CN106754366A - For the disposable intelligent digester systems of animal cell culture - Google Patents
For the disposable intelligent digester systems of animal cell culture Download PDFInfo
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- CN106754366A CN106754366A CN201710218361.7A CN201710218361A CN106754366A CN 106754366 A CN106754366 A CN 106754366A CN 201710218361 A CN201710218361 A CN 201710218361A CN 106754366 A CN106754366 A CN 106754366A
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Classifications
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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
- C12M41/12—Means for regulation, monitoring, measurement or control, e.g. flow regulation of temperature
-
- 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
- C12M23/00—Constructional details, e.g. recesses, hinges
- C12M23/58—Reaction vessels connected in series or in parallel
-
- 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
- C12M27/00—Means for mixing, agitating or circulating fluids in the vessel
- C12M27/02—Stirrer or mobile mixing elements
-
- 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
- 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
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- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biotechnology (AREA)
- Sustainable Development (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Biomedical Technology (AREA)
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- Clinical Laboratory Science (AREA)
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- Thermal Sciences (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
Abstract
The invention discloses a kind of disposable intelligent digester systems for animal cell culture, including disposable digester unit and intelligent control unit, the disposable digester unit includes at least filling the closed chamber of fluid, retention component and mixing component are provided with the closed chamber, retention component and the lower loop in the closed chamber is around being connected, wherein, the retention component is at least used to make scattered cell stream to next stage bioreactor and empty carrier and carrier with cell is trapped in the closed chamber, the mixing component is at least used to make the fluid in the closed chamber to mix.Disposable intelligent digester systems of the invention eliminate the step such as sterilization system on line and on-line cleaning, rigging up and debugging, simplify operating process, save production cost and human cost, it is to avoid cross pollution between batches；And controlling digestion process by using intelligent program so that cell dissociation loss late is minimum up to 2%.
Description
Technical field
Free cell is obtained the present invention relates to a kind of separation with microcarrier for cell during animal cell culture
Technology, relates more particularly to the disposable intelligent digester systems for animal cell culture.
Background technology
When the high added value such as vaccine, antibody, protein medicaments biological products are produced, some mammalian cells used
Can not directly be suspended in nutrient solution to grow could grow, it is necessary to depend on the carrier surface with a small amount of positive charge, and its is basic
Process is：Mammalian cell is made cell suspension after mechanical dispersion or digestion, is followed by through filtering, centrifugation, purifying, rinsing
Plant and cultivated in the reactor containing fresh culture.It is good with the cell growth of this method culture and be easy to observation, but the method
Only it is suitable to laboratory research.However, in cell pilot scale culture, be inoculated with and spread cultivation during, the cell of adherent growth has contact
The characteristic of suppression, once cell covers with surface, growth will be suppressed, and influence final cell yield.Accordingly, it would be desirable to will be thin
Born of the same parents separate with vector digestion, enter on new carrier.
At present, the method for cell dissociation mainly has digestive inoculation, directly digestion in site inoculation, the method such as inoculation.
But, the above no matter which kind of digestion method, the digester for being used still be rolling bottle, conical flask, mechanical agitation fermentation
Tank etc..These digesters are that the reaction vessel that is made up of glass, steel or preferred stainless steel and control unit are constituted.Each
After use, to ensure that digester reaches aseptic cleaning effect, it is necessary to which, through dismounting repeatedly, cleaning and sterilization treatment, those are clear
Clean process is in itself a time-consuming, laborious process, and the cleaning method for being used increased production cost, and still suffer from remaining
The risk of Organic Pollution.
In addition, traditional digestion method is simply to be detached from the carrier cell or directly carry out cell switching, entirely
Process is that, by the manually operated digester of technical staff, empirical to judge whether digestion process completes, this not only causes to digest
Cell largely loses in journey, and result is difficult to repeat batch and batch between.Therefore, cell is detached from the carrier acquisition free cell
It is still the big technical barrier during cell pilot scale culture.
The content of the invention
It is a primary object of the present invention to provide a kind of disposable intelligent digester systems for animal cell culture, with
Overcome the deficiencies in the prior art.
To achieve these goals, technical scheme is as follows：
A kind of disposable intelligent digester systems for animal cell culture are the embodiment of the invention provides, including once
Property digester unit and intelligent control unit, the disposable digester unit includes at least can be used to house the stream of cultured cells
The aseptic closed chamber of body and digestive juice, at least charging aperture connected with the closed chamber, at least a gas outlet, at least one
Air inlet, at least a digestive juice entrance, at least an at least filter washing water inlet, a culture medium entrance, at least a cleaning fluid and digestion
Liquid is exported and an at least sample tap, and retention component and mixing component, described section are at least additionally provided with the closed chamber
Component is stayed at least to be used in the closed chamber retain the carrier in fluid and pass through zooblast, the mixing component
At least it is used to the material mixing in the closed chamber.
As one of preferable preferred embodiment, for the disposable intelligent digester systems of animal cell culture, including
Closed bag, the inner chamber of the closed bag forms the closed chamber, be provided with the closed bag charging aperture, gas outlet,
Air inlet, digestive juice entrance, filter washing water inlet, culture medium entrance, while the closed bag bottom is additionally provided with described cleaning fluid
With digestive juice outlet and sample tap；
Further, the retention component is located at the closed bag inner chamber bottom, and close with the closed bag inner wall surrounding
Envelope connection；Preferably, at least an acid solution entrance and at least an alkali liquor inlet are additionally provided with the closed bag；
Further, an at least cell switching access and the switching outlet of an at least cell are additionally provided with the closed bag；
Further, it is preferred that the closed bag top and sidepiece form multiple ports, and described multiple ports are used respectively
Make the charging aperture, gas outlet, air inlet, digestive juice entrance, filter washing water inlet, culture medium entrance, cleaning fluid and digestive juice to go out
Mouth and sample tap；
Further, the port at least through cap, female Luer, hose barb joint, check valve, sampler,
Any one in sterilizing filter is isolated with external environment.
