CN108611271A - Totally enclosed type intelligent biology production system and production method - Google Patents
Totally enclosed type intelligent biology production system and production method Download PDFInfo
- Publication number
- CN108611271A CN108611271A CN201810443540.5A CN201810443540A CN108611271A CN 108611271 A CN108611271 A CN 108611271A CN 201810443540 A CN201810443540 A CN 201810443540A CN 108611271 A CN108611271 A CN 108611271A
- Authority
- CN
- China
- Prior art keywords
- cabin
- culture
- production
- cell
- unit
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- 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
- C12M23/02—Form or structure of the vessel
- C12M23/14—Bags
-
- 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
- C12M33/00—Means for introduction, transport, positioning, extraction, harvesting, peeling or sampling of biological material in or from the apparatus
-
- 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
- C12M37/00—Means for sterilizing, maintaining sterile conditions or avoiding chemical or biological contamination
-
- 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
- C12M41/14—Incubators; Climatic chambers
-
- 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
-
- 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
- C12M41/36—Means for regulation, monitoring, measurement or control, e.g. flow regulation of concentration of biomass, e.g. colony counters or by turbidity measurements
-
- 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
- C12M41/48—Automatic or computerized control
-
- 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
- C12M47/00—Means for after-treatment of the produced biomass or of the fermentation or metabolic products, e.g. storage of biomass
- C12M47/04—Cell isolation or sorting
Abstract
The present invention relates to totally enclosed type intelligent biology production system and production methods, the system includes shell, center movement cabin is equipped in shell, liquid operational window, culture cabin, quality of production detection cabin, material enter cabin and material outflow cabin, center movement cabin, liquid operational window, culture cabin, quality of production detection cabin, material, which enter between cabin and material outflow cabin, is equipped with isolation gas-tight door；It is equipped in liquid operational window for carrying out separation and cleaning treatment and the isolated location of inoculation to cell batch, culture cabin is equipped with the culture unit that culture preparation is carried out for the cell to inoculation, the quality of production detects cabin, material enters cabin and material outflow cabin and is equipped with to be detected and classify for the cell to acquisition and produces the aggregation units of processing, center movement cabin is equipped with the centrifugation transfection unit of cell progress virus centrifugation transfection and cell harvest for being prepared to culture, the present invention is conducive to the quality and pollution risk and relevant all types of losses that effective management and control from the root cause is brought by use environment.
Description
Technical field
The present invention relates to biological production systems, more specifically refer to totally enclosed type intelligent biology production system and production
Method.
Background technology
In recent years, biologics product flourishes, and such as CAR-T, TCR-T, the novel medicines such as stem cell medicine obtain successively
It must ratify, and put into clinical application.Cell technology is the basic support of related new drug, is paid close attention to by each side, state
Inside and outside policy vigorously supports industry development, and industry welcomes development air port, is proposed to the production of extensive, high quality cell huge
Big demand.
The outer cell production of Current Domestic is mainly manual production mode, and Semi-automatic device is relied on to be assisted.By hand
The major defect of mode is：Production cost is high；Production capacity extension is limited；The quality fluctuation and risk that human factor generates；It is artificial because
The contamination of products that element generates；The operating mistake that human factor generates；The core production intellectual property leakage that human factor generates；It is raw
In the extension of production capacity power：The high cost and long period of staff training, the certification repeatedly of facility and highly difficult, regulatory agency's routine monitoring
Difficulty is larger.And for Semi-automatic device, although improving production efficiency to a certain extent, not fundamentally
It solves the problems, such as, still remains a large amount of defects：Single set equipment can be only done the operation of single batch, and production capacity is promoted limited；It enhances production capacities,
Cost of equipment linear increase, investment return efficiency-cost ratio are undesirable；Solidification consumable purchase based on specific flow is of high cost, and uses
The inconvenience complicated for operation such as cleaning are replaced in the process；Because consumptive material cures, weak to new process adaptability, it cannot be satisfied technique and quickly become
Change related needs；A large amount of manual operation is still needed, pollution that human factor is brought, quality equivalent risk still remain；It needs
The installation space of high-cleanness, high, Facilities Construction are of high cost with cost of use；Equipment operation is more complex, needs the personnel of higher cost
With staff training；Effective data collection is cannot achieve to use with analysis；
While cell mass produces, biological manufacturing field is equally determined to large-scale virus production, on a large scale
There are similar demands for albumen pharmaceutical production processed, and have with the cell technological process of production in the technological process of production high similar
Property and comparativity.After cell production is realized in scale, there are great need to other biological production field to transfer the relevant technologies
Ask, quality, production capacity, cost bottleneck urgently new solution is broken through.
Therefore, it is necessary to design a kind of new biological production system, multiple batches of full-automatic production biology, and full envelope are realized
The culture environment of enclosed is conducive to quality that effective management and control from the root cause is brought by use environment and pollution risk and relevant each
Type is lost.
Invention content
It is an object of the invention to overcome the deficiencies of existing technologies, totally enclosed type intelligent biology production system and life are provided
Production method.
