A method and apparatus for controlling a bioreactor, and an electronic device

Abstract

The present application relates to the technical field of bioengineering, and particularly relates to a control method and device of a bioreactor and an electronic device, wherein the control method of the bioreactor comprises: obtaining a pH measurement value and a carbon dioxide partial pressure measurement value of the bioreactor; determining a control mode of the bioreactor according to the pH measurement value and the carbon dioxide partial pressure measurement value; determining a control parameter corresponding to the control mode, generating a control instruction according to the control parameter, and driving an actuator of the bioreactor to act. By simultaneously monitoring the pH and the carbon dioxide, the passive situation that must wait for the pH to be problematic before remedying is changed, the abnormal signs of cell metabolism can be found in advance and the root cause can be found, the control is performed before the pH fluctuates greatly, the cell culture environment is more stable, and thus more and better products can be produced.

Description

Technical Field

[0001] This invention relates to the field of bioengineering technology, specifically to a control method, device, and electronic equipment for a bioreactor. Background Technology

[0002] Bioreactors are core equipment in fields such as biopharmaceuticals, cell culture, and fermentation engineering. Their main function is to provide a controlled and stable environment for the growth and metabolism of microorganisms or cells in vitro, enabling the large-scale production of target products. pH is a critical process parameter; deviations from the set point not only affect cell health and reduce product yield but also increase the proportion of product impurities (such as acidic / basic variants). Furthermore, frequent additions of acid / alkali solutions for correction can lead to increased osmotic pressure in the culture medium, thereby triggering cellular stress. Therefore, improving the pH control level of bioreactor systems is crucial.

[0003] A complete bioreactor system typically consists of three parts: a sensing unit, a controller, and an execution unit. The measurements collected by the sensors serve as input to the controller. After data processing and decision-making, the controller outputs commands to the execution unit. The execution unit receives the commands and initiates corresponding actions to correct deviations within the reactor, thus forming a closed-loop control. Traditional bioreactor pH control often employs simple feedback control strategies (such as PID control), meaning that neutralization and correction are only performed by adding acid / alkali solutions or adjusting gas flow rates after a pH deviation from the setpoint is detected.

[0004] Existing pH control methods for bioreactors based on single PID feedback mainly rely on historical errors for hysteresis adjustment. This makes it difficult to overcome the inherent large hysteresis and strong nonlinearity of biological culture systems. As a result, the response to pH deviations is sluggish and prone to large overshoot and continuous oscillations, causing drastic fluctuations in the culture environment. This severely reduces the accuracy of pH control and the stability of the biological culture process, thereby affecting the yield and quality of the target product. Summary of the Invention

[0005] This invention provides a control method, device, and electronic equipment for a bioreactor to solve the problems of low control accuracy, poor process stability, and product quality caused by response hysteresis and overshoot oscillation in existing bioreactor pH control.

[0006] In a first aspect, the present invention provides a method for controlling a bioreactor, the method comprising the following steps: acquiring pH measurement values ​​and carbon dioxide partial pressure measurement values ​​of the bioreactor; determining a control mode of the bioreactor based on the pH measurement values ​​and carbon dioxide partial pressure measurement values; determining control parameters corresponding to the control mode; generating control commands based on the control parameters; and driving the actuators of the bioreactor to operate.

[0007] The bioreactor control method provided by this invention, by simultaneously monitoring two indicators, pH and carbon dioxide, overcomes the limitations of traditional single PID feedback control that relies solely on historical errors for hysteresis adjustment. It can detect changes in metabolic state in advance and accurately locate the causes of pH fluctuations, thereby dynamically matching the optimal control strategy to implement targeted adjustments before significant pH deviations. This significantly overcomes defects such as control response hysteresis, overshoot oscillation, and actuator malfunctions, effectively improving the accuracy and robustness of pH control. While ensuring a highly stable culture environment, it significantly improves the yield and quality of the target product.

[0008] In some optional implementations, determining the control mode of the bioreactor based on the pH measurement and the carbon dioxide partial pressure measurement includes: determining whether the carbon dioxide partial pressure measurement falls within a preset first range; determining whether the pH measurement falls within a preset second range; when the carbon dioxide partial pressure measurement falls within the first range and the pH measurement falls within the second range, determining the control mode as a steady-state maintenance mode; when the carbon dioxide partial pressure measurement does not fall within the first range and the pH measurement falls within the second range, determining the control mode as a first control mode; and when the carbon dioxide partial pressure measurement does not fall within the first range and the pH measurement does not fall within the second range, determining the control mode as a second control mode.

[0009] This implementation precisely classifies the operating state of the bioreactor into a steady-state maintenance mode, a first control mode, and a second control mode by determining whether the carbon dioxide partial pressure measurement value falls within a first range and the pH measurement value falls within a second range. This classification strategy based on the relationship between the two measurement values ​​and preset ranges allows the system to remain stationary when all parameters are normal to avoid interference, intervene in advance to prevent pH fluctuations when only the carbon dioxide partial pressure is abnormal, and initiate deep regulation when both are abnormal. This achieves on-demand matching of control strategies and effectively improves the system's response accuracy and operational stability.

[0010] In some optional implementations, the first control mode includes a first sub-mode and a second sub-mode. Determining the specific sub-mode of the first control mode includes: when the pH measurement value is within the second range and the carbon dioxide partial pressure measurement value is greater than the maximum value of the first range, the first control mode is determined to be the first sub-mode; when the pH measurement value is within the second range and the carbon dioxide partial pressure measurement value is less than the minimum value of the first range, the first control mode is determined to be the second sub-mode.

[0011] This implementation subdivides the first control mode into a first sub-mode and a second sub-mode. This subdivision enables the system to accurately distinguish between two opposing operating conditions: high and low carbon dioxide levels. This allows the system to perform targeted operations to accelerate the removal or replenishment of gas, significantly improving the accuracy and response efficiency of gas concentration regulation.

[0012] In some optional implementations, the second control mode includes a third sub-mode, a fourth sub-mode, a fifth sub-mode, and a sixth sub-mode. Determining the specific sub-mode of the second control mode includes: when the pH measurement value is not within the second range, acquiring the pH measurement value and the carbon dioxide partial pressure measurement value from the previous moment; calculating the pH deviation change rate and the carbon dioxide partial pressure deviation change rate based on the difference between the current and previous pH measurement values ​​and the difference between the current and previous carbon dioxide partial pressure measurement values; and when the pH measurement value is less than the minimum value of the second range, the carbon dioxide partial pressure measurement value is greater than the maximum value of the first range, the pH deviation change rate is less than 0, and the carbon dioxide partial pressure deviation change rate is greater than... When the pH value is 0, the second control mode is determined as the third sub-mode; when the pH measurement value is less than the minimum value of the second range, the carbon dioxide partial pressure measurement value is less than or equal to the maximum value of the first range, and the pH deviation change rate is less than 0, the second control mode is determined as the fourth sub-mode; when the pH measurement value is greater than the maximum value of the second range, the carbon dioxide partial pressure measurement value is less than the minimum value of the first range, the pH deviation change rate is greater than 0, and the carbon dioxide partial pressure deviation change rate is less than 0, the second control mode is determined as the fifth sub-mode; when the pH measurement value is greater than the maximum value of the second range, the carbon dioxide partial pressure measurement value is greater than or equal to the minimum value of the first range, and the pH deviation change rate is greater than 0, the second control mode is determined as the sixth sub-mode.

[0013] When the pH measurement value does not fall within the second range, this implementation method uses data from the previous moment to calculate the pH deviation change rate and the carbon dioxide partial pressure deviation change rate. Combining the magnitude of the current measurement value, it accurately subdivides complex acid-base anomalies into the third to sixth sub-modes. This effectively distinguishes pH fluctuations caused by carbon dioxide accumulation, metabolic acid accumulation, carbon dioxide escape, and other reasons, thereby implementing differentiated control strategies for different root causes. This avoids the misadjustment and overshoot oscillations caused by the inability to identify the source of the fault in traditional solutions, and significantly improves the control accuracy and process stability under complex operating conditions.

[0014] In some optional implementations, determining control parameters corresponding to the control mode, generating control commands based on the control parameters, and driving the actuators of the bioreactor to operate includes: when the control mode is a first sub-mode, calculating a first adjustment factor based on the carbon dioxide partial pressure deviation value, its integral term, and its rate of change; when the control mode is a third sub-mode, calculating a first adjustment factor based on the pH deviation value, its integral term, and its rate of change; generating a first control command based on the first adjustment factor to adjust the first gas-liquid mass transfer conditions, and driving the actuators of the bioreactor to execute the first control command to reduce the carbon dioxide partial pressure by enhancing carbon dioxide escape and / or reducing carbon dioxide inlet; when the control mode is a second ... first adjustment factor to adjust the first gas-liquid mass transfer conditions, and driving the actuators of the bioreactor to execute the first control command to reduce the carbon dioxide partial pressure by enhancing carbon dioxide escape and / or reducing carbon dioxide inlet; and when the control mode is a second sub-mode, calculating a first adjustment factor based on the first adjustment factor to adjust the first gas-liquid mass transfer conditions, and driving the actuators of the bioreactor to execute the first control command to reduce the carbon dioxide partial pressure by enhancing carbon dioxide escape and / or reducing carbon dioxide inlet. A second adjustment factor is calculated based on the carbon partial pressure deviation, its integral term, and its rate of change. When the control mode is the fifth sub-mode, the second adjustment factor is calculated based on the pH deviation, its integral term, and its rate of change. A second control command is generated based on the second adjustment factor to adjust the second gas-liquid mass transfer conditions, driving the bioreactor's actuator to execute the second control command to increase the carbon dioxide partial pressure by suppressing carbon dioxide escape and / or increasing carbon dioxide inlet. When the control mode is the fourth or sixth sub-mode, a third adjustment factor is calculated based on the pH deviation, its integral term, and its rate of change. A third control command is generated based on the third adjustment factor to increase the alkali addition rate or acid addition rate, driving the alkali pump or acid pump to execute the third control command.

[0015] This implementation method flexibly utilizes actuators or acid-base pumps to adjust gas-liquid mass transfer conditions for different root causes, achieving optimal matching between control measures and fault sources, and significantly improving adjustment efficiency and the stability of the culture environment.

[0016] In some optional embodiments, the bioreactor control method further includes the following steps: when the control mode is the third sub-mode, generating a fourth control command for locking the output of the alkali pump, driving the alkali pump to set the output to zero; when the control mode is the fifth sub-mode, generating a fifth control command for locking the output of the acid pump, driving the acid pump to set the output to zero.