Further, an at least air inlet pipe inserts the closed chamber by the air inlet, the air inlet pipe lower end with
Air sparger is connected, and the air sparger is located at the fluid level lower section in the closed chamber；
Further, the air sparger includes ventilation ring, and a plurality of ventilations are evenly distributed with the ventilation ring
Hole, the diameter of the aperture less than carrier of the passage；
Further, flowmeter and filter are also connected with the air inlet pipe；
Further, pressure gauge or pressure sensor and pressure-control valve are also associated with the escaping pipe；
Further, the pressure in the closed chamber is maintained between 0.01-0.05Mpa；
Further, the material of the closed bag includes rigid, semi-rigid or flexible plastics；
Further, the plastics include makrolon, polyester, fluoropolymer, acrylic acid, PET, polyvinyl chloride,
Any one in ABS, PC, PS, GAG, acrylic and polyolefin or two or more combinations；Further, the modeling
Material includes polyolefin.
Used as one of preferable preferred embodiment, the disposable digester unit includes supporting construction, the support knot
Structure is at least used to support the closed bag；
Further, the supporting construction is included in the fixed buckle that the closed bag upper and lower part stretches out；
Further, the supporting construction includes the support frame outside the closed bag, and the closed bag is arranged on
On support frame as described above or in support frame as described above, support frame as described above is fixing support rack or removable support frame；
Further, the supporting construction includes the support frame in the closed bag；
Further, the supporting construction is at least selected from any one in metal drum, Plastic Drum, wooden barrel or glass tank.
Used as one of preferable preferred embodiment, the mixing component is connected with drive mechanism, the drive mechanism
It is connected with the supporting construction, and is arranged on outside the closed bag or internal；
Preferably, the drive mechanism includes motor.
Used as one of preferable preferred embodiment, the mixing component includes mechanical agitation mechanism and/or magnetic stirrer
Structure；
Used as one of preferable preferred embodiment, the mixing component includes agitating shaft and agitating paddle, the agitating paddle with
Agitating shaft one end is fixedly connected and in the closed chamber, and the other end of the agitating shaft is located at outside the closed chamber
And with drive mechanism drive connection, and the agitating shaft and the closed chamber locular wall joint also through more than one sealing ring
It is tightly connected；
Further, the agitating paddle is at least selected from straight oar, arrow leaf oar, curved leaf oar, the propeller of single or multiple lift
Any one.
Used as one of preferable preferred embodiment, the retention component includes at least a sieve plate or filter screen, the sieve plate or
The aperture of filter screen is more than the diameter of zooblast and less than the diameter of microcarrier.
Used as one of preferable preferred embodiment, the intelligent control unit includes any one in following assemblies or two
Plant the combination of the above：
Temperature-controlling module, is at least used to control the temperature in the closed chamber；
PH control assemblies, are at least used to monitor the pH value of the fluid in the closed chamber；
Dissolved oxygen component, is at least used to detect the dissolved oxygen change in the closed chamber；
Online living cells sensor cluster, is at least used to monitor the number of viable cells change wandered about as a refugee in digestion process；
Weigh assembly, at least to on-line monitoring fluid inlet；
Central controller, is at least used to control the running status of each component；
The temperature-controlling module, pH control assemblies, dissolved oxygen component, online living cells sensor cluster and weigh assembly are equal
It is connected with the central controller and the closed chamber；
Further, the temperature-controlling module, pH control assemblies, dissolved oxygen component, online living cells sensor cluster and
Weigh assembly is disposable assembly；
Preferably, the intelligent control unit is also including any one in following assemblies or two or more combinations, institute
The following assemblies stated are connected with the central controller：
Carbon dioxide sensing component, is at least used to detect the carbon dioxide change in the closed chamber；
Mixing rate sensory package, is at least used to detect the troubled water of the fluid in the closed chamber；
Photoelectric sensing component, is at least used to detect the turbidity of the fluid in the closed chamber.
Further, the temperature-controlling module includes heater, chuck circulation and plug-in type or non-intrusive
Formula temperature electrode.
Further, the PH control assemblies include pH value electrode.
Further, the dissolved oxygen component includes dissolved oxygen electrode.
Further, the online living cells sensor cluster is as a plug or non-insertion mode is installed on the closing
Chamber sidepiece, and the online living cells sensor cluster is close to the retention component.
Further, the weigh assembly include more than one Weighing module of the supporting disposable digester unit and
Terminal box, the Weighing module is electrically connected with terminal box.
Further, the weigh assembly includes being installed on 3-4 at the leg of the disposable digester unit
Weighing module.
Used as one of preferable preferred embodiment, the intelligent control unit also includes liquid pumping component, the liquid
Pump include cleaning liquid pump, digestion liquid pump, culture medium pump, sour pump, alkali pump, cleaning fluid excavationg pump, digestive juice excavationg pump with
And any one in cell shifting pump or two or more combinations, the cleaning liquid pump, digestion liquid pump, culture medium pump, sour pump,
Alkali pump, cleaning fluid excavationg pump, digestive juice excavationg pump and cell shifting pump are connected with the central controller respectively.
Used as one of preferable preferred embodiment, the central controller also includes wireless communication module, the center control
Device processed is through the wireless communication module and remote terminal wireless connection.
Compared with prior art, advantages of the present invention at least that:
1) present invention eliminates SIP (sterilization system on line) and CIP (on-line cleaning), the equipment step such as installation and debugging repeatedly, letter
Change operating process, fundamentally alleviated the line service of instrument and equipment, because step simplifies, save steam, water, clear
The consumption of washing lotion, saves the rigging up and debugging time, so as to save production cost and human cost.
2) disposable assembly is not used in follow-up technological operation using being abandoned after finishing, it is to avoid between batches
Cross pollution, improves production stability and product quality.
3) use of disposable assembly reduces the complexity of GMP checkings, because almost without repeatedly used component,
Substantial amounts of sterilizing, cleaning validation flow are saved, so as to simplify GMP authentication periods in R＆D process, when shortening launch
Between.
