Automatically-controlled full-automatic cell culture system control scheme

Abstract

The invention discloses an automatically-controlled full-automatic cell culture system control scheme, relates to the technical field of cell culture and automatic control, and constructs a distributed control network with an industrial personal computer in a man-machine interaction system as a central command center. Real-time and two-way communication with local control panels of all functional systems is established through various field bus protocols, and each system is an execution unit with independent processing capacity and is responsible for receiving high-level process instructions and analyzing the high-level process instructions into accurate pulse control over a bottom servo motor and a stepping motor, so that the control precision of the system is improved. According to the framework, the central controller can efficiently arrange space-time action sequences of the six-axis robot, the electric clamping jaw and all functional systems in a task scheduling mode, whole-course automatic assembly line work from taking out of a cell bottle from a storage rack, transferring, uncovering, pipetting, liquid adding and centrifuging to finally putting into an incubator is achieved, manual intervention nodes are eliminated, and the working efficiency is improved. And the absolute standardization and repeatability of the operation are ensured.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of cell culture and automatic control technology, in particular to a full-automatic cell culture system control scheme with automatic control. BACKGROUND

[0002] As a core basic technology of life science research and biopharmaceutical industry, cell culture involves multiple fine and highly repetitive operations such as resuscitation, subculture, liquid change, observation, centrifugation, etc. At present, the existing cell culture mode still highly depends on manual operation of experimenters in a limited space such as a biological safety cabinet. This way not only requires high skill proficiency and operation standardization of the operators, but also takes a long time, which becomes a bottleneck restricting experimental throughput, result consistency and large-scale production.

[0003] In the prior art, cell culture mainly relies on operators to complete incubation, pipetting, centrifugation, observation and other operations in a biological safety cabinet. This mode has significant limitations: the operation process is greatly affected by human subjective initiative, and the operation methods and reaction speeds of different personnel vary, resulting in poor experimental repeatability and difficulty in forming a unified standard; during manual operation, the contact between personnel and the culture environment increases the risk of microbial contamination, and it is impossible to accurately control key parameters such as temperature, carbon dioxide concentration and liquid transfer volume in the culture process in real time; in addition, manual operation is inefficient and difficult to adapt to large-scale culture needs, and once the culture fails, not only will it cause high consumable and time cost losses, but also will directly affect the project progress. At the same time, the existing semi-automatic equipment lacks system linkage of each link and can only realize the automation of single operation, cannot form a complete culture closed loop, still needs manual intervention to connect, and cannot fundamentally solve the problem of manual dependence, making it difficult to quickly adapt to diversified culture processes.

[0004] Therefore, there is an urgent need for a systematic control scheme that can deeply integrate mechanical execution, environmental control and information management. This scheme needs to decompose the whole process of cell culture into programmable and accurately controllable standardized steps, fundamentally solve the problems of low automation, poor process continuity and difficult operation consistency, and promote the development of cell culture towards standardization, intelligentization and high throughput. SUMMARY

[0005] The application aims at solving the problems in the prior art, and provides an automatic cell culture system control scheme, which comprises a robot control system, a transfer window system, a storage rack control system, a cell recovery system, an opening and closing cover control system, a pipetting control system, a liquid adding control system, a centrifugation control system, a culture box control system, a protection and sterilization system, an incubation control system, a microscopic observation control system, a man-machine interaction system and a power supply system.

[0006] The application aims at solving the problems in the prior art, and provides an automatic cell culture system control scheme, which comprises a robot control system, a transfer window system, a storage rack control system, a cell recovery system, an opening and closing cover control system, a pipetting control system, a liquid adding control system, a centrifugation control system, a culture box control system, a protection and sterilization system, an incubation control system, a microscopic observation control system, a man-machine interaction system and a power supply system. The man-machine interaction system is in communication connection with the robot control system, the storage rack control system, the pipetting control system, the liquid adding control system, the centrifugation control system, the culture box control system, the cell recovery system, the protection and sterilization system, the incubation control system and the microscopic observation control system, and is used for coordinating the work of the systems and executing the automatic cell culture process control. The man-machine interaction system comprises an industrial computer, a touch screen and a loudspeaker, the industrial computer is electrically connected with the touch screen and the loudspeaker, the touch screen is used for displaying cell culture software and a self-defined culture scheme, the industrial computer is connected with control boards or controllers of the control systems through a communication bus, so as to realize instruction issuing and data acquisition, and the loudspeaker is used for playing equipment running state prompt sound. The power supply system comprises a surge protector, a filter, an AC contactor, a switching power supply and a power supply master switch, the surge protector, the filter and the AC contactor are electrically connected in sequence, the power supply master switch is electrically connected with the AC contactor, and the switching power supply converts AC voltage into DC voltage, so as to provide power support for the control systems.

[0007] Further, the robot control system comprises a six-axis robot, a robot controller and an electric clamp. The robot controller is electrically connected with the six-axis robot and the electric clamping jaw respectively, the robot controller receives control instructions through the human-computer interaction system, drives the six-axis robot to complete the moving operation, and controls the electric clamping jaw to realize the grabbing and placing of the cell culture consumables.

[0008] Further, the delivery window control system comprises a boat switch, a ballast, an ultraviolet lamp, a blower and a high-efficiency filter. The boat switch is electrically connected with the ballast and the blower respectively, the ballast is electrically connected with the ultraviolet lamp, and the delivery window control system is independent of the human-computer interaction system, and the start and stop of the blower and the opening and closing of the ultraviolet lamp are controlled through manual operation of the boat switch to perform the purification and disinfection in the material delivery process.

