A control method, controller, and cell culture equipment for a cell culture device.

Abstract

This application relates to a control method, controller, and cell culture equipment for a cell culture device. By acquiring the real-time temperature value within the culture equipment, and based on the real-time temperature value and a target temperature value, a heating control quantity for the heating element within the culture equipment is obtained using a PID control algorithm. A heating control signal is then sent to the heating element according to the heating control quantity to control its heating. Simultaneously, based on the correspondence between the heating control quantity and the rotational speed of the circulating fan within the culture equipment, a rotational speed control signal is sent to the circulating fan according to the heating control quantity to adjust the fan's rotational speed. In this application, by dynamically changing the rotational speed of the circulating fan with the heating control quantity, a coordinated matching of heating power and convection intensity can be achieved.

Description

Technical Field

[0001] This application belongs to the field of control technology for cell culture equipment, and in particular relates to a control method, controller and cell culture equipment for cell culture equipment. Background Technology

[0002] Cell culture equipment (such as CO2 incubators) is widely used in biomedicine, tissue engineering, and other fields. One of its core functions is to provide a stable temperature environment for cell growth. Typically, the equipment is equipped with heating elements and a circulating fan. The heating elements heat the air inside the chamber, and the fan forces convection to make the temperature distribution inside the chamber more uniform.

[0003] Currently, most cell culture equipment employs an independent control strategy: the temperature controller adjusts the output power of the heating element based on the deviation between the real-time temperature and the set temperature; the fan operates at a constant speed or a segmented fixed speed. However, in practical applications, this control method has the following shortcomings: First, when the heating element is operating at high power, heat can easily accumulate in local areas inside the chamber, resulting in poor temperature uniformity in different locations and affecting the uniformity of cell growth.

[0004] Second, when the heating element is operating at a lower power, the overall energy consumption of the equipment is relatively high, and when the airflow velocity inside the chamber is too high, it may cause additional mechanical disturbance to the cells in suspension culture.

[0005] Third, under special working conditions such as high-temperature disinfection, the temperature response speed of the equipment during the heating stage is not ideal, and the overall energy efficiency needs to be improved.

[0006] Therefore, how to improve the uniformity of the temperature field inside cell culture equipment, reduce operating energy consumption, and enhance response performance under special working conditions while ensuring temperature control accuracy is a technical problem that urgently needs to be solved in this field. Summary of the Invention

[0007] The purpose of this application is to provide a control method, controller, and cell culture equipment for cell culture. The control method, controller, and cell culture equipment provided by this application can achieve coordinated matching between heating power and convection intensity by dynamically changing the rotation speed of the circulating fan with the heating control quantity. In the high-efficiency heating stage, the fan speed is increased to accelerate heat diffusion and improve the temperature uniformity inside the equipment. In the low-power heating stage, the fan speed is reduced to reduce energy consumption and avoid excessive airflow causing mechanical disturbance to the suspended cells. Under high-temperature sterilization conditions, the fan speed is increased synchronously to shorten the heating time and improve response speed and energy efficiency.

[0008] This application provides a method for controlling a cell culture device, including: Obtain the real-time temperature value inside the culture equipment; Based on the real-time temperature value and the target temperature value, the heating control quantity of the heating element in the cultivation device is obtained using a PID control algorithm. A heating control signal is sent to the heating element according to the heating control quantity to control the heating element to perform heating. At the same time, based on the correspondence between the heating control quantity and the rotation speed of the circulating fan in the culture device, a rotation speed control signal is sent to the circulating fan according to the heating control quantity to adjust the rotation speed of the circulating fan.

[0009] Optionally, the correspondence is a linear proportional relationship, whereby the rotational speed of the circulating fan is directly proportional to the heating control quantity.

[0010] Optionally, it also includes: Obtain the real-time carbon dioxide concentration value within the culture device; Based on the real-time carbon dioxide concentration value and the target carbon dioxide concentration value, the carbon dioxide adjustment amount is obtained using a PID control algorithm. The opening control signal is sent to the carbon dioxide valve according to the carbon dioxide adjustment amount to adjust the opening of the carbon dioxide valve.

[0011] Optionally, it also includes: After the target cells and culture medium are delivered to the cell culture container in the culture device, the flipping platform in the culture device is controlled to cause the cell culture container carried on the flipping platform to perform at least one of the following movements: flipping, rotating and vibrating, in order to disperse the target cells and culture medium.

[0012] Optionally, it also includes: Cell images inside the culture device are acquired in real time using a microscope camera; The cell images are analyzed to obtain parameters reflecting the density of cell growth; When the parameters meet the first preset condition, a liquid addition control signal is sent to the nutrient solution addition device to add nutrient solution to the cell culture container. When the parameters meet the second preset condition, an enzyme addition control signal is sent to the digestive enzyme addition device to add digestive enzyme to the cell culture container; When the parameters meet the third preset condition, a harvest control signal is sent to the harvest execution mechanism to start the harvesting action.