4) the designed intelligent control unit of the present invention, can automatically control the whole process of digestion reaction, greatly reduce thin
Born of the same parents digest loss late, and loss late is minimum up to 2%.
5) the disposable digester unit designed by the present invention Vessel Design, stirring design, in terms of ventilation strategies with warp
The muptiple-use digester design principle of allusion quotation is consistent, and geometric similarity is kept in different reactor scale, therefore, process transfer and work
Skill is amplified and will not increase extra risk, is contributed in existing process transfer to existing industrial reaction equipment.
Brief description of the drawings
It is right with reference to the accompanying drawings and detailed description in order to illustrate more clearly of architectural feature of the present invention and technical essential
The present invention is described in detail.
Fig. 1 is digestion reaction implementing procedure figure in comparative example 1；
Fig. 2 is the structural representation of disposable digester unit in the embodiment of the present invention 1；
Fig. 3 is the front view of the closed chamber of disposable digester unit in the embodiment of the present invention 1；
Fig. 4 is the rearview of the closed chamber of disposable digester unit in the embodiment of the present invention 1；
Fig. 5 is digestion reaction implementing procedure figure in the embodiment of the present invention 1；
Fig. 6 is digestion reaction implementing procedure figure in the embodiment of the present invention 2.
Description of reference numerals：1- motor, 2- supporting constructions, 3- weigh assemblies, 4- acid solution entrances, 5- alkali liquor inlets, 6-
Cell switching access, 7- filter washing water inlets, 8- closed chambers, 9- mixing components, 10- temperature-controlling modules, 11-pH control groups
Part, 12- sample taps 2,13- cleaning fluids/digestive juice outlet, 14- charging apertures, 15- digestive juice entrances, 16- sample taps 1,17- dissolved oxygens
Component, 18- living cells sensor clusters, the switching outlet of 19- cells, 20- escaping pipes, 21- air inlet pipe, 22- air spargers,
23- retains component.
Specific embodiment
Below with reference to the accompanying drawing in the present embodiment, the technical scheme in embodiment is carried out specifically, clearly and completely retouch
State.
Term is defined
When term " digestion " refers to that the zooblast with adherent growth characteristic covers with carrier surface, to avoid between cell
Mutually suppress, it is necessary to cell is separated with old carrier, be transferred to the process on new support.
" disposable digester unit " is mainly as cell dissociation course of reaction provides disposable reacting environment.
Digested referring to shown in Fig. 2-4, the embodiment of the invention provides a kind of disposable intelligence for animal cell culture
Device system, including disposable digester unit and intelligent control unit, disposable digester unit include at least can be used to house
Retention component 23 and mixing component 9 are provided with the fluid of cultured cells and the aseptic closed chamber 8 of digestive juice, closed chamber 8,
Retention component 23 is tightly connected with the inner wall surrounding of closed chamber 8, wherein, retention component 23 is at least used in closed chamber 8
Carrier in fluid is retained and passes through zooblast, mixing component 9 is at least used to the material mixing in closed chamber 8.
Preferably, intelligent control unit includes：Temperature-controlling module 10, is at least used to control the temperature in closed chamber 8；
PH control assemblies 11, are at least used to detect the pH value of the fluid in closed chamber 8；Dissolved oxygen component 17, is at least used to detect closing
Dissolved oxygen change in chamber 8；Online living cells sensor cluster 18, is at least used to monitor the viable count wandered about as a refugee in digestion process
Mesh changes；Weigh assembly 3, at least to on-line monitoring fluid inlet, weigh assembly 3 by monitoring digester weight change,
So as to the inlet of fluid can be monitored；Central controller, is at least used to control the running status of each component；Temperature-controlling module
10th, pH control assemblies 11, dissolved oxygen component 17, online living cells sensor cluster 18 and weigh assembly 3 respectively with central controller
And closed chamber 8 is connected.
It is more highly preferred to, the intelligent control unit is also including any one in following assemblies or two or more groups
Close：Carbon dioxide sensing component, is at least used to detect the carbon dioxide change in the closed chamber；Mixing rate sensing group
Part, is at least used to detect the troubled water of the fluid in the closed chamber；Photoelectric sensing component, is at least used to detect the envelope
The turbidity of the fluid in closed chamber room；Described carbon dioxide sensing component, mixing rate sensory package and photoelectric sensing component are equal
It is connected with the central controller：
It is more highly preferred to, temperature-controlling module 10, pH control assemblies 11, dissolved oxygen component 17, online living cells sensor group
Part 18 and weigh assembly 3 are disposable assembly.And, each component is securable in closed chamber 8, can be also embedded in or is bonded in
The surface of closed chamber 8.
Preferably, the port passed in and out for material and gas is provided with closed chamber 8, port includes and closed chamber 8
The upper end charging aperture 14, digestive juice entrance 15, filter washing water inlet 7, acid solution entrance 4, the alkali liquor inlet 5, cell that are connected
Switching access 6 and each component interface, cleaning fluid/digestive juice outlet 13 that port also includes being connected with the bottom of closed chamber 8,
Sample tap 12 and cell switching outlet 19, port also includes the air inlet and the gas outlet that are communicated with the upper end of closed chamber 8.
Further, air inlet pipe 21 and escaping pipe 20, air inlet pipe 21 and outlet are inserted with respectively in air inlet and gas outlet
Pipe 20 is extended in closed chamber 8, and the lower end of air inlet pipe 21 connects with air sparger, and air sparger is located in closed chamber
Fluid level lower section.
Further, air sparger should select ventilation ring, and passage is evenly equipped with ventilation ring, and the aperture of passage is small
Gas is passed through in the diameter of microcarrier, air inlet pipe 21, to cause that pressure maintains setting value in closed chamber 8, and is caused close
Closed chamber body rapid shaping and sizing.Wherein, be passed through filtrated air, oxygen or carbon dioxide in air inlet pipe 21, air, oxygen,
The air inlet pipe 21 of carbon dioxide can be connected in parallel, there is provided the bubbling of closed bag content.