To achieve the above object, the present invention uses following technical scheme：Totally enclosed type intelligent biology production system, including
Shell, center movement cabin is equipped in the shell, liquid operational window, culture cabin, quality of production detection cabin, material enter cabin and
Material spreads out of cabin, and the center movement cabin, liquid operational window, culture cabin, quality of production detection cabin, material enter cabin and material
Isolation gas-tight door is equipped between outflow cabin；The center movement cabin, liquid operational window, culture cabin, quality of production detection cabin, material
It is respectively equipped with H2O2 sterilization pipelines in into cabin and material outflow cabin；Isolated location is equipped in the liquid operational window,
Culture unit is equipped in the culture cabin, quality of production detection cabin, material, which enter in cabin and material outflow cabin, is equipped with collection
Unit is closed, centrifugation transfection unit is equipped in the center movement cabin, wherein the isolated location, for being carried out to cell batch
Separation and cleaning treatment and inoculation；The culture unit carries out culture preparation for the cell to inoculation；The centrifugation transfection
Unit, the cell for being prepared to culture carries out virus centrifugation transfection and cell harvests；The aggregation units, for obtaining
Cell be detected and classify and produce processing.
Its further technical solution is：The center movement cabin, liquid operational window, culture cabin, quality of production detection cabin, object
For material into the operational unit for being equipped with operating biology between cabin and material outflow cabin, the operational unit includes six degree of freedom GMP
He Gui robots, linear motor module and clamping jaw, the fixture is connect with the six degree of freedom GMP He Gui robots, described
Linear motor module is connect with the six degree of freedom GMP He Gui robots.
Its further technical solution is：The culture unit includes incubator and culture vessel storage module.
Its further technical solution is：The centrifugation transfection unit includes centrifuge and centrifugation bracket, the centrifugation support
Frame is connect with the centrifuge.
Its further technical solution is：The aggregation units include the detection module for being set to quality of production detection cabin, are set to
Material spreads out of the material discharging module and waste material memory module in cabin；
The detection module, acquisition and detection for carrying out gross data to the biology of acquisition；
The material discharging module is used for the discharging of manufactured goods；
The waste material memory module has used consumptive material and medicament for storing.
Its further technical solution is：The detection module includes image detecting apparatus and flow cytometer, wherein figure
As detection device obtains the image of biological culture, progress image analysis；Flow cytometer obtains biological culture and is analyzed and divided
Choosing.
Its further technical solution is：The system also includes environment control units；
The environment control unit, for controlling at isolated location, culture unit, centrifugation transfection unit and aggregation units
Gnotobasis is advised in the conjunction of GMP.
Its further technical solution is：The system also includes mobile terminal, the mobile terminal is for inputting biological life
The condition of production, and start the flow of remote production.
Its further technical solution is：The system comprises server, the server for storing data and controls institute
State isolated location, the culture unit, the circulation for centrifuging flow between transfection unit and the aggregation units.
The present invention also provides the production method of totally enclosed type intelligent biology production system, the method includes：
Separation and cleaning treatment and inoculation are carried out to cell batch；
Culture preparation is carried out to the cell of inoculation；
Virus centrifugation transfection and cell harvest are carried out to cell prepared by culture；
The cell of acquisition is detected and is classified and produces processing.
Compared with the prior art, the invention has the advantages that：The totally enclosed type intelligent biology production process of the present invention,
By the way that the space in shell is divided into several independent cabins using isolation gas-tight door, Each performs its own functions in each cabin, respectively
Batch system is handled and is inoculated with, the cell of inoculation cultivated, to the cell of culture carry out centrifugation transfection and
Detection output, is run on cell in each cabin using operational unit is automatically controlled, and each incubation forms a module,
Multiple batches of full-automatic production biology can be achieved, and using the air curtain of gas-tight door isolation, form fully closed culture environment, have
The quality brought by use environment conducive to effective management and control from the root cause and pollution risk and relevant all types of losses.
The invention will be further described in the following with reference to the drawings and specific embodiments.
Description of the drawings
Fig. 1 is the structure diagram for the totally enclosed type intelligent biology production system that the specific embodiment of the invention provides；
Fig. 2 is the operating flow diagram for the totally enclosed type intelligent biology production system that the specific embodiment of the invention provides；
Fig. 3 is the production structure diagram for the totally enclosed type intelligent biology production system that the specific embodiment of the invention provides；
Fig. 4 is the structure diagram for the aggregation units that the specific embodiment of the invention provides；
Fig. 5 is the flow of the production method for the totally enclosed type intelligent biology production system that the specific embodiment of the invention provides
Figure.
Specific implementation mode
In order to more fully understand the present invention technology contents, with reference to specific embodiment to technical scheme of the present invention into
One step introduction and explanation, but not limited to this.
The specific embodiment as shown in Fig. 1~5, totally enclosed type intelligent biology production system provided in this embodiment, can
To be used in the various cells such as culture immunocyte, stem cell, adult cell；Realize multiple batches of full-automatic production biology, and
Fully closed culture environment is conducive to quality that effective management and control from the root cause is brought by use environment and pollution risk and related
All types of losses.
