910002092 carbon dioxide Inorganic materials 0.000 claims description 60
- 239000001569 carbon dioxide Substances 0.000 claims description 60
- 239000000523 sample Substances 0.000 claims description 39
- 239000000203 mixture Substances 0.000 claims description 29
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 21
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 18
- 229910052760 oxygen Inorganic materials 0.000 claims description 18
- 239000001301 oxygen Substances 0.000 claims description 18
- 238000004891 communication Methods 0.000 claims description 10
- 229910052751 metal Inorganic materials 0.000 claims description 10
- 239000002184 metal Substances 0.000 claims description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims description 10
- 229910052799 carbon Inorganic materials 0.000 claims description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 7
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 7
- 229910000831 Steel Inorganic materials 0.000 claims description 7
- 239000000741 silica gel Substances 0.000 claims description 7
- 229910002027 silica gel Inorganic materials 0.000 claims description 7
- 239000010959 steel Substances 0.000 claims description 7
- 238000012549 training Methods 0.000 claims description 7
- 241000790917 Dioxys <bee> Species 0.000 claims description 5
- 230000005540 biological transmission Effects 0.000 claims description 5
- 230000008859 change Effects 0.000 claims description 4
- 238000012546 transfer Methods 0.000 claims description 4
- 239000003292 glue Substances 0.000 claims description 3
- 241000208340 Araliaceae Species 0.000 claims 2
- 235000005035 Panax pseudoginseng ssp. pseudoginseng Nutrition 0.000 claims 2
- 235000003140 Panax quinquefolius Nutrition 0.000 claims 2
- 235000008434 ginseng Nutrition 0.000 claims 2
- 229910001873 dinitrogen Inorganic materials 0.000 claims 1
- 230000029058 respiratory gaseous exchange Effects 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 9
- 229960004424 carbon dioxide Drugs 0.000 description 53
- 239000003570 air Substances 0.000 description 21
- 239000007788 liquid Substances 0.000 description 11
- 238000010586 diagram Methods 0.000 description 9
- 230000004663 cell proliferation Effects 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 5
- 230000001105 regulatory effect Effects 0.000 description 5
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 4
- 230000010261 cell growth Effects 0.000 description 4
- 238000012544 monitoring process Methods 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 229910002090 carbon oxide Inorganic materials 0.000 description 3
- 230000003068 static effect Effects 0.000 description 3
- 230000036760 body temperature Effects 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 238000000465 moulding Methods 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 239000004408 titanium dioxide Substances 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 1
- 241001206171 Stomoxys omega Species 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 238000004378 air conditioning Methods 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 239000012159 carrier gas Substances 0.000 description 1
- 239000012930 cell culture fluid Substances 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 230000005611 electricity Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012806 monitoring device Methods 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
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- 238000004088 simulation Methods 0.000 description 1
- 230000036413 temperature sense Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
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- 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
- C12M23/00—Constructional details, e.g. recesses, hinges
- C12M23/02—Form or structure of the vessel
- C12M23/14—Bags
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- C12M23/00—Constructional details, e.g. recesses, hinges
- C12M23/24—Gas permeable parts
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- C12M23/00—Constructional details, e.g. recesses, hinges
- C12M23/48—Holding appliances; Racks; Supports
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- C12M27/00—Means for mixing, agitating or circulating fluids in the vessel
- C12M27/16—Vibrating; Shaking; Tilting
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- C12M29/26—Conditioning fluids entering or exiting the reaction vessel
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- C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
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- C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
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- C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
- C12M41/12—Means for regulation, monitoring, measurement or control, e.g. flow regulation of temperature
- C12M41/18—Heat exchange systems, e.g. heat jackets or outer envelopes
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- 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
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Abstract
The invention discloses cell culture system and methods, including main control unit, sub-control unit, closed box and gas permeability cell culture bags；Main control unit, which is used to receive the parameter information of user setting and controls each sub-control unit according to parameter information, executes corresponding operating；When the air pressure of mixed gas in the closed box reaches limit value, the gas stop valve that main control unit control is set at the gas output interface of closed box is opened until control gas stop valve is closed when air pressure is down in limit value.Pass through the effect of closed box, a stable gas concentration lwevel environment (5%) is provided for gas permeability cell culture bags, also it can effectively avoid heat loss, prevent temperature in gas permeability cell culture bags from larger fluctuation occur, provide a stable temperature environment (37 DEG C).
Description
Technical field
The present invention relates to bio-medical technology fields, in particular to a kind of cell culture system and method.
Background technique
Traditional cell culture mode is to be cultivated using culture dish or culture bottle in carbon dioxide incubator, in dioxy
Change gas concentration lwevel (5%), humidity (95%) and temperature (37 that simulation in carbon incubator box body forms the growth of a cell
DEG C) environment.
With it is traditional with culture dish or culture bottle culture cell compared with, gas permeability cell culture bags have that culture amount is big, effect
Rate height, safe operation, it is not easy to pollute the advantages that, also be used to be placed on the training that cell is carried out in carbon dioxide incubator at present
It supports.
In existing culture systems, gas permeability cell culture bags, which are generally suspended in carbon dioxide incubator, to be stood
Cell culture causes the mixing of bag inner cell mixed liquor to be not enough and uniformly since gas permeability cell culture bags are static conditions,
Influence the speed of cell proliferation and growth.Based on gas permeability cell culture bags gas-permeable, liquid-impermeable and isolation bacterium and virus
Characteristic, the carbon dioxide gas mixture in carbon dioxide incubator slowly penetrate gas permeability cell culture under the action of pressure difference
Bag is simultaneously dissolved in cell mixture；It is a kind of in addition, being directly heated in existing carbon dioxide incubator cabinet using six faces
Radiant heating method, heating efficiency is low, and because the mixed liquor capacity in gas permeability cell culture bags is larger, leads to cell mixture
It heats up slower, and then influences the speed of cell proliferation and growth.
Summary of the invention
It is an object of the invention to overcome existing gas permeability cell culture bags to hang on to stand training in carbon dioxide incubator
The mode for supporting cell has that the speed of cell proliferation and growth is impacted, provides a kind of new cell culture system and side
Method.