[0017] In the third sub-mode (CO2 accumulation leading to acidification) and the fifth sub-mode (CO2 escape leading to alkaliness), the root cause of pH anomalies is the disruption of gas dissolution equilibrium, not an absolute surplus or deficit of chemical substances. If acid-base reagents are conventionally added for neutralization, although the pH reading can be temporarily corrected, the previously added chemical reagents will lose their neutralizing target when gas balance is subsequently restored by adjusting stirring or aeration. This causes the pH value to rebound sharply in the opposite direction, resulting in severe overshoot oscillations. This implementation method, by forcibly locking the acid-base pump output in a specific mode, cuts off interference from chemical reagents, ensuring that the system restores gas balance from the root cause solely through physical means. This avoids the severe reverse pH rebound caused by the superposition of chemical neutralization and gas regulation, effectively eliminating the risk of overshoot and significantly improving control stability and culture safety.

[0018] In some optional implementations, the bioreactor control method further includes the following steps: during the execution of the first sub-mode or the second sub-mode, continuously monitoring the pH measurement value and the carbon dioxide partial pressure measurement value; when the following conditions are met simultaneously, switching the control mode back to the steady-state maintenance mode: (1) First parameter regression condition: the carbon dioxide partial pressure measurement value returns to the first range; (2) First trend stabilization condition: the absolute value of the carbon dioxide partial pressure deviation change rate is less than the preset first carbon dioxide partial pressure stability threshold; (3) First duration condition: the duration of the state in which the first parameter regression condition and the first trend stabilization condition are met simultaneously is not less than the preset first stable maintenance time; during the execution of any of the third to sixth sub-modes, continuously monitoring the pH measurement value and the carbon dioxide partial pressure measurement value; when the following conditions are met simultaneously, switching the control mode back to the steady-state maintenance mode: (1) Second parameter regression condition: the pH measurement value returns to the second range, and the carbon dioxide partial pressure measurement value returns to the first range; (2) Second trend stabilization condition: the absolute value of the pH deviation change rate is less than the preset pH stability threshold, and the absolute value of the carbon dioxide partial pressure deviation change rate is less than the preset second carbon dioxide partial pressure stability threshold; (3) Second duration condition: The duration of the state in which the second parameter regression condition and the second trend stability condition are simultaneously satisfied is not less than the preset second stability maintenance time.

[0019] This implementation method achieves refined and intelligent control strategy. For the first and second sub-modes, it is only necessary to monitor the return and stabilization of carbon dioxide partial pressure before exiting, which is a rapid response and avoids misjudgment and frequent switching of control modes caused by small pH fluctuations, thus improving the system's recovery efficiency under single parameter disturbances. For the third to sixth sub-modes, it is required that both pH and carbon dioxide partial pressure return to the normal range and remain stable, ensuring that the system can fully stabilize after experiencing dual parameter anomalies, thereby improving the overall stability and reliability of the bioreactor operation.

[0020] Secondly, the present invention also provides a control device for a bioreactor, the device comprising an acquisition module, a control mode determination module, and an action execution module; the acquisition module is used to acquire the pH measurement value and the carbon dioxide partial pressure measurement value of the bioreactor; the control mode determination module is used to determine the control mode of the bioreactor based on the pH measurement value and the carbon dioxide partial pressure measurement value; the action execution module is used to determine the control parameters corresponding to the control mode, generate control commands based on the control parameters, and drive the actuator of the bioreactor to act.

[0021] Thirdly, the present invention provides an electronic device comprising: a memory and a processor, the memory and the processor being communicatively connected to each other, the memory storing computer instructions, and the processor executing the computer instructions to perform the bioreactor control method of the first aspect or any corresponding embodiment described above.

[0022] Fourthly, the present invention provides a computer-readable storage medium storing computer instructions for causing a computer to execute the control method for a bioreactor according to the first aspect or any corresponding embodiment thereof.

[0023] Fifthly, the present invention provides a computer program product, including computer instructions for causing a computer to execute the control method for a bioreactor according to the first aspect or any corresponding embodiment thereof. Attached Figure Description

[0024] To more clearly illustrate the specific embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the specific embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of the present invention. For those skilled in the art, other drawings can be obtained from these drawings without creative effort.

[0025] Figure 1 This is a schematic diagram of an application scenario according to an embodiment of the present invention; Figure 2 This is a first flowchart of a bioreactor control method according to an embodiment of the present invention; Figure 3 This is a second flowchart of a bioreactor control method according to an embodiment of the present invention; Figure 4 This is a schematic diagram of an example of a bioreactor control method according to an embodiment of the present invention; Figure 5 This is a schematic diagram of another example of a bioreactor control method according to an embodiment of the present invention; Figure 6This is a structural block diagram of a bioreactor control device according to an embodiment of the present invention; Figure 7 This is a schematic diagram of the hardware structure of an electronic device according to an embodiment of the present invention. Detailed Implementation

[0026] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0027] It is understood that before using the technical solutions disclosed in the various embodiments of the present invention, users should be informed of the types, scope of use, and usage scenarios of the personal information involved in the present invention and their authorization should be obtained in accordance with relevant laws and regulations through appropriate means.

[0028] The terms "first" and "second" are used for descriptive purposes only and should not be construed as indicating or implying relative importance or implicitly specifying the number of technical features indicated. Thus, a feature defined as "first" or "second" may explicitly or implicitly include one or more of that feature. In the description of this invention, "a plurality of" means two or more, unless otherwise explicitly specified.

[0029] Bioreactors are core equipment in the fields of biopharmaceuticals and cell culture, providing a controlled environment for cell growth. pH is a critical parameter; deviations can affect cell health, reduce yield, and increase impurities. Frequent additions of acid / alkali solutions to correct pH can also increase osmotic pressure, triggering cellular stress. Therefore, maintaining high pH control is crucial. The causes of pH changes are complex and varied, primarily including the accumulation of acidic / alkaline substances produced by cell metabolism, the dissolution of CO2 produced by cellular respiration, changes in the buffering capacity of the culture medium, and excessive accumulation or escape of CO2 gas. Among these, CO2, as a major byproduct of cell metabolism, forms carbonic acid upon dissolution, which is one of the key factors affecting the pH of the culture medium. However, current methods using only pH sensors cannot distinguish between these different causes, making targeted and precise control difficult. The main reasons are: (1) Control hysteresis: It takes time for CO2 produced by cell metabolism to accumulate in the liquid phase. There is a significant delay in the response from CO2 production to dissolution to form carbonic acid and then to pH change. Traditional systems only start to act after the pH has deviated, by which time CO2 may have accumulated in large quantities, resulting in a severely sluggish control response. In addition, the gas-liquid mass transfer process itself has a delay, and there is still a time difference between the actuator action (such as increasing ventilation) and the actual pH change, which further exacerbates the control hysteresis, causing the deviation to continue to expand before correction.

[0030] (2) Risk of misjudging the root cause: pH changes can have various causes, including the accumulation of metabolic acids produced by cell metabolism, excessive CO2 buildup leading to increased acidity, or excessive CO2 release leading to increased alkalinity. Existing solutions cannot analyze the true cause and often adopt uniform corrective measures. For example, when CO2 accumulation leads to a low pH, the system may mistakenly add alkali to neutralize it. However, after the CO2 is removed, the previously added alkali will cause the pH to overshoot and become alkaline. This misjudgment of the root cause not only fails to solve the problem efficiently but may also introduce new disturbances, causing the control to fall into a vicious cycle.

[0031] (3) Risks of overshoot and oscillation: The inherent buffering capacity and gas-liquid mass transfer delay of the culture system result in significant inertia in pH control. When a pH deviation is detected, the PID controller outputs an adjustment signal, but due to the mass transfer delay, the effect of the actuator action takes a certain amount of time to be reflected in the pH measurement. During this period, the controller may continuously output an adjustment signal, leading to over-adjustment. When the effect is finally reflected, the pH has exceeded the set range, and the controller adjusts in the opposite direction, thus triggering continuous oscillation. This periodic fluctuation causes repeated stress to the cells, seriously affecting culture stability and product quality.

[0032] Based on this, the present invention provides a control method, apparatus, and electronic device for a bioreactor. As an optional application scenario of this invention, such as... Figure 1As shown, the bioreactor system includes a tank container, a controller, multiple sensors, and multiple actuators. The tank container is the actual carrier for containing culture medium and for the growth of microorganisms or cells. Sensors and actuators can be built-in components of the tank or controller, or separate components associated with them. Specifically, a pH sensor is used to collect the pH value of the culture medium in the tank in real time; a pCO2 sensor is installed on the exhaust pipe or in the top space inside the bioreactor to collect the partial pressure of CO2 gas in the exhaust gas phase in real time. The controller is connected to the pH sensor, pCO2 sensor, and stirring motor via communication cables. A peristaltic pump and a gas flow controller are built-in components of the controller, which contains the aforementioned control program. Feed bottles containing acid and alkali solutions are connected to the inlet at the top of the tank via hoses, which are also connected to the peristaltic pump. The feed rate is controlled by changing the speed of the peristaltic pump. The gas flow controller is used to precisely control the flow rate of air, oxygen, or carbon dioxide gas. Its outlet is connected to the top of a vent pipe on the tank via a hose, and the gas exits from the bottom of the vent pipe into an outlet hole below the culture medium surface. The stirring motor is coupled to the stirring shaft of the tank and drives it to rotate. The stirring shaft is equipped with blades inside the tank to stir and mix the culture medium. The stirring motor is connected to the controller and can receive commands to change the rotation speed.

[0033] According to an embodiment of the present invention, a method for controlling a bioreactor is provided. It should be noted that the steps shown in the flowchart in the accompanying drawings can be executed in a computer system such as a set of computer-executable instructions. Furthermore, although a logical order is shown in the flowchart, in some cases, the steps shown or described may be executed in a different order than that shown here.

[0034] This embodiment provides a control method for a bioreactor, which can be used in the controller described above. Figure 2 This is a first flowchart of a bioreactor control method according to an embodiment of the present invention, such as... Figure 2 As shown, the process includes the following steps: Step S201: Obtain the pH measurement value and carbon dioxide partial pressure measurement value of the bioreactor.

[0035] The partial pressure of carbon dioxide can be obtained by detecting the gas composition in the exhaust gas path of the bioreactor or the top space inside the bioreactor.