Further, connection flow gauge and filter in air inlet pipe 21, escaping pipe 20 connection pressure gauge or pressure sensing
Device and pressure-control valve, pressure gauge or pressure sensor are used to detect the pressure in closed chamber 8 so that in closed chamber 8
Pressure is maintained between 0.01-0.05Mpa, to ensure the rapid shaping of closed chamber 8, it is to avoid the formation of fold.Pressure-control valve
For discharging the waste gas in closed chamber 8.
Further, each above-mentioned port by cap, female Luer, hose barb joint, check valve, sampler,
Any one mode in sterilizing filter is isolated from the outside.
Preferably, disposable digester unit can use the inner chamber of this simple form of closed bag, closed bag to form institute
The closed chamber 8 stated, wherein, be provided with closed bag charging aperture 14, digestive juice entrance 15, filter washing water inlet 7, acid solution entrance 4,
Outlet 13, sample tap 12, the cell switching outlet 19, air inlet of alkali liquor inlet 5, cell switching access 6, cleaning fluid/digestive juice and
Gas outlet, is inserted with air inlet pipe 21 and escaping pipe 20 respectively in air inlet and gas outlet.
Further, the material of closed bag is rigid, semi-rigid or flexible plastics；Still more preferably, plastics bag
In including makrolon, polyester, fluoropolymer, acrylic acid, PET, polyvinyl chloride, ABS, PC, PS, GAG, acrylic and polyolefin
Any one or two or more combinations；Still further preferably, plastics include polyolefin.
Preferably, disposable digester unit includes at least one supporting construction 2 for being used to support closed chamber 8.
Preferably, the upper and lower part of closed chamber 8 stretches out the fixation to be formed for fixing and supporting closed chamber 8
Buckle.
Further, supporting construction 2 includes the support frame outside closed bag, and closed bag is arranged on support frame as described above
Or in support frame, support frame as described above is fixing support rack or removable support frame；Further, the supporting construction includes setting
Support frame in closed bag.
Further, supporting construction 2 is at least using any one in metal drum, Plastic Drum, wooden barrel or glass tank.
Preferably, at least closed chamber 8 and the sterilized treatment of each component, sterilization treatment mode include gamma-ray irradiation, β
Any one or two or more combinations in x ray irradiation x, ethylene oxide gas treatment and steam sterilizing, by gamma-rays,
β rays, ethylene oxide sterilizing, steam sterilizing treatment can also be reused.
Preferably, retention component 23 includes sieve plate or filter screen obtained at least one of which plastics, and the aperture of sieve plate or filter screen is big
Diameter in cell and the diameter less than microcarrier.
Preferably, mixing component 9 includes mechanical agitation mechanism and/or magnetic agitation mechanism；Mixing component 9 can use center
Setting, centroclinal, eccentric setting, eccentric inclined mode are installed.
Further, mixing component 9 includes agitating shaft and agitating paddle, and agitating paddle is fixedly connected and is located at agitating shaft one end
In closed chamber 8, the other end of agitating shaft is located at outside closed chamber 8 and is connected with motor 1, and agitating shaft and closing
The joint of the locular wall of chamber 8 is also tightly connected through more than one sealing ring.
Further, agitating paddle is using any in straight oar, arrow leaf oar, curved leaf oar, the propeller of single or multiple lift
One or more combination.
Further, the material of agitating shaft and/or agitating paddle is through gamma-rays, β rays, ethylene oxide sterilizing or steam
The high density polyethylene (HDPE) of sterilization treatment.
Preferably, temperature-controlling module 10 includes heater, chuck circulation and plug-in type or non-insertion temperature
Degree electrode, plug-in type or non-insertion temperature electrode are used to adjust heater, the keying of chuck circulation.It is selectable
It is that temperature-controlling module 10 can be coupled on the housing of supporting construction 2.Temperature-controlling module 10 can also be applied to the cold of blast pipe
On solidifying, so that the gas condensation of discharge prevents filter from getting wet influence gas filtration effect.
Preferably, pH control assemblies 11 include pH value electrode, and control acid solution, alkali lye, the stream of culture medium add.
Preferably, dissolved oxygen component 17 includes dissolved oxygen electrode, dissolved oxygen and rotating speed, feed supplement, pressure correlation connection.
Preferably, online living cells sensor cluster 18 is as a plug or non-insertion mode is installed on the side of closed chamber 8
Portion, and online living cells sensor cluster 18 is close to retention component 23.
Preferably, weigh assembly 3 includes 3-4 Weighing module being installed at the leg of disposable digester unit and connects
Line box, terminal box is electrically connected with each Weighing module, and terminal box gets in touch with the signal of each Weighing module, and according to the stand under load feelings of each module
Condition adjusts the weight difference at each leg, and the signal after terminal box will be collected afterwards is delivered to central controller.
Preferably, intelligent control unit also includes liquid pumping component, and liquid pumping component includes cleaning liquid pump, digestive juice
Pump, culture medium pump, sour pump, alkali pump, cleaning fluid excavationg pump, digestive juice excavationg pump and cell shifting pump, cleaning liquid pump, digestive juice
Pump, culture medium pump, sour pump, alkali pump, cleaning fluid excavationg pump, digestive juice excavationg pump and cell shifting pump respectively with central controller
Connection, and it is respectively used to transfer cleaning fluid, digestive juice, culture medium, acid solution, alkali lye, the culture medium rich in free cell.Liquid
Pump connects central controller by data wire, the acceptable central controller instruction of each pump housing, realizes the automatic of pump operating
With control manually.
Preferably, the central controller also include wireless communication module, central controller through wireless communication module with it is remote
Journey terminal wireless is connected.