To achieve the above object, the cell culture system designed by the present invention, including：It is main control unit, sub-control unit, close
Closed box and the gas permeability cell culture bags in the closed box case；The main control unit is used to receive the parameter of user setting
Information simultaneously controls each sub-control unit execution corresponding operating according to parameter information；The sub-control unit includes that temperature control is single
Member, gas control unit and shake control unit；
The main control unit includes operating system and the central controller that is electrically connected with the operating system；The operation system
System include the parameter information for receiving user setting and by parameter information be sent to the central controller input system and
What is be electrically connected with the input system is used to show and be arranged the operation interface of parameter information；
The parameter information includes temperature parameter information, gas parameter information and shake parameter information；The temperature parameter
Information includes the temperature information that need to be heated and maintain；The gas parameter information includes the type, concentration and flow information of gas；
The parameter information that shakes includes angle, speed and the location information shaken；
Internally the gas permeability containing cell mixture is thin according to parameter information control heating device for the temperature control unit
Born of the same parents' culture bag heats, and the heating shape for the temperature data adjustment heating device for acquiring and feeding back in real time according to temp probe
State；
The shake control unit controls agitating device according to parameter information and starts or stops；The agitating device is for driving
The dynamic closed box for carrying gas permeability cell culture bags carries out eccentric rotary；
The gas control unit enters the concentration of carbon dioxide in gas mixture in closed box according to parameter information control,
And the concentration is adjusted in real time according to density of carbon dioxide gas sensor feedback data；
The closed box is equipped with for the gas input interface of mixed gas input and exports for extra mixed gas
Gas output interface；The gas input interface is communicated with HEPA filter；The gas output interface is communicated with gas and cuts
Only valve；When the air pressure of mixed gas in the closed box reaches limit value, the main control unit control gas stop valve is opened
Until control gas stop valve is closed when air pressure is down in limit value.
Preferably, the temperature control unit include with the temperature control modules of the central controller communication connection, with
The heating device controller and central temperature probe of temperature control modules electrical connection and with the heating device controller electricity
The heating device for connecting and being placed in the closed box；The central temperature probe is for acquiring gas permeability cell culture bags temperature
Degree, and by the central temperature data real-time transmission of acquisition to temperature control modules；The central controller and the temperature control
Real-Time Signal Transfer is carried out between module；Central temperature data are compared the central controller with temperature parameter information sentences
It is disconnected to obtain central temperature comparison result signal and central temperature comparison result signal is fed back into the temperature control modules；It is described
Central temperature comparison result signal is sent to the heating device controller by temperature control modules；The heating device controller
The heated condition of heating device is controlled according to central temperature comparison result signal.
Still further, the temperature control unit further includes being electrically connected with the temperature control modules for acquiring institute
State the heating device temp probe of heating device temperature；The heating device temp probe is real-time by the heating temperature data of acquisition
It is sent to temperature control modules；Heating temperature data are compared judgement with temperature parameter information and obtained by the central controller
Heating temperature comparison result signal is simultaneously fed back to the temperature control modules by heating temperature comparison result signal；The temperature control
Heating temperature comparison result signal is sent to the heating device controller by molding block；The heating device controller according to plus
The heated condition of hot temperature comparison result signal control heating device.
Further, the temperature control unit further includes that the environment temperature being electrically connected with the temperature control modules is visited
Head；The ambient temperature data information of acquisition is sent to the center through temperature control modules and controlled by the environment temperature probe
Ambient temperature data information is fed back to the operation interface of the operating system by device, the central controller.
Preferably, the heating device includes horizontally disposed metal plate, glue connection in the silica gel plate of the metal plate lower end
And the resistance wire inside the silica gel plate；The metal plate upper end is abutted with the gas permeability cell culture bags.Heat
Device heats gas permeability cell culture bags by the way of contact heating.
Further, the gas control unit includes and the Gas Control Module of central controller communication connection, multiple
Gas bomb, set on gas bomb output end and be electrically connected with Gas Control Module gas ratio valve, with gas ratio valve connect
Logical gas mixer and inside gas mixer or the density of carbon dioxide gas sensor of output end；The gas
The output end of body mixing arrangement is connected to the gas input interface of closed box；The density of carbon dioxide gas sensor is by dioxy
Change carbon gas concentration information Real-time Feedback to the Gas Control Module；The Gas Control Module controls each according to parameter information
The opening-closing size of gas ratio valve, and each gas ratio valve is adjusted according to density of carbon dioxide gas sensor feedback data information
Opening-closing size.
Still further, the gas control unit further includes multiple gas flowmeters, each gas ratio valve is corresponding extremely
A few gas flowmeter；The gas flowmeter input terminal is connected to the gas ratio valve output end, and gas flowmeter is defeated
Outlet is connected to gas mixer input terminal.
Further, the gas ratio valve includes carbon dioxide ratio valve, nitrogen ratios valve, oxygen proportion valve and sky
Gas proportioning valve；The gas flowmeter includes carbon dioxide stream meter, nitrogen stream meter, oxygen flow meter and air flow meter；
The gas bomb includes carbon dioxide steel cylinder, nitrogen cylinder, air steel cylinder and oxygen bottle.
Preferably, the shake control unit include with the shake control module of central controller communication connection and with shake
Control module electrical connection agitating device and with shake control module be electrically connected be used for monitor agitating device waving angle/speed
Degree/position angle/speed/positional sensor.
The present invention also provides a kind of cell culture processes, include the following steps：
A) the interior gas permeability cell culture bags equipped with cell mixture are placed on heating device, heating device are placed in close
In closed box, seal box is placed on agitating device；
B parameter information) is input to main control unit by operating system；Main control unit relies on parameter information control
It controls unit and executes corresponding operating control cell culture parameter；Wherein, the sub- control unit includes temperature control unit, gas control
Unit and shake control unit；
Internally the gas permeability containing cell mixture is thin according to parameter information control heating device for the temperature control unit
Born of the same parents' culture bag heats, and the heating shape for the temperature data adjustment heating device for acquiring and feeding back in real time according to temp probe
State；
The shake control unit controls agitating device according to parameter information and starts or stops；The agitating device is for driving
The dynamic closed box for carrying gas permeability cell culture bags carries out eccentric rotary；
The gas control unit enters the concentration of carbon dioxide in gas mixture in closed box according to parameter information control,
And the concentration is adjusted in real time according to density of carbon dioxide gas sensor feedback data；
C) mixed gas is input in closed box, and when air pressure reaches limit value in closed box, main control unit control
Gas stop valve at closed box gas output interface is opened, and mixed gas extra in closed box is discharged.
