CN111948968A - High-throughput micro-reaction cell culture flexible automatic control system and method - Google Patents
High-throughput micro-reaction cell culture flexible automatic control system and method Download PDFInfo
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- 238000004113 cell culture Methods 0.000 title claims abstract description 55
- 238000000034 method Methods 0.000 title claims abstract description 53
- 238000006243 chemical reaction Methods 0.000 title claims abstract description 18
- 230000003993 interaction Effects 0.000 claims description 30
- 230000007613 environmental effect Effects 0.000 claims description 11
- 238000013519 translation Methods 0.000 claims description 11
- 238000004140 cleaning Methods 0.000 claims description 10
- 238000012937 correction Methods 0.000 claims description 8
- 238000012545 processing Methods 0.000 claims description 7
- 230000005540 biological transmission Effects 0.000 claims description 6
- 238000012258 culturing Methods 0.000 claims description 3
- 230000002159 abnormal effect Effects 0.000 claims description 2
- 238000001914 filtration Methods 0.000 claims description 2
- 230000010355 oscillation Effects 0.000 claims description 2
- 230000000737 periodic effect Effects 0.000 claims description 2
- 230000003068 static effect Effects 0.000 claims description 2
- 230000010354 integration Effects 0.000 abstract description 2
- 238000010586 diagram Methods 0.000 description 7
- 238000012544 monitoring process Methods 0.000 description 3
- 238000004891 communication Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 238000002372 labelling Methods 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000002457 bidirectional effect Effects 0.000 description 1
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- 238000012423 maintenance Methods 0.000 description 1
- 238000003032 molecular docking Methods 0.000 description 1
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- G05B19/00—Programme-control systems
- G05B19/02—Programme-control systems electric
- G05B19/04—Programme control other than numerical control, i.e. in sequence controllers or logic controllers
- G05B19/042—Programme control other than numerical control, i.e. in sequence controllers or logic controllers using digital processors
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- G—PHYSICS
- G05—CONTROLLING; REGULATING
- G05B—CONTROL OR REGULATING SYSTEMS IN GENERAL; FUNCTIONAL ELEMENTS OF SUCH SYSTEMS; MONITORING OR TESTING ARRANGEMENTS FOR SUCH SYSTEMS OR ELEMENTS
- G05B2219/00—Program-control systems
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Abstract
The invention relates to a high-throughput micro-reaction cell culture flexible automatic control system and a method, which realize effective integration of data of different devices by introducing an intelligent agent module and applying a SiLA automation protocol standard and an intelligent agent framework MAS in the cell culture process, establish condition drive which can be set by a user in a self-defined way, realize flexible automatic control of the whole system and meet the requirements of the user on diverse and complex application scenes in cell culture reaction.
Description
Technical Field
The invention relates to the technical field of bioengineering, in particular to a high-throughput micro-reaction cell culture flexible automatic control system and a method.
Background
The process control condition of cell culture is complex, the data volume is large, the current control system has low data processing efficiency and insufficient support of logic control condition, still needs a large amount of manual intervention, and can not realize the full-automatic operation of the whole system; meanwhile, the system automation control software has low flexibility and insufficient flexibility, the change situation of the client application scene cannot be completely expected in the software design stage, and the use is severely limited in the actual operation.
Because the high-throughput micro-reaction system adopted by the cell culture is composed of various automatic devices, the interface protocol and the data format are not unified, the integration and development cost is high, the error correction is difficult, the expansibility of the control system is poor, and the maintenance upgrading cost is high.
Disclosure of Invention
In order to solve the defects of the prior art, the invention provides a high-throughput micro-reaction cell culture flexible automatic control system and a high-throughput micro-reaction cell culture flexible automatic control method.