Digestion process for the disposable intelligent digester systems of animal cell culture is as follows：
(i) installation and debugging stage：Closed bag is fixed on the outer wall of digester supporting construction 2 by fixed buckle, is passed through
Gas and fluid pipeline on the aseptic closed bag of connection of snap joint, acid solution, alkali lye, digestive juice, cleaning fluid, culture medium, cleaning
Liquid and digestive juice discharge, cell adapting pipe are installed on corresponding peristaltic pump.Complete gas flow component 21, temperature control group
Part 10, pH control assemblies 11, dissolved oxygen control assembly 17, pressure control assembly (air inlet pipe, escaping pipe, flowmeter, filter and pressure
Force control valve forms described pressure control assembly), weigh assembly 3, online living cells sensor cluster 18, mixing component 9 with
The connection of central controller.It is passed through compressed air, oxygen or carbon dioxide to enter inside closed bag through air source inlet, maintains pressure
In 0.01-0.05Mpa, to ensure closed bag rapid shaping, while checking the air-tightness of closed bag and the connection of each pipeline.According to disappearing
Change condition, sets initial parameter, including throughput, temperature, pH, dissolved oxygen, pressure, rotating speed.
(ii) incipient stage is digested：After debugging to be installed is finished, open digestive juice and enter step, existed by weigh assembly 3
Line monitors digestive juice inlet；Meanwhile, according to default pH, the stream of system automatic acid solution or alkali lye adds；According to default
Temperature, system automatic heater heated or started chuck circulation and cooled down；According to default dissolved oxygen,
By the control of the parameter associations such as dissolved oxygen and throughput, pressure, rotating speed；With the carrying out of digestion reaction process, dissociate suspension living cells
Number gradually rises, and after a certain time, free suspension number of viable cells is not further added by, and online living cells sensor 18 is online
Complete monitoring digestion process, the signal transmission that free suspension number of viable cells is changed to central control system；When free suspension
After number of viable cells reaches preset value, the disposable intelligent digester systems are automatically switched off pH control assemblies 11, temperature control group
Part 10, opens digestive juice discharge step, and digestive juice is quickly discharged through digesting liquid pump, and carrier is trapped component and is trapped in closed chamber
In 8.
(iii) wash phase is digested：After digestive juice is drained, cleaning step is opened, reduce rotating speed, adjust the temperature to cell training
Temperature is supported, cleaning fluid addition and wash number (generally 1-3 times) is set, system is opened according to cleaning procedure set in advance
The cleaning liquid pump of cleaning fluid passage is opened, cleaning fluid enters in closed chamber 8, and online living cells sensor 18 monitors loss cell feelings
Condition.
(iv) termination phase is digested：It is to be cleaned finish after, open digestion terminate step.Improve speed of agitator, regulation temperature
Degree and pH controls set culture medium addition in the range of cultivation temperature and pH, by the ginseng such as dissolved oxygen and throughput, pressure, rotating speed
Number association, control is associated by pH with feed supplement, acid, alkali.System opens culture medium passage according to digestion terminator set in advance
Culture medium pump, culture medium enter closed chamber 8 in.The process can be with last longer, when free suspension cell number is protected
Maintain an equal level steady, or cytoactive begins to decline, then be considered as digestion and terminate.
(v) cell transition phase：After digestion terminator terminates, cell can be transferred to down by following two modes
First-stage reactor：A) digester tank pressure is improved to 0.03-0.05Mpa, reduces the tank pressure of next stage reactor to 0.01-
0.02Mpa, by pressure differential method by nutrient solution force feed to next stage reactor；B) peristaltic pump of cell transfering channel is opened, is rich in
The cell transfer of free suspension cell is pumped to next stage reactor, and empty carrier is trapped component and is trapped in closed chamber 8.
1-2,1,5 and 6 pairs of technical schemes of comparative example 1 and accompanying drawing are done further with reference to embodiments
It is bright.
Embodiment 1
Shown in Figure 5, the 10L disposable bioreactors in the embodiment are used as seed reactor, carry out microcarrier
Cell suspension cultures；The disposable digesters of 10L are used as the place of the seed cell digestion reaction that culture is completed, and realize that PK-15 is thin
Born of the same parents separate with microcarrier, and free cell is transferred to 50L disposable bioreactors and carries out continuation culture.Many times of 10L and 50L
The working volume of property bioreactor is respectively 7L and 35L, the ratio of height to diameter 1.8 of reactor：1.0, agitating paddle is lifted using individual layer
Band oar, oar footpath is with reactor diameter ratio：1.0:1.8.The disposable digester cellular constructions of 10L are designed as shown in Figure 2,3, 4, work
It is 7L as volume.The Cytodex-1 that the disposable digester mounting mediums of 10L are produced using GE companies, 3g/L, cell density is
2.5×106cells/mL.Digestion reaction implementation process is as shown in Fig. 2 specific implementation step is as follows：
(i) liquid dosage stage：Prepare cleaning fluid 20L, digestive juice 1L, culture medium 5L, acid solution (1N HCl) 2L, alkali lye
(3N NaOH) 2L, contains 3% NBCS wherein in culture medium.
(ii) the installation and debugging stage：Closed bag is fixed on the outer wall of digester support by fixed buckle, by quick
Joint causes gas pipeline and fluid pipeline (acid solution, alkali lye, digestive juice, cleaning fluid, culture medium pipeline) and phase on closed bag
The peristaltic pump answered realizes aseptic connection；Completion temperature-controlling module, pH control assemblies, dissolved oxygen component, weigh assembly, online work are thin
The connection of born of the same parents' sensor cluster, mixing component and central controller.Compressed air, oxygen or carbon dioxide is passed through to enter through air inlet pipe
Enter inside closed bag, maintain pressure in 0.01-0.05Mpa, so as to realize the control of pressure, to ensure closed bag rapid shaping,
Check that closed bag and each pipeline are connected simultaneously airtight；According to digestion condition, initial parameter is set, including throughput 0.5vvm,
37 DEG C of temperature, pH7.0, pressure 0.02Mpa, rotating speed 25rpm.
(iii) incipient stage is digested：After debugging to be installed is finished, by the nutrient solution of 10L single use bioreactor cultures
It is directly transferred in 10L single use digesters.Open digestive juice and enter step, by weigh assembly on-line monitoring digestive juice
Inlet, 0.6L digestive juices are pumped in the closed bag of digester by digestive juice；Design temperature is 37 DEG C, and rotating speed is
25rpm, pH are 7.0, while according to default pH, the stream of system automatic acid solution or alkali lye adds；According to default temperature,
System automatic heater heats or starts the cooling of chuck circulation；According to default dissolved oxygen, by dissolved oxygen and throughput,
The parameter associations such as pressure, rotating speed are controlled.The online living cells online complete monitoring digestion process of sensor, by free suspension living cells
The signal transmission of number of variations is to central control system；When cell number is not further added by, then it is considered as digestion process completion；Reach
After preset value, the digester systems are automatically switched off pH control assemblies, temperature-controlling module, open digestive juice discharge step.Digestion
Liquid is quickly discharged through digesting liquid pump, and carrier is trapped component 23 and is trapped in the closed bag of the digester.