Further, the parameter information includes temperature parameter information, gas parameter information and shake parameter information；It is described
Temperature parameter information includes the temperature information that need to be heated and maintain；The gas parameter information include the type of gas, concentration and
Flow information；The parameter information that shakes includes angle, speed and the location information shaken.
The beneficial effects of the invention are as follows：A confined space is created by closed box, is on the one hand gas permeability cell culture
Bag provides a stable gas concentration lwevel environment (5%), on the other hand can effectively avoid heat loss, prevents gas permeability
There is larger fluctuation in temperature in cell culture bags, provides a stable temperature environment (37 DEG C).Using the side of contact heating
Formula preferably improves the heating efficiency of the cell mixture in gas permeability cell culture bags, improves the speed of cell proliferation and growth
Degree.By the effect of temperature control unit, can the heated condition of real-time control heating device (starting heating stops heating, continues
Heating), realize the real-time monitoring and control to feedback temperature final in gas permeability cell culture bags；Pass through gas control unit
Effect, not only accelerates the exchange rate of mixed gas in gas permeability cell culture bags, improves dissolved oxygen rate and two in culture solution
Carbonoxide dissolution rate；And can fast, accurately reach parameter value set by user, regulating time is greatly saved, is being
User can also be received in real time to the modification of flow, concentration and gas species parameter and is responded rapidly while system work；
By shaking the effect of control unit, gas permeability cell culture bags can be made to carry out eccentric rotary, to make its internal culture cell
Centering type vortex is carried out, cell can be quickly sufficiently mixed, and due to using external shake power, make gas permeability cell culture
The cell mixture of bag mixes more sufficiently and uniform, is conducive to improve cell state, raising cell density and yield；Pass through
One main control unit controls temperature control unit, gas control unit respectively and shakes control unit, in system architecture and structure
It is different from existing disposable bioreactor in form, and every height control unit belongs to a kind of closed-loop control, so that entirely
System control precision is high, and control stability is good, and system response is fast.
Detailed description of the invention
Fig. 1 is the main control unit of cell culture system of the present invention and the structural block diagram of son control unit.
Fig. 2 is the structural block diagram of temperature control unit in Fig. 1.
Fig. 3 is the partial structural diagram of Fig. 2.
Fig. 4 is that isometric liquid in gas permeability cell culture bags is close with this system in carbon dioxide incubator respectively
The contrast schematic diagram of required heating time when increasing mutually synthermal in closed box.
Fig. 5 is the structural block diagram of gas control unit in Fig. 1.
Fig. 6 is the oxygen dissolving value comparison of the pure water in the gas permeability cell culture bags in carbon dioxide incubator and closed box
Schematic diagram.
Fig. 7 is the structural block diagram that control unit is shaken in Fig. 1.
Fig. 8 is that agitating device is equipped with the structural schematic diagram after closed box in Fig. 7.
Fig. 9 is that the cell liquid of the identical type of equal volume is cultivated in carbon dioxide incubator and closed box respectively
The cell proliferation contrast schematic diagram of same period afterwards.
In figure, 1. main control units；1.1. operating system；1.1.1. input system；1.1.2. operation interface；1.2. center control
Device processed；2. sub-control unit；3. temperature control unit；3.1. temperature control modules；3.2. heating device controller；3.3. center
Temp probe；3.4. heating device；3.4.1. metal plate；3.4.2. silica gel plate；3.4.3. resistance wire；3.5. heating device temperature
Probe；3.6. environment temperature is popped one's head in；4.HEPA filter；5. gas control unit；5.1. Gas Control Module；5.2. gas steel
Bottle；5.3. gas ratio valve；5.4. gas mixer；5.5. density of carbon dioxide gas sensor；5.6. gas flowmeter；
6. shaking control unit；6.1. control module is shaken；6.2. agitating device；6.2.1. driving motor；6.2.2. eccentric shaft；
6.2.3. elastic spacing one；6.3. angle/speed/positional sensor；7. closed box；8. gas permeability cell culture bags；9. gas
Input interface；10. gas output interface；11. gas stop valve.
Specific embodiment
Below in conjunction with the drawings and specific embodiments, the present invention is described in further detail.
Cell culture system as shown in figure 1-9, including main control unit 1, sub-control unit 2, closed box 7 and be set to it is close
Gas permeability cell culture bags 8 in closed box 7 casees；Main control unit 1 is used to receive the parameter information of user setting and is believed according to parameter
Breath controls each sub-control unit 2 and executes corresponding operating；Sub-control unit 2 include temperature control unit 3, gas control unit 5 and
Shake control unit 6；Main control unit 1 includes operating system 1.1 and passes through RS485 bus or wireless telecommunications with operating system 1.1
The central controller 1.2 of connection；
Operating system 1.1 includes the parameter information for receiving user setting and parameter information is sent to central controller
1.2 input system 1.1.1 and the operation interface for being used to show and be arranged parameter information being electrically connected with input system 1.1.1
1.1.2 (can be the combination of touch screen displays or display and operation keyboard).
Parameter information includes temperature parameter information, gas parameter information and shake parameter information；Temperature parameter information includes
The temperature information that need to be heated and maintain；Gas parameter information includes the type, concentration and flow information of gas；Shake parameter information
Angle, speed and location information including shake.