[0009] Further, the storage rack control system comprises a storage rack control board, a storage rack servo motor, a servo motor driver, a photoelectric sensor and a photoelectric detection device. The storage rack control board is electrically connected with the servo motor driver and the photoelectric detection device respectively, the photoelectric detection device is electrically connected with the photoelectric sensor, the storage rack servo motor is electrically connected with the servo motor driver, the storage rack control board receives instructions through the human-computer interaction system, drives the storage rack servo motor to drive the storage rack to move to a specified position, and detects the material storage state through the photoelectric sensor and feeds back to the human-computer interaction system.

[0010] Further, the cell recovery system comprises a cell recovery instrument, the cell recovery instrument is electrically connected with an industrial computer in the human-computer interaction system in communication, the cell recovery instrument executes the accurate, rapid and efficient recovery operation of the cells according to the parameter instructions issued by the industrial computer, and guarantees the high survival rate of the cells.

[0011] Further, the opening and closing cover control system comprises an opening and closing cover control board, an opening and closing cover rotating motor, an opening and closing cover rotating motor driver, an opening and closing cover tight and loose motor and an opening and closing cover tight and loose motor driver. The opening and closing cover control board is electrically connected with the opening and closing cover rotating motor driver and the opening and closing cover tight and loose motor driver respectively, the opening and closing cover rotating motor driver is electrically connected with the opening and closing cover rotating motor, and the opening and closing cover tight and loose motor driver is electrically connected with the opening and closing cover tight and loose motor, the opening and closing cover control board receives instructions of the human-computer interaction system, drives the opening and closing cover tight and loose motor to realize the clamping and loosening of the bottle cap, and drives the opening and closing cover rotating motor to realize the opening and closing actions.

[0012] Further, the pipetting control system and the liquid adding control system are linked and arranged, wherein: The pipetting control system comprises a pipetting control board, a pipetting suction motor, a pipetting suction motor driver, a pipetting suction motor sensor, a pipetting rotating motor, a pipetting rotating motor driver and a pipetting rotating motor sensor. The pipetting control board is electrically connected with a pipetting suction motor driver, a pipetting suction motor sensor, a pipetting rotation motor driver and a pipetting rotation motor sensor respectively, the pipetting suction motor is electrically connected with the pipetting suction motor driver, the pipetting rotation motor is electrically connected with the pipetting rotation motor driver, and the pipetting control board controls the pipetting suction motor to complete liquid suction and discharge and controls the pipetting rotation motor to adjust the pipetting direction according to the instruction of the human-computer interaction system, and position information of movement is fed back through the sensor; The liquid adding control system comprises a liquid adding control board, a liquid adding motor and a liquid adding motor driver. The liquid adding control board communicates with the human-computer interaction system, controls the start and stop of the liquid adding motor and the liquid adding amount according to the action feedback of the pipetting control system, and performs automatic linkage control of pipetting and liquid adding.

[0013] Further, the incubator control system is linked with the protection and sterilization system, and the air supply and exhaust and the sterilization time length of the ultraviolet lamp of the protection and sterilization system are adjusted according to the environmental data in the incubator. The incubator control system comprises an incubator control board, a box door rotation motor, a box door rotation motor driver, a door lock motor, a door lock motor driver, a door sensor, a culture rack rotation motor, a culture rack rotation motor driver, a culture rack rotation motor sensor, incubator heating wires, a temperature sensor, a carbon dioxide sensor and an incubator fan. The incubator control board is electrically connected with the box door rotation motor driver, the door lock motor driver, the door sensor, the culture rack rotation motor driver, the culture rack rotation motor sensor, the incubator heating wires, the temperature sensor, the carbon dioxide sensor and the incubator fan respectively, the box door rotation motor driver is electrically connected with the box door rotation motor, the door lock motor driver is electrically connected with the door lock motor, the culture rack rotation motor driver is electrically connected with the culture rack rotation motor, and the incubator control board receives the instruction of the human-computer interaction system, controls the opening and closing of the box door and the locking of the door lock, drives the culture rack to rotate to a specified position, adjusts the incubator heating wires, the fan and the carbon dioxide supply according to the detection data of the temperature sensor and the carbon dioxide sensor, and maintains the stability of the environment in the incubator. The protection and sterilization system comprises a protection and sterilization control board, an air supply fan, an air exhaust fan, an anemometer, a lighting lamp, an ultraviolet lamp and a ballast. The protection and sterilization control board is electrically connected with the air supply fan, the air exhaust fan, the anemometer, the lighting lamp and the ballast respectively, the ballast is electrically connected with the ultraviolet lamp, and the protection and sterilization control board adjusts the running gear position of the air supply fan and the air exhaust fan, controls the opening and closing of the lighting lamp and the sterilization time length of the ultraviolet lamp according to the instruction of the human-computer interaction system and the detection data of the anemometer.

[0014] Further, the centrifugal control system is cooperatively arranged with the incubation control system. The centrifugal control system includes a centrifugal control board, a centrifugal servo motor driver, and a centrifugal servo motor. The centrifuge control board receives instructions from the human-machine interaction system via a communication protocol, and drives the centrifuge servo motor to achieve precise speed and time control. The incubation control system includes an incubation control board, an incubation heating wire, and an incubation temperature sensor; The incubation control board communicates with the human-machine interface system and adjusts the heating wires based on the cell processing requirements after centrifugation through the incubation temperature sensor to maintain a stable temperature in the incubation area.