[0013] Optionally, it also includes: Detect the open / closed status of the door lock of the culture equipment; When the door lock is detected to be open, an alarm signal is sent to the display screen for display.

[0014] Optionally, it also includes: Obtain the real-time humidity value inside the cultivation equipment; The real-time humidity value is sent to the display screen for display.

[0015] This application also provides a controller, including: a processor, a memory, and a communication bus; The communication bus is used to realize the connection and communication between the processor and the memory; The processor is used to execute a control program for the cell culture device stored in the memory to implement the steps of the control method for the cell culture device as described in any of the above claims.

[0016] This application also provides a cell culture device, comprising: Temperature sensors are used to collect real-time temperature values ​​within the culture equipment; Heating element, used for heating according to heating control signal; A circulating fan is used to adjust the speed according to a speed control signal; The controller described above is electrically connected to the temperature sensor, the heating element, and the circulating fan, respectively.

[0017] Optionally, it also includes: a carbon dioxide sensor and a carbon dioxide valve; The carbon dioxide sensor is used to collect real-time carbon dioxide concentration values ​​within the culture equipment; The carbon dioxide valve is used to adjust the amount of carbon dioxide entering according to the opening control signal. The controller is electrically connected to both the carbon dioxide sensor and the carbon dioxide valve.

[0018] Compared with existing technologies, the control method, controller, and cell culture equipment provided in this application acquire real-time temperature values ​​within the culture equipment. Based on the real-time temperature values ​​and target temperature values, a heating control quantity for the heating element within the culture equipment is obtained using a PID control algorithm. A heating control signal is then sent to the heating element according to the heating control quantity to control its heating. Simultaneously, based on the correspondence between the heating control quantity and the rotational speed of the circulating fan within the culture equipment, a rotational speed control signal is sent to the circulating fan according to the heating control quantity to adjust its rotational speed. In this application, by dynamically changing the rotational speed of the circulating fan with the heating control quantity, a coordinated match between heating power and convection intensity can be achieved. During high-efficiency heating, the fan speed is increased to accelerate heat diffusion and improve temperature uniformity within the equipment. During low-power heating, the fan speed is reduced to reduce energy consumption and prevent excessive airflow from causing mechanical disturbance to the suspended cells. Under high-temperature sterilization conditions, the fan speed is increased synchronously to shorten the heating time, thereby improving response speed and energy efficiency. Attached Figure Description

[0019] To more clearly illustrate the technical solutions in the embodiments of this application or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of this application. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0020] Figure 1 This is a flowchart illustrating a control method for a cell culture device provided in an embodiment of this application; Figure 2 This is a structural block diagram of a controller provided in an embodiment of this application; Figure 3 This is a schematic diagram of the structure of a cell culture device provided in an embodiment of this application; Figure 4 This is a schematic diagram of another cell culture device provided in the embodiments of this application. Detailed Implementation

[0021] To enable those skilled in the art to better understand the technical solutions in this application, the technical solutions in the embodiments of this application will be clearly and completely described below. Obviously, the described embodiments are only a part of the embodiments of this application, and not all of the embodiments. Based on the embodiments in this application, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this application.

[0022] It should be noted that when a component is referred to as being "fixed to" or "set on" another component, it can be directly on or indirectly set on the other component; when a component is referred to as being "connected to" another component, it can be directly connected to or indirectly connected to the other component.

[0023] It should be noted that the structures, proportions, sizes, etc., shown in the accompanying drawings of this specification are only for the purpose of assisting those skilled in the art in understanding and reading the content disclosed in the specification, and are not intended to limit the conditions under which this application can be implemented. Therefore, they have no substantial technical significance. Any modifications to the structure, changes in the proportions, or adjustments to the size should still fall within the scope of the technical content disclosed in this application, provided that they do not affect the effects and purposes that this application can produce.

[0024] The culture device in this application embodiment may specifically be a carbon dioxide incubator (hereinafter referred to as an incubator), but it is not limited to this, and may also be other cell culture devices with temperature control, gas control and / or humidity control requirements.

[0025] like Figure 1 As shown in the figure, this application provides a control method for a cell culture device, including: S11. Obtain the real-time temperature value inside the culture equipment; In this embodiment, a high-precision temperature sensor, such as a PT100 platinum resistance temperature sensor, is installed inside the culture equipment (e.g., an incubator). This sensor is installed at a representative location within the incubator cavity (such as the central airflow circulation area or near the cell culture container) to collect the gas temperature inside the incubator in real time. The controller reads the resistance change of the temperature sensor at a preset sampling frequency (e.g., 10 times per second) through an analog-to-digital converter circuit and converts it into the corresponding temperature value, thereby obtaining the real-time temperature value inside the culture equipment. To ensure data accuracy, median filtering or moving average processing can be applied to the values ​​collected multiple times consecutively to suppress transient interference. Obtaining accurate real-time temperature values ​​is the foundation for achieving closed-loop isothermal control and provides reliable feedback signals for subsequent PID calculations.