Temperature control unit 3 is thin to the interior gas permeability containing cell mixture according to parameter information control heating device 3.4
Born of the same parents' culture bag 8 heats, and the heating for the temperature data adjustment heating device 3.4 for acquiring and feeding back in real time according to temp probe
State；
Control unit 6 is shaken to be started or stoped according to parameter information control agitating device 6.2；Agitating device 6.2 is for driving
The dynamic closed box 7 for carrying gas permeability cell culture bags 8 carries out eccentric rotary；
Gas control unit 5 enters the concentration of carbon dioxide in gas mixture in closed box 7 according to parameter information control, and
The concentration is adjusted in real time according to 5.5 feedback data of density of carbon dioxide gas sensor；
Closed box 7 is equipped with for the gas input interface 9 of mixed gas input and for the output of extra mixed gas
Gas output interface 10；Gas input interface 9 is communicated with HEPA filter 4；Gas output interface 10 is communicated with gas stop valve
11；When the air pressure of mixed gas in closed box 7 reaches limit value, main control unit 1 controls gas stop valve 11 and opens until gas
Gas stop valve 11 is controlled when in pressure drop to limit value to close.
Temperature control unit 3 as shown in Figure 2,3 includes the temperature control modules with 1.2 communication connection of central controller
3.1, be electrically connected with temperature control modules 3.1 heating device controller 3.2 and central temperature probe 3.3 and with heating device control
The heating device 3.4 processed device 3.2 electrical connection and be placed in closed box 7；Central temperature probe 3.3 is for acquiring the training of gas permeability cell
8 temperature of bag is supported, and by the central temperature data real-time transmission of acquisition to temperature control modules 3.1；Central controller 1.2 and temperature
Real-Time Signal Transfer is carried out between control module 3.1；Central controller 1.2 carries out central temperature data and temperature parameter information
Contrast judgement obtains central temperature comparison result signal and central temperature comparison result signal is fed back to temperature control modules
3.1；Central temperature comparison result signal is sent to heating device controller 3.2 by temperature control modules 3.1；Heating device control
Device 3.2 controls the heated condition of heating device 3.4 according to central temperature comparison result signal.Pass through heating device controller 3.2
The heated condition that heating device 3.4 is controlled according to central temperature comparison result signal, solves existing cell culture system temperature
Unstable problem is controlled, acquisition 8 temperature of gas permeability cell culture bags, real-time control add in real time by central temperature probe 3.3
The heated condition (including starting heating, stopping heating, continuous heating) of thermal 3.4, realizes to gas permeability cell culture bags 8
The real-time monitoring and control of interior final feedback temperature.
Temperature control unit 3 further includes being electrically connected with temperature control modules 3.1 for acquiring 3.4 temperature of heating device
Heating device temp probe 3.5；Heating device temp probe 3.5 controls the heating temperature data real-time transmission of acquisition to temperature
Module 3.1；Heating temperature data judgement are compared with temperature parameter information and show that heating temperature compares by central controller 1.2
Heating temperature comparison result signal is simultaneously fed back to temperature control modules 3.1 by consequential signal；Temperature control modules 3.1 will heat temperature
Degree comparison result signal is sent to heating device controller 3.2；Heating device controller 3.2 is believed according to heating temperature comparison result
Number control heating device 3.4 heated condition.The temperature of heating device 3.4 can be acquired in real time by heating device temp probe 3.5
Degree is realized to the real-time monitoring and control for initially entering temperature in gas permeability cell culture bags 8, and heating device 3.4 is avoided to heat
Cell in the excessively high damage gas permeability cell culture bags 8 of temperature.
Temperature control unit 3 further includes the environment temperature probe 3.6 being electrically connected with temperature control modules 3.1；Environment temperature
The ambient temperature data information of acquisition is sent to central controller 1.2, center control through temperature control modules 3.1 by probe 3.6
Ambient temperature data information is fed back to the operation interface 1.1.2 of operating system 1.1 by device 1.2.User can pass through operation interface
1.1.2 it checks real time environment temperature information, external temperature environment, such as the temperature of air-conditioning is adjusted by ambient temperature data information
Degree.It can effectively avoid that ambient temperature is too high or too low to impact cell culture by environment temperature probe 3.6.Operation
Interface 1.1.2 can be preferably electronic display.
Heating device 3.4 includes horizontally disposed metal plate 3.4.1, glue connection in the silica gel plate of the lower end metal plate 3.4.1
3.4.2 the resistance wire 3.4.3 and inside silica gel plate 3.4.2；The upper end metal plate 3.4.1 is supported with gas permeability cell culture bags 8
It connects.
The closed box 7 of this system may include cabinet and case lid, case lid and cabinet is hinged or removable connection.Gas permeability cell
Culture bag 8 is placed in the cabinet of closed box 7；Heating device 3.4 is placed in 7 bottom of closed box and gas permeability cell culture bags 8 are placed in
On heating device 3.4, heating device 3.4 is made to be connected to 8 lower end outer wall of gas permeability cell culture bags and by the side of contact heating
Formula transfers heat to the cell mixture in gas permeability cell culture bags 8.Central temperature probe 3.3 is set as being connected to ventilative
Property 8 outer wall of cell culture bags, for example central temperature 3.3 lower ends of popping one's head in are fixed on 7 bottom of closed box, and upper end passes through heating device
The temperature sense part of 3.4 rear center's temp probes 3.3 is connected to gas permeability cell culture bags 8.Environment temperature probe 3.6 can be straight
It is arranged in 7 cabinet exterior of closed box and its induction part is placed in air.It the induction part of heating device temp probe 3.5 can be straight
It connects and is connected to heating device 3.4 or heating device temp probe 3.5 is placed directly in heating device 3.4.User passes through operation system
It unites 1.1 input temp parameter informations, for example the temperature for needing to heat, the temperature, maximum temperature, the minimum temperature that need to maintain etc. are i.e.
Can, system will be heated to cell culture required temperature automatically, and temperature is not too high or too low.