[0036] Specifically, a pH sensor can be used to obtain the pH value of the culture medium in the bioreactor, and a pCO2 sensor can be used to obtain the carbon dioxide partial pressure in the bioreactor exhaust gas or the CO2 partial pressure in the top space of the bioreactor. The pH sensor is used to collect the pH value of the culture medium in the tank in real time; the pCO2 sensor is installed on the exhaust pipe to collect the CO2 gas partial pressure in the exhaust gas phase in real time.

[0037] Step S202: Determine the control mode of the bioreactor based on the pH measurement and carbon dioxide partial pressure measurement.

[0038] Among them, the control mode refers to the type of control strategy selected by the bioreactor system according to the current state. Different control modes correspond to different parameter adjustment methods and actuator actions.

[0039] Step S203: Determine the control parameters corresponding to the control mode, generate control commands based on the control parameters, and drive the actuators of the bioreactor to perform actions according to the control commands.

[0040] Control parameters refer to the adjustment calculation basis and execution target values ​​that match the control mode, used to quantify the adjustment range of the actuator. For example, control parameters may include deviation value, deviation change rate, adjustment factor, target stirring speed, target air flow rate, target pump speed, etc., where deviation value refers to the difference between the measured value and the set range, target stirring speed refers to the required rotational speed of the stirring motor, and target air flow rate refers to the required flow rate of the gas flow controller.

[0041] Control commands refer to specific action signals generated based on control parameters and used to drive actuators. An actuator is a device in a bioreactor system that can receive control commands and perform physical actions. For example, an actuator may include at least one of the following: a stirring motor for adjusting the stirring speed of the bioreactor; a gas flow controller for adjusting the inflow rate of air, oxygen, or carbon dioxide; an acid pump for adding acid to the bioreactor; and an alkali pump for adding alkali to the bioreactor.

[0042] The bioreactor control method provided in this embodiment, by simultaneously monitoring two indicators, pH and carbon dioxide, changes the passive situation of traditional methods that can only be remedied when pH problems occur. It can detect abnormal signs of cell metabolism in advance and pinpoint the root cause, and can prescribe the right medicine. It can precisely adjust stirring, aeration or add acid or alkali before the pH fluctuates significantly, effectively avoiding problems such as slow control reaction, fluctuating values, and using the wrong method, making the cell culture environment more stable, thereby producing more and better products.

[0043] This embodiment provides a control method for a bioreactor, which can be used in the controller described above. Figure 3 This is a second flowchart of a bioreactor control method according to an embodiment of the present invention, as shown below. Figure 3 As shown, the process includes the following steps: Step S301: Obtain the pH measurement value and carbon dioxide partial pressure measurement value of the bioreactor.

[0044] Step S302: Determine the control mode of the bioreactor based on the pH measurement and carbon dioxide partial pressure measurement.

[0045] Specifically, step S302 includes the following steps S3021 to S3025.

[0046] Step S3021: Determine whether the carbon dioxide partial pressure measurement value falls within the preset first range.

[0047] The first range refers to the normal setting range of carbon dioxide partial pressure, which is determined by the preset lower limit of carbon dioxide partial pressure pCO. 2L and the upper limit of carbon dioxide partial pressure pCO 2H Composition. For example, pCO 2L It can be set to 40 mmHg, pCO 2H It can be set to 60 mmHg. When the measured partial pressure of carbon dioxide is greater than or equal to pCO... 2L And less than or equal to pCO 2H When the carbon dioxide partial pressure measurement value falls within the first range, it is determined that the carbon dioxide partial pressure measurement value is within the first range; when the carbon dioxide partial pressure measurement value is less than pCO... 2L or greater than pCO 2H When the carbon dioxide partial pressure measurement value is not within the first range, it is determined that the measurement value is not within the first range.

[0048] Step S3022: Determine whether the pH measurement value falls within the preset second range.

[0049] The second range refers to the normal setting range of pH value, which is determined by the preset lower pH limit. L and pH upper limit H Composition, exemplary pH L It can be set to 7.10, pH H It can be set to 7.30; when the pH measurement value is greater than or equal to pH L and less than or equal to pH H When the pH measurement value falls within the second range, it is determined that the pH measurement value is within the second range; when the pH measurement value is less than pH... L or greater than pH H If the pH measurement value does not fall within the second range, then it is determined that the pH measurement value does not fall within the second range.

[0050] Step S3023: When the carbon dioxide partial pressure measurement value is within the first range and the pH measurement value is within the second range, determine the control mode as steady-state maintenance mode.

[0051] The steady-state maintenance mode refers to the equilibrium maintenance state in which the pH value and carbon dioxide partial pressure value in the bioreactor are both within the normal set range. In this mode, no adjustment intervention is required, and all actuators maintain their current working state.

[0052] Step S3024: When the carbon dioxide partial pressure measurement value is not within the first range and the pH measurement value is within the second range, the control mode is determined to be the first control mode.

[0053] Furthermore, the first control mode includes a first sub-mode and a second sub-mode. The specific sub-mode for determining the first control mode includes: when the pH measurement value is within the second range and the carbon dioxide partial pressure measurement value is greater than the maximum value of the first range, the first control mode is determined to be the first sub-mode; when the pH measurement value is within the second range and the carbon dioxide partial pressure measurement value is less than the minimum value of the first range, the first control mode is determined to be the second sub-mode.

[0054] Step S3025: When the carbon dioxide partial pressure measurement value does not belong to the first range and the pH measurement value does not belong to the second range, determine the control mode as the second control mode.

[0055] Furthermore, the second control mode includes a third sub-mode, a fourth sub-mode, a fifth sub-mode, and a sixth sub-mode. Determining the specific sub-mode of the second control mode includes: when the pH measurement value is not within the second range, obtaining the pH measurement value and carbon dioxide partial pressure measurement value from the previous moment; calculating the pH deviation change rate and carbon dioxide partial pressure deviation change rate based on the difference between the current and previous pH measurement values ​​and the difference between the current and previous carbon dioxide partial pressure measurement values; when the pH measurement value is less than the minimum value of the second range, the carbon dioxide partial pressure measurement value is greater than the maximum value of the first range, the pH deviation change rate is less than 0, and the carbon dioxide partial pressure deviation change rate is greater than 0, determining the sixth sub-mode. The second control mode is the third sub-mode; when the pH measurement value is less than the minimum value of the second range, the carbon dioxide partial pressure measurement value is less than or equal to the maximum value of the first range, and the pH deviation change rate is less than 0, the second control mode is determined to be the fourth sub-mode; when the pH measurement value is greater than the maximum value of the second range, the carbon dioxide partial pressure measurement value is less than the minimum value of the first range, the pH deviation change rate is greater than 0, and the carbon dioxide partial pressure deviation change rate is less than 0, the second control mode is determined to be the fifth sub-mode; when the pH measurement value is greater than the maximum value of the second range, the carbon dioxide partial pressure measurement value is greater than or equal to the minimum value of the first range, and the pH deviation change rate is greater than 0, the second control mode is determined to be the sixth sub-mode.

[0056] To determine the control mode, it is necessary to calculate the deviation and the rate of change of deviation. For deviation calculation, when the pH measurement value is... m When the pH value is above the second range, the pH deviation value e pH Equal to pH m Subtract pH H When the pH measurement is below the second range, e pH Equal to pH m Subtract pH LSimilarly, when the measured partial pressure of carbon dioxide is pCO... 2m When the carbon dioxide partial pressure deviation value e is higher than the first range pCO2 equal to pCO 2m Subtract pCO 2H When the measured partial pressure of carbon dioxide is below the first range, e pCO2 equal to pCO 2m Subtract pCO 2L The rate of change of deviation is obtained by dividing the difference between the deviation values ​​at the current time and the previous time by the time interval Δt, thus yielding the pH deviation rate of change Δe. pH / Δt and the rate of change of carbon dioxide partial pressure deviation Δe pCO2 / Δt.

[0057] The state flag function is used to characterize the state of the measured value relative to the normal range, where the pH state flag S pH A value of -1 indicates low, 0 indicates normal, and 1 indicates high. Specifically, when pH... m Less than pH L Time S pH =-1, when pH m greater than pH H Time S pH The value is 1 when pH m At pH L To pH H Between S pH The value is 0. The carbon dioxide partial pressure status indicator S... pCO2 The rules for taking values ​​and S pH Same, that is, when pCO 2m Less than pCO 2L Time S pCO2 =-1, when pCO 2m Greater than pCO 2H Time S pCO2 When pCO is 1 2m In pCO 2L to pCO 2H Between S pCO2 It is 0.

[0058] The controller determines the control mode based on the combination of pH status flag and carbon dioxide partial pressure status flag, as shown in Table 1.

[0059] Table 1 Control Mode Decision Matrix

[0060] In this table, scenario A is the steady-state holding mode, scenarios B1 and B2 are the first control mode (also known as feedforward control mode), and scenario C is the second control mode (also known as optimized feedback control mode). Table 1 is used to initially determine the control mode type. After determining the second control mode through Table 1, it is necessary to further combine the deviation value, integral term and its rate of change, and determine the specific sub-modes of the second control mode through Table 2, namely the third sub-mode C1, the fourth sub-mode C2, the fifth sub-mode C3 and the sixth sub-mode C4.

[0061] Table 2. Judgment Criteria for Second Control Mode Submode

[0062] In Table 2, "arbitrary" means that ΔepCO2 / Δt can be in any state, or that ΔepCO2 / Δt is not considered.

[0063] It should be noted that the execution order of steps S3021 and S3022 is not strictly limited; they can be performed simultaneously or in any order. Furthermore, although steps S3023 to S3025 are... Figure 3 The branches are arranged vertically, but logically they belong to mutually exclusive branches under the same decision step. That is, one mode is selected to be executed based on the decision result, rather than being executed sequentially.

[0064] Step S303: Determine the control parameters corresponding to the control mode, generate control commands based on the control parameters, and drive the actuators of the bioreactor to operate.

[0065] Specifically, step S303 includes the following steps S3031 to S3033.

[0066] Step S3031: When the control mode is the first sub-mode, calculate the first adjustment factor based on the carbon dioxide partial pressure deviation value, its integral term and its rate of change; when the control mode is the third sub-mode, calculate the first adjustment factor based on the pH deviation value, its integral term and its rate of change; generate a first control command based on the first adjustment factor to adjust the first gas-liquid mass transfer conditions, and drive the actuator of the bioreactor to execute the first control command to reduce the carbon dioxide partial pressure by enhancing carbon dioxide escape and / or reducing carbon dioxide inlet.