[0015] Furthermore, the microscopic observation control system includes a microscopic observation controller, an optical microscope, a front and rear motion motor, a front and rear motion motor driver, a left and right motion motor, and a left and right motion motor driver. The microscopic observation controller is electrically connected to the optical microscope, the front and rear motion motor driver, and the left and right motion motor driver. The front and rear motion motor driver is electrically connected to the front and rear motion motor, and the left and right motion motor driver is electrically connected to the left and right motion motor.

[0016] Compared with existing technologies, this fully automated cell culture system control scheme has the following advantages: This invention constructs a distributed control network with the industrial control computer in the human-machine interaction system as the central command hub. It establishes real-time, bidirectional communication with the local control boards of each functional system through various fieldbus protocols. Each system is an execution unit with independent processing capabilities, responsible for receiving high-level process instructions and parsing them into precise pulse control of the underlying servo motors and stepper motors. This architecture enables the central controller to efficiently arrange the spatiotemporal action sequences of the six-axis robot, electric gripper, and various functional systems in a task scheduling manner. It realizes a fully automated production line operation from cell flask removal from the storage rack, transfer, opening, pipetting, adding liquid, centrifugation to final placement in the incubator, eliminating manual intervention nodes and ensuring absolute standardization and repeatability of operations.

[0017] Other advantages, objectives and features of the invention will be set forth in part in the description which follows, and in part will be apparent to those skilled in the art from the following examination or study, or may be learned from the practice of the invention. Attached Figure Description

[0018] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the accompanying drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are merely some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without any creative effort.

[0019] Figure 1 This is a schematic diagram of the control principle of the fully automated cell culture system of the present invention. Figure 2 This is a circuit diagram of the fully automated cell culture system with automated control according to the present invention. Detailed Implementation

[0020] To better understand the above technical solutions, a detailed description of the solutions will be provided below in conjunction with the accompanying drawings and specific embodiments. Obviously, the described embodiments are merely some, not all, of the embodiments of the present invention. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are within the scope of protection of the present invention.

[0021] To address the problems of low standardization, high risk of contamination, poor reproducibility, and efficiency bottlenecks caused by the heavy reliance on manual operation in existing cell culture technologies, this invention first describes the application scenarios of the fully automated cell culture involved in this invention. This invention is primarily applied to scenarios requiring large-scale, standardized, and high-quality cell preparation, such as biopharmaceuticals, cell therapy, and basic life science research. In these scenarios, precise operation and aseptic control of multiple stages, including cell resuscitation, passage, medium change, centrifugation, observation, and culture, are crucial to ensuring cell viability and the reproducibility of experimental results. Traditional manual operation not only has limited throughput but is also prone to introducing human error and contamination, while existing fragmented automated equipment cannot achieve a closed-loop process from material loading to cell culture completion. This invention, through modular subsystem design, centralized collaborative control, and multi-sensor feedback, aims to provide a complete, efficient, reliable, and user-customizable fully automated cell culture solution.

[0022] The following will combine Figure 1 and Figure 2 The specific embodiments of the present invention will be described in detail below.

[0023] Specifically, such as Figure 1 and Figure 2 As shown, a fully automated cell culture system control scheme includes: a robot control system, a transfer window control system, a storage rack control system, a cell resuscitation system, a cap opening and closing control system, a pipetting control system, a liquid addition control system, a centrifugation control system, an incubator control system, a protection and disinfection system, an incubation control system, a microscopic observation control system, a human-computer interaction system, and a power supply system.

[0024] The human-machine interface system communicates with the robot control system, storage rack control system, pipetting control system, liquid addition control system, centrifugation control system, incubator control system, cell resuscitation system, disinfection and sterilization system, incubation control system, and microscopic observation control system. It coordinates the operation of each system and executes the fully automated cell culture process control. The human-machine interface system serves as the window for the operator to interact with the automated equipment, parsing user-defined culture protocols and converting them into a sequence of control commands executable by the underlying functional modules, while also monitoring the overall system's operational status in real time.

[0025] In its implementation, the human-computer interaction system includes an industrial control computer, a touch screen, and a speaker. The industrial control computer, serving as the core computing and communication unit, is electrically connected to both the touch screen and the speaker. The industrial control computer runs fully automated cell culture control software, which provides a graphical user interface. This interface allows users to define a complete culture process, including cell resuscitation, medium replacement, passage, observation, and centrifugation, or any sub-step thereof, through parameter settings on the touch screen, thus creating a customized culture protocol program.

[0026] During operation, after completing the program design, the user issues a start command via the touchscreen. The industrial control computer (ICC) then enters the process execution state. First, the ICC parses the high-level, logical training steps into a series of low-level, atomic equipment control commands and sends them to the corresponding subsystem control boards or controllers. Simultaneously, the ICC continuously receives feedback data from sensors in each subsystem and updates equipment status, material location, environmental parameters, and process execution progress in real time on the touchscreen using graphics, numerical values, and flowcharts, achieving full-process visualization. The speakers, based on the ICC's instructions, play operation prompts, process stage completion notifications, or system alarm sounds, enhancing the intuitiveness of human-machine interaction. This centralized scheduling and distributed execution architecture ensures reliable operation of complex processes and rapid response to abnormal situations.

[0027] The power supply system provides a stable, safe, and interference-resistant power supply to all electronic devices and actuators. The system includes surge protectors, filters, AC contactors, switching power supplies, and a main power switch, which serves as the manual on / off control point for the main power supply. When the main power switch is closed, current flows through the AC contactors. An industrial control computer can control the energization and de-energization of the AC contactor coils via I / O signals, thereby achieving remote, programmed control of the entire system's power supply.