The control section of the temperature control unit 3 of this control system is actually a kind of closed-loop control system.Wherein, it operates
System 1.1 is preferably 7 operating system 1.1 of Windows, and central controller 1.2 is preferably MCU central controller 1.2；Temperature control
Molding block 3.1 is preferably embedded temperature control modules 3.1 comprising the pid algorithm based on ARM chip development platform；Using
Serial ports based on RS485 communications protocol is connect with MCU central controller 1.2；For example increment type PID algorithm is used, formula is as follows：
U (k)=kp × error (k)+λ × ki ∑ error (j)+kd (error (k)-error (k-1))
Wherein u (k) is the controlling value at k moment, and error (k) is the relative error at k moment, and kp is proportionality coefficient, and ki is product
Divide coefficient, kd is differential coefficient, and λ is subsection integral variation coefficient.The value of λ changes with the absolute value of relative error and is changed,
When the absolute value of relative error is bigger, i.e., when measured value deviation setting value is bigger, λ takes smaller value, on the contrary, λ takes the larger value.
When the temperature that center temp probe 3.3 acquires is less than 20 DEG C, λ=1.0
When the temperature that center temp probe 3.3 acquires is less than 35 DEG C, λ=0.9
When the temperature that center temp probe 3.3 acquires is less than 40 DEG C, λ=0.6
DB type electric hot plate or the HTL-500/400/300EX type nanometer heating plate of NanoHeat can be selected in heating device 3.4；
The SWK-XCXB type temperature controller or internal exploitation embedded control panel of prosperous sincerity can be selected in heating device controller 3.2；
The RTD-809 type surface temperature probe of U.S. omega can be selected in central temperature probe 3.3 and heating device temp probe 3.5；Ring
The P-L-1/10-1/4-6-1/8-P-3 type temperature sensor of omega can be selected in border temp probe 3.6.
In order to disclose the practical heating effect of this system, radiation in existing carbon dioxide incubator is added under the same conditions
Contact heating method compares experiment in closed box 7 in hot mode and this system.Experiment purpose is verifying gas permeability cell training
The isometric liquid supported in bag 8 is mutually synthermal with raising in 7 cabinet of the closed box of this system in carbon dioxide incubator respectively
When heating time comparison.Experimental method is that 400ml liquid is put into gas permeability cell culture bags 8, measures liquid initial temperature
Degree is 20 DEG C, is respectively placed in carbon dioxide incubator and in 7 cabinet of closed box of this system, measures and rises in fluid temperature
Required length of time when to 37 ± 0.2 DEG C.If table 1 and Fig. 4 test result are shown, the gas permeability of carbon dioxide incubator is thin
The liquid of born of the same parents' culture bag 8 just makes temperature be heated to 36.8 DEG C by or so 10 hours, the gas permeability cell culture in closed box 7
Only or so 1 hour just makes temperature be heated to 36.8 DEG C to liquid in bag 8, and contact heating method compares dioxy in closed box 7
Changing radiant heating method in carbon culture has higher heating efficiency.
Table 1：Isometric liquid in gas permeability cell culture bags is close with this system in carbon dioxide incubator respectively
Required heating time contrast table when increasing mutually synthermal in closed box
Gas control unit 5 as shown in Figure 5 include with the Gas Control Module 5.1 of 1.2 communication connection of central controller,
Multiple gas bombs 5.2, set on 5.2 output end of gas bomb and the gas ratio valve that is electrically connected with Gas Control Module 5.1
5.3, the gas mixer 5.4 that is connected to gas ratio valve 5.3 and set on the two of 5.4 inside of gas mixer or output end
Carbon oxide gas concentration sensor 5.5；The output end of gas mixer 5.4 is connected to gas permeability cell culture bags 8；Titanium dioxide
Carbon gas concentration sensor 5.5 is by density of carbon dioxide gas information Real-time Feedback to Gas Control Module 5.1；Gas controls mould
Block 5.1 controls the opening-closing size of each gas ratio valve 5.3 according to parameter information, and according to density of carbon dioxide gas sensor
5.5 feedback data information adjust the opening-closing size of each gas ratio valve 5.3.
Gas control unit 5 further includes multiple gas flowmeters 5.6, at least one corresponding gas of each gas ratio valve 5.3
Flowmeter body 5.6；5.6 input terminal of gas flowmeter is connected to 5.3 output end of gas ratio valve, 5.6 output end of gas flowmeter
It is connected to 5.4 input terminal of gas mixer.Mixed gas flow is preferably 50-1000ml.
Gas ratio valve 5.3 includes carbon dioxide ratio valve, nitrogen ratios valve, oxygen proportion valve and AIR Proportional valve；Gas
Flowmeter body 5.6 includes carbon dioxide stream meter, nitrogen stream meter, oxygen flow meter and air flow meter；Gas bomb 5.2 wraps
Include carbon dioxide steel cylinder, nitrogen cylinder, air steel cylinder and oxygen bottle.
Gas Control Module 5.1 is dense by the carbon dioxide gas of 5.5 real-time monitoring of density of carbon dioxide gas sensor
It spends information dynamic regulation gas ratio valve 5.3 (carbon dioxide ratio valve, nitrogen ratios valve, oxygen proportion valve and AIR Proportional valve)
Opening size, be allowed in proportion enter gas mixer 5.4, the mixture through gas mixer 5.4, then pass through dioxy
Change carbon gas concentration sensor 5.5, density of carbon dioxide gas sensor 5.5 feeds back to Gas Control Module for data are acquired again
5.1, Gas Control Module 5.1 is judged according to feedback data information and readjusts the aperture of each gas ratio valve 5.3
Size, until reaching the concentration (5%) of required carbon dioxide.
The mixed gas regulated is entered in closed box 7 by the gas input interface and HEPA filter of closed box 7, and
Finally dissolve in the cell mixture in gas permeability cell culture bags 8；And works as mixed gas air pressure in closed box 7 and reach limit value
When, main control unit controls the gas stop valve at the gas output interface of closed box 7 and opens, until when air pressure is down in limit value
Main control unit controls gas stop valve closing again.Certainly, the settable air pressure prison being connect with main control unit electric signal in closed box 7
Device is surveyed, can also be used to monitor the flowmeter of input mixed gas flow by the gas input interface setting in closed box 7, and
The air pressure in closed box is obtained by the calculating of main control unit.