In order to achieve the above purpose, the technical scheme adopted by the invention comprises the following steps:
a high-throughput micro-reaction cell culture flexible automatic control system comprises a plurality of data acquisition interfaces respectively and correspondingly connected with different culture equipment, a plurality of intelligent agent modules, a database module and a human-computer interaction module, wherein the intelligent agent modules are in one-to-one correspondence with the data acquisition interfaces;
the data acquisition interface is connected with the intelligent agent module, transmits the acquired equipment working state data to the intelligent agent module, and simultaneously receives a cell culture control instruction transmitted by the intelligent agent module and transmits the cell culture control instruction to the connected culture equipment;
the intelligent agent module is in data connection with the data acquisition interface, the database module and the man-machine interaction module, and comprises a data acquisition interface connection unit, a SiLA translation unit, a control unit, a knowledge unit and a capability unit; the data acquisition interface connecting unit is connected with the data acquisition interface, receives the equipment working state data sent by the data acquisition interface and sends a cell culture control instruction to the data acquisition interface; the SiLA translation unit translates the equipment working state data into standard equipment working state data of a standardized protocol, and/or translates equipment control logic and an equipment control method into cell culture control instructions directly used for controlling the culture equipment; the control unit collects real-time equipment working state data, historical equipment working state data, environmental parameters and operation instructions transmitted by the human-computer interaction module and generates equipment control logic and an equipment control method, and the equipment control logic and the equipment control method are sent to the human-computer interaction module; the knowledge unit stores and manages related variables, process variables and/or operating logic; the capacity unit stores and manages a basic operation closed loop of a pre-packaged intelligent agent module;
the database module comprises a master database and a slave database; the database module is in data connection with the intelligent agent module and the man-machine interaction module, the master database receives and stores standard equipment working state data, real-time equipment working state data, historical equipment working state data and environmental parameters sent by the intelligent agent module, and equipment control logic and an equipment control method sent by the man-machine interaction module, and the slave database synchronizes data with the master database at regular intervals or according to operation and responds to a data calling request;
the human-computer interaction module receives and displays one or more of standard equipment working state data, real-time equipment working state data, historical equipment working state data, environmental parameters, equipment control logic and an equipment control method from the database module according to selection of an operator, and simultaneously sends an operation instruction input by the operator to the intelligent agent module;
the cell culture control instructions comprise condition driven instructions; the conditional driver instructions include a target variable, a target threshold, a comparison relationship, and an associated driver.
Further, the intelligent agent modules are connected with one another to form a network to form a distributed control network and perform data transmission.
Further, the intelligent agent module also comprises a data cleaning unit; the data cleaning unit is used for carrying out data cleaning operation on the equipment working state data sent by the data acquisition interface and sending the cleaned equipment working state data to the SiLA translation unit for translation; and the data cleaning operation comprises removing abnormal equipment working state data of which the oscillation amplitude exceeds a preset threshold value from the equipment working state data.
Further, the intelligent agent module further comprises a data correction unit; and the data correction unit is used for correcting the equipment working state data sent by the data acquisition interface according to the environmental parameters.
Further, the condition driven instruction further comprises an additional logic condition; the additional logic conditions include control variable periodic fluctuation, static interval and data noise filtering conditions.
Further, the intelligent agent module also comprises an automatic control unit; the automatic control unit prestores or pre-inputs the general equipment control logic and equipment control method of the cell culture process and the equipment working state data standard value; and in the cell culture process, when the relative error between the measured working state data of the equipment and the standard value of the working state data of the equipment is within the range of a preset threshold value, the general equipment control logic and the equipment control method are directly called to control the cell culture process, and when the relative error between the measured working state data of the equipment and the standard value of the working state data of the equipment is outside the range of the preset threshold value, a prompt is sent by a human-computer interaction module and an operation instruction input by an operator is preferentially called.
The invention also relates to a flexible automatic control method for high-throughput micro-reaction cell culture, which comprises the following steps:
s1, setting equipment control logic and an equipment control method;
s2, translating the cell culture control command into a cell culture control command by the equipment control logic and the equipment control method, and transmitting the cell culture control command to the culture equipment by the data acquisition interface to start cell culture to obtain equipment working state data;
s3, processing the equipment working state data, and translating the data into standard equipment working state data;
s4, generating a condition driving command;
s5, culturing the cells according to the condition driving command.