[0028] During operation, the current then passes sequentially through the surge protector and the filter. The surge protector absorbs transient overvoltages from the power grid, protecting downstream precision electronic equipment from damage. The filter suppresses high-frequency noise interference from the power grid, preventing it from interfering with the normal operation of sensitive circuits such as controllers and sensors. The purified AC power is then supplied to multiple switching power supplies. These switching power supplies convert the input AC voltage and stably output various DC voltages required by the system to power all electrical units, including the robot controller, control boards of various subsystems, motor drivers, and sensors, ensuring the stable operation of the entire control system in a complex electrical environment.

[0029] The robot control system is responsible for performing the tasks of grasping, transporting, and placing consumables with high precision and repeatability in three-dimensional space, and serves as the physical link connecting various functional modules. In its specific implementation, the robot control system includes a six-axis robot, a robot controller, and an electric gripper. The robot controller is electrically connected to the servo drives of each joint of the six-axis robot and the electronic control unit of the electric gripper. The robot controller itself maintains high-speed data exchange with the industrial control computer of the human-machine interface system via a communication bus.

[0030] During operation, when the industrial control computer issues a command, the robot controller receives the command and performs kinematic and trajectory planning calculations. First, the controller controls the electric gripper to open to a preset width via I / O signals, driving the six-axis robot to move to the pickup point above storage shelf position X. Upon arrival, the controller controls the electric gripper to close, clamping the cell vials. Subsequently, the controller plans a smooth, efficient, and collision-avoiding motion trajectory, driving the six-axis robot to carry the cell vials to the designated placement point at the cap-opening / closing station. Upon arrival, the controller controls the electric gripper to open, releasing the cell vials and sending a placement completion signal back to the industrial control computer. The robot controller internally stores the three-dimensional spatial coordinates of all key workstations. By calling these coordinates through the program and combining them with real-time feedback joint encoder data, the positioning accuracy of the end effector is achieved. The electric gripper, depending on the object being gripped, has its opening and closing range and clamping force controlled by the program to ensure a stable grip without damaging the consumables.

[0031] The aforementioned pass-through window control system performs purification and disinfection functions before materials are introduced. Its design is independent of the human-machine interface system to ensure the absolute reliability of basic safety functions. In its specific implementation, the pass-through window control system includes a rocker switch, a ballast, a UV lamp, a blower, and a high-efficiency filter. The pass-through window has two interlocked doors, and the UV lamp and blower unit are installed inside its cavity. The rocker switch, as a multi-position rotary or toggle switch, is installed on the outside of the pass-through window in an easily accessible position, and its electrical contacts are connected to the power circuits of the blower and the ballast. The ballast is electrically connected to the UV lamp, providing it with a stable operating voltage. The high-efficiency filter is installed at the outlet of the blower.

[0032] During operation, the operator places the material to be transferred outside the transfer window and closes the outer door. Then, the operator manually operates the boat-shaped switch. When the switch is turned to the disinfection position, the ballast and UV lamp circuit are connected, and the UV lamp illuminates, periodically irradiating the surface of the material and the air inside the chamber with ultraviolet light for sterilization. After disinfection, the switch is turned to the purification position. At this time, the blower starts, drawing outside air through a high-efficiency filter and then sending it into the transfer window chamber in a laminar flow manner to purge and replace any remaining particles while maintaining a relative positive pressure within the chamber. After purification, the operator can open the inner door from the inside, and a robot will retrieve the purified material into the system.

[0033] The aforementioned storage rack control system is responsible for storing various cell culture consumables and can move them to the robot's grasping position according to instructions. In its specific implementation, the storage rack control system includes a storage rack control board, storage rack servo motors, servo motor drivers, photoelectric sensors, and photoelectric detection devices. The storage rack is a multi-layer, multi-column shelf. The storage rack servo motors drive the shelf movement through a transmission mechanism. The servo motor drivers receive pulse and direction signals to precisely control the speed and angle of the servo motors. The photoelectric sensors are installed at specific positions on the shelf to detect whether materials are present in the corresponding locations. The photoelectric detection devices process the switching signals from the photoelectric sensors. The storage rack control board, as the local controller of this subsystem, is connected to the industrial control computer of the human-machine interface system via a communication bus, and is also electrically connected to the servo motor drivers and photoelectric detection devices.

[0034] During operation, the industrial control computer sends instructions to the storage rack control board according to the training plan. After parsing the instructions, the storage rack control board sends pulse signals to the servo motor driver. The servo motor driver drives the storage rack servo motor to move, causing the entire shelf or the layer / column where the target storage location is located to move precisely to the preset robot storage and retrieval position. At the same time, the storage rack control board polls or reads the status of the photoelectric sensors of each storage location in real time through the photoelectric detection device. When the sensor detects material, it outputs a low level. This status information is processed by the photoelectric detection device and uploaded to the storage rack control board. The storage rack control board then feeds back to the industrial control computer through the bus. The industrial control computer updates its internal material inventory management database accordingly and displays the storage location occupancy status on the touch screen with different colors or icons, realizing digital management of materials. The robot then grabs or places consumables from the moved storage location according to the instructions of the industrial control computer.

[0035] The cell resuscitation system is responsible for rapidly and uniformly warming frozen cells to obtain a high-viability initial cell population. In a specific implementation, the cell resuscitation system includes a cell resuscitator, which connects to an industrial electromechanical system via a communication interface and is controlled by a program.