[0026] S12. Based on the real-time temperature value and the target temperature value, the heating control quantity of the heating element in the cultivation equipment is obtained using the PID control algorithm. In this embodiment, the controller stores a user-defined target temperature value (e.g., 37.0°C is typically set for mammalian cell culture). The controller calculates the deviation between the real-time temperature value and the target temperature value (deviation = target temperature). (Real-time temperature); then, the deviation value is input into the digital PID (proportional-integral-derivative) controller, which calculates the heating control quantity according to the following formula: Heating control quantity = Kp × deviation + Ki × deviation integral + Kd × deviation change rate; Wherein, Kp, Ki, and Kd are the proportional, integral, and differential coefficients obtained in advance through tuning.

[0027] The proportional term responds quickly to the current deviation, the integral term eliminates static errors, and the derivative term predicts the trend of deviation changes to suppress overshoot. These three terms work synergistically to avoid severe overshoot during the heating phase, smoothly approach the target temperature, and quickly recover stability after external disturbances (such as door opening for cooling). The calculated heating control quantity is typically expressed as the duty cycle (0~100%) of the PWM (Pulse Width Modulation) signal. The larger the duty cycle, the higher the effective heating power of the heating element per unit time.

[0028] S13. Send a heating control signal to the heating element according to the heating control quantity to control the heating element to heat. At the same time, based on the correspondence between the heating control quantity and the rotation speed of the circulating fan in the culture equipment, send a rotation speed control signal to the circulating fan according to the heating control quantity to adjust the rotation speed of the circulating fan.

[0029] In this embodiment, the controller sends the heating control quantity (e.g., PWM duty cycle) calculated in step S12 as a heating control signal to the heating element (e.g., electric heating wire), so that the heating element is energized and heated according to the corresponding power, thereby increasing the gas temperature in the incubator; at the same time, the controller also determines the fan speed value corresponding to the current heating control quantity based on the preset correspondence between the heating control quantity and the circulating fan speed, and sends the corresponding speed control signal (e.g., PWM signal or DC voltage signal) to the driving circuit of the circulating fan to adjust the fan speed.

[0030] During isothermal culture, the heat generated by the heating element needs to be rapidly and evenly distributed throughout the entire incubator cavity. Otherwise, the temperature near the heating source will be too high, and the temperature far from the heating source will be too low, creating a temperature gradient. By linking the fan speed with the heating control, that is, when the heating power is higher, the fan speed will also increase accordingly, which can force stronger convection circulation and quickly transfer heat to all corners of the chamber; when the heating power is reduced, the fan speed will also decrease to maintain a gentle airflow environment. This linkage mechanism avoids the problems caused by the fan always running at a fixed speed: too low a speed may lead to uneven heat distribution, while too high a speed may cause excessive blowing on the surface of the cell culture container, accelerate evaporation, and generate unnecessary noise and energy consumption.

[0031] By dynamically adjusting the fan speed to match the heating power, the temperature uniformity within the incubator is significantly improved, while physical interference to cells caused by prolonged high-speed fan operation is avoided. This also reduces energy consumption and operating noise. Furthermore, because temperature control and airflow circulation work in tandem, a stable thermal field distribution is maintained within the incubator even during the steady-state adjustment phase with frequent on / off cycles of the heating elements, providing reliable and consistent environmental conditions for cell growth.

[0032] Compared with existing technologies, the control method, controller, and cell culture equipment provided in this application acquire real-time temperature values ​​within the culture equipment. Based on the real-time temperature values ​​and target temperature values, a heating control quantity for the heating element within the culture equipment is obtained using a PID control algorithm. A heating control signal is then sent to the heating element according to the heating control quantity to control its heating. Simultaneously, based on the correspondence between the heating control quantity and the rotational speed of the circulating fan within the culture equipment, a rotational speed control signal is sent to the circulating fan according to the heating control quantity to adjust its rotational speed. In this application, by dynamically changing the rotational speed of the circulating fan with the heating control quantity, a coordinated match between heating power and convection intensity can be achieved. During high-efficiency heating, the fan speed is increased to accelerate heat diffusion and improve temperature uniformity within the equipment. During low-power heating, the fan speed is reduced to reduce energy consumption and prevent excessive airflow from causing mechanical disturbance to the suspended cells. Under high-temperature sterilization conditions, the fan speed is increased synchronously to shorten the heating time, thereby improving response speed and energy efficiency.

[0033] In one implementation method, the correspondence in this application embodiment is a linear proportional relationship, where the rotational speed of the circulating fan is directly proportional to the heating control quantity.