Further, the step S1 includes inputting an operation command through the human-computer interaction module and converting the operation command into a device control logic and a device control method by the intelligent agent module, and/or calling a general device control logic and a device control method pre-stored or pre-input by the automatic control unit and a standard value of the device operating state data.
Further, the step S3 includes data cleaning and/or data correction.
Further, the step S4 includes outputting the corresponding associated driver according to the additional logic condition by the ratio of the target variable to the target threshold according to the comparison relationship.
The invention has the beneficial effects that:
by adopting the high-throughput micro-reaction cell culture flexible automatic control system and method, the uniform standardized processing of differential data protocols in the cell culture process is realized by utilizing the bidirectional translation conforming to the SiLA automation standard, and further the data protocol unification of the whole cell culture process is realized.
Drawings
FIG. 1 is a schematic structural diagram of a flexible automatic control system for high-throughput micro-reaction cell culture.
FIG. 2 is a schematic flow chart of the flexible automatic control method for high-throughput micro-reaction cell culture according to the present invention.
FIG. 3 is a diagram illustrating a data flow process according to the present invention.
Fig. 4 is a schematic structural diagram of an intelligent agent module according to an embodiment of the present invention.
FIG. 5 is a schematic diagram of the logic architecture of the system of the present invention.
Detailed Description
For a clearer understanding of the contents of the present invention, reference will be made to the accompanying drawings and examples.
FIG. 1 is a schematic structural diagram of a flexible automatic control system for high-throughput micro-reaction cell culture, which comprises a plurality of data acquisition interfaces respectively connected with different culture devices, a plurality of intelligent agent modules corresponding to the data acquisition interfaces one by one, a database module and a human-computer interaction module. The data acquisition interface is connected with the intelligent agent module, transmits the acquired equipment working state data to the intelligent agent module, and simultaneously receives a cell culture control instruction transmitted by the intelligent agent module and transmits the cell culture control instruction to the connected culture equipment; the intelligent agent module is in data connection with the data acquisition interface, the database module and the man-machine interaction module, and comprises a data acquisition interface connection unit, a SiLA translation unit, a control unit, a knowledge unit and a capability unit; the data acquisition interface connecting unit is connected with the data acquisition interface, receives the equipment working state data sent by the data acquisition interface and sends a cell culture control instruction to the data acquisition interface; the SiLA translation unit translates the equipment working state data into standard equipment working state data of a standardized protocol, and/or translates equipment control logic and an equipment control method into cell culture control instructions directly used for controlling the culture equipment; the control unit collects real-time equipment working state data, historical equipment working state data, environmental parameters and operation instructions transmitted by the human-computer interaction module and generates equipment control logic and an equipment control method, and the equipment control logic and the equipment control method are sent to the human-computer interaction module; the knowledge unit stores and manages related variables, process variables and/or operating logic; the capacity unit stores and manages a basic operation closed loop of a pre-packaged intelligent agent module; the intelligent agent modules are connected with one another to form a distributed control network and perform data transmission, and the intelligent agent modules have the characteristics of independence and autonomy while realizing process cooperation capacity; preferably, the intelligent agent module and the distributed control network may also be provided with an interface for connecting a third-party platform (for example, CRM, ERP, or other systems), so that the third-party platform can directly call data. The database module comprises a master database and a slave database; the database module is in data connection with the intelligent agent module and the man-machine interaction module, the main database receives and stores standard equipment working state data, real-time equipment working state data, historical equipment working state data and environmental parameters sent by the intelligent agent module, and equipment control logic and an equipment control method sent by the man-machine interaction module, and the slave database synchronizes data with the main database periodically or according to operation and responds to a data calling request. The human-computer interaction module receives and displays one or more of standard equipment working state data, real-time equipment working state data, historical equipment working state data, environmental parameters, equipment control logic and equipment control methods from the database module according to selection of operators, and simultaneously sends operation instructions input by the operators to the intelligent agent module.
Fig. 3 is a schematic diagram of a circulation path of a monitoring data transmission process, and working state data of the device is acquired and converted by the data acquisition interface and the intelligent agent module, and is finally displayed on the human-computer interaction module after data processing, so as to perform distributed real-time control on each component device of cell culture.