[0036] During operation, the robot removes cryovials containing frozen cells from the transfer window, transports them, and places them on the support of the cell resuscitation instrument. The industrial control computer sends control parameters to the cell resuscitation instrument via a communication protocol. These parameters include: initial resuscitation temperature, target resuscitation temperature, heating rate, holding time at the target temperature, and whether to activate oscillation and its frequency. Upon receiving the command, the cell resuscitation instrument's internal controller initiates a closed-loop control system with heating and temperature sensor feedback, rapidly heating the cell suspension in the cryovials according to preset parameters to avoid ice crystal damage caused by slow rewarming. After the resuscitation process is complete, the cell resuscitation instrument sends a resuscitation completion signal to the industrial control computer, which then dispatches the robot to transport the resuscitated cell suspension to the next station for further processing. Programmed control of the resuscitation parameters ensures a high degree of consistency in resuscitation conditions between different batches, laying a solid foundation for subsequent culture.

[0037] The aforementioned cap opening and closing control system is used to automatically open and close the caps of containers such as cell culture flasks and centrifuge tubes, which is a prerequisite for subsequent pipetting and liquid addition. In its specific implementation, the cap opening and closing control system includes a cap opening and closing control board, a cap opening and closing rotary motor, a cap opening and closing rotary motor driver, a cap opening and closing tension / relaxation motor, and a cap opening and closing tension / relaxation motor driver. This system is an independent workstation equipped with a clamping mechanism and a rotating mechanism. The cap opening and closing control board acts as a local controller, receiving commands from the industrial control computer via a communication bus, and is electrically connected to the cap opening and closing rotary motor driver and the cap opening and closing tension / relaxation motor driver, respectively.

[0038] During operation, the robot transports the container that needs to be opened and places it on the positioning fixture at the opening and closing station. The industrial control computer sends an opening command to the opening and closing control board. The opening and closing control board first controls the opening and closing tightening motor driver to drive the opening and closing tightening motor to move forward and firmly clamp the container cap. After the clamping action is in place, the sensor on the gripper feeds back a signal. The opening and closing control board then controls the opening and closing rotary motor driver to drive the opening and closing rotary motor to rotate according to the preset rotation direction and number of rotations, thereby loosening and unscrewing the cap from the bottle mouth. After the cap is opened, the rotary motor stops, and the tightening motor releases the clamp on the cap. The robot can then remove the opened bottle for subsequent operations or remove the cap. The closing process is the reverse: first clamp the cap, then rotate clockwise to tighten it to the preset torque. By precisely controlling the number of pulses in the motor and the current of the driver, the opening and closing control board achieves standardized opening and closing actions, avoiding poor sealing or damage to the bottle mouth caused by inconsistent force and angle during manual operation.

[0039] The aforementioned pipetting control system and liquid addition control system are used to accurately transfer and add reagents such as cell culture medium, trypsin, and PBS. In specific implementation, the pipetting control system includes a pipetting control board, a pipetting aspiration motor, a pipetting aspiration motor driver, a pipetting aspiration motor sensor, a pipetting rotary motor, a pipetting rotary motor driver, and a pipetting rotary motor sensor. The pipetting system consists of a multi-channel or single-channel electric pipette, mounted on a rotatable robotic arm. The pipetting control board acts as a local controller, connected to an industrial computer via a bus, and electrically connected to the aforementioned drivers and sensors.

[0040] The pipetting aspiration motor drives the piston movement of the pipette via a ball screw or piston mechanism to achieve liquid aspiration and dispensing. The pipetting aspiration motor sensor monitors the precise position of the piston in real time, thereby indirectly and with high precision measuring the liquid volume. The pipetting rotary motor drives the entire pipette assembly to rotate in the horizontal plane to align with different reagent bottles or culture containers. The pipetting rotary motor sensor provides feedback on the rotation angle.

[0041] The liquid addition control system is used for adding fixed or large-volume reagents. It includes a liquid addition control board, a liquid addition motor, and a liquid addition motor driver. The liquid addition control board also communicates with the industrial control computer. During the linkage operation, the steps for performing the liquid replacement operation are as follows: The industrial control computer first dispatches the robot to transport the culture bottle to the pipetting station and completes the opening of the cap; The industrial control computer sends instructions to the pipetting control board to control the pipetting rotary motor to rotate the pipetting tip above the waste liquid collection position, and then controls the pipetting suction motor to discharge any liquid that may remain in the tip; The pipette is instructed to rotate above the culture flask, and the pipetting motor performs the aspiration action. Based on the sensor feedback, the old culture medium in the flask is accurately aspirated to the set volume, and then rotated to the waste liquid tank for disposal. This process can be repeated to aspirate all the old liquid. The industrial control computer instructs the pipette to rotate above the reagent bottle containing fresh culture medium for precise aspiration. After aspiration, the pipette rotates back above the culture bottle to perform the discharge action, injecting the new culture medium into the bottle. For reagents that need to be added in large quantities, the industrial control computer can instruct the liquid addition control system to drive the peristaltic pump or syringe pump to add the liquid quantitatively into the bottle through a dedicated tubing. Throughout the process, the liquid addition control board achieves quantitative addition based on real-time feedback from the pipetting aspiration motor sensor and the pipetting rotation motor sensor.

[0042] The centrifugation control system is used to perform the precipitation step of cell suspension. In its specific implementation, the centrifugation control system includes a centrifugation control board, a centrifugation servo motor driver, and a centrifugation servo motor. The centrifugation control board is connected to an industrial control computer via a dedicated communication protocol and is electrically connected to the centrifugation servo motor driver.