[0034] In this embodiment, the controller pre-stores a linear proportional coefficient k (positive value). After calculating the current heating control quantity (represented by the PWM duty cycle D, ranging from 0 to 100%) using the PID algorithm, the controller calculates the target speed of the circulating fan according to the following formula: Fan speed = k × D; where, when D = 0%, the fan speed is 0 (or the minimum safe speed; to avoid local overheating due to fan stoppage, a minimum speed limit can be set, but the linear relationship is still maintained); when D = 100%, the fan speed reaches the preset maximum speed value. To ensure stable operation of the fan throughout the entire heating range, the value of the proportional coefficient k must ensure that the fan speed corresponding to the maximum heating power does not exceed the fan's rated speed, while generating sufficient airflow to achieve uniform temperature.

[0035] Because the heating control quantity and fan speed maintain a fixed proportional relationship, the fan speed strictly follows the change in heating power linearly. When the incubator needs to heat up rapidly, the heating control quantity is large, and the fan rotates at high speed synchronously, forcing rapid airflow circulation within the cavity to quickly deliver the heat generated by the heating element to all corners, avoiding localized overheating or temperature lag. When the incubator approaches the target temperature and the heating control quantity decreases, the fan speed also decreases linearly to maintain a gentle airflow environment, reducing direct blowing on the cell culture container and evaporation of the culture medium. This linear proportional relationship makes the control logic extremely simple, eliminating the need for complex lookup tables or piecewise functions, thus reducing the computational burden on the controller.

[0036] First, the linear proportional relationship ensures that the fan speed changes smoothly with heating demand, without nonlinear abrupt changes or oscillations, which is conducive to the stable establishment of the temperature field. Second, the control parameter has only a single proportional coefficient k, making on-site debugging and calibration very convenient. Third, the fan strategy, which is fully linked to the heating control, can more accurately match the real-time heat load compared to schemes that run the fan at a constant speed or switch in segments only according to the temperature threshold, achieving energy saving and noise reduction while ensuring temperature uniformity.

[0037] As one implementation method, this application embodiment further includes: S21. Obtain the real-time carbon dioxide concentration value inside the culture equipment; In this embodiment, a carbon dioxide concentration sensor is installed inside the incubation equipment (e.g., a carbon dioxide incubator). Commonly used types include infrared absorption sensors. This sensor measures the degree of absorption of infrared light of a specific wavelength by the gas inside the incubator and outputs an electrical signal (such as voltage or current) corresponding to the CO2 concentration in real time. The controller reads the sensor's output value at a preset sampling frequency (e.g., once per second), and after analog-to-digital conversion and calibration curve conversion, obtains the real-time carbon dioxide concentration value in volume percentage form (e.g., 5.0%). To ensure measurement stability, the concentration values ​​collected multiple times consecutively can be processed by first-order low-pass filtering or moving average to eliminate instantaneous jumps caused by slight fluctuations in the gas inside the incubator or sensor noise.

[0038] Accurately obtaining the real-time CO2 concentration is a prerequisite for maintaining a stable pH in the cell culture environment, because CO2 and sodium bicarbonate in the culture medium together form a buffer system, and concentration drift will directly affect the pH of the culture medium.

[0039] S22. Based on the real-time carbon dioxide concentration value and the target carbon dioxide concentration value, the carbon dioxide adjustment amount is obtained using a PID control algorithm. In this embodiment, the controller internally stores the user-defined target carbon dioxide concentration value (typically between 5.0% and 10.0% for most mammalian cell cultures, with 5.0% being a typical value). The controller calculates the deviation between the real-time concentration value and the target concentration value (deviation = target concentration). (Real-time concentration). Input this deviation value into the digital PID controller, and calculate the carbon dioxide adjustment amount according to the following formula: Carbon dioxide adjustment amount = Kp_CO2 × deviation + Ki_CO2 × deviation integral + Kd_CO2 × deviation change rate; Wherein, Kp_CO2, Ki_CO2, and Kd_CO2 are the proportional, integral, and derivative coefficients obtained in advance through tuning. The proportional term is quickly adjusted according to the current deviation; the integral term eliminates long-term steady-state errors (such as slow concentration decreases caused by slight leakage of the door seal); and the derivative term compensates in advance according to the rate of change of the deviation to avoid overshoot or oscillation caused by the inertia of the gas valve opening and closing.

[0040] The calculated carbon dioxide regulation amount is usually expressed as a percentage of the valve opening (0~100%). The larger the regulation amount, the more CO2 gas needs to be introduced to increase the concentration in the chamber. If the regulation amount is negative (indicating that the concentration is too high), the valve will not be opened temporarily, and the concentration will be reduced by cell metabolism and natural diffusion, or it can be combined with an exhaust device.

[0041] S23. Send an opening control signal to the carbon dioxide valve according to the carbon dioxide adjustment amount to adjust the opening of the carbon dioxide valve.