Central controller 1.2 fast, accurately reaches parameter value set by user, significantly by built-in pid algorithm
Regulating time has been saved, user can also be received in real time to flow, concentration and gas species parameter while system work
It modifies and responds rapidly；Such as, the modified mixed gas total flow F of user is received while work, is tested gas
After the instruction of concentration C, tested gas outflow magnitude F1=F/ (100/C) is calculated first；Carrier gas output stream magnitude F2=
F1 × (100/C-1) is directly adjusted by regulating gas proportioning valve 5.3 to this flow.
Shake control unit 6 as shown in Figure 7,8 includes the shake control module with 1.2 communication connection of central controller
6.1 and with shake the agitating device 6.2 that be electrically connected of control module 6.1 and be used to monitor with shake that control module 6.1 is electrically connected
6.2 waving angles of agitating device/speed/positional angle/speed/positional sensor 6.3.By the work for shaking control unit 6
With gas permeability cell culture bags 8 being made to carry out eccentric rotary, so that its internal culture cell be made to carry out centering type vortex, cell
It can quickly be sufficiently mixed.
Specifically, agitating device 6.2 may include shell 10.1, driving motor 6.2.1 (output shaft is vertical shape) and be set to
With the eccentric shaft 6.2.2 of certain tilt angle on driving motor 6.2.1 output shaft；It the upper end eccentric shaft 6.2.2 can be with closed box 7
The connection of lower end center, and the elastic spacing one 6.2.3 of bellows etc, the elastic spacing can be arranged with outside eccentric shaft 6.2.2
The upper end part 6.2.3 is connect with closed box 7, the shell 10.1 or driving motor 6.2.1 cage connection of lower end and agitating device 6.2.
The shake parameter information of the reception user setting of operating system 1.1, the information such as speed, angle, position including selected shake, this
A little information are sent to central controller 1.2 by RS485 bus, and central controller 1.2 passes the speed of shake and angle information
It passs and shakes control module 6.1 and issue start command, shake the speed that control module 6.1 issues signal adjustment agitating device 6.2
Degree and angle, agitating device 6.2 start to shake and drive closed box 7, and closed box 7 drives thin in gas permeability cell culture bags 8
Born of the same parents' mixed liquor carries out centering type vortex and shakes, and then meets the needs of cell mixing；Simultaneously angular transducer, velocity sensor and
Position sensor feeds back to the angle monitored, speed and location information again shakes control module 6.1, shakes control module
6.1 the speed to agitating device 6.2 and angle can be adjusted based on the feedback signal.When the sending of operating system 1.1 is ceased and desisted order
When, the shake speed of agitating device 6.2 will be controlled by shaking control module 6.1, pass through the anti-of velocity sensor and position sensor
Feedforward information makes agitating device 6.2 stop at fixed position.The rate of waving of agitating device 6.2 is preferably 5-40rpm.
In order to disclose the practical shake mixed effect of this system, under the same conditions to ventilative in carbon dioxide incubator
The dissolved oxygen of the liquid in gas permeability cell culture bags 8 in the dissolved oxygen and this system closed box 7 of liquid in property cell culture bags
Comparative experiments is carried out.Operating procedure is as follows, 400ml pure water is separately input into two gas permeability cell culture bags 8, so
After be respectively put into carbon dioxide incubator and shaken in static placement and closed box 7, and be continually fed into mixed gas,
The motion mode of gas permeability cell culture bags 8 is 360 ° of rotary shakes in closed box 7, and revolving speed 10rpm, angle is 8 °,
Inside culture cell carries out centering type vortex.1 hour of every minor tick is measured respectively in carbon dioxide incubator and in closed box 7
Gas permeability cell culture bags 8 in pure water oxygen dissolving value, measurement result is as shown in Figure 6.It is found through experiments that, gas permeability is thin
The oxygen dissolving value of pure water in born of the same parents' culture bag 8 is higher than under static condition under shake state.As it can be seen that more being helped under shake state
In the increase of cell culture fluid dissolved oxygen content, be conducive to the amplification breeding of cell.
In order to disclose the cell culture effect of this system, the cell liquid of the identical type of equal volume is input to respectively
Inside gas cell culture bags 8, then it is respectively put into carbon dioxide incubator and closed box 7, is placed in titanium dioxide
The cell mixture condition of culture in gas permeability cell culture bags in carbon incubator is：Stationary culture, case body temperature are 37
± 0.2 DEG C, humidity 95%RH, gas concentration lwevel 5%；It is placed in the gas permeability cell culture bags 8 in closed box 7
Cell mixture condition of culture is：Culture (speed 10rpm, 8 ° of angle) is shaken, case body temperature is 37 ± 0.2 DEG C, in cabinet
Without humidity environment, gas concentration lwevel 5%.Cell proliferation situation is counted in the same period, measurement result such as Fig. 9
Shown, being placed in the cell quantities of gas permeability cell culture bags 8 in closed box 7, to be higher than gas permeability in carbon dioxide incubator thin
The cell quantity of born of the same parents' culture bag.
Therefore, cell culture system of the invention passes through the common work of closed box 7, agitating device 6.2 and heating device 3.4
With, a stable gas concentration lwevel environment (5%) and temperature environment (37 DEG C) are provided for gas permeability cell culture bags 8,
Cell proliferation and the speed of growth can be effectively improved.
In addition, the control routine of cell culture system of the present invention is as follows：
The control routine of temperature control unit is：
Shake control unit control routine be：
The control routine of gas control unit is：
The present invention also provides a kind of cell culture processes, include the following steps：
A) the interior gas permeability cell culture bags equipped with cell mixture are placed on heating device, heating device are placed in close
In closed box, seal box is placed on agitating device；
B parameter information) is input to main control unit by operating system；It is single that main control unit relies on parameter information control son control
Member executes corresponding operating and controls cell culture parameter；Wherein, sub- control unit includes temperature control unit, gas control unit and shakes
Dynamic control unit；
Temperature control unit controls the heating device internally gas permeability cell training containing cell mixture according to parameter information
Feeding bag is heated, and the heated condition for the temperature data adjustment heating device for acquiring and feeding back in real time according to temp probe；
Control unit is shaken to be started or stoped according to parameter information control agitating device；Agitating device is carried for driving
The closed box of gas permeability cell culture bags carries out eccentric rotary；
Gas control unit enters the concentration of carbon dioxide in gas mixture in closed box, and root according to parameter information control
The concentration is adjusted in real time according to density of carbon dioxide gas sensor feedback data；
C) mixed gas is input in closed box, and when air pressure reaches limit value in closed box, main control unit control
Gas stop valve at closed box gas output interface is opened, and mixed gas extra in closed box is discharged.