[0043] During operation, the robot places centrifuge tubes containing cell suspension into the designated adapter of the centrifuge rotor. The industrial control computer sends centrifugation parameter instructions to the centrifugation control board, including target speed, acceleration, centrifugation time, and deceleration curve. After parsing the instructions, the centrifugation control board performs precise vector control on the centrifugation servo motor through the centrifugation servo motor driver. The servo motor driver generates corresponding three-phase current to drive the servo motor to rotate according to the instructions, and realizes closed-loop feedback of speed and position through the built-in encoder. After the set time is reached, the driver controls the motor to stop according to the preset smooth deceleration curve to avoid disturbing the settled cell clusters due to sudden stops. After centrifugation, the centrifugation control board sends a centrifugation completion signal to the industrial control computer, which then dispatches the robot to remove the centrifuge tubes and transfer them to the next station for operations such as supernatant disposal and cell resuspension. By controlling the centrifugation parameters in a programmed manner, the consistency of cell precipitation conditions for different batches is ensured.

[0044] The incubator control system is used to provide stable temperature, humidity, and CO2 concentration, and to automate the storage and retrieval of culture containers. In its specific implementation, the incubator control system includes an incubator control board, a door rotation motor, a door rotation motor driver, a door lock motor, a door lock motor driver, a door sensor, a culture rack rotation motor, a culture rack rotation motor driver, a culture rack rotation motor sensor, an incubator heating wire, a temperature sensor, a carbon dioxide sensor, and an incubator fan. The incubator control board communicates with an industrial computer via a bus and manages the electrical connections to all the aforementioned actuators and sensors.

[0045] During operation, when a culture bottle needs to be placed or removed, the industrial control computer sends a command to the incubator control board. The incubator control board first checks the door sensor status to confirm that the door is closed and locked. Then, it controls the door lock motor driver to drive the door lock motor to unlock the door. It then controls the door rotation motor driver to drive the door rotation motor to rotate and open the door to a preset angle. After the door is open, the robot transports the culture bottle to the front of the door. Then, the incubator control board controls the culture rack rotation motor driver to drive the culture rack rotation motor to rotate or translate an empty culture rack position inside to the storage position at the door. The culture rack rotation motor sensor provides feedback on the position to ensure accurate positioning. After the robot places the bottle into the empty position, it exits. The incubator control board then drives the culture rack to move the bottle back into the depth of the incubator and closes and locks the door.

[0046] In terms of environmental maintenance, temperature and carbon dioxide sensors continuously monitor the environment inside the chamber. Based on the deviation between the temperature sensor feedback value and the set value, the control board uses solid-state relays and other switching elements to control the power output of the incubator heating wire in a PWM manner, achieving precise and stable temperature control. Based on the feedback from the carbon dioxide sensor, the control board uses a solenoid valve to control the injection of CO2 gas, maintaining the concentration at the set level. The incubator fan is continuously or intermittently driven by the control board to promote air circulation inside the chamber, ensuring the uniformity of temperature and gas concentration. All environmental data and equipment status are uploaded to the industrial control computer in real time via a bus, and centrally monitored on a touch screen, realizing fully automated and digital management of the incubator from physical access to environmental control.

[0047] The aforementioned protective and disinfection system provides biosafety protection and local environmental purification. In its specific implementation, the system includes a protective and disinfection control board, a blower, an exhaust fan, an anemometer, lighting fixtures, ultraviolet lamps, and a ballast. The protective and disinfection control board is connected to an industrial computer via a bus and is electrically connected to the aforementioned equipment.

[0048] Before the workstation is started and enters the operation mode, the industrial control computer can instruct the protection and disinfection control board to turn on the supply fan and exhaust fan. The anemometer monitors the air speed of the air supplied to the operating area in real time. Based on the feedback value of the anemometer, the protection and disinfection control board adjusts the motor speed of the supply fan and exhaust fan to dynamically maintain the air speed within the safe standard range, ensuring an effective one-way airflow barrier and preventing aerosols from escaping from the operating area.

[0049] When a batch of culture processes is completed, or when the workstation needs to be idle for an extended period, the industrial control computer can schedule the robot to clear all consumables from the operating area. Then, it instructs the protection and disinfection control board to turn off the lighting and fans and turn on the ultraviolet lamps. The ballast provides a stable operating voltage to the ultraviolet lamps, which periodically irradiate and disinfect open surfaces such as the workbench and robotic arm surfaces to inactivate any remaining microorganisms. After disinfection, the ultraviolet lamps automatically turn off. The protection and disinfection control board feeds back information such as fan speed and equipment on / off status to the industrial control computer in real time. This system, through its linkage with incubator control and other systems, further optimizes the overall protection strategy.

[0050] The aforementioned incubation control system provides a short-term, localized temperature control environment required during cell processing. In a specific implementation, the incubation control system includes an incubation control board, an incubation heating wire, and an incubation temperature sensor. It may be a small heating table or incubation module integrated on the operating table. The incubation control board communicates with an industrial computer via a bus and is electrically connected to the incubation heating wire and the incubation temperature sensor.

[0051] When the process requires an incubation step, the robot places the container at the designated location on the incubation control module. The industrial control computer sends the temperature setpoint to the incubation control board, which then initiates closed-loop temperature control: the incubation temperature sensor detects the temperature of the module surface in real time and transmits the signal to the control board. The control board compares the measured value with the setpoint and controls the energizing time of the solid-state relay to the incubation heating wire, thereby precisely ensuring that the module surface temperature reaches and stabilizes at the setpoint. After the incubation time is reached, the industrial control computer instructs the robot to remove the container for the next step, avoiding environmental fluctuations caused by frequent opening and closing of the large incubator door.

[0052] The aforementioned microscopic observation and control system is used for non-invasive online monitoring of cells during culture, acquiring image information such as cell morphology and density to provide a basis for judging cell status and deciding on the next operation. In its specific implementation, the microscopic observation and control system includes a microscopic observation controller, an optical microscope, a front-to-back motion motor, a front-to-back motion motor driver, a left-to-right motion motor, and a left-to-right motion motor driver. The system consists of an automated inverted microscope and a two-dimensional moving platform. The microscopic observation controller is connected to an industrial control computer via a dedicated bus and is electrically connected to the electric components of the optical microscope and the front-to-back / left-to-right motion motor drivers.