[0042] In this embodiment, the controller converts the carbon dioxide adjustment amount (e.g., expressed as a percentage) calculated in step S22 into a corresponding valve drive signal and sends it to the actuator of the carbon dioxide valve. The carbon dioxide valve typically employs a proportional solenoid valve or a combination of a PWM-controlled switching valve and a throttling orifice, capable of continuously adjusting the gas flow cross-sectional area according to the control signal. When the adjustment amount is positive, the valve opens to the corresponding degree, allowing gas from an external CO2 source (such as a gas cylinder via a pressure reducing valve) to enter the incubator cavity; the larger the adjustment amount, the larger the valve opening, and the more CO2 enters per unit time. To ensure rapid and uniform gas distribution, after each valve adjustment, the controller maintains the normal rotation of the circulating fan inside the chamber (i.e., a fan linkage mechanism) to quickly stir and mix the newly entered CO2 gas, avoiding excessively high or low local concentrations. Simultaneously, the controller continuously monitors concentration feedback, forming a closed-loop regulation until the real-time concentration stabilizes within the allowable error range (e.g., ±0.1%) near the target value. In addition, to prevent danger caused by prolonged full opening of the valve due to sensor failure or gas path blockage, the system is equipped with safety logic: if the continuous output exceeds 80% opening for more than a preset time (such as 3 minutes) and the concentration does not rise significantly, an alarm will be triggered and the gas valve will be closed.

[0043] By using an independent PID control loop to regulate CO2 concentration in a closed loop, the carbon dioxide concentration in the incubator can be precisely controlled near the target value, with a steady-state error within ±0.1%, providing a stable pH environment for cell culture. The PID algorithm balances response speed and stability: when the concentration drops sharply after the door is opened for ventilation, the proportional term provides a rapid initial opening for quick recovery; the integral term ensures no cumulative offset during long-term operation; and the derivative term suppresses slight overshoot caused by valve inertia. Simultaneously, linking the gas valve regulation with fan circulation ensures rapid and uniform distribution of the added CO2 gas within the incubator, avoiding the formation of local concentration gradients. This method ensures that cells remain in a stable gas environment throughout the entire culture cycle, improving the reproducibility and reliability of cell culture experiments.

[0044] As one embodiment, this application further includes: after the target cells and culture medium are transported to the cell culture container in the culture device, controlling the flipping platform in the culture device to cause the cell culture container carried on the flipping platform to perform at least one of flipping, rotating and vibrating movements to disperse the target cells and culture medium.

[0045] In this embodiment, the culture device is equipped with a movable flipping platform to support the cell culture container (e.g., a multilayer culture flask or culture dish). After the target cell suspension and fresh culture medium are delivered into the cell culture container, the cells are often not yet evenly distributed on the bottom surface of the container, but rather clustered near the filling port or deposited in layers. At this time, the controller sends control commands to the drive mechanism of the flipping platform (e.g., a stepper motor or servo motor and its corresponding transmission mechanism), driving the platform to perform one or more of the following movements: flipping, rotating, and vibrating.

[0046] Flipping motion: The platform rotates around a horizontal axis (such as the X-axis or Y-axis) at a certain angle (e.g., 0°~90° or 0°~180°), causing the liquid in the container to flow slowly under the action of gravity, covering different bottom areas. Through repeated flipping, the aggregated cells can be redistributed.

[0047] Rotational motion: The platform rotates around the vertical axis (Z-axis), causing the liquid inside the container to flow circumferentially, which helps to distribute the cells evenly from the center of the container to the periphery.

[0048] Vibration motion: The platform reciprocates in a straight line or circular motion with a small amplitude and a high frequency, which generates micro-vortices in the liquid, breaks up cell clumps, and promotes full contact between individual cells and the culture medium.

[0049] The three movements described above can be performed individually or in combination. For example, a slow inversion can be performed first to spread the liquid across the entire bottom surface, followed by short-term vibration to break up the cells from their aggregated state, and finally, a few rotations can be performed to further homogenize them. The amplitude, speed, acceleration, and duration of each movement can be parameterized according to the cell type, culture container specifications, and medium volume.

[0050] In a static state, cells tend to settle and accumulate at the lowest point due to gravity. Tilting motion utilizes the change in the direction of gravity, causing the liquid to repeatedly wash over the bottom of the container, propelling cells to other areas. Rotational motion, using centrifugal and shear forces, pushes cells outwards, preventing central accumulation. Vibrational motion, through high-frequency, small-displacement disturbances, disrupts weak cell aggregations while simultaneously promoting culture medium flow and renewing the microenvironment surrounding the cells. These three forces work synergistically or alternately, enabling gentle and efficient homogeneous mixing of cells and culture medium without the need for mechanical stirring paddles (to avoid shear damage).