Wherein, parameter information includes temperature parameter information, gas parameter information and shake parameter information；Temperature parameter information
Including the temperature information that need to be heated and maintain；Gas parameter information includes the type, concentration and flow information of gas；Shake parameter
Information includes angle, speed and the location information shaken.
Main control unit includes operating system and is controlled with operating system by the center that RS485 bus or wireless telecommunications are connect
Device；Operating system includes the parameter information for receiving user setting and parameter information is sent to the input system of central controller
It unites and what is be electrically connected with input system (can be touch screen displays or display for showing and being arranged the operation interface of parameter information
With the combination of operation keyboard).Above-mentioned parameter information can be input to input system by operation interface first by user；Main control unit
It receives and sends corresponding operating message command to each sub- control unit after relevant parameter information；Each sub- control unit control respectively executes member
When part executes the corresponding command, the execution state or effect information of executive component are fed back to each sub- control by corresponding each sensing component
Unit, sub- control unit adjust control instruction according to feedback information again, until reaching required parameter information.
Specifically, temperature control unit controls heating device internally containing the gas permeability of cell mixture according to parameter information
Cell culture bags are heated, and the heating shape for the temperature data adjustment heating device for acquiring and feeding back in real time according to temp probe
State；Gas control unit according to parameter information control enter gas permeability cell culture bags in carbon dioxide in gas mixture it is dense
Degree, and the concentration is adjusted in real time according to density of carbon dioxide gas sensor feedback data；For example, adjusting multiple gas bombs
The gas ratio valve opening size that (being stored with carbonoxide, nitrogen, oxygen and air respectively) exports out is allowed to enter gas in proportion
Then body mixing arrangement, the mixture through gas mixer pass through density of carbon dioxide gas sensor, carbon dioxide gas is dense
Degree sensor will acquire data and feed back to gas control unit again, and gas control unit is judged simultaneously according to feedback data information
The opening size of each gas ratio valve is readjusted, until reaching the concentration (5%) of required carbon dioxide；What is regulated is mixed
It closes gas to enter in closed box by the gas input interface and HEPA filter of closed box, and finally dissolves in the training of gas permeability cell
It supports in the cell mixture in bag；And when mixed gas air pressure reaches limit value in closed box, main control unit controls closed box
Gas output interface at gas stop valve open, until air pressure when being down in limit value main control unit control gas cut-off again
Valve is closed；Certainly, the settable air pressure monitoring device connecting with main control unit electric signal in closed box, can also be by closed box
The setting of gas input interface for monitor the flowmeter of input mixed gas flow, and it is close by the calculating of main control unit acquisition
Air pressure in closed box.Control unit is shaken to be started or stoped according to parameter information control agitating device；Agitating device is for driving
The closed box for carrying gas permeability cell culture bags carries out eccentric rotary.
Claims (11)
1. a kind of cell culture system, it is characterised in that：Including main control unit (1), sub-control unit (2), closed box (7) and set
Gas permeability cell culture bags (8) in the closed box (7) case；The main control unit (1) is used to receive the ginseng of user setting
Number information simultaneously controls each sub-control unit (2) execution corresponding operating according to parameter information；The sub-control unit (2) includes temperature
Control unit (3), gas control unit (5) and shake control unit (6)；
The main control unit (1) includes operating system (1.1) and the central controller that is electrically connected with the operating system (1.1)
(1.2)；The operating system (1.1) includes the parameter information for receiving user setting and parameter information is sent in described
It entreats the input system (1.1.1) of controller (1.2) and what is be electrically connected with the input system (1.1.1) is used to showing and being arranged ginseng
The operation interface (1.1.2) of number information；
The parameter information includes temperature parameter information, gas parameter information and shake parameter information；The temperature parameter information
Including the temperature information that need to be heated and maintain；The gas parameter information includes the type, concentration and flow information of gas；It is described
Shaking parameter information includes angle, speed and the location information shaken；
The temperature control unit (3) controls heating device (3.4) internally breathing freely containing cell mixture according to parameter information
Property cell culture bags (8) heated, and acquire and feed back in real time according to temp probe temperature data adjustment heating device
(3.4) heated condition；
The shake control unit (6) controls agitating device (6.2) according to parameter information and starts or stops；The agitating device
(6.2) for driving the closed box (7) for carrying gas permeability cell culture bags (8) to carry out eccentric rotary；
The gas control unit (5) enters the dense of closed box (7) interior carbon dioxide in gas mixture according to parameter information control
Degree, and the concentration is adjusted according to density of carbon dioxide gas sensor (5.5) feedback data in real time；
The closed box (7) is defeated equipped with the gas input interface (9) for mixed gas input and for extra mixed gas
Gas output interface (10) out；The gas input interface (9) is communicated with HEPA filter (4)；The gas output interface
(10) gas stop valve (11) are communicated with；When the air pressure of the closed box (7) interior mixed gas reaches limit value, the master control
Unit (1) control gas stop valve (11) is opened until control gas stop valve (11) is closed when air pressure is down in limit value.
2. cell culture system according to claim 1, it is characterised in that：The temperature control unit (3) includes and institute
It states the temperature control modules (3.1) of central controller (1.2) communication connection, be electrically connected with the temperature control modules (3.1)
Heating device controller (3.2) and central temperature pop one's head in (3.3) and are electrically connected and are placed in the heating device controller (3.2)
Heating device (3.4) in the closed box (7)；The central temperature probe (3.3) is for acquiring gas permeability cell culture bags
(8) temperature, and by the central temperature data real-time transmission of acquisition to temperature control modules (3.1)；The central controller (1.2)
Real-Time Signal Transfer is carried out between the temperature control modules (3.1)；The central controller (1.2) is by central temperature data
Judgement is compared with temperature parameter information and obtains central temperature comparison result signal and central temperature comparison result signal is anti-
It is fed to the temperature control modules (3.1)；Central temperature comparison result signal is sent to institute by the temperature control modules (3.1)
State heating device controller (3.2)；The heating device controller (3.2) controls according to central temperature comparison result signal and heats
The heated condition of device (3.4).