[0067] Specifically, the first gas-liquid mass transfer condition includes at least one of the following: increasing the stirring speed, increasing the air flow rate, or decreasing the carbon dioxide flow rate.

[0068] For example, when the control mode is the first sub-mode (i.e., scenario B1, where pH is normal but carbon dioxide partial pressure is high), the controller commands enhance the physical means used to drive carbon dioxide escaping and / or reduce carbon dioxide intake. First, the first adjustment factor K for the stirring rate and aeration rate is calculated. B1 To accelerate CO2 removal and / or reduce CO2 intake, the calculation formula is as follows: K B1 = Kp B1 × e pCO2 (t) + Ki B1 × ∫e pCO2 dt + Kd B1 × (Δe pCO2 / Δt) Among them, K B1 Kp is the first adjustment factor, used to quantify the adjustment range of stirring speed and aeration rate; B1 e is the proportional gain coefficient, used to determine the adjustment intensity based on the current deviation magnitude; pCO2 (t) represents the carbon dioxide partial pressure deviation at the current moment, which is equal to the measured carbon dioxide partial pressure value minus the upper limit of the first range; Ki B1 ∫e is the integral gain coefficient, used to determine the adjustment intensity based on the duration of the deviation; pCO2 dt is the integral of the carbon dioxide partial pressure deviation, reflecting the cumulative effect of the deviation over time; Kd B1 The differential gain coefficient is used to determine the adjustment strength based on the trend of deviation change; Δe pCO2 / Δt is the rate of change of carbon dioxide partial pressure deviation, which is equal to the difference between the deviation value at the current time and the deviation value at the previous time divided by the time interval.

[0069] The first adjustment factor is allocated to the actuator, and the calculation formulas for the stirring speed adjustment and aeration rate adjustment are as follows: ΔRPM B1 (t) = α × K B1 × RPM max ΔAirflow B1 (t) = β × K B1 × Airflow max ΔCO2flow B1 (t) = -γ × K B1 ×CO2flow max Wherein, ΔRPM B1 (t) represents the stirring speed adjustment at time t; α is the stirring distribution coefficient, used to determine the proportion of the first adjustment factor allocated to the stirring motor; RPM maxThe maximum permissible speed of the stirring motor; ΔAirflow B1 (t) represents the ventilation rate adjustment at time t; β is the air distribution coefficient, used to determine the proportion of the first adjustment factor allocated to the air flow controller; Airflow max ΔCO2flow represents the maximum permissible flow rate of the air gas flow controller. B1 (t) represents the ventilation rate adjustment at time t; γ is the carbon dioxide gas distribution coefficient, used to determine the proportion of the first adjustment factor allocated to the carbon dioxide gas flow controller; CO2flow max This represents the maximum permissible flow rate of the carbon dioxide gas flow controller. α, β, and γ are distribution coefficients used to allocate the adjustment amount between stirring and aeration; α plus β plus γ equals 1.

[0070] When the control mode is the third sub-mode (i.e., scenario C1, where CO2 accumulation leads to a low pH), the controller also instructs enhanced physical means to drive carbon dioxide escape. First, the first adjustment factor K for the stirring rate and aeration rate is calculated. C1 The calculation formula is as follows: K C1 = Kp C1 × e pH (t) + Ki C1 × ∫e pH dt + Kd C1 × (Δe pH / Δt) Among them, K C1 Kp is the first adjustment factor, used to quantify the adjustment range of stirring speed and aeration rate; C1 e is the proportional gain coefficient; pH (t) represents the pH deviation at the current moment, which is equal to the pH measurement value minus the lower limit of the second range; Ki C1 For the integral gain coefficient; ∫e pH dt is the integral of the pH deviation value; Kd C1 The differential gain coefficient; Δe pH / Δt represents the rate of change of pH deviation.

[0071] The first adjustment factor is allocated to the actuator, and the calculation formulas for the stirring speed adjustment and aeration rate adjustment are as follows: ΔRPM C1 (t) = α × K C1 × RPM max ΔAirflow C1 (t) = β × K C1 × Airflow max ΔCO2flow C1 (t) = -γ × K C1 ×CO2flow max Wherein, ΔRPM C1 (t) represents the stirring speed adjustment at time t in scenario C1; ΔAirflow C1 (t) represents the air ventilation regulation rate at time t in scenario C1; ΔCO2flow C1 (t) represents the carbon dioxide ventilation adjustment at time t in scenario C1. Simultaneously, the alkali pump output is completely shut off, even if the pH is low. This is a crucial overflush prevention measure to avoid pH overflush to alkalinity after subsequent CO2 removal.

[0072] At the same time, completely shut off the alkali pump output or limit the alkali pump output to below a preset first threshold. For example, the first threshold can be 10% of the alkali pump's maximum speed. Even if the pH is low, this is a key anti-overflow measure to prevent the pH from over-flushing to alkalinity after subsequent CO2 replenishment. The calculation formula is as follows: AlkaliPump(t) = 0 Where AlkaliPump(t) is the output of the alkali pump at time t, and setting it to 0 indicates that the alkali pump is completely locked.

[0073] In other words, when the control mode is the first sub-mode, a command to lock the output of the alkali pump is generated; the bioreactor is driven to execute the first control command, and the alkali pump is driven to execute the lock command.

[0074] It should be noted that although both the first and third sub-modes employ control strategies of increasing stirring speed and / or increasing air flow and / or decreasing carbon dioxide flow, they differ in the following ways: the adjustment factor in the first sub-mode is calculated based on the carbon dioxide partial pressure deviation, constituting feedforward control and intervening before the pH deviates; the adjustment factor in the third sub-mode is calculated based on the pH deviation, constituting feedback control and correcting the root cause after the pH has deviated. Furthermore, the third sub-mode requires locking the alkali pump output, while the first sub-mode does not.

[0075] Step S3032: When the control mode is the second sub-mode, calculate the second adjustment factor based on the carbon dioxide partial pressure deviation value, its integral term and its rate of change; when the control mode is the fifth sub-mode, calculate the second adjustment factor based on the pH deviation value, its integral term and its rate of change; generate a second control command based on the second adjustment factor to adjust the second gas-liquid mass transfer conditions, and drive the actuator of the bioreactor to execute the second control command to increase the carbon dioxide partial pressure by suppressing carbon dioxide escape and / or increasing carbon dioxide inlet.

[0076] The second gas-liquid mass transfer condition includes at least one of the following: reducing the stirring speed, reducing the air flow rate, or increasing the carbon dioxide flow rate.

[0077] For example, when the control mode is the second sub-mode (i.e., scenario B2, where pH is normal but carbon dioxide partial pressure is low), the controller generates control commands to suppress carbon dioxide escape and / or increase carbon dioxide inlet to improve the liquid phase carbon dioxide partial pressure. First, the second adjustment factor K for the carbon dioxide inlet flow rate is calculated. B2 To increase the driving force for the dissolution of liquid CO2, the calculation formula is as follows: K B2 = Kp B2 × e pCO2 (t) + Ki B2 × ∫e pCO2 dt + Kd B2 × (Δe pCO2 / Δt) Among them, K B2 Kp is the second adjustment factor, used to quantify the adjustment range of the carbon dioxide injection flow rate; B2 e is the proportional gain coefficient, used to determine the adjustment intensity based on the current deviation magnitude; pCO2 (t) represents the carbon dioxide partial pressure deviation at the current moment, which is equal to the measured carbon dioxide partial pressure value minus the lower limit of the first range; Ki B2 ∫e is the integral gain coefficient, used to determine the adjustment intensity based on the duration of the deviation; pCO2 dt is the integral of the carbon dioxide partial pressure deviation, reflecting the cumulative effect of the deviation over time; Kd B2 The differential gain coefficient is used to determine the adjustment strength based on the trend of deviation change; Δe pCO2 / Δt is the rate of change of carbon dioxide partial pressure deviation, which is equal to the difference between the deviation value at the current time and the deviation value at the previous time divided by the time interval.

[0078] Secondly, the second adjustment factor is allocated to the actuator, and the formula for calculating the carbon dioxide flow rate adjustment is as follows: ΔCO2flow B2 (t) = α × K B2 × CO2flow max ΔRPM B2 (t) = -β × K B2 × RPM max ΔAirflow B2 (t) = -γ × K B2 × Airflow max Where, ΔCO2flow B2 (t) represents the carbon dioxide flow rate regulation at time t; α is the carbon dioxide gas distribution coefficient, used to determine the proportion of the second regulation factor allocated to the carbon dioxide gas flow controller; CO2flowmax is the maximum safe flow rate of the carbon dioxide gas flow controller; ΔRPM B2 (t) represents the stirring speed adjustment at time t; β is the stirring distribution coefficient, used to determine the proportion of the second adjustment factor allocated to the stirring motor; RPM max The maximum permissible speed of the stirring motor; ΔAirflow B2 (t) represents the airflow regulation at time t; γ is the air distribution coefficient, used to determine the proportion of the second regulation factor allocated to the airflow controller; Airflow max This represents the maximum permissible flow rate of the air / gas flow controller. α, β, and γ are distribution coefficients used to allocate the regulation amount between stirring and venting; α plus β plus γ equals 1.

[0079] When the control mode is in the fifth sub-mode (i.e., scenario C3, where CO2 escape leads to a higher pH), the controller instructs to increase the dissolved carbon dioxide level. First, the second adjustment factor K for the carbon dioxide inlet flow rate is calculated. C3 To increase the driving force for the dissolution of liquid CO2, the calculation formula is as follows: K C3 = Kp C3 × e pH (t) + Ki C3 × ∫e pH dt + Kd C3 × (Δe pH / Δt) Among them, K C3 Kp is the second adjustment factor, used to quantify the adjustment range of the carbon dioxide injection flow rate; C3 e is the proportional gain coefficient, used to determine the adjustment intensity based on the current deviation magnitude; pH (t) represents the pH deviation at the current moment, which is equal to the pH measurement value minus the upper limit of the second range; Ki C3 ∫e is the integral gain coefficient, used to determine the adjustment intensity based on the duration of the deviation; pH dt is the integral of the pH deviation value, reflecting the cumulative effect of the deviation over time; Kd C3 The differential gain coefficient is used to determine the adjustment strength based on the trend of deviation change; Δe pH / Δt is the pH deviation rate of change, which is equal to the difference between the deviation value at the current time and the deviation value at the previous time divided by the time interval.