[0051] First, it significantly improves the uniformity of cell seeding, avoiding uneven cell distribution that leads to overly dense or sparse areas, thus promoting consistent cell growth and confluence. Second, it reduces cell clumping, especially for cell lines prone to aggregation (such as certain stem cells or tumor cells). Dispersion increases the proportion of single cells and improves experimental reproducibility. Third, the process is fully automated within a closed culture device, eliminating the need for manual shaking or opening, reducing the risk of contamination and lessening the manual labor intensity for operators. Fourth, by parameterizing the intensity and duration of flipping, rotating, and vibrating, dispersion strategies can be optimized for different cell types, achieving a standardized and traceable seeding process. For example, for adherent cells, slow flipping combined with gentle vibration is sufficient; for suspension cells, the rotation speed can be appropriately increased to maintain uniform suspension.

[0052] As one implementation method, this application embodiment further includes: S31. Real-time acquisition of cell images within the culture device using a microscope camera; In this embodiment, a microscope camera module is installed inside the culture device. This module includes an optical objective (e.g., 4×, 10×, or 20× adjustable magnification), an illumination source (e.g., an LED ring light source), and an image sensor (CMOS or CCD). The controller triggers the camera to take pictures of the cells inside the cell culture container at preset time intervals (e.g., every 15 minutes or every hour). The camera can traverse multiple representative fields of view on the bottom of the container through autofocus and a movement mechanism (e.g., a lead screw guide) to acquire multiple frames of images, ensuring the representativeness of the sampling. To reduce the impact of light on cell growth, the illumination source adopts a near-infrared or low-light short-pulse mode, illuminating only at the moment of taking the picture. The acquired raw image data is temporarily stored in the controller's memory for subsequent image analysis.

[0053] S32. Analyze the cell images to obtain parameters reflecting the density of cell growth; In this embodiment, the controller runs a built-in image processing algorithm to analyze the acquired cell images. First, the images are preprocessed, including grayscale conversion, Gaussian filtering for noise reduction, and histogram equalization to enhance contrast. Then, threshold segmentation (such as Otsu's method) or a deep learning semantic segmentation model is used to separate the cell regions from the background regions. For adherent cells, the percentage of cell coverage area to the total image area is calculated, i.e., cell confluence, which serves as the main parameter reflecting the density of cell growth. For suspended cells, the number of cells per unit field of view can be calculated using cell counting algorithms (such as contour detection or watershed algorithms), or the average size of cell clusters can be calculated. The final output parameter can be a single numerical value (such as confluence percentage) or a multi-dimensional vector (such as confluence plus average cluster size). To ensure accuracy, the algorithm averages or takes the median of parameters from multiple fields of view and removes abnormal frames caused by bubbles or impurities.

[0054] S33. When the parameters meet the first preset condition, send a liquid addition control signal to the nutrient solution addition device to add nutrient solution to the cell culture container. In this embodiment, the controller stores a first preset condition, such as cell confluence being less than 40%. To avoid false positives, it is typically required that the condition be met in two consecutive tests. When the condition is met, the controller sends a nutrient solution addition device (e.g., an automated replenishment system including a peristaltic pump, sterile tubing, and a reservoir bag) a nutrient solution addition control signal. This signal includes the target volume (e.g., 50 mL) and flow rate parameters. After receiving the signal, the nutrient solution addition device pumps fresh culture medium into the cell culture container according to the set amount. Simultaneously, during the pumping process, a flow sensor provides closed-loop feedback to ensure the accuracy of the addition. After the addition is complete, the controller records the addition event and enters a preset waiting time (e.g., 30 minutes) to allow the cells to fully recover and adapt in the fresh nutrient solution. After the waiting time expires, the controller performs another image acquisition to evaluate the nutrient solution addition effect or determine whether further operation is needed.

[0055] S34. When the parameters meet the second preset conditions, send an enzyme addition control signal to the digestive enzyme addition device to add digestive enzyme to the cell culture container. In this embodiment, the second preset condition corresponds to the cell growth reaching the required density for passage, for example, cell confluence exceeding 90%, and optionally, the appearance of rounding after contact inhibition in cell morphology. When the second preset condition is met, the controller sends an enzyme addition control signal to the digestive enzyme addition device, which may include a sterile trypsin solution storage container, a metering pump, and tubing. The controller controls the pump to add the digestive enzyme solution to the culture container at a preset volume (e.g., the amount needed to cover the entire cell growth area). To ensure digestion effectiveness, the controller can also coordinate with the flipping platform to ensure the digestive enzyme evenly covers all cells and control the incubator temperature to remain stable at 37°C to promote enzyme activity. During digestion, images can be periodically acquired to observe whether cells detach and become round, in order to determine whether the third preset condition is met.

[0056] S35. When the parameters meet the third preset condition, a harvest control signal is sent to the harvest execution mechanism to start the harvest action.