As shown in Figure 1, present embodiments providing totally enclosed type intelligent biology production system comprising shell, the shell
Enter cabin and material outflow cabin equipped with center movement cabin, liquid operational window, culture cabin, quality of production detection cabin, material in vivo,
Center movement cabin, liquid operational window, culture cabin, quality of production detection cabin, material, which enter between cabin and material outflow cabin, to be equipped with
Gas-tight door is isolated；The center movement cabin, liquid operational window, culture cabin, quality of production detection cabin, material enter cabin and material
Outflow is respectively equipped with H2O2 sterilization pipelines in cabin；It is equipped with isolated location 1 in the liquid operational window, is set in the culture cabin
There is culture unit 2, quality of production detection cabin, material, which enter in cabin and material outflow cabin, is equipped with aggregation units 4, in described
The heart, which moves, is equipped with centrifugation transfection unit 3 in cabin, wherein the isolated location 1, for being carried out at separation and cleaning to cell batch
Reason and inoculation；The culture unit 2 carries out culture preparation for the cell to inoculation；The centrifugation transfects unit 3, is used for
Virus centrifugation transfection and cell harvest are carried out to cell prepared by culture；The aggregation units 4, for the cell of acquisition into
Processing is produced in row detection and classification.
In addition, above-mentioned center movement cabin, liquid operational window, culture cabin, the quality of production detection cabin, material enter cabin and
Material is equipped with the biological operational unit 5 of operating between spreading out of cabin, and operational unit 5 includes six degree of freedom GMP He Gui robots, straight line
Motor module and clamping jaw, fixture are connect with the six degree of freedom GMP He Gui robots, the linear motor module and described six
Degree of freedom GMP He Gui robots connect.
In other embodiment, above-mentioned operational unit 5 further includes electric cylinders module and dust-proof the linear guide, linear motor mould
Group pushes electric cylinders module, electric cylinders module that robot is pushed to be moved in dust-proof the linear guide.
The operational unit 5 executes the transhipment in different operating intermodule such as patient's cell sample, preparation consumptive material, and participates in adding
The technological operations such as liquid.
Whole system is divided into center movement cabin, liquid operational window, culture cabin, the quality of production detection cabin, material enter cabin,
The independent cabin that material outflow cabin etc. is isolated by airtight door body completely, each independent cabin are furnished with independent laminar flow unit, pass through and are
Uniting, import/exhaust channel is independent to carry out gas exchanges with installation environment, reaches A grades of layers of dynamic required by pharmaceutical production GMP standards
Environment is flowed, while independent H2O2 sterilizations pipeline is installed in each cabin, can be executed each periodically or according to actual production demand
The independent sterilization operation in cabin, reaches the pharmaceutical equipment sterilization requirement of GMP requirements, substantially reduces production environment standard
Demand, and greatly reduce environment usable floor area, is greatly lowered construction and use cost, and from the root cause effective management and control because making
The quality and pollution risk brought with environment and relevant all types of losses.
Cell is transported automatically in each culture unit 2, automatically cultivates cell, improves culture efficiency, and collect
At the robot operational unit 5 based on high-freedom degree and Jing Guo GMP certifications, simulation human hand carries out core process equipment operation, tool
The standby human hand operation high degree of adaptability that update operation changes shock processing during technique research and development, while meeting raw in batch
It produces in link, to the high degree of adaptability of production technology adjustment upgrading.
Further, include incubator and culture vessel storage module for above-mentioned culture unit 2, cultivate cell
When, it is cultivated in cultivating the incubator in cabin, which is customization H2O2 automatically cleaning CO2 incubators, avoids operating
Pollution in journey.
In addition, include centrifuge and centrifugation bracket for above-mentioned centrifugation transfection unit 3, the centrifugation bracket with it is described
Centrifuge connects.Centrifuge executes the operations such as virus (centrifugation) transfection, cell harvest.Specifically, above-mentioned centrifuge is customization
H2O2 automatically cleaning temperature controllable general purpose centrifuges, centrifugation bracket is the dedicated centrifugation bracket of each container.
Preferably, aggregation units 4 include the detection module 41 for being set to quality of production detection cabin, spread out of going out for cabin set on material
Expect module 42 and waste material memory module 43.
Detection module 41, acquisition and detection for carrying out gross data to the biology of acquisition.
Material discharging module 42 is used for the discharging of manufactured goods.
Waste material memory module 43 has used consumptive material and medicament for storing.
Above-mentioned detection module 41 includes image detecting apparatus and flow cytometer, wherein image detecting apparatus obtains
The image of biological culture carries out image analysis；Flow cytometer obtains biological culture and is analyzed and sorted.By customizing streaming
Instrument and software, full-automatic vision detector and software, fluorescence colour code instrument and software, inverted microscope and software, realization execute system
The acquisition of gross data during standby, such as total number of cells, cell proliferation rate, Cell viability, transfection efficiency, cell subsets
Detection.