[0080] Secondly, the second adjustment factor is allocated to the actuator, and the formula for calculating the carbon dioxide flow rate adjustment is as follows: ΔCO2flow C3 (t) = α × K C3 × CO2flow max ΔRPM C3 (t) = -β × K C3 × RPM max ΔAirflow C3 (t) = -γ × K C3 × Airflow max Where, ΔCO2flow C3 (t) represents the carbon dioxide flow rate regulation at time t; α is the carbon dioxide gas distribution coefficient, used to determine the proportion of the second regulation factor allocated to the carbon dioxide gas flow controller; CO2flow max The maximum safe flow rate for the carbon dioxide gas flow controller; ΔRPM C3 (t) represents the stirring speed adjustment at time t; β is the stirring distribution coefficient, used to determine the proportion of the second adjustment factor allocated to the stirring motor; RPM max This represents the maximum permissible speed of the stirring motor. ΔAirflow C3 (t) represents the airflow regulation at time t; γ is the air distribution coefficient, used to determine the proportion of the second regulation factor allocated to the airflow controller; Airflow max This represents the maximum permissible flow rate of the air / gas flow controller. α, β, and γ are distribution coefficients used to allocate the regulation amount between stirring and venting; α plus β plus γ equals 1.

[0081] At the same time, completely shut off the acid pump output or limit the acid pump output to below a preset second threshold. For example, the second threshold can be 10% of the acid pump's maximum speed. Even if the pH is high, this is a key anti-overflow measure to prevent the pH from over-flushing to acidic levels after subsequent CO2 replenishment. The calculation formula is as follows: AcidPump(t) = 0 Where AcidPump(t) is the acid pump output at time t, and setting it to 0 indicates that the acid pump is completely locked.

[0082] In other words, when the control mode is the fifth sub-mode, a command to lock the acid pump output is generated; the carbon dioxide gas flow controller is driven to execute the second control command, and the acid pump is driven to execute the lock command.

[0083] Step S3033: When the control mode is the fourth sub-mode or the sixth sub-mode, calculate the third adjustment factor based on the pH deviation value, its integral term and its rate of change; generate a third control command based on the third adjustment factor to increase the alkali addition rate or acid addition rate; drive the alkali pump or acid pump to execute the third control command.

[0084] In other words, when the control mode is the fourth sub-mode, the third adjustment factor is calculated based on the pH deviation value, its integral term and its rate of change. The third control command is generated based on the third adjustment factor to increase the alkali addition rate. The alkali pump is driven to execute the third control command to neutralize the excess acidic substances caused by metabolic accumulation, quickly and stably bring the low pH value back to above the lower limit of the target range, while keeping the ventilation and stirring parameters constant to avoid interfering with dissolved oxygen control.

[0085] When the control mode is the sixth sub-mode, the third adjustment factor is calculated based on the pH deviation value, its integral term and its rate of change; the third control command is generated based on the third adjustment factor to increase the acid addition rate; the acid pump is driven to execute the third control command to neutralize the excessively high pH value caused by non-carbon dioxide escaping factors (such as excessive alkali or buffer imbalance), and accurately bring it back below the upper limit of the target range, while keeping the aeration and stirring parameters constant to ensure the single variable principle of the adjustment process.

[0086] For example, when the control mode is the fourth sub-mode (i.e., scenario C2, where metabolic acid accumulation leads to a low pH), the controller command adds alkali solution while maintaining constant aeration rate and stirring speed. First, the third adjustment factor K for the alkali pump addition rate is calculated. C2 To neutralize accumulated metabolic acids, the calculation formula is as follows: K C2 = Kp C2 × e pH (t) + Ki C2 × ∫e pH dt + Kd C2 × (Δe pH / Δt) Among them, K C2 The third adjustment factor is used to quantify the adjustment range of the alkali pump addition rate; Kp C2 e is the proportional gain coefficient, used to determine the adjustment intensity based on the current deviation magnitude; pH (t) represents the pH deviation at the current moment, which is equal to the pH measurement value minus the lower limit of the second range; Ki C2 ∫e is the integral gain coefficient, used to determine the adjustment intensity based on the duration of the deviation; pH dt is the integral of the pH deviation value, reflecting the cumulative effect of the deviation over time; Kd C2The differential gain coefficient is used to determine the adjustment strength based on the trend of deviation change; Δe pH / Δt is the pH deviation rate of change, which is equal to the difference between the deviation value at the current time and the deviation value at the previous time divided by the time interval.

[0087] Secondly, the third adjustment factor is allocated to the actuator, and the formula for calculating the output of the alkali pump is as follows: AlkaliPump(t) = K C2 × AlkaliPump Max Where AlkaliPump(t) is the output of the alkali pump at time t (e.g., speed or flow rate); K C2 The third regulating factor; AlkaliPump Max This refers to the maximum permissible speed or maximum flow rate of the alkali pump.

[0088] Meanwhile, the stirring speed and aeration flow rate remain at their current levels, calculated using the following formula: RPM(t) = RPM(t-1) Airflow(t) = Airflow(t-1) CO2flow(t) = CO2flow(t-1) Where RPM(t) is the stirring speed at time t, and RPM(t-1) is the stirring speed at the previous time; Airflow(t) is the air flow rate at time t, and Airflow(t-1) is the air flow rate at the previous time; CO2flow(t) is the carbon dioxide flow rate at time t, and CO2flow(t-1) is the carbon dioxide flow rate at the previous time.

[0089] When the control mode is the sixth sub-mode (i.e., scenario C4, where the pH is high due to other reasons), the controller command takes measures to add acid while maintaining the aeration rate and stirring speed unchanged. First, the third adjustment factor K for the acid pump addition rate is calculated. C4 To lower the excessively high pH value, the calculation formula is as follows: K C4 = Kp C4 × e pH (t) + Ki C4 × ∫e pH dt + Kd C4 × (Δe pH / Δt) Among them, K C4 The third adjustment factor is used to quantify the adjustment range of the acid pump addition rate; Kp C4 e is the proportional gain coefficient; pH(t) represents the pH deviation at the current moment, which is equal to the pH measurement value minus the upper limit of the second range; Ki C4 For the integral gain coefficient; ∫e pH dt is the integral of the pH deviation value; Kd C4 The differential gain coefficient; Δe pH / Δt represents the rate of change of pH deviation.

[0090] Secondly, the third adjustment factor is allocated to the actuator, and the formula for calculating the acid pump output is as follows: ΔAcidPump(t) = K C4 × AcidPump Max Where ΔAcidPump(t) is the acid pump output adjustment at time t; K C4 It is the third regulating factor; AcidPump Max This is the maximum permissible flow rate of the acid pump.

[0091] Meanwhile, the stirring speed and aeration flow rate remain at their current levels, calculated using the following formula: RPM(t) = RPM(t-1) Airflow(t) = Airflow(t-1) CO2flow(t) = CO2flow(t-1) Where RPM(t) is the stirring speed at time t, and RPM(t-1) is the stirring speed at the previous time; Airflow(t) is the air flow rate at time t, and Airflow(t-1) is the air flow rate at the previous time; CO2flow(t) is the carbon dioxide flow rate at time t, and CO2flow(t-1) is the carbon dioxide flow rate at the previous time.

[0092] It should be noted that although both the fourth and sixth sub-modes employ an acid-base pump control strategy, they differ in the following ways: the fourth sub-mode targets scenarios with low pH and drives the alkali pump to add alkali solution; the sixth sub-mode targets scenarios with high pH and drives the acid pump to add acid solution. Furthermore, both modes maintain the stirring and aeration strategies unchanged, correcting pH deviations solely through chemical addition.

[0093] It should be noted that although steps S3031 to S3033 are arranged vertically in the flowchart, they are logically mutually exclusive branches under the same decision step. That is, one mode is selected to be executed according to the decision result, rather than being executed sequentially.

[0094] In addition, this embodiment also sets an exit mechanism for the first sub-mode and the second sub-mode. During the execution of the first sub-mode or the second sub-mode, the pH measurement value and the carbon dioxide partial pressure measurement value are continuously monitored; when the following conditions are met at the same time, the control mode is switched back to the steady-state maintenance mode: (1) First parameter regression condition: the carbon dioxide partial pressure measurement value returns to the first range; (2) First trend stabilization condition: the absolute value of the carbon dioxide partial pressure deviation change rate is less than the preset first carbon dioxide partial pressure stability threshold; (3) First duration condition: the duration of the state in which the first parameter regression condition and the first trend stabilization condition are met at the same time is not less than the preset first stable maintenance time.

[0095] For example, after the first or second sub-mode is executed, the system continuously monitors pCO. 2m and pH m (1) If pCO 2m Returning to normal range [pCO] 2L pCO 2H Within ], and |ΔepCO2 / Δt| < η (η is a constant, such as 2 mmHg / min) remains stable for more than a preset time T_stable (e.g., 120 seconds), the feedforward control objective is determined to be achieved, and the system returns to steady-state mode (scenario A); (2) if pCO 2m It has not yet returned to the set range, and pHm has also deviated from the set range [pH]. L pH H If ], the system enters scenario C.

[0096] This embodiment also sets an exit mechanism (termination condition) for the third to sixth sub-modes. Continuously monitor pH measurement and carbon dioxide partial pressure measurement; when the following conditions are met simultaneously, switch the control mode back to steady-state maintenance mode: (1) Second parameter regression condition: pH measurement returns to the second range, and carbon dioxide partial pressure measurement returns to the first range; (2) Second trend stabilization condition: the absolute value of pH deviation change rate is less than the preset pH stability threshold, and the absolute value of carbon dioxide partial pressure deviation change rate is less than the preset second carbon dioxide partial pressure stability threshold; (3) Second duration condition: the duration of the state in which the second parameter regression condition and the second trend stabilization condition are met simultaneously is not less than the preset second stabilization maintenance time.

[0097] Wherein, the second carbon dioxide partial pressure stability threshold is less than or equal to the first carbon dioxide partial pressure stability threshold, and the second stability holding time is greater than or equal to the first stability holding time.

[0098] In other words, the exit thresholds for the third to sixth sub-modes are significantly raised: not only are smaller parameter fluctuations required (stricter stability thresholds), but also a longer stable state is maintained (longer hold time). This design effectively prevents the system from prematurely switching back to steady-state mode after severe disturbances due to brief, superficial recovery, and prevents control oscillations or repeated adjustments caused by premature switching back to steady-state maintenance mode, thereby ensuring the recovery quality and long-term operational safety of the bioreactor after experiencing deep anomalies.