[0057] In this embodiment, the third preset condition can be defined as follows: after adding digestive enzymes and waiting for an appropriate time (e.g., 3-10 minutes), image analysis reveals that most cells (e.g., over 90%) have detached from the culture surface and are suspended in the liquid, with the cell morphology becoming round and translucent. When this condition is met, the controller sends a harvest control signal to the harvesting actuator, which may include: a suction tube, a collection container, and a centrifuge. The control signal instructs the actuator to start, extracting the cell suspension containing detached cells from the culture container and transporting it to a collection bag or bottle, completing the cell harvesting process. After harvesting, the controller can issue a prompt to the operator and automatically begin the cleaning or preparation steps for the next round of culture. The entire process achieves an automated closed loop from image detection to enzyme digestion and harvesting, significantly reducing manual intervention.

[0058] By analyzing real-time images from a microscope camera, different stages of cell growth are automatically identified (not dense - requires rehydration, highly dense - requires digestion, digestion complete - ready for harvest), triggering corresponding automated operations (rehydration, enzyme addition, harvesting). This method reduces subjective errors from human observation, ensures precise timing of operations, and avoids the risk of contamination caused by frequent opening of the container. For large-scale cell culture (such as cell factories), unattended continuous production can be achieved, significantly improving production efficiency and batch-to-batch consistency.

[0059] As one implementation method, this application embodiment further includes: S41. Detect the open / closed status of the door lock of the culture equipment; In this embodiment, a door lock status detection sensor is installed between the door and the chamber of the cultivation equipment. This sensor can be a non-contact component such as a microswitch, reed switch, or Hall sensor. When the door lock is closed, the sensor outputs an electrical signal (e.g., high or low level); when the door lock is open, the sensor outputs the opposite electrical signal. The controller reads this signal through timed polling or interrupt triggering to obtain the door lock's open / closed status in real time. To eliminate brief misjudgments caused by mechanical jitter, the controller can perform de-jitter processing on the acquired signal (e.g., confirming the status change only after three consecutive consistent readings). This detection is independent of other control loops and can quickly respond to changes in the door lock status.

[0060] S42. When the door lock is detected to be open, an alarm signal is sent to the display screen for display.

[0061] In this embodiment, when the controller determines that the door lock is open, it immediately generates an alarm signal and sends it to the display screen of the culture equipment via the communication interface. Upon receiving the alarm signal, the display screen visually alerts the user, for example, by displaying a flashing red icon or text reminder, "Door lock is open, please close carefully," and can also record the event in the operation log. The alarm signal lasts for the entire period during which the door lock is open. Once the door lock is closed again, the controller sends a clear signal to restore the display screen to normal. This immediate alarm effectively reminds operators to close the chamber door promptly, preventing temperature, CO2 concentration, and humidity from spiraling out of control due to an improperly closed door, thus protecting the culture. Simultaneously, because it only displays the alarm without interfering with the operation of heating, fans, or gas valves (although additional control logic can be added in other embodiments), the equipment can still maintain basic environmental control, preventing drastic fluctuations caused by power outages or misoperation.

[0062] By linking door lock status detection with display alarms, operators can be notified of any improper door closure via panel prompts even when away from the equipment, allowing for timely correction. This solution is simple in structure, responds quickly, and significantly reduces the risk of culture failure caused by accidental door opening or incomplete closure, thereby improving the safety and reliability of the equipment.

[0063] As one implementation method, this application embodiment further includes: S51. Obtain the real-time humidity value inside the culture equipment; In this embodiment, a humidity sensor, such as a capacitive or resistive humidity sensor, is installed inside the culture device. This sensor is mounted on the inner wall of the chamber or in the airflow circulation channel and can detect the relative humidity (RH) of the gas inside the culture chamber in real time. The controller reads the output voltage or digital signal of the humidity sensor at a preset sampling frequency (e.g., once per second). After analog-to-digital conversion and calibration curve calculation, the real-time humidity value inside the chamber is obtained and expressed as a percentage (e.g., 85%). To ensure data stability, a simple moving average filter can be applied to the values ​​read multiple times consecutively to eliminate instantaneous jumps caused by airflow disturbances within the chamber.

[0064] S52. Send the real-time humidity value to the display screen for display.

[0065] In this embodiment, the controller sends the acquired real-time humidity value to the display screen of the cultivation equipment via a communication interface. The display screen updates and shows the current humidity value in a designated area of ​​the user interface in real time. The humidity value can be presented along with other environmental parameters to help operators understand the humidity status inside the chamber.

[0066] In some embodiments, the culture equipment may also include a humidification device (such as an ultrasonic humidifier or a heated humidification tray) and / or a dehumidification device. The controller performs closed-loop control of the humidity based on the deviation between the real-time humidity value and the target humidity value to automatically maintain stable humidity inside the chamber. In the solution provided in this embodiment, the main function is to achieve real-time monitoring and display of humidity. Users can determine whether it is necessary to manually replenish the sterile water in the humidification tray or check the airtightness of the chamber door based on the displayed information. This method has advantages in cost-sensitive or structurally simplified equipment, and is especially suitable for cell culture scenarios where humidity accuracy requirements are not very stringent.

