Perfusion exchange methods, devices, systems, and computer equipment for cell culture

Abstract

The application relates to a perfusion and replacement method, device, system and computer equipment for cell culture, wherein the perfusion and replacement method for cell culture comprises the following steps: based on preset operation parameters, controlling an inlet peristaltic pump and an outlet peristaltic pump to perform a perfusion and replacement operation on target cells; when the perfusion and replacement operation is performed on the target cells, acquiring an inlet cumulative flow of the inlet peristaltic pump and an outlet cumulative flow of the outlet peristaltic pump in real time; and further comparing the inlet cumulative flow and the outlet cumulative flow, and adjusting a replacement rate corresponding to the perfusion and replacement operation in real time based on a comparison result. Through the application, the problem that the replacement rate in the perfusion process cannot be adjusted in real time is solved, and the replacement rate is reasonably adjusted in the cell culture process, so that a stable cell growth environment is provided.

Description

Technical Field

[0001] This application relates to the field of cell culture technology, and in particular to perfusion media exchange methods, apparatus, systems and computer equipment for cell culture. Background Technology

[0002] With the widespread application of biotechnology drugs in the diagnosis, treatment and prevention of human diseases, cell culture technology, as one of the key technologies in the field of biopharmaceuticals, has also developed rapidly. In order to effectively prevent contamination and cross-contamination during cell culture, single-use biological systems are usually selected for cell culture. Among them, perfusion culture technology is a common culture technology based on single-use biological systems.

[0003] Current perfusion culture methods, based on the comparison between preset liquid weight and actual liquid weight, control the operating rate of the peristaltic pump through a weighing system. This ensures that the total amount of culture medium does not decrease during the perfusion process while updating the culture medium. However, this method, while maintaining a constant total amount of cell culture medium, does not consider the adverse effects of an unreasonable perfusion rate on the culture medium. For example, a low perfusion rate can lead to insufficient nutrients for cell growth and rapid accumulation of harmful metabolic waste, thereby reducing the quality of the cell product.

[0004] There is currently no effective solution to the problem that the fluid exchange rate cannot be adjusted in real time during the perfusion process in related technologies. Summary of the Invention

[0005] This embodiment provides a perfusion fluid exchange method, apparatus, system, and computer equipment to solve the problem in related technologies that the fluid exchange rate cannot be adjusted in real time during the perfusion process.

[0006] Firstly, this embodiment provides a perfusion medium replacement method for