[0099] For example, when the following three conditions are met simultaneously, the controller determines that the system has returned to stability and automatically switches the control mode back to steady-state hold mode (Scenario A). Condition 1 is: Key parameters return to normal range: pH measurement value returns to the second range [pH...]. L pH H Within the range, and the measured carbon dioxide partial pressure returns to the first range [pCO]. 2L pCO 2H Condition 2 is: The trend of change tends to be stable: the absolute value of the pH deviation change rate is less than the preset threshold Ω (e.g., 0.2 / min), and the absolute value of the carbon dioxide partial pressure deviation change rate is less than the preset threshold η (e.g., 2 mmHg / min); Condition 3 is: The stable duration meets the standard: the state of regression and trend stability of the above parameters is maintained for a continuous time of not less than T_stable (e.g., 4 minutes).

[0100] The bioreactor control method provided in this embodiment upgrades the control strategy from single hysteresis feedback to multimodal precise feedforward / feedback coordination by constructing a state recognition matrix and a rate of change trend analysis mechanism based on the coupling of pH and carbon dioxide partial pressure. This method can not only accurately distinguish four fundamental causes of acidification based on real-time deviations, namely, acidification caused by CO2 accumulation, acidification caused by metabolic production, alkalization caused by CO2 escape, and alkalization caused by non-gas phase factors, but also dynamically match the optimal execution path for physical regulation of stirring and aeration or chemical neutralization of acid and base for different causes. In critical scenarios, it can intelligently lock complementary actuators to prevent overshoot oscillation, thereby eliminating abnormal signs before the pH deviates significantly. This significantly improves the response speed, robustness, and stability of the culture environment of the control system, and ultimately effectively improves the yield and quality of bioproducts.

[0101] To illustrate the control method of the bioreactor in this embodiment more clearly, a specific example is given, which includes: (1) Prepare a 3L bioreactor tank container, and install the pH sensor, air inlet pipe, exhaust pipe, acid solution pipe, alkali solution pipe and inoculation pipe into the corresponding positions on the top cover of the tank, and install the pCO2 sensor onto the exhaust pipe.

[0102] (2) Connect the communication lines of the pH sensor, pCO2 sensor, and stirring motor to the controller and confirm that the controller can receive the sensor readings normally.

[0103] (3) Install the acid / alkali pipes onto the acid pump / alkali pump respectively, and confirm that the controller can issue commands to accurately control the pump.

[0104] (4) Connect the air source and CO2 source to the gas flow controller and confirm that the controller can issue commands to adjust the gas flow.

[0105] (5) Set the target pH range in the controller to 7.10~7.30 (i.e., pH L =7.10, pH H =7.30), set the target range for pCO2 to 40~60 mmHg (i.e., pCO2 = 7.30), and set the target range for pCO2 to 40~60 mmHg (i.e., pCO2 = 7.30). 2L =40, pCO 2H =60).

[0106] (6) Set other process parameters: target temperature 37℃, basic stirring speed 200 rpm, dissolved oxygen (DO) setting 50%.

[0107] (7) Add 1.5L of culture medium to the bioreactor tank, turn on the temperature control until the set temperature of 37°C is reached, and then add CHO cell seed solution for inoculation.

[0108] (8) Start the automatic control program for all parameters of the reactor to begin the cell culture process.

[0109] (9) During the cultivation process, the controller automatically collects sensor readings in real time, and automatically calculates and issues commands according to the preset control logic. The actuator performs corresponding adjustment actions according to the commands.

[0110] (10) At a certain point during the initial stage of cultivation, the pH measurement value pHm was 7.20 (normal), and the pCO2 measurement value pCO2m was 80 mmHg (high). The controller determined to enter the first sub-mode (B1). Deviation calculation: epCO2 = pCO2m - pCO2H = 80 - 60 = 20 mmHg. Adjustment factor calculation: The first adjustment factor KB1 was calculated according to the formula KB1 = KpB1 × epCO2(t) + KiB1 × ∫epCO2dt + KdB1 × (ΔepCO2 / Δt). Execution action: According to ΔRPM(t) = α × KB1 × RPMmax, ΔAirflow(t) = β × KB1 × Airflowmax, and ΔCO2flowB1(t) = -γ × KB1 × CO2flowmax, the controller issued commands to increase the stirring speed by 5 rpm, increase the air flow rate by 5 mL / min, and decrease the carbon dioxide flow rate by 5 mL / min. Results: pCO2 gradually decreased to 50 mmHg, satisfying the stability condition of |ΔepCO2 / Δt|<η (i.e., <5 mmHg / min). After 2 minutes, the mode was exited and returned to steady-state maintenance mode (A).

[0111] (11) At a certain point during the initial stage of cultivation, pHm was 7.20 (normal) and pCO2m was 30 mmHg (low). The controller determined to enter the second sub-mode (B2). Deviation calculation: epCO2 = pCO2m - pCO2L = 30 - 40 = -10 mmHg. Adjustment factor calculation: The adjustment factor KB2 was calculated according to the formula KB2 = KpB2 × epCO2(t) + KiB2 × ∫epCO2dt + KdB2 × (ΔepCO2 / Δt). Execution action: According to ΔCO2flowB2(t) = α × KB2 × CO2flowmax, ΔRPMB2(t) = -β × KB2 × RPMmax, and ΔAirflowB2(t) = -γ × KB2 × Airflowmax, the controller issued commands to increase the carbon dioxide flow rate by 5 mL / min, decrease the stirring speed by 5 rpm, and decrease the air flow rate by 5 mL / min. Results: pCO2 gradually increased to 50 mmHg, satisfying the stability condition of |ΔepCO2 / Δt|<η (i.e., <5 mmHg / min), and exited the mode after 2 minutes, returning to the steady-state maintenance mode (A).

[0112] (12) At a certain point during the mid-stage of cultivation, within 4 minutes, pHm decreased from 7.10 to 6.90 (too low), and pCO2m increased from 60 to 80 mmHg (too high). At this time, epH = -0.20 < 0, epCO2 = 20 > 0, ΔepH / Δt = -0.05 < 0, and ΔepCO2 / Δt = 5 > 0. The controller determines that it is entering the third sub-mode (C1). The regulation factor KC1 is calculated according to the formula KC1 = KpC1 × epH(t) + KiC1 × ∫epHdt + KdC1 × (ΔepH / Δt). Action executed: Based on ΔRPMC1(t) = α × KC1 × RPMmax, ΔAirflowC1(t) = β × KC1 × Airflowmax, and ΔCO2flowC1(t) = -γ × KC1 × CO2flowmax, the controller issued commands to increase the stirring speed by 10 rpm and the air flow rate by 10 mL / min, and to decrease the carbon dioxide flow rate by 10 mL / min; simultaneously, the alkali pump output was locked, i.e., AlkaliPump(t) = 0. Result: The pH rose to 7.10 without overshoot, and pCO2 decreased to 55 mmHg, satisfying the stability conditions of |ΔepH / Δt| < Ω (i.e., < 0.05 / min) and |ΔepCO2 / Δt| < η (i.e., < 5 mmHg / min). After 4 minutes, it returned to steady-state maintenance mode (A).

[0113] (13) At a certain point during the mid-stage of cultivation, within 6 minutes, pHm decreased from 7.15 to 7.05 (low), and pCO2m decreased from 52 to 48 mmHg (fluctuation within the normal range). At this time, epH = -0.15 < 0, epCO2 = -2 ≤ 0, and ΔepH / Δt = -0.017 < 0. The controller determines that it has entered the fourth sub-mode (C2). Calculation of the regulation factor: According to the formula KC2 = KpC2 × epH(t) + KiC2 × ∫epHdt + KdC2 × (ΔepH / Δt), the regulation factor KC2 is calculated. Action executed: Based on AlkaliPump(t) = KC2 × AlkaliPumpMax, the controller issued a command to increase the alkali pump speed by 5 rpm; simultaneously, aeration and stirring maintained the current strategy, i.e., RPM(t) = RPM(t-1), Airflow(t) = Airflow(t-1), CO2flow(t) = CO2flow(t-1). Result: The pH rose to 7.20 without overshoot, and pCO2 remained at 48 mmHg, satisfying the stability conditions of |ΔepH / Δt| < Ω (i.e., < 0.05 / min) and |ΔepCO2 / Δt| < η (i.e., < 5 mmHg / min). After 4 minutes, it returned to steady-state maintenance mode (A).

[0114] (14) At a certain point during the mid-stage of cultivation, within 5 minutes, pHm increased from 7.25 to 7.35 (too high), and pCO2m decreased from 45 to 30 mmHg (too low). At this time, epH = 0.15 > 0, epCO2 = -10 < 0, ΔepH / Δt = 0.03 > 0, and ΔepCO2 / Δt = -3 < 0. The controller determines that it has entered the fifth sub-mode (C3). Calculation of the adjustment factor: According to the formula KC3 = KpC3 × epH(t) + KiC3 × ∫epHdt + KdC3 × (ΔepH / Δt), the adjustment factor KC3 is calculated. Actions executed: Based on ΔCO2flowC3(t) = α × KC3 × CO2flowmax, ΔRPMC3(t) = -β × KC3 × RPMmax, and ΔAirflowC3(t) = -γ × KC3 × Airflowmax, the controller issued commands to increase the carbon dioxide flow rate by 10 mL / min, decrease the stirring speed by 10 rpm, and decrease the air flow rate by 10 mL / min; simultaneously, the acid pump was completely shut off, i.e., AcidPump(t) = 0. Results: The pH decreased to 7.20, and pCO2m rose back to 45 mmHg, satisfying the stability conditions of |ΔepH / Δt| < Ω (i.e., < 0.05 / min) and |ΔepCO2 / Δt| < η (i.e., < 5 mmHg / min). After 4 minutes, it returned to steady-state maintenance mode (A).