[0053] During operation, when the culture program includes an observation step, the industrial control computer (ICC) directs the robot to remove the culture container to be observed from the incubator or hatching area and precisely place it onto the stage positioning device of the microscopic observation system. Subsequently, the ICC sends observation commands to the microscopic observation controller, which include parameters such as the coordinates of the observation site, objective magnification, focal length, and exposure time.

[0054] After parsing the instructions, the microscopic observation controller first controls the left and right motion motor drivers and the front and back motion motor drivers to move the stage in the X and Y directions, precisely positioning the target observation area directly below the microscope objective. The controller then automatically focuses the image through the microscope's internal electric focusing mechanism, ensuring a clear cell image. Next, the controller triggers the microscope camera to capture high-quality digital images of the cells. The image data is transmitted back to the industrial control computer via a high-speed interface. The image processing software on the industrial control computer can automatically analyze the cell confluence, morphology, and other characteristics of the image, or display the image on a touchscreen for manual review. After observation, the controller moves the stage away, and the robot retrieves the container and returns it to its original position. Through automated microscopic observation, timed and quantitative monitoring of the cell growth process is achieved, providing crucial data input for intelligent and adaptive culture processes.

[0055] In summary, this invention constructs a closed-loop automated cell culture solution encompassing the entire process—from material input, cell resuscitation, liquid handling, environmental culture, to online observation—through the deep integration and collaborative control of multiple subsystems. The human-machine interface system acts as the central command, translating user-defined culture logic into a precise spatiotemporal control command flow; the power supply system provides a stable foundation; the robotic system handles physical interconnection; specialized functional machines efficiently execute standardized operations; and pass-through windows and protective systems ensure biosafety. All actions are based on sensor feedback to achieve closed-loop control, and all states and data are centrally and visually managed. By ensuring the consistency of machine execution and the precise digital control of process parameters, the invention solves the problems of subjectivity, contamination risk, and result volatility associated with manual operation, achieving standardized, high-throughput, and traceable cell culture. This provides a technological tool for large-scale, high-quality cell production and research in the biopharmaceutical field.

[0056] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any way. Although the present invention has been disclosed above with reference to preferred embodiments, it is not intended to limit the present invention. Any person skilled in the art can make some modifications or alterations to the above-disclosed technical content to create equivalent embodiments without departing from the scope of the present invention. Any simple modifications, equivalent changes and alterations made to the above embodiments based on the technical essence of the present invention without departing from the scope of the present invention shall still fall within the scope of the present invention.

Claims

1. A control scheme for a fully automated cell culture system, characterized in that, The control scheme includes a robot control system, a transfer window system, a storage rack control system, a cell resuscitation system, a lid opening and closing control system, a pipetting control system, a liquid addition control system, a centrifugation control system, an incubator control system, a protective and disinfection system, an incubation control system, a microscopic observation control system, a human-computer interaction system, and a power supply system, among which: The human-computer interaction system is communicatively connected to the robot control system, storage rack control system, pipetting control system, liquid addition control system, centrifugation control system, incubator control system, cell resuscitation system, protection and disinfection system, incubation control system, and microscopic observation control system, and is used to coordinate the work of each system and execute fully automated cell culture process control. The human-computer interaction system includes an industrial control computer, a touch screen, and a speaker. The industrial control computer is electrically connected to both the touch screen and the speaker. The touch screen is used to display cell culture software and customized culture protocols. The industrial control computer is connected to the control boards or controllers of various control systems via a communication bus to issue commands and acquire data. The speaker is used to play equipment operation status prompts. The power supply system includes a surge protector, a filter, an AC contactor, a switching power supply, and a main power switch. The surge protector, filter, AC contactor, and switching power supply are electrically connected in sequence. The main power switch is electrically connected to the AC contactor. The switching power supply converts AC voltage to DC voltage to provide power support for each control system.

2. The control scheme for a fully automated cell culture system according to claim 1, characterized in that, The robot control system includes a six-axis robot, a robot controller, and an electric gripper. The robot controller is electrically connected to the six-axis robot and the electric gripper. The robot controller receives control commands through the human-machine interaction system, drives the six-axis robot to complete the handling action, and controls the electric gripper to grasp and place cell culture consumables.

3. The control scheme for a fully automated cell culture system according to claim 1, characterized in that, The pass-through window control system includes a rocker switch, a ballast, an ultraviolet lamp, a blower, and a high-efficiency filter; The rocker switch is electrically connected to the ballast and the blower, respectively. The ballast is electrically connected to the ultraviolet lamp. The transfer window control system is independent of the human-machine interface system. The start and stop of the blower and the opening and closing of the ultraviolet lamp are controlled by manually operating the rocker switch to perform purification and disinfection during the material transfer process.

4. The control scheme for a fully automated cell culture system according to claim 1, characterized in that, The storage rack control system includes a storage rack control board, a storage rack servo motor, a servo motor driver, a photoelectric sensor, and a photoelectric detection device. The storage rack control board is electrically connected to the servo motor driver and the photoelectric detection device. The photoelectric detection device is electrically connected to the photoelectric sensor. The storage rack servo motor is electrically connected to the servo motor driver. The storage rack control board receives instructions through the human-machine interaction system, drives the storage rack servo motor to move the storage rack to the designated position, and at the same time detects the material storage status through the photoelectric sensor and feeds it back to the human-machine interaction system.