[0067] like Figure 2 As shown, this application embodiment also provides a controller 100, including: a processor 110, a memory 120 and a communication bus 130; Communication bus 130 is used to realize the connection and communication between processor 110 and memory 120; The processor 110 is used to execute the control program of the cell culture device stored in the memory 120 to implement the steps of any of the cell culture device control methods described above.

[0068] like Figure 3 As shown in the illustration, this application also provides a cell culture device, including: Temperature sensor 200 is used to collect real-time temperature values ​​inside the culture equipment; Heating element 300 is used for heating according to heating control signal; The circulating fan 400 is used to adjust the speed according to the speed control signal; The controller 100 described above is electrically connected to the temperature sensor 200, the heating element 300, and the circulating fan 400, respectively.

[0069] like Figure 4 As shown, in one embodiment, this application also includes: a carbon dioxide sensor 500 and a carbon dioxide valve 600; The carbon dioxide sensor 500 is used to collect real-time carbon dioxide concentration values ​​within the culture equipment. Carbon dioxide valve 600 is used to adjust the amount of carbon dioxide entering the valve according to the opening control signal. The controller 100 is electrically connected to the carbon dioxide sensor 500 and the carbon dioxide valve 600, respectively.

[0070] The above description is merely an embodiment of the present invention. It should be noted that those skilled in the art can make improvements without departing from the inventive concept of the present invention, but these improvements all fall within the protection scope of the present invention.

Claims

1. A control method for a cell culture device, characterized in that, include: Obtain the real-time temperature value inside the culture equipment; Based on the real-time temperature value and the target temperature value, the heating control quantity of the heating element in the cultivation device is obtained using a PID control algorithm. A heating control signal is sent to the heating element according to the heating control quantity to control the heating element to perform heating. At the same time, based on the correspondence between the heating control quantity and the rotation speed of the circulating fan in the culture device, a rotation speed control signal is sent to the circulating fan according to the heating control quantity to adjust the rotation speed of the circulating fan.

2. The method according to claim 1, characterized in that, The correspondence is a linear proportional relationship, and the rotational speed of the circulating fan is directly proportional to the heating control quantity.

3. The method according to claim 1, characterized in that, Also includes: Obtain the real-time carbon dioxide concentration value within the culture device; Based on the real-time carbon dioxide concentration value and the target carbon dioxide concentration value, the carbon dioxide adjustment amount is obtained using a PID control algorithm. The opening control signal is sent to the carbon dioxide valve according to the carbon dioxide adjustment amount to adjust the opening of the carbon dioxide valve.

4. The method according to claim 1, characterized in that, Also includes: After the target cells and culture medium are delivered to the cell culture container in the culture device, the flipping platform in the culture device is controlled to cause the cell culture container carried on the flipping platform to perform at least one of the following movements: flipping, rotating and vibrating, in order to disperse the target cells and culture medium.

5. The method according to claim 1, characterized in that, Also includes: Cell images inside the culture device are acquired in real time using a microscope camera; The cell images are analyzed to obtain parameters reflecting the density of cell growth; When the parameters meet the first preset condition, a liquid addition control signal is sent to the nutrient solution addition device to add nutrient solution to the cell culture container. When the parameters meet the second preset condition, an enzyme addition control signal is sent to the digestive enzyme addition device to add digestive enzyme to the cell culture container; When the parameters meet the third preset condition, a harvest control signal is sent to the harvest execution mechanism to start the harvesting action.

6. The method according to claim 1, characterized in that, Also includes: Detect the open / closed status of the door lock of the culture equipment; When the door lock is detected to be open, an alarm signal is sent to the display screen for display.

7. The method according to any one of claims 1 to 6, characterized in that, Also includes: Obtain the real-time humidity value inside the cultivation equipment; The real-time humidity value is sent to the display screen for display.

8. A controller, characterized in that, include: Processor, memory, and communication bus; The communication bus is used to realize the connection and communication between the processor and the memory; The processor is used to execute a control program for a cell culture device stored in the memory to implement the steps of the control method for a cell culture device as described in any one of claims 1 to 7.

9. A cell culture device, characterized in that, include: Temperature sensors are used to collect real-time temperature values ​​within the culture equipment; Heating element, used for heating according to heating control signal; A circulating fan is used to adjust the speed according to a speed control signal; The controller as described in claim 8 is electrically connected to the temperature sensor, the heating element, and the circulating fan, respectively.

10. The cell culture apparatus according to claim 9, characterized in that, Also includes: Carbon dioxide sensor and carbon dioxide valve; The carbon dioxide sensor is used to collect real-time carbon dioxide concentration values ​​within the culture equipment; The carbon dioxide valve is used to adjust the amount of carbon dioxide entering according to the opening control signal. The controller is electrically connected to both the carbon dioxide sensor and the carbon dioxide valve.

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