(iv) wash phase is digested：After digestive juice is drained, cleaning step is opened, rotating speed is improved to 50rpm, adjusted the temperature to
37 DEG C, set cleaning fluid addition 5L and wash number 2 times, scavenging period 10min.System is according to cleaning journey set in advance
Sequence, opens the cleaning liquid pump of cleaning fluid passage, and cleaning fluid enters in the closed bag of digester；After cleaning is finished, automatic is clear
Washing lotion excavationg pump quickly drains cleaning fluid, online living cells Sensor monitoring loss cell situation.
V () digests termination phase：It is to be cleaned finish after, open digestion terminate step.Improve speed of agitator, design temperature
For 37 DEG C, rotating speed are 100rpm, culture medium addition 5L is set, pH is associated into control with acid, alkali.System is according to set in advance
Digestion terminator, opens the culture medium pump of culture medium passage, and culture medium enters in the closed bag of digester；After 5min,
The free suspension cell number of line living cells Sensor monitoring starts to raise, and then a period of time free suspension cell number keeps flat
Surely, just can be considered that digestion terminates.
(vi) cell transition phase：After digestion terminator terminates, the cell shifting pump of cell transfering channel is opened, it is rich
Culture medium containing free suspension cell is pumped to 50L disposable bioreactors, and carrier is trapped component and is trapped in 10L once
In property digester.It is 0.49 × 10 that data monitoring obtains free cell number6Cells/mL, cell attachment is to new after 11 hours
On carrier, loss cell rate is only 2.01%.
Embodiment 2
Shown in Figure 6, the 90L disposable bioreactors in the embodiment are used as seed reactor, carry out microcarrier
Cell suspension cultures；The disposable digesters of 90L are used as the place of the seed cell digestion reaction that culture is completed, and realize that PK-15 is thin
Born of the same parents separate with microcarrier, and free cell is transferred to 300L disposable bioreactors and carries out continuation culture.90L and 300L mono-
The working volume of secondary property bioreactor is respectively 63L and 210L, the ratio of height to diameter 1.8 of reactor：1.0, agitating paddle uses individual layer
Elevator belt oar, oar footpath is with reactor diameter ratio：1.0:1.8.The disposable digesters of 90L and the disposable digesters of 10L have several
What similarity feature, other digestion reaction steps are with reference to embodiment 2, specific implementing procedure figure as shown in fig. 6, no longer go to live in the household of one's in-laws on getting married herein
State.
Culture medium rich in free suspension cell is pumped to 300L disposable bioreactors, and carrier is trapped component and cuts
Stay in the disposable digesters of 90L.It is 0.48 × 10 that data monitoring obtains free cell number6Cells/mL is thin after 11 hours
Born of the same parents are pasted on new carrier, and loss cell rate is only 3.98%.
Comparative example 1
Shown in Figure 1, the muptiple-use bioreactors of the 10L (stainless steel fermentation tank) in the comparative example reacts as seed
Device, carries out microcarrier cell suspension culture；The muptiple-use digesters of 10L are used as the field of the seed cell digestion reaction that culture is completed
Institute, realizes that PK-15 cells are separated with microcarrier, and free cell is transferred to the muptiple-use bioreactors of 50L, and (stainless steel ferments
Tank) carry out continuation culture.Wherein, the muptiple-use digesters of 10L are identical with the design of the muptiple-use bioreactors of 10L.10L and 50L
The working volume of muptiple-use bioreactor is respectively 7L and 35L, the ratio of height to diameter 1.8 of reactor：1.0, agitating paddle uses individual layer
Elevator belt oar, oar footpath is with reactor diameter ratio：1.0:1.8.1L bioreactors mounting medium is produced using GE companies
Cytodex-1,3g/L, cell density are 2.5 × 106cells/mL.Digestion reaction implementation process is as shown in figure 1, specific implementation
Step is as follows：
(i) liquid dosage stage：Prepare cleaning fluid 20L, digestive juice 1L, culture medium 5L, acid solution (1N HCl) 2L, alkali lye
(3N NaOH) 2L, contains 3% NBCS wherein in culture medium.
(ii) digester erection stage：Come loose reactor cap and each line connection screw, is covered on reactor of dismantling, and unloads
Each electrode, stopple, cap head, are cleaned up with rag, and clean with pure water rinsing.At docking port, reactor wall and stirring dress
Sealing part is put, is cleaned with pure water emphasis, punching residue and raffinate to the greatest extent.Check each packing ring, apron whether aged deterioration, and in time more
Change.The connection of each conduit component is finished, and electrode is connected with central controller by electrode wires, to pH value electrode, dissolved oxygen electricity
Pole carries out Zero calibration and slope is demarcated.Air pressurize is passed through, the air-tightness of reactor is checked.
(iii) digester sterilization phase：121 DEG C of empty elimination bacterium 30min.Insertion pH value electrode and dissolved oxygen electrode, digester
Built with 7L pure water, 121 DEG C of real elimination bacterium 30min.
(iv) the digester debugging stage：After sterilizing is finished, start-up temperature control assembly, design temperature is 37 DEG C, and system is led to
Circulation is crossed to cool to design temperature；PID control heater is heated and circulating water, and temperature is maintained at 37 DEG C.