Further, further include environment control unit 6 for above-mentioned system；Environment control unit 6, for control every
Gnotobasis is advised in the conjunction that GMP is in from unit 1, culture unit 2, centrifugation transfection unit 3 and aggregation units 4.Above-mentioned environment
Control unit 6 includes each cabin system layer stream, each unit H2O2 sterilizations, each cabin isolating door, Temperature Humidity Sensor, miniature
Particle intelligent measurement sensor-based system, microorganism intelligent measurement sensor-based system；The integration environment controls in system, and each cabin is independent sealed
Formed A grades of dynamic layer fluid spaces, equipment can installation and operation in D grades of environment, which can flexibly be mounted on hospital, clinic, life
In object service company, pharmacy corporation workshop, there is the adaptability of height to environment.Sterilization system is integrated in system simultaneously, is fitted
Answer the sterilization requirements of various processes.
In addition, as preferred embodiment, above-mentioned system further includes liquid operating unit 7, specifically, liquid operation
Unit 7 includes low consumption of the liquid high-precision liquid operation module, large capacity liquid pump group (band automatically cleaning), bottle inversion/bag module, liquid behaviour
Make liquid operation of the unit 7 for executing different capabilities in each processing step, different accuracy requirement.
System further includes including the refrigerator group of -80 DEG C, -20 DEG C, 4 DEG C three temperature grades, to provide the rings such as Cord blood
Border.
System further includes electronic control unit 8, and specifically, electronic control unit 8 includes High performance industrial server 11, embedding assembly
Unit, PLC, various kinds of sensors (position, temperature, humidity) etc..
In addition, system further includes storage element 9, in the system for the material which is used to use in production process
It is temporary.System further includes the units such as data collection, quality management and distant client service, adapts to traditional preparation center production
Pattern, while creating completely new distributed cell and preparing production model, it provides close to terminal user and directly services, to different lifes
Production pattern has the adaptability of height with business model.
Above-mentioned system includes server 11, and the server 11 for storing data and controls the isolated location 1, institute
The circulation stated culture unit 2, centrifuge flow between transfection unit 3 and the aggregation units 4.
Personnel need to only carry out simple production material feeding and be operated with manufactured goods blanking, and pilot process is all automatic by system
Change and complete, the requirement to personnel's operative skill and related training substantially reduces, and improves system to operating with the adaptation of personnel
Property.
System and consumptive material, the technique that forms a complete production network can be ratified by supervision department's uniform auditing, facilitate user in (more regions)
It branches out, improves production capacity.Simultaneity factor can provide the operation of systematization in production process, quality inspection report, facilitate supervision department
Efficient supervision to cell therapy finished product.The expenses such as equipment purchase, Facilities Construction and consumable purchase are kept to be not higher than traditional hand
Under the premise of work method, operation cost is substantially reduced；Industrially scalable cell is set to prepare production and distributed cell production service
New mode be possibly realized, meet the rigid need of industry；The interference that artificial and environmental factor is brought in preparation of the production process is excluded, is had
Effect improves product homogeneity, and effectively reducing environmental pollution influences；And the artificial data manipulation mistake effectively avoided, it reduces because of personnel
The core that fluxion strap comes prepares the disclosure risk of intellectual property, and the great number cost that repetition staff training is brought is greatly lowered；It is real
Now full-automatic, full-range data collection and management, accelerate the data collection analysis in R＆D process and program decisions, effectively change
Audit management of the kind regulatory agency to production procedure and finished product quality；Convenient for equipment user client business in the world
Duplication expand, form the scale and benefit of entire industry.
In addition, above-mentioned system further includes mobile terminal 10, the mobile terminal 10 is used to input the condition of biological production,
And start the flow of remote production.
In other embodiment, above-mentioned system further includes man machine operation interface, Database Unit, network module, production stream
Journey editor and management module, Intelligent planning and scheduling module, material storage and management module, production daily record, quality testing daily record,
Batch report and system and modular debugging test module.
Based on technological process file, full-automatic Intelligent planning and scheduling is realized.The intelligent Service of standard is provided simultaneously,
Such as：Produce daily record (each single -step operation of each batch records), embedded quality testing daily record (each detection of each batch
Operation), the daily record of system sterilization, every batch of intelligent batch report-Batch Report.After flow file importing,
Operating personnel only need to carry out the operation of upper and lower sample/material, sample/material and technological process binding, substantially reduce to operation
The requirement of personnel ability and training, and greatly reduce operating personnel's quantity.After installation, production system is as distributed intelligent terminal
Persistent collection production, quality inspection, treatment data, and distal end passes real time data back to large data center, carries out production technology, treatment side
The big data of case etc. stores and intellectual analysis, Continuous optimization production technology and therapeutic scheme.Tumor targets can be carried out simultaneously
The applications such as analysis, big crowd's genetic analysis, pharmaceutical effectiveness analysis.In R＆D process, it can accelerate to expend a large amount of manpower objects now
The batch contrast test of power carries out intellectualized operation and experimental data statistical analysis.