[0115] (15) At a certain point in the later stage of cultivation, within 3 minutes, pHm rose from 7.20 to 7.35 (high), and pCO2m rose slightly from 50 to 52 mmHg (normal). At this time, epH = 0.15 > 0, epCO2 = 2 ≥ 0, and ΔepH / Δt = 0.05 > 0. The controller determined to enter the sixth sub-mode (C4). Adjustment factor calculation: The adjustment factor KC4 was calculated according to the formula KC4 = KpC4 × epH(t) + KiC4 × ∫epHdt + KdC4 × (ΔepH / Δt). Execution action: According to ΔAcidPump(t) = KC4 × AcidPumpMax, the controller issued a command to increase the acid pump speed by 5 rpm; at the same time, aeration and stirring remained unchanged, i.e., RPM(t) = RPM(t-1), Airflow(t) = Airflow(t-1), CO2flow(t) = CO2flow(t-1). Results: When the pH decreased to 7.25, the pCO2 remained constant at 52 mmHg, satisfying the stability conditions of |ΔepH / Δt|<Ω (i.e., <0.05 / min) and |ΔepCO2 / Δt|<η (i.e., <5mmHg / min). After 4 minutes, it returned to steady-state maintenance mode (A).

[0116] (16) After about 7 days of culture, the cells die naturally and the viability drops to below 80%. Then, shut down all control systems and end the culture.

[0117] (17) The control results obtained show that the pH value did not deviate significantly during the entire culture period; during the correction of deviation, the system responded quickly and did not produce overshoot or oscillation, effectively ensuring the stability of cell growth.

[0118] Steps (1) to (15) above describe in detail the specific execution process of the control logic of the present invention under different operating conditions. To more intuitively understand this control logic, Figure 4 and Figure 5 The control strategy in this example is illustrated using flowcharts. Figure 4 The focus is on describing the synergistic control strategy of pH and pCO2. When both pH and pCO2 are abnormal, the system prioritizes adjusting the aeration rate and stirring speed to correct the abnormality and maintain the physical balance of the system. Figure 5 and Figure 4 The main difference lies in prioritizing the activation of the acid-base pump for adjustment. Under specific operating conditions, the system prioritizes the rapid response of the acid-base pump to correct pH deviations, while simultaneously adjusting the gas flow rate to achieve precise pH restoration. Figure 4 and Figure 5This is a graphical representation of the control algorithm and logical judgment in the above embodiments.

[0119] In summary, the bioreactor control method provided in this embodiment has the following beneficial effects: (1) The pCO2 of the exhaust gas is elevated to a critical process parameter (KPP). By analyzing this parameter, changes in cell metabolism can be detected in advance before significant changes occur in the liquid phase pH, the trend of pH change can be predicted, and a feedforward control strategy can be established to correct it. (2) An intelligent decision-making system for the coordinated analysis of pH and exhaust gas pCO2 was constructed, which can determine the root cause of pH fluctuations and further refine the traditional feedback control strategy, making the control action more precise and direct, and thus avoiding side effects such as overshoot and oscillation. (3) Moving the pCO2 monitoring site from the liquid phase to the reactor tail gas effectively avoids sensor contamination, improves the lifespan and quality of the sensor, and significantly enhances the long-term stability and reliability of the data. (4) It is suitable for addressing the challenges posed by the rapid accumulation of metabolic byproducts during high-density cell culture. It makes the process more robust to fluctuations in metabolic activity. When scaling up from laboratory to production scale, gas transfer and mixing efficiencies change, and this composite control strategy can better adapt to these changes, reducing the risk of process scale-up and improving the success rate of scale-up.

[0120] This embodiment also provides a control device for a bioreactor, which is used to implement the above embodiments and preferred embodiments; details already described will not be repeated. As used below, the term "module" can refer to a combination of software and / or hardware that performs a predetermined function. Although the device described in the following embodiments is preferably implemented in software, hardware implementation, or a combination of software and hardware, is also possible and contemplated.

[0121] This embodiment provides a control device for a bioreactor, such as... Figure 6 As shown, it includes: The acquisition module 601 is used to acquire the pH measurement value and carbon dioxide partial pressure measurement value of the bioreactor; The control mode determination module 602 is used to determine the control mode of the bioreactor based on the pH measurement value and the carbon dioxide partial pressure measurement value. The action execution module 603 is used to determine the control parameters corresponding to the control mode, generate control commands based on the control parameters, and drive the actuators of the bioreactor to move.

[0122] In some optional implementations, the control mode determination module 602 is specifically used to: determine whether the carbon dioxide partial pressure measurement value belongs to a preset first range; determine whether the pH measurement value belongs to a preset second range; when the carbon dioxide partial pressure measurement value belongs to the first range and the pH measurement value belongs to the second range, determine the control mode as a steady-state maintenance mode; when the carbon dioxide partial pressure measurement value does not belong to the first range and the pH measurement value belongs to the second range, determine the control mode as a first control mode; when the carbon dioxide partial pressure measurement value does not belong to the first range and the pH measurement value does not belong to the second range, determine the control mode as a second control mode.

[0123] In some optional implementations, the first control mode includes a first sub-mode and a second sub-mode. The control mode determination module 602 is specifically used to: determine the first control mode as the first sub-mode when the pH measurement value is within the second range and the carbon dioxide partial pressure measurement value is greater than the maximum value of the first range; and determine the first control mode as the second sub-mode when the pH measurement value is within the second range and the carbon dioxide partial pressure measurement value is less than the minimum value of the first range.

[0124] In some optional implementations, the second control mode includes a third sub-mode, a fourth sub-mode, a fifth sub-mode, and a sixth sub-mode. The control mode determination module 602 is specifically used for: when the pH measurement value is not within the second range, acquiring the pH measurement value and the carbon dioxide partial pressure measurement value from the previous moment; calculating the pH deviation change rate and the carbon dioxide partial pressure deviation change rate based on the difference between the current and previous pH measurement values ​​and the difference between the current and previous carbon dioxide partial pressure measurement values; and when the pH measurement value is less than the minimum value of the second range, the carbon dioxide partial pressure measurement value is greater than the maximum value of the first range, the pH deviation change rate is less than 0, and the carbon dioxide partial pressure deviation change rate is greater than 0... The second control mode is determined as the third sub-mode; when the pH measurement value is less than the minimum value of the second range, the carbon dioxide partial pressure measurement value is less than or equal to the maximum value of the first range, and the pH deviation change rate is less than 0, the second control mode is determined as the fourth sub-mode; when the pH measurement value is greater than the maximum value of the second range, the carbon dioxide partial pressure measurement value is less than the minimum value of the first range, the pH deviation change rate is greater than 0, and the carbon dioxide partial pressure deviation change rate is less than 0, the second control mode is determined as the fifth sub-mode; when the pH measurement value is greater than the maximum value of the second range, the carbon dioxide partial pressure measurement value is greater than or equal to the minimum value of the first range, and the pH deviation change rate is greater than 0, the second control mode is determined as the sixth sub-mode.

[0125] In some optional implementations, the action execution module 603 is specifically configured to: calculate a first adjustment factor based on the carbon dioxide partial pressure deviation value, its integral term, and its rate of change when the control mode is a first sub-mode; calculate a first adjustment factor based on the pH deviation value, its integral term, and its rate of change when the control mode is a third sub-mode; generate a first control command based on the first adjustment factor to adjust the first gas-liquid mass transfer conditions, and drive the actuator of the bioreactor to execute the first control command to reduce the carbon dioxide partial pressure by enhancing carbon dioxide escape and / or reducing carbon dioxide inlet; and calculate a first control factor based on the carbon dioxide partial pressure deviation value, its integral term, and its rate of change when the control mode is a second sub-mode. The second adjustment factor is calculated. When the control mode is the fifth sub-mode, the second adjustment factor is calculated based on the pH deviation value, its integral term, and its rate of change. Based on the second adjustment factor, a second control command is generated to adjust the second gas-liquid mass transfer conditions, and the actuator of the bioreactor is driven to execute the second control command to increase the carbon dioxide partial pressure by suppressing carbon dioxide escape and / or increasing carbon dioxide inlet. When the control mode is the fourth or sixth sub-mode, a third adjustment factor is calculated based on the pH deviation value, its integral term, and its rate of change. Based on the third adjustment factor, a third control command is generated to increase the alkali addition rate or acid addition rate, and the alkali pump or acid pump is driven to execute the third control command.

[0126] In some optional implementations, the action execution module 603 is further configured to: generate a fourth control command for locking the output of the alkali pump when the control mode is the third sub-mode, driving the alkali pump to set the output to zero; and generate a fifth control command for locking the output of the acid pump when the control mode is the fifth sub-mode, driving the acid pump to set the output to zero.

[0127] In some optional implementations, the control mode determination module 602 is further configured to: continuously monitor the pH measurement value and the carbon dioxide partial pressure measurement value during the execution of the first sub-mode or the second sub-mode; and switch the control mode back to the steady-state maintenance mode when the following conditions are met simultaneously: (1) First parameter regression condition: the carbon dioxide partial pressure measurement value returns to the first range; (2) First trend stabilization condition: the absolute value of the carbon dioxide partial pressure deviation change rate is less than the preset first carbon dioxide partial pressure stability threshold; (3) First duration condition: the duration of the state in which the first parameter regression condition and the first trend stabilization condition are met simultaneously is not less than the preset first stable maintenance time; and continuously monitor the pH measurement value and the carbon dioxide partial pressure measurement value during the execution of any of the third to sixth sub-modes; and switch the control mode back to the steady-state maintenance mode when the following conditions are met simultaneously: (1) Second parameter regression condition: pH measurement value returns to the second range, and carbon dioxide partial pressure measurement value returns to the first range; (2) Second trend stability condition: pH deviation change rate absolute value is less than the preset pH stability threshold, and carbon dioxide partial pressure deviation change rate absolute value is less than the preset second carbon dioxide partial pressure stability threshold; (3) Second duration condition: the duration of the state in which the second parameter regression condition and the second trend stability condition are simultaneously satisfied is not less than the preset second stability maintenance time.

[0128] The bioreactor control device provided in this embodiment of the invention can execute the bioreactor control method provided in any embodiment of the invention, and has the corresponding functional modules and beneficial effects for executing the method. Further functional descriptions of the various modules and units described above are the same as in the corresponding embodiments described above, and will not be repeated here.

[0129] Figure 7 This is a schematic diagram of the structure of an electronic device provided in an embodiment of the present invention.

[0130] The following is a detailed reference. Figure 7 This diagram illustrates a suitable structural schematic for implementing an electronic device according to embodiments of the present invention. The electronic device may include a processor (e.g., a central processing unit, graphics processor, etc.) 701, which can perform various appropriate actions and processes based on a program stored in read-only memory (ROM) 702 or a program loaded from memory 708 into random access memory (RAM) 703. The RAM 703 also stores various programs and data required for the operation of the electronic device. The processor 701, ROM 702, and RAM 703 are interconnected via a bus 704. An input / output (I / O) interface 705 is also connected to the bus 704.