V () digests wash phase：Discharge valve is opened, pure water is discharged from tank body.Digestive juice dump valve is closed, is opened
Cleaning fluid enters valve, and cleaning fluid 5L is added by pressure differential method, rinses tank body 30min；Cleaning fluid dump valve is opened, cleaning is drained
Liquid.Clean 1-3 times repeatedly, until cleaning checking noresidue.The nutrient solution of the muptiple-use bioreactor cultures of 10L is settled, is transferred
, be transferred to sedimentation liquid in the muptiple-use digesters of 10L by tank body bottom valve by clear liquid.Cleaning fluid 5L is added to clear again in digester
Wash, settle.During cleaning, design temperature is 37 DEG C, rotating speed is 50rpm.After cleaning is finished, stop stirring, emptied after settling clear
Washing lotion.
(vi) incipient stage is digested：After stage to be cleaned terminates, open digestive juice and enter valve, 0.6L digestive juices are pumped to
In digester, design temperature is 37 DEG C, and rotating speed is 25rpm, and pH is 7.0.Free cell number is measured by sampling every 10min, when
When cell number is not further added by, it is considered as digestion process completion, closes stirring, pH, opens digestive juice dump valve, emptying digestive juice.
(vii) termination phase is digested：After treating that digestion terminates, open culture medium and enter valve, 5L culture mediums are pumped to and are disappeared
Change in device, design temperature is 37 DEG C, rotating speed is 100rpm.Every 10min, free cell number is measured by sampling, works as cell number
It is not further added by or cytoactive declines, is considered as digestion and terminates.
(viii) cell transition phase：After digesting and terminating, cell transfer valve is opened, be transferred to cell by pressure differential method
In the muptiple-use bioreactors of 50L.It is 0.3 × 10 that free cell number is measured by sampling6Cells/mL, cell attachment after 14 hours
To new carrier, loss cell rate is 41.56%.
Muptiple-use digester in comparative example 1 needs installation and debugging repeatedly, it is necessary to carry out disinfection and clean online, thus wave
Time-consuming and manpower, and the loss cell rate of muptiple-use intelligent digester is up to 41.56%, and the disposable of present invention offer disappears
Change device and eliminate SIP (sterilization system on line) and CIP (on-line cleaning), the equipment step such as installation and debugging repeatedly, simplify operating process,
Save material resources, human cost；And, disposable digester loss late is minimum up to 2%, greatly reduces cell dissociation loss
Rate.
Above-mentioned specific embodiment, only illustrates technology design of the invention and architectural feature, it is therefore intended that allow and be familiar with this
The stakeholder of item technology can implement according to this, but above said content is not intended to limit protection scope of the present invention, every foundation
Any equivalent change or modification that Spirit Essence of the invention is made, all should fall under the scope of the present invention.
Claims (10)
1. a kind of disposable intelligent digester systems for animal cell culture, it is characterised in that：Including disposable digester
Unit and intelligent control unit, the disposable digester unit include at least can be used to house fluid and the digestion of cultured cells
The aseptic closed chamber of liquid, at least charging aperture connected with the closed chamber, an at least gas outlet, an at least air inlet,
An at least digestive juice entrance, an at least filter washing water inlet, an at least culture medium entrance, an at least cleaning fluid and digestive juice outlet with
And retention component and mixing component are at least additionally provided with an at least sample tap, and the closed chamber, the retention component is extremely
Few to be used in the closed chamber retain the carrier in fluid and pass through zooblast, the mixing component is at least used to
By the material mixing in the closed chamber.
2. disposable intelligent digester systems for animal cell culture according to claim 1, its spy is：Including
Closed bag, the inner chamber of the closed bag forms the closed chamber, be provided with the closed bag charging aperture, gas outlet,
Air inlet, digestive juice entrance, filter washing water inlet, culture medium entrance, at the same the closed bag bottom be additionally provided with the cleaning fluid and
Digestive juice is exported and sample tap；
Preferably, the retention component is located at the closed bag inner chamber bottom, and is tightly connected with the closed bag inner wall surrounding；
Preferably, at least an acid solution entrance and at least an alkali liquor inlet are additionally provided with the closed bag；
Preferably, an at least cell switching access and the switching outlet of an at least cell are additionally provided with the closed bag；
Preferably, the closed bag top and sidepiece form multiple ports, described multiple ports be used separately as the charging aperture,
The outlet of gas outlet, air inlet, digestive juice import, cleaning fluid import, culture medium import, cleaning fluid and digestive juice and sample tap；
Preferably, the port is at least through cap, female Luer, hose barb joint, check valve, sampler, aseptic filtration
Any one in device is isolated with external environment.
Preferably, an at least air inlet pipe inserts the closed chamber, the air inlet pipe lower end and air point by the air inlet
Cloth device is connected, and the air sparger is located at the fluid level lower section in the closed chamber, and an at least escaping pipe is by described
Insert the closed chamber in gas outlet；
Preferably, the air sparger includes ventilation ring, and a plurality of passages are evenly distributed with the ventilation ring, described logical
Diameter of the aperture of stomata less than carrier；
Preferably, flowmeter and filter are also connected with the air inlet pipe；Preferably, it is also associated with pressure gauge in the escaping pipe
Or pressure sensor and pressure-control valve；Preferably, the pressure in the closed chamber is maintained between 0.01-0.05Mpa；
Preferably, the material of the closed bag includes rigid, semi-rigid or flexible plastics；Preferably, the plastics include poly-
Appointing in carbonic ester, polyester, fluoropolymer, acrylic acid, PET, polyvinyl chloride, ABS, PC, PS, GAG, acrylic and polyolefin
Anticipate one or more combination；Especially preferred, the plastics include polyolefin.