Using general nucleus module and consumptive material, meet biological production common requirement, by system software, client can be according to
Actual demand carries out the exploitation of new technological process and test is verified, it is no longer necessary to which the technological process of open core is supplied to equipment
Quotient is customized, it is ensured that the core process flow of client is the exclusive core I P of client, meets the practical need of the quick evolution of technique
Ask, modular design, system, which can facilitate, meets the different process equipment quick-replaceable of cell, virus, albumen, while it is default with
The interface for freezing system, clearance quality detecting system etc. makes full-automatic biological factory solution become a reality.With FDA/
The correlation pharmaceutical production accordance such as CFDA, GMP is that design basis can after system, consumptive material, production procedure scheme are disposably ratified
Accelerating deployment in the world, forms effective market scale, system software can automatically save all productions and qualitative data, and
It can be that special data channel is opened in supervision, effectively reduce the threshold supervised in industry expanding course and risk.
Above-mentioned totally enclosed type intelligent biology production process, by dividing the space in shell using isolation gas-tight door
At several independent cabins, Each performs its own functions in each cabin, carries out that batch system is handled and is inoculated with respectively, to inoculation
Cell is cultivated, and carries out centrifugation transfection to the cell of culture and detection exports, transported cell using operational unit 5 is automatically controlled
Turn in each cabin, each incubation forms a module, it can be achieved that multiple batches of full-automatic production is biological, and uses gas
The air curtain of Mi Men isolation, forms fully closed culture environment, is conducive to what effective management and control from the root cause was brought by use environment
Quality and pollution risk and relevant all types of losses.
As shown in figure 5, the present embodiment additionally provides the production method of totally enclosed type intelligent biology production system, this method
Including：
S1, separation and cleaning treatment and inoculation are carried out to cell batch；
S2, culture preparation is carried out to the cell of inoculation；
S3, virus centrifugation transfection and cell harvest are carried out to the cell of culture preparation；
S4, the cell of acquisition is detected and is classified and produces processing.
Obtain cell batch；Cell batch is detached using density-gradient centrifugation method；Cell after separation is carried out
Cleaning；Counting is sampled to the cell after cleaning；OKT3 is added, adjusts density, carries out cell inoculation；To the cell of inoculation into
Row sampling number of computations and survival rate, preservation of taking pictures；It is dispensed according to quantity；IL-2 and culture medium is added；Culture is made
Cell in standby is tested；Several hours of Virus culture are added into empty package bag；Blood is moved into packaging bag, culture
Several hours；Substance in packaging bag is cleaned, and is transferred in new culture bag；, obtain cell in new culture bag；To thin
Born of the same parents clean；Counting is sampled to the cell after cleaning；Manufacture test is carried out to the cell after counting；Manufacture will be met to survey
The cell freezing of examination is stored and is stored in probe tube.
The preparation of integrated universal/quality inspection equipment in systems forms hardware and software platform solution, integrates usual cell and produces institute
It operated, cultivated with separation sorting, infection, liquid, collected, freezing the techniques such as encapsulation in one, building full-automatic intelligence production
System, and the quality detection module 4141 during forming a complete production network are general and by the core work of long-term actual production verification
Skill equipment, meets the high-adaptability demand of the different process such as stem cell, immunocyte, the IN process editing machine of the system integration with
Flow control software can allow client to carry out flexible adjustment and modification to production procedure.
Cell is transported automatically in each culture unit 2, automatically cultivates cell, improves culture efficiency, and collect
At the robot operational unit 5 based on high-freedom degree and Jing Guo GMP certifications, simulation human hand carries out core process equipment operation, tool
The standby human hand operation high degree of adaptability that update operation changes shock processing during technique research and development, while meeting raw in batch
It produces in link, to the high degree of adaptability of production technology adjustment upgrading.
The integration environment control, each independent sealed A grades of dynamic layer fluid spaces of formation in cabin, equipment can installation and operation in D grades of rings
In border, which can flexibly be mounted in hospital, clinic, biological service company, pharmacy corporation workshop, have height to fit environment
Ying Xing.Sterilization system is integrated in system simultaneously, adapts to the sterilization requirements of various processes.
Traditional preparation center production model is adapted to, while creating completely new distributed cell and preparing production model, close to
Terminal user, which provides, directly to be serviced, and has the adaptability of height to different production models and business model.
Personnel need to only carry out simple production material feeding and be operated with manufactured goods blanking, and pilot process is all automatic by system
Change and complete, the requirement to personnel's operative skill and related training substantially reduces, and improves system to operating with the adaptation of personnel
Property.