[0131] Typically, the following devices can be connected to I / O interface 705: input devices 706 including, for example, touchscreens, touchpads, keyboards, mice, cameras, microphones, accelerometers, gyroscopes, etc.; output devices 707 including, for example, liquid crystal displays (LCDs), speakers, vibrators, etc.; memory devices 708 including, for example, magnetic tapes, hard disks, etc.; and communication devices 709. Communication device 709 allows electronic devices to exchange data via wireless or wired communication with other devices. Although Figure 7 Electronic devices with various devices are shown, but it should be understood that it is not required to implement or have all of the devices shown, and more or fewer devices may be implemented or have instead.

[0132] In particular, according to embodiments of the present invention, the processes described above with reference to the flowcharts can be implemented as computer software programs. For example, embodiments of the present invention include a computer program product comprising a computer program carried on a non-transitory computer-readable medium, the computer program containing program code for performing the methods shown in the flowcharts. In such embodiments, the computer program can be downloaded and installed from a network via a communication device 709, or installed from a memory 708, or installed from a ROM 702. When the computer program is executed by the processor 701, it performs the functions defined in the bioreactor control method of the embodiments of the present invention.

[0133] Figure 7 The electronic device shown is merely an example and should not be construed as limiting the functionality and scope of use of the embodiments of the present invention.

[0134] This invention also provides a computer-readable storage medium. The methods described above according to embodiments of the invention can be implemented in hardware or firmware, or implemented as computer code that can be recorded on a storage medium, or implemented as computer code downloaded via a network and originally stored on a remote storage medium or a non-transitory machine-readable storage medium and then stored on a local storage medium. Thus, the methods described herein can be processed by software stored on a storage medium using a general-purpose computer, a dedicated processor, or programmable or dedicated hardware. The storage medium can be a magnetic disk, optical disk, read-only memory, random access memory, flash memory, hard disk, or solid-state drive, etc.; further, the storage medium can also include combinations of the above types of memory. It is understood that computers, processors, microprocessor controllers, or programmable hardware include storage components capable of storing or receiving software or computer code. When the software or computer code is accessed and executed by the computer, processor, or hardware, the bioreactor control method shown in the above embodiments is implemented.

[0135] A portion of this invention can be applied as a computer program product, such as computer program instructions, which, when executed by a computer, can invoke or provide the methods and / or technical solutions according to the invention through the operation of the computer. Those skilled in the art will understand that the forms in which computer program instructions exist in a computer-readable medium include, but are not limited to, source files, executable files, installation package files, etc. Correspondingly, the ways in which computer program instructions are executed by a computer include, but are not limited to: the computer directly executing the instructions, or the computer compiling the instructions and then executing the corresponding compiled program, or the computer reading and executing the instructions, or the computer reading and installing the instructions and then executing the corresponding installed program. Here, the computer-readable medium can be any available computer-readable storage medium or communication medium accessible to a computer.

[0136] Although embodiments of the invention have been described in conjunction with the accompanying drawings, those skilled in the art can make various modifications and variations without departing from the spirit and scope of the invention, and such modifications and variations all fall within the scope defined by the appended claims.

Claims

1. A method for controlling a bioreactor, characterized in that, The method includes: Obtain pH and carbon dioxide partial pressure measurements from the bioreactor; The control mode of the bioreactor is determined based on the pH measurement value and the carbon dioxide partial pressure measurement value. Determine the control parameters corresponding to the control mode, generate control commands based on the control parameters, and drive the actuators of the bioreactor to perform actions according to the control commands.

2. The method according to claim 1, characterized in that, Determining the control mode of the bioreactor based on the measured pH value and the measured carbon dioxide partial pressure value includes: Determine whether the measured carbon dioxide partial pressure value falls within a preset first range; Determine whether the pH measurement value falls within a preset second range; When the measured value of carbon dioxide partial pressure is within the first range and the measured value of pH is within the second range, the control mode is determined to be a steady-state maintenance mode. When the measured value of carbon dioxide partial pressure is not within the first range and the measured value of pH is within the second range, the control mode is determined to be the first control mode; When the measured value of carbon dioxide partial pressure is not within the first range and the measured value of pH is not within the second range, the control mode is determined to be the second control mode.

3. The method according to claim 2, characterized in that, The first control mode includes a first sub-mode and a second sub-mode. Determining the specific sub-mode of the first control mode includes: When the pH measurement value is within the second range and the carbon dioxide partial pressure measurement value is greater than the maximum value of the first range, the first control mode is determined to be the first sub-mode; When the pH measurement value falls within the second range and the carbon dioxide partial pressure measurement value is less than the minimum value of the first range, the first control mode is determined to be the second sub-mode.

4. The method according to claim 3, characterized in that, The second control mode includes a third sub-mode, a fourth sub-mode, a fifth sub-mode, and a sixth sub-mode, wherein determining the specific sub-mode of the second control mode includes: When the pH measurement value is not within the second range, obtain the pH measurement value and the carbon dioxide partial pressure measurement value of the previous moment. The pH deviation rate and the carbon dioxide partial pressure deviation rate are calculated based on the difference between the pH measurement value at the current time and the previous time, and the difference between the carbon dioxide partial pressure measurement value at the current time and the previous time. When the pH measurement value is less than the minimum value of the second range, the carbon dioxide partial pressure measurement value is greater than the maximum value of the first range, the pH deviation change rate is less than 0 and the carbon dioxide partial pressure deviation change rate is greater than 0, the second control mode is determined to be the third sub-mode; When the pH measurement value is less than the minimum value of the second range, the carbon dioxide partial pressure measurement value is less than or equal to the maximum value of the first range, and the pH deviation change rate is less than 0, the second control mode is determined to be the fourth sub-mode; When the pH measurement value is greater than the maximum value of the second range, the carbon dioxide partial pressure measurement value is less than the minimum value of the first range, the pH deviation change rate is greater than 0 and the carbon dioxide partial pressure deviation change rate is less than 0, the second control mode is determined to be the fifth sub-mode. When the pH measurement value is greater than the maximum value of the second range, the carbon dioxide partial pressure measurement value is greater than or equal to the minimum value of the first range, and the pH deviation change rate is greater than 0, the second control mode is determined to be the sixth sub-mode.

5. The method according to claim 4, characterized in that, The step of determining the control parameters corresponding to the control mode, generating control commands based on the control parameters, and driving the actuators of the bioreactor to operate includes: When the control mode is the first sub-mode, a first adjustment factor is calculated based on the carbon dioxide partial pressure deviation value, its integral term, and its rate of change. When the control mode is the third sub-mode, the first adjustment factor is calculated based on the pH deviation value, its integral term, and its rate of change. A first control command for adjusting the first gas-liquid mass transfer conditions is generated based on the first adjustment factor, and the actuator of the bioreactor is driven to execute the first control command to reduce the carbon dioxide partial pressure by enhancing carbon dioxide escape and / or reducing carbon dioxide inlet. When the control mode is the second sub-mode, a second adjustment factor is calculated based on the carbon dioxide partial pressure deviation value, its integral term, and its rate of change. When the control mode is the fifth sub-mode, a second adjustment factor is calculated based on the pH deviation value, its integral term, and its rate of change. A second control command is generated based on the second adjustment factor to adjust the second gas-liquid mass transfer conditions, driving the actuator of the bioreactor to execute the second control command to increase the carbon dioxide partial pressure by suppressing carbon dioxide escape and / or increasing carbon dioxide inlet. When the control mode is the fourth sub-mode or the sixth sub-mode, a third adjustment factor is calculated based on the pH deviation value, its integral term and its rate of change; a third control command is generated based on the third adjustment factor to increase the alkali addition rate or acid addition rate; and the alkali pump or acid pump is driven to execute the third control command.

6. The method according to claim 5, characterized in that, Also includes: When the control mode is the third sub-mode, a fourth control command is generated to lock the output of the alkali pump, limiting the output opening of the alkali pump to below a preset first threshold or controlling it to zero. When the control mode is the fifth sub-mode, a fifth control command is generated to lock the acid pump output, limiting the output opening of the acid pump to below a preset second threshold or controlling it to zero.

7. The method according to claim 5, characterized in that, Also includes: During the execution of the first sub-mode or the second sub-mode, the pH measurement value and the carbon dioxide partial pressure measurement value are continuously monitored; When the following conditions are met simultaneously, the control mode is switched back to the steady-state holding mode: (1) First parameter regression condition: the carbon dioxide partial pressure measurement value returns to the first range; (2) First trend stabilization condition: the absolute value of the carbon dioxide partial pressure deviation change rate is less than the preset first carbon dioxide partial pressure stability threshold; (3) First duration condition: the duration of the state in which the first parameter regression condition and the first trend stabilization condition are met simultaneously is not less than the preset first stabilization holding time. During the execution of any of the third to sixth sub-modes, the pH measurement value and the carbon dioxide partial pressure measurement value are continuously monitored; when the following conditions are met simultaneously, the control mode is switched back to the steady-state maintenance mode: (1) Second parameter regression condition: the pH measurement value returns to the second range, and the carbon dioxide partial pressure measurement value returns to the first range; (2) Second trend stabilization condition: The absolute value of the pH deviation change rate is less than the preset pH stability threshold, and the absolute value of the carbon dioxide partial pressure deviation change rate is less than the preset second carbon dioxide partial pressure stability threshold; (3) Second duration condition: The duration of the state in which the second parameter regression condition and the second trend stabilization condition are simultaneously satisfied is not less than the preset second stability maintenance time.

8. A control device for a bioreactor, characterized in that, The device includes: The acquisition module is used to acquire pH and carbon dioxide partial pressure measurements of the bioreactor. A control mode determination module is used to determine the control mode of the bioreactor based on the pH measurement value and the carbon dioxide partial pressure measurement value. The action execution module is used to determine the control parameters corresponding to the control mode, generate control commands based on the control parameters, and drive the actuators of the bioreactor to operate.

9. An electronic device, characterized in that, include: A memory and a processor are communicatively connected, the memory storing computer instructions, and the processor executing the computer instructions to perform the control method of the bioreactor according to any one of claims 1 to 7.

10. A computer-readable storage medium, characterized in that, The computer-readable storage medium stores computer instructions for causing a computer to perform the control method for the bioreactor according to any one of claims 1 to 7.

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