3. disposable intelligent digester systems for animal cell culture according to claim 2, it is characterised in that：Institute
Stating disposable digester unit includes supporting construction, and the supporting construction is at least used to support the closed bag；Preferably, it is described
Supporting construction is included in the fixed buckle that the closed bag upper and lower part stretches out；Preferably, the supporting construction includes
Support frame outside the closed bag, the closed bag is arranged on support frame as described above or in support frame as described above, the branch
Support is fixing support rack or removable support frame；Preferably, the supporting construction includes the support in the closed bag
Frame；Preferably, the supporting construction is at least selected from any one in metal drum, Plastic Drum, wooden barrel or glass tank.
4. disposable intelligent digester systems for animal cell culture according to claim 3, it is characterised in that：Institute
State mixing component to be connected with drive mechanism, the drive mechanism is connected with the supporting construction, and is arranged on described closed
It is outside bag or internal；Preferably, the drive mechanism includes motor.
5. disposable intelligent digester systems for animal cell culture according to claim 1 or 4, its feature exists
In：The mixing component includes mechanical agitation mechanism and/or magnetic agitation mechanism；Preferably, the mixing component includes stirring
Axle and agitating paddle, the agitating paddle are fixedly connected and in the closed chamber with agitating shaft one end, the agitating shaft it is another
One end is located at outside the closed chamber and is connected with drive mechanism, and the agitating shaft and the closed chamber locular wall
Joint is also tightly connected through more than one sealing ring；Preferably, the agitating paddle at least selected from single or multiple lift straight oar,
Any one in arrow leaf oar, curved leaf oar, propeller.
6. disposable intelligent digester systems for animal cell culture according to claim 1, it is characterised in that：Institute
Stating retention component includes at least a sieve plate or filter screen, the aperture of the sieve plate or filter screen more than zooblast diameter and less than micro-
The diameter of carrier.
7. disposable intelligent digester systems for animal cell culture according to claim 2, its spy is：It is described
Intelligent control unit includes：
Temperature-controlling module, is at least used to control the temperature in the closed chamber；
And/or, pH control assemblies are at least used to monitor the pH value of the fluid in the closed chamber；
And/or, dissolved oxygen component is at least used to detect the dissolved oxygen change in the closed chamber；
And/or, online living cells sensor cluster is at least used to monitor the number of viable cells change wandered about as a refugee in digestion process；
And/or, weigh assembly, at least to on-line monitoring fluid inlet；
And/or, central controller is at least used to control the running status of each component；
The temperature-controlling module, pH control assemblies, dissolved oxygen component, online living cells sensor cluster and weigh assembly are and institute
State central controller and closed chamber connection；
Preferably, the temperature-controlling module, pH control assemblies, dissolved oxygen component, online living cells sensor cluster and weighing group
Part is disposable assembly；
Preferably, the intelligent control unit also includes：
Carbon dioxide sensing component, is at least used to detect the carbon dioxide change in the closed chamber；
And/or, mixing rate sensory package is at least used to detect the troubled water of the fluid in the closed chamber；
And/or, photoelectric sensing component is at least used to detect the turbidity of the fluid in the closed chamber；
The carbon dioxide sensing component, mixing rate sensory package and photoelectric sensing component connect with the central controller
Connect.
8. disposable intelligent digester systems for animal cell culture according to claim 7, it is characterised in that：Institute
Stating temperature-controlling module includes heater, chuck circulation and plug-in type or non-insertion temperature electrode；And/or, institute
Stating PH control assemblies includes pH value electrode；And/or, the dissolved oxygen component includes dissolved oxygen electrode；And/or, the online living cells
Sensor cluster is as a plug or non-insertion mode is installed on the closed chamber sidepiece, and the online living cells sensor
Component is close to the retention component；And/or, the weigh assembly include one of the supporting disposable digester unit with
Upper Weighing module and terminal box, the Weighing module are electrically connected with terminal box；Preferably, the weigh assembly includes being installed on institute
State 3-4 Weighing module at the leg of disposable digester unit.
9. disposable intelligent digester systems for animal cell culture according to claim 7, it is characterised in that：Institute
Stating intelligent control unit also includes liquid pumping component, and the liquid pumping component includes cleaning liquid pump, digestion liquid pump, culture medium
In pump, sour pump, alkali pump, cleaning fluid excavationg pump, digestive juice excavationg pump and cell shifting pump any one or it is two or more
Combination, the cleaning liquid pump, digestion liquid pump, culture medium pump, sour pump, alkali pump, cleaning fluid excavationg pump, digestive juice excavationg pump and thin
Born of the same parents' shifting pump is connected with the central controller respectively.
10. disposable intelligent digester systems for animal cell culture according to claim 1, it is characterised in that：
The central controller also includes wireless communication module, the central controller through the wireless communication module and remote terminal without
Line is connected.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710218361.7A CN106754366A (en) | 2017-04-05 | 2017-04-05 | For the disposable intelligent digester systems of animal cell culture |
Applications Claiming Priority (1)
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| CN107400632A (en) * | 2017-08-14 | 2017-11-28 | 广州齐志生物工程设备有限公司 | A kind of cell dissociation amplifying device |
| CN107603870A (en) * | 2017-11-10 | 2018-01-19 | 上海保兴生物设备工程有限公司 | A kind of digestion filter for micro-carriers cell culture |
| CN108004122A (en) * | 2017-12-12 | 2018-05-08 | 黄山市中新生物科技有限公司 | A kind of fixed-bed type bioreactor |
| CN108315259A (en) * | 2018-05-09 | 2018-07-24 | 武汉赛科成科技有限公司 | A kind of disposable film device of fluid bed cell culture of filling chip carrier |
| CN110438003A (en) * | 2019-08-30 | 2019-11-12 | 英诺维尔智能科技（苏州）有限公司 | A kind of big batch cell products large-scale production system |
| CN111770790A (en) * | 2017-10-03 | 2020-10-13 | Abec公司 | Reactor system |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN107400632A (en) * | 2017-08-14 | 2017-11-28 | 广州齐志生物工程设备有限公司 | A kind of cell dissociation amplifying device |
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| CN110438003A (en) * | 2019-08-30 | 2019-11-12 | 英诺维尔智能科技（苏州）有限公司 | A kind of big batch cell products large-scale production system |
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