3. cell culture system according to claim 2, it is characterised in that：The temperature control unit (3) further include with
The heating device temp probe for being used to acquire the heating device (3.4) temperature of temperature control modules (3.1) electrical connection
(3.5)；The heating device temp probe (3.5) is by the heating temperature data real-time transmission of acquisition to temperature control modules
(3.1)；Heating temperature data are compared judgement with temperature parameter information and obtain heating temperature by the central controller (1.2)
Heating temperature comparison result signal is simultaneously fed back to the temperature control modules (3.1) by comparison result signal；The temperature control
Heating temperature comparison result signal is sent to the heating device controller (3.2) by module (3.1)；The heating device control
Device (3.2) controls the heated condition of heating device (3.4) according to heating temperature comparison result signal.
4. cell culture system according to claim 2, it is characterised in that：The temperature control unit (3) further include with
The environment temperature of temperature control modules (3.1) electrical connection pops one's head in (3.6)；Environment temperature probe (3.6) is by acquisition
Ambient temperature data information is sent to the central controller (1.2), the central controller through temperature control modules (3.1)
(1.2) ambient temperature data information is fed back to the operation interface (1.1.2) of the operating system (1.1).
5. according to cell culture system described in Claims 2 or 3 or 4, it is characterised in that：The heating device (3.4) includes
Horizontally disposed metal plate (3.4.1), glue connection are in the silica gel plate (3.4.2) of the lower end the metal plate (3.4.1) and set on described
The internal resistance wire (3.4.3) of silica gel plate (3.4.2)；The metal plate upper end (3.4.1) and the gas permeability cell culture bags
(8) it abuts.
6. cell culture system according to claim 1, it is characterised in that：The gas control unit (5) includes in
It entreats the Gas Control Module (5.1) of controller (1.2) communication connection, multiple gas bombs (5.2), be set to gas bomb (5.2)
Output end and the gas ratio valve (5.3) being electrically connected with Gas Control Module (5.1), the gas being connected to gas ratio valve (5.3)
Body mixing arrangement (5.4) and the density of carbon dioxide gas sensor for being set to gas mixer (5.4) inside or output end
(5.5)；The output end of the gas mixer (5.4) is connected to the gas input interface of closed box (7)；The carbon dioxide
Gas concentration sensor (5.5) is by density of carbon dioxide gas information Real-time Feedback to the Gas Control Module (5.1)；It is described
Gas Control Module (5.1) controls the opening-closing size of each gas ratio valve (5.3) according to parameter information, and according to carbon dioxide gas
Concentration sensors (5.5) feedback data information adjusts the opening-closing size of each gas ratio valve (5.3).
7. cell culture system according to claim 6, it is characterised in that：The gas control unit (5) further includes more
A gas flowmeter (5.6), at least one corresponding gas flowmeter (5.6) of each gas ratio valve (5.3)；The gas flow
Meter (5.6) input terminal is connected to gas ratio valve (5.3) output end, gas flowmeter (5.6) output end and gas mixing
The connection of device (5.4) input terminal.
8. cell culture system according to claim 7, it is characterised in that：The gas ratio valve (5.3) includes dioxy
Change carbon proportioning valve, nitrogen ratios valve, oxygen proportion valve and AIR Proportional valve；The gas flowmeter (5.6) includes carbon dioxide
Flowmeter, nitrogen stream meter, oxygen flow meter and air flow meter；The gas bomb (5.2) includes carbon dioxide steel cylinder, nitrogen
Gas cylinder, air steel cylinder and oxygen bottle.
9. cell culture system according to claim 1, it is characterised in that：The shake control unit (6) includes in
The agitating device entreating the shake control module (6.1) of controller (1.2) communication connection and being electrically connected with shake control module (6.1)
(6.2) and with shake control module (6.1) angle for being used to monitor agitating device (6.2) waving angle/speed/positional being electrically connected
Degree/speed/positional sensor (6.3).
10. a kind of cell culture processes, it is characterised in that：Include the following steps：
A) the interior gas permeability cell culture bags equipped with cell mixture are placed on heating device, heating device is placed in closed box
It is interior, seal box is placed on agitating device；
B parameter information) is input to main control unit by operating system；It is single that main control unit relies on the parameter information control son control
Member executes corresponding operating and controls cell culture parameter；Wherein, the sub- control unit includes temperature control unit, gas control unit
And shake control unit；
The temperature control unit controls the heating device internally gas permeability cell training containing cell mixture according to parameter information
Feeding bag is heated, and the heated condition for the temperature data adjustment heating device for acquiring and feeding back in real time according to temp probe；
The shake control unit controls agitating device according to parameter information and starts or stops；The agitating device is held for driving
The closed box for being loaded with gas permeability cell culture bags carries out eccentric rotary；
The gas control unit enters the concentration of carbon dioxide in gas mixture in closed box, and root according to parameter information control
The concentration is adjusted in real time according to density of carbon dioxide gas sensor feedback data；
C) mixed gas is input in closed box, and when air pressure reaches limit value in closed box, main control unit control is closed
Gas stop valve at case gas output interface is opened, and mixed gas extra in closed box is discharged.
11. cell culture processes according to claim 10, it is characterised in that：The parameter information includes temperature parameter letter
Breath, gas parameter information and shake parameter information；The temperature parameter information includes the temperature information that need to be heated and maintain；It is described
Gas parameter information includes the type, concentration and flow information of gas；The parameter information that shakes includes the angle shaken, speed
And location information.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
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| CN113699042A (en) * | 2021-08-17 | 2021-11-26 | 华艾博越(上海)生物医疗科技有限公司 | Control system of cell culture box |
| CN115551989A (en) * | 2020-02-14 | 2022-12-30 | 艾克斯赛尔生物科学公司 | Gas and liquid flow regulation systems for cell culture |
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Application publication date: 20181116 |