System and consumptive material, the technique that forms a complete production network can be ratified by supervision department's uniform auditing, facilitate user in (more regions)
It branches out, improves production capacity.Simultaneity factor can provide the operation of systematization in production process, quality inspection report, facilitate supervision department
Efficient supervision to cell therapy finished product.The expenses such as equipment purchase, Facilities Construction and consumable purchase are kept to be not higher than traditional hand
Under the premise of work method, operation cost is substantially reduced；Industrially scalable cell is set to prepare production and distributed cell production service
New mode be possibly realized, meet the rigid need of industry；The interference that artificial and environmental factor is brought in preparation of the production process is excluded, is had
Effect improves product homogeneity, and effectively reducing environmental pollution influences；And the artificial data manipulation mistake effectively avoided, it reduces because of personnel
The core that fluxion strap comes prepares the disclosure risk of intellectual property, and the great number cost that repetition staff training is brought is greatly lowered；It is real
Now full-automatic, full-range data collection and management, accelerate the data collection analysis in R＆D process and program decisions, effectively change
Audit management of the kind regulatory agency to production procedure and finished product quality；Convenient for equipment user client business in the world
Duplication expand, form the scale and benefit of entire industry.
Whole system is divided into center movement cabin, liquid operational window, culture cabin, the quality of production detection cabin, material enter cabin,
The independent cabin that material outflow cabin etc. is isolated by airtight door body completely, each independent cabin are furnished with independent laminar flow unit, pass through and are
Uniting, import/exhaust channel is independent to carry out gas exchanges with installation environment, reaches A grades of layers of dynamic required by pharmaceutical production GMP standards
Environment is flowed, while independent H2O2 sterilizations pipeline is installed in each cabin, can be executed each periodically or according to actual production demand
The independent sterilization operation in cabin, reaches the pharmaceutical equipment sterilization requirement of GMP requirements, substantially reduces production environment standard
Demand, and greatly reduce environment usable floor area, is greatly lowered construction and use cost, and from the root cause effective management and control because making
The quality and pollution risk brought with environment and relevant all types of losses.
The production method of above-mentioned totally enclosed type intelligent biology production process, by the way that the space in shell is used isolation
Gas-tight door is divided into several independent cabins, and Each performs its own functions in each cabin, carries out that batch system is handled and connect respectively
Kind, the cell of inoculation is cultivated, centrifugation transfection is carried out to the cell of culture and detection exports, it is single using operating is automatically controlled
Member 5 runs on cell in each cabin, and each incubation forms a module, it can be achieved that multiple batches of full-automatic production life
Object, and using the air curtain of gas-tight door isolation, form fully closed culture environment, be conducive to effective management and control from the root cause because using
The quality that environment is brought and pollution risk and relevant all types of losses.
It is above-mentioned only with embodiment come the technology contents that further illustrate the present invention, in order to which reader is easier to understand, but not
It represents embodiments of the present invention and is only limitted to this, any technology done according to the present invention extends or recreation, by the present invention's
Protection.Protection scope of the present invention is subject to claims.
Claims (10)
1. totally enclosed type intelligent biology production system, which is characterized in that including shell, center movement is equipped in the shell
Cabin, liquid operational window, culture cabin, the quality of production detects cabin, material enters cabin and material outflow cabin, the center movement cabin,
Liquid operational window, culture cabin, quality of production detection cabin, material, which enter between cabin and material outflow cabin, is equipped with isolation gas-tight door；
The center movement cabin, liquid operational window, culture cabin, quality of production detection cabin, material enter in cabin and material outflow cabin and divide
It She You not H2O2 sterilization pipelines；It is equipped with isolated location in the liquid operational window, culture unit is equipped in the culture cabin,
Quality of production detection cabin, material, which enter in cabin and material outflow cabin, is equipped with aggregation units, is set in the center movement cabin
There is centrifugation transfection unit, wherein the isolated location, for carrying out separation and cleaning treatment and inoculation to cell batch；Institute
Culture unit is stated, culture preparation is carried out for the cell to inoculation；The centrifugation transfects unit, the cell for being prepared to culture
Carry out virus centrifugation transfection and cell harvest；The aggregation units, be detected for the cell to acquisition and classify turn
Go out processing.
2. totally enclosed type intelligent biology production system according to claim 1, which is characterized in that the center movement
Cabin, liquid operational window, culture cabin, quality of production detection cabin, material, which enter between cabin and material outflow cabin, is equipped with operating biology
Operational unit, the operational unit includes six degree of freedom GMP He Gui robots, linear motor module and clamping jaw, the folder
Tool is connect with the six degree of freedom GMP He Gui robots, the linear motor module and the six degree of freedom GMP He Gui robots
Connection.
3. totally enclosed type intelligent biology production system according to claim 1, which is characterized in that the culture unit packet
Include incubator and culture vessel storage module.
4. totally enclosed type intelligent biology production system according to claim 1, which is characterized in that the centrifugation transfection is single
Member includes that centrifuge and centrifugation bracket, the centrifugation bracket are connect with the centrifuge.
5. totally enclosed type intelligent biology production system according to claim 1, which is characterized in that the aggregation units packet
It includes the detection module set on quality of production detection cabin, spread out of the material discharging module and waste material memory module in cabin set on material；
The detection module, acquisition and detection for carrying out gross data to the biology of acquisition；
The material discharging module is used for the discharging of manufactured goods；
The waste material memory module has used consumptive material and medicament for storing.
6. totally enclosed type intelligent biology production system according to claim 5, which is characterized in that the detection module packet
Include image detecting apparatus and flow cytometer, wherein image detecting apparatus obtains the image of biological culture, carries out image point
Analysis；Flow cytometer obtains biological culture and is analyzed and sorted.