An embodiment structure of the intelligent agent module is shown in fig. 4, although the intelligent agent modules for different culture devices have corresponding differences, the intelligent agent modules themselves adopt the same architecture, wherein the isomorphic parts include: the device comprises a data acquisition interface connection unit, a control unit, a knowledge unit and a capability unit. And aiming at different culture devices, the control unit can correspondingly load different (customized) device control logics and device control methods, wherein the device control logics are preferably written by XML files, and the device control methods preferably inherit standard interfaces provided by the capability unit and then are packaged in DLL files, so that the intelligent agent module is supported to be dynamically loaded during starting.
Fig. 5 is a schematic diagram of the overall logic architecture of the high-throughput micro-reaction cell culture flexible automatic control system, which is controlled by equipment automatically, has different levels of interpersonal interaction function, database storage and docking application with a third-party platform, and adopts different industrial labeling and laboratory automatic communication protocols according to function layered deployment to ensure the requirements of each functional layer on data and control real-time property on the premise of not increasing system data transmission load, wherein the requirements on the real-time property of data in the intelligent agent module part are higher than those of the database module storage and the human-computer interaction module. The equipment monitoring and related data acquisition are preferably based on an OPC protocol, and the communication of the environment monitoring sensor is preferably based on an MQTT protocol, so that the timeliness and stability of data transmission of the data in a complex environment are ensured. The interactive application of the upper layer to the client is based on a SaaS framework, and the unification of usability and expansibility is realized through front-end and back-end separation and functional interface labeling encapsulation; the SaaS service structure has the advantages that the front end and the back end are separated, the function is labeled as an interface, and the same background system can support various human-computer interaction platforms such as a computer end and a mobile end, so that the user operation friendliness degree is improved, and the development cost is reduced.
The invention also provides a flexible automatic control method for high-throughput micro-reaction cell culture, the flow is shown in figure 2, and the method specifically comprises the following steps:
s1, setting equipment control logic and equipment control method, including the operator through the man-machine interaction module input operation instructions and the intelligent agent module will the operation instructions will be transformed into equipment control logic and equipment control method, and/or, transfer the automatic control unit to pre-store or pre-input the general equipment control logic and equipment control method and equipment working state data standard value;
s2, translating the cell culture control command into a cell culture control command by the equipment control logic and the equipment control method, and transmitting the cell culture control command to the culture equipment by the data acquisition interface to start cell culture to obtain equipment working state data;
s3, processing the equipment working state data, translating the data into standard equipment working state data, and particularly, carrying out data cleaning and/or data correction on the equipment working state data;
s4, generating a condition driving command; in particular, the method comprises the steps of outputting corresponding associated drive according to the ratio of target variable to target threshold value according to comparison relation and additional logic condition
S5, culturing the cells according to the condition driving command.
The above description is only for the preferred embodiment of the present invention, but the scope of the present invention is not limited thereto, and any changes or substitutions that can be easily conceived by those skilled in the art within the technical scope of the present invention are included in the scope of the present invention. Therefore, the protection scope of the present invention shall be subject to the protection scope of the claims.