5. The control scheme for a fully automated cell culture system according to claim 1, characterized in that, The cell resuscitation system includes a cell resuscitation device, which is electrically connected to an industrial control computer in the human-machine interaction system. The cell resuscitation device performs cell resuscitation operations according to the parameter instructions issued by the industrial control computer, and ensures a high cell survival rate.

6. The control scheme for a fully automated cell culture system according to claim 1, characterized in that, The opening and closing cover control system includes an opening and closing cover control board, an opening and closing cover rotary motor, an opening and closing cover rotary motor driver, an opening and closing cover tightening and loosening motor, and an opening and closing cover tightening and loosening motor driver. The opening and closing cap control board is electrically connected to the opening and closing cap rotary motor driver and the opening and closing cap tightening and loosening motor driver. The opening and closing cap rotary motor driver is electrically connected to the opening and closing cap rotary motor, and the opening and closing cap tightening and loosening motor driver is electrically connected to the opening and closing cap tightening and loosening motor. The opening and closing cap control board receives instructions from the human-machine interaction system, drives the opening and closing cap tightening and loosening motor to achieve the cap clamping and loosening, and drives the opening and closing cap rotary motor to achieve the cap opening and tightening action.

7. The control scheme for a fully automated cell culture system according to claim 1, characterized in that, The pipetting control system and the liquid addition control system are linked, wherein: The pipetting control system includes a pipetting control board, a pipetting aspiration motor, a pipetting aspiration motor driver, a pipetting aspiration motor sensor, a pipetting rotary motor, a pipetting rotary motor driver, and a pipetting rotary motor sensor. The pipetting control board is electrically connected to the pipetting aspiration motor driver, the pipetting aspiration motor sensor, the pipetting rotary motor driver, and the pipetting rotary motor sensor, respectively. The pipetting aspiration motor is electrically connected to the pipetting aspiration motor driver, and the pipetting rotary motor is electrically connected to the pipetting rotary motor driver. The pipetting control board controls the pipetting aspiration motor to complete liquid aspiration and discharge according to the instructions of the human-machine interaction system, controls the pipetting rotary motor to adjust the pipetting direction, and feeds back the motion position information through the sensor. The liquid addition control system includes a liquid addition control board, a liquid addition motor, and a liquid addition motor driver; The liquid addition control board communicates with the human-machine interface system and controls the start / stop of the liquid addition motor and the liquid addition volume based on the action feedback of the liquid addition control system, thus performing automated linkage control of liquid addition and liquid addition.

8. The control scheme for a fully automated cell culture system according to claim 1, characterized in that, The incubator control system is linked to the protection and disinfection system, adjusting the air supply and exhaust of the protection and disinfection system and the duration of ultraviolet lamp disinfection based on the environmental data inside the incubator. The incubator control system includes an incubator control board, a door rotation motor, a door rotation motor driver, a door lock motor, a door lock motor driver, a door sensor, a culture rack rotation motor, a culture rack rotation motor driver, a culture rack rotation motor sensor, an incubator heating wire, a temperature sensor, a carbon dioxide sensor, and an incubator fan. The incubator control board is electrically connected to the door rotation motor driver, door lock motor driver, door sensor, culture rack rotation motor driver, culture rack rotation motor sensor, incubator heating wire, temperature sensor, carbon dioxide sensor, and incubator fan. The door rotation motor driver is electrically connected to the door rotation motor, the door lock motor driver is electrically connected to the door lock motor, and the culture rack rotation motor driver is electrically connected to the culture rack rotation motor. The incubator control board receives instructions from the human-machine interface system, controls the door opening and closing and the door lock locking, drives the culture rack to rotate to the designated position, and adjusts the incubator heating wire, fan, and carbon dioxide supply according to the detection data of the temperature sensor and carbon dioxide sensor to maintain a stable environment inside the incubator. The protective and disinfection system includes a protective and disinfection control board, a blower, an exhaust fan, an anemometer, lighting, ultraviolet lamps, and a ballast. The protective disinfection control board is electrically connected to the blower, exhaust fan, anemometer, lighting lamp, and ballast. The ballast is electrically connected to the ultraviolet lamp. The protective disinfection control board adjusts the operating speed of the blower and exhaust fan, controls the opening and closing of the lighting lamp, and controls the disinfection duration of the ultraviolet lamp according to the instructions of the human-machine interaction system and the detection data of the anemometer.

9. The control scheme for a fully automated cell culture system according to claim 1, characterized in that, The centrifugation control system and the incubation control system are configured in conjunction, wherein: The centrifugal control system includes a centrifugal control board, a centrifugal servo motor driver, and a centrifugal servo motor. The centrifuge control board receives instructions from the human-machine interaction system via a communication protocol, and drives the centrifuge servo motor to achieve precise speed and time control. The incubation control system includes an incubation control board, an incubation heating wire, and an incubation temperature sensor; The incubation control board communicates with the human-machine interface system and adjusts the heating wires based on the cell processing requirements after centrifugation through the incubation temperature sensor to maintain a stable temperature in the incubation area.

10. The control scheme for a fully automated cell culture system according to claim 1, characterized in that, The microscopic observation control system includes a microscopic observation controller, an optical microscope, a front and rear motion motor, a front and rear motion motor driver, a left and right motion motor, and a left and right motion motor driver. The microscopic observation controller is electrically connected to the optical microscope, the front and rear motion motor driver, and the left and right motion motor driver. The front and rear motion motor driver is electrically connected to the front and rear motion motor, and the left and right motion motor driver is electrically connected to the left and right motion motor.

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