7. totally enclosed type intelligent biology production system according to any one of claims 1 to 6, which is characterized in that described
System further includes environment control unit；
The environment control unit is in for controlling isolated location, culture unit, centrifugation transfection unit and aggregation units
Gnotobasis is advised in the conjunction of GMP.
8. totally enclosed type intelligent biology production system according to claim 7, which is characterized in that the system also includes
Mobile terminal, the mobile terminal are used to input the condition of biological production, and start the flow of remote production.
9. totally enclosed type intelligent biology production system according to claim 8, which is characterized in that the system comprises clothes
Be engaged in device, the server for storing data and control the isolated location, the culture unit, the centrifugation transfect unit with
And between the aggregation units flow circulation.
10. the production method of totally enclosed type intelligent biology production system, which is characterized in that the method includes：
Separation and cleaning treatment and inoculation are carried out to cell batch；
Culture preparation is carried out to the cell of inoculation；
Virus centrifugation transfection and cell harvest are carried out to cell prepared by culture；
The cell of acquisition is detected and is classified and produces processing.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810443540.5A CN108611271A (en) | 2018-05-10 | 2018-05-10 | Totally enclosed type intelligent biology production system and production method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810443540.5A CN108611271A (en) | 2018-05-10 | 2018-05-10 | Totally enclosed type intelligent biology production system and production method |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN108611271A true CN108611271A (en) | 2018-10-02 |
Family
ID=63662694
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810443540.5A Pending CN108611271A (en) | 2018-05-10 | 2018-05-10 | Totally enclosed type intelligent biology production system and production method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108611271A (en) |
Cited By (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108641953A (en) * | 2018-05-16 | 2018-10-12 | 余春 | Totally enclosed type intelligent biology production system and production method |
| 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 |
| CN110484448A (en) * | 2019-09-18 | 2019-11-22 | 杭州捷诺飞生物科技股份有限公司 | Biological tissue's process units |
| CN110540937A (en) * | 2019-09-09 | 2019-12-06 | 英诺维尔智能科技（苏州）有限公司 | Multi-compartment unit culture system suitable for GMP (good manufacturing practice) compliance automatic production |
| WO2020000533A1 (en) * | 2018-06-26 | 2020-01-02 | 深圳市北科生物科技有限公司 | High-adaptive full-automatic cell culture system and method therefor |
| CN110908329A (en) * | 2019-12-23 | 2020-03-24 | 深圳赛动生物自动化有限公司 | Stem cell feeding and discharging bin control system and control method based on programmable controller |
| CN110968033A (en) * | 2019-12-23 | 2020-04-07 | 深圳赛动生物自动化有限公司 | Stem cell liquid distribution bin control system based on programmable controller and control method thereof |
| CN111019825A (en) * | 2019-12-23 | 2020-04-17 | 深圳赛动生物自动化有限公司 | Stem cell feeding bin control system based on programmable controller and control method thereof |
| CN112961762A (en) * | 2021-01-18 | 2021-06-15 | 英诺维尔智能科技（苏州）有限公司 | Full-automatic operation method for puncturing operation of high-performance culture bottle |
| CN113101984A (en) * | 2021-04-16 | 2021-07-13 | 英诺维尔智能科技（苏州）有限公司 | High-cleanliness biological pharmaceutical sterile liquid operation platform based on magnetic suspension technology |
| EP4025681A1 (en) * | 2019-09-04 | 2022-07-13 | Embrient, Inc. | Incubator with air curtain |
| WO2023005842A1 (en) * | 2021-07-28 | 2023-02-02 | 英诺维尔智能科技（苏州）有限公司 | System for expression, purification, and detection and screening of biological drugs |
| WO2023065747A1 (en) * | 2021-10-21 | 2023-04-27 | 英诺维尔智能科技（苏州）有限公司 | System for macromolecule extraction |
| WO2023083311A1 (en) * | 2021-11-13 | 2023-05-19 | 英诺维尔智能科技（苏州）有限公司 | Intelligent gene synthesis and monoclonal selection system |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1598415A1 (en) * | 2004-05-20 | 2005-11-23 | The Automation Partnership (Cambridge) Limited | Smart cell culture |
| KR100745362B1 (en) * | 2006-03-14 | 2007-08-02 | 세원셀론텍(주) | A cell therapy product facility use method and network franchise market business method |
| CN102093954A (en) * | 2010-12-16 | 2011-06-15 | 汪华 | Cell culture device and cell culture method |
| CN106701576A (en) * | 2017-03-02 | 2017-05-24 | 深圳华云智能装备科技有限公司 | Fully-automatic cell culture room and control method thereof |
-
2018
- 2018-05-10 CN CN201810443540.5A patent/CN108611271A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1598415A1 (en) * | 2004-05-20 | 2005-11-23 | The Automation Partnership (Cambridge) Limited | Smart cell culture |