Claims (10)
1. A high-throughput micro-reaction cell culture flexible automatic control system comprises a plurality of data acquisition interfaces respectively and correspondingly connected with different culture equipment, a plurality of intelligent agent modules, a database module and a human-computer interaction module, wherein the intelligent agent modules are in one-to-one correspondence with the data acquisition interfaces;
the data acquisition interface is connected with the intelligent agent module, transmits the acquired equipment working state data to the intelligent agent module, and simultaneously receives a cell culture control instruction transmitted by the intelligent agent module and transmits the cell culture control instruction to the connected culture equipment;
the intelligent agent module is in data connection with the data acquisition interface, the database module and the man-machine interaction module, and comprises a data acquisition interface connection unit, a SiLA translation unit, a control unit, a knowledge unit and a capability unit; the data acquisition interface connecting unit is connected with the data acquisition interface, receives the equipment working state data sent by the data acquisition interface and sends a cell culture control instruction to the data acquisition interface; the SiLA translation unit translates the equipment working state data into standard equipment working state data of a standardized protocol, and/or translates equipment control logic and an equipment control method into cell culture control instructions directly used for controlling the culture equipment; the control unit collects real-time equipment working state data, historical equipment working state data, environmental parameters and operation instructions transmitted by the human-computer interaction module and generates equipment control logic and an equipment control method, and the equipment control logic and the equipment control method are sent to the human-computer interaction module; the knowledge unit stores and manages related variables, process variables and/or operating logic; the capacity unit stores and manages a basic operation closed loop of a pre-packaged intelligent agent module;
the database module comprises a master database and a slave database; the database module is in data connection with the intelligent agent module and the man-machine interaction module, the master database receives and stores standard equipment working state data, real-time equipment working state data, historical equipment working state data and environmental parameters sent by the intelligent agent module, and equipment control logic and an equipment control method sent by the man-machine interaction module, and the slave database synchronizes data with the master database at regular intervals or according to operation and responds to a data calling request;
the human-computer interaction module receives and displays one or more of standard equipment working state data, real-time equipment working state data, historical equipment working state data, environmental parameters, equipment control logic and an equipment control method from the database module according to selection of an operator, and simultaneously sends an operation instruction input by the operator to the intelligent agent module;
the cell culture control instructions comprise condition driven instructions; the conditional driver instructions include a target variable, a target threshold, a comparison relationship, and an associated driver.
2. The system of claim 1, wherein the plurality of intelligent agent modules are interconnected in a network to form a distributed control network and perform data transmission.
3. The system of claim 1, wherein the intelligent agent module further comprises a data cleansing unit; the data cleaning unit is used for carrying out data cleaning operation on the equipment working state data sent by the data acquisition interface and sending the cleaned equipment working state data to the SiLA translation unit for translation; and the data cleaning operation comprises removing abnormal equipment working state data of which the oscillation amplitude exceeds a preset threshold value from the equipment working state data.
4. The system of claim 1, wherein the intelligent agent module further comprises a data correction unit; and the data correction unit is used for correcting the equipment working state data sent by the data acquisition interface according to the environmental parameters.
5. The system of claim 1, wherein the condition driven instruction further comprises an additional logic condition; the additional logic conditions include control variable periodic fluctuation, static interval and data noise filtering conditions.
6. The system of claim 1, wherein the intelligent agent module further comprises an automation control unit; the automatic control unit prestores or pre-inputs the general equipment control logic and equipment control method of the cell culture process and the equipment working state data standard value; and in the cell culture process, when the relative error between the measured working state data of the equipment and the standard value of the working state data of the equipment is within the range of a preset threshold value, the general equipment control logic and the equipment control method are directly called to control the cell culture process, and when the relative error between the measured working state data of the equipment and the standard value of the working state data of the equipment is outside the range of the preset threshold value, a prompt is sent by a human-computer interaction module and an operation instruction input by an operator is preferentially called.
7. A flexible automatic control method for high-throughput micro-reaction cell culture comprises the following steps:
s1, setting equipment control logic and an equipment control method;
s2, translating the cell culture control command into a cell culture control command by the equipment control logic and the equipment control method, and transmitting the cell culture control command to the culture equipment by the data acquisition interface to start cell culture to obtain equipment working state data;
s3, processing the equipment working state data, and translating the data into standard equipment working state data;
s4, generating a condition driving command;
s5, culturing the cells according to the condition driving command.
8. The method according to claim 7, wherein the step S1 comprises the human operator inputting operation commands through the human-computer interaction module and the intelligent agent module converting the operation commands into the device control logic and the device control method, and/or calling the standard values of the general device control logic and the device control method and the device working state data, which are pre-stored or pre-input by the automatic control unit.
9. The method of claim 7, wherein the step S3 equipment working state data processing includes data cleaning and/or data correction.
10. The method of claim 7, wherein the step S4 includes outputting the corresponding associated driver in combination with an additional logic condition in a ratio of the target variable to the target threshold in accordance with the comparison.
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