| KR100745362B1 (en) * | 2006-03-14 | 2007-08-02 | 세원셀론텍(주) | A cell therapy product facility use method and network franchise market business method |
| CN102093954A (en) * | 2010-12-16 | 2011-06-15 | 汪华 | Cell culture device and cell culture method |
| CN106701576A (en) * | 2017-03-02 | 2017-05-24 | 深圳华云智能装备科技有限公司 | Fully-automatic cell culture room and control method thereof |
Cited By (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108641953A (en) * | 2018-05-16 | 2018-10-12 | 余春 | Totally enclosed type intelligent biology production system and production method |
| WO2020000533A1 (en) * | 2018-06-26 | 2020-01-02 | 深圳市北科生物科技有限公司 | High-adaptive full-automatic cell culture system and method therefor |
| CN110643509A (en) * | 2018-06-26 | 2020-01-03 | 深圳市北科生物科技有限公司 | High-adaptability full-automatic cell culture system and method thereof |
| 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 |
| EP4025681A4 (en) * | 2019-09-04 | 2023-10-11 | Embrient, Inc. | Incubator with air curtain |
| EP4025681A1 (en) * | 2019-09-04 | 2022-07-13 | Embrient, Inc. | Incubator with air curtain |
| CN110540937A (en) * | 2019-09-09 | 2019-12-06 | 英诺维尔智能科技（苏州）有限公司 | Multi-compartment unit culture system suitable for GMP (good manufacturing practice) compliance automatic production |
| CN110484448A (en) * | 2019-09-18 | 2019-11-22 | 杭州捷诺飞生物科技股份有限公司 | Biological tissue's process units |
| CN111019825A (en) * | 2019-12-23 | 2020-04-17 | 深圳赛动生物自动化有限公司 | Stem cell feeding bin control system based on programmable controller and control method thereof |
| CN110968033A (en) * | 2019-12-23 | 2020-04-07 | 深圳赛动生物自动化有限公司 | Stem cell liquid distribution bin control system based on programmable controller and control method thereof |
| CN110908329A (en) * | 2019-12-23 | 2020-03-24 | 深圳赛动生物自动化有限公司 | Stem cell feeding and discharging bin control system and control method based on programmable controller |
| CN112961762A (en) * | 2021-01-18 | 2021-06-15 | 英诺维尔智能科技（苏州）有限公司 | Full-automatic operation method for puncturing operation of high-performance culture bottle |
| CN113101984A (en) * | 2021-04-16 | 2021-07-13 | 英诺维尔智能科技（苏州）有限公司 | High-cleanliness biological pharmaceutical sterile liquid operation platform based on magnetic suspension technology |
| WO2023005842A1 (en) * | 2021-07-28 | 2023-02-02 | 英诺维尔智能科技（苏州）有限公司 | System for expression, purification, and detection and screening of biological drugs |
| WO2023065747A1 (en) * | 2021-10-21 | 2023-04-27 | 英诺维尔智能科技（苏州）有限公司 | System for macromolecule extraction |
| WO2023083311A1 (en) * | 2021-11-13 | 2023-05-19 | 英诺维尔智能科技（苏州）有限公司 | Intelligent gene synthesis and monoclonal selection system |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN108611271A (en) | Totally enclosed type intelligent biology production system and production method | |
| US11376587B2 (en) | Fluid connector | |
| CN109661582A (en) | Automatic cytological processing system and method | |
| CN108641953A (en) | Totally enclosed type intelligent biology production system and production method | |
| US4154652A (en) | Method for automatically and successively cultivating tissues or cells of a body | |
| CN101558409A (en) | Automated cell therapy system | |
| WO2015076391A1 (en) | Automatic culture system and cell management system | |
| CN107287119B (en) | Cell culture counting assembly | |
| CN109153954A (en) | Automated production and collection | |
| JP3231664U (en) | Robot arm fully automatic cell culture system | |
| CN113514652A (en) | Intelligent system for biological medicine expression purification and detection screening | |
| CN107354093B (en) | Cell preparation apparatus | |
| CN107287165A (en) | A kind of preparation method of CAR T cells | |
| CN206843495U (en) | Ezyme bio-reactor and intelligent enzyme reaction work station | |
| WO2010130302A1 (en) | Modular system for the automatic production of three-dimensional tissue structures | |
| CN111334429A (en) | Modular multifunctional cell workstation | |
| US20190390153A1 (en) | Fully automatic cell culture method and system thereof based on mechanical arm | |
| CN109486655A (en) | A kind of full-automation biological products system | |
| CN110643509A (en) | High-adaptability full-automatic cell culture system and method thereof | |
| CN113549553A (en) | GMP (good manufacturing practice) compliance high-flux intelligent biological medicine production system | |
| CN219603592U (en) | Automatic organoid liquid partial shipment system | |
| CN115612614A (en) | Liquid partial shipment system before kind organ handles | |
| CN107687999A (en) | A kind of cell quality detection method and system | |
| JP2020108375A (en) | Method for providing self-cultured cell culture information | |
| CN116121168A (en) | Preparation method of exosomes and cell incubator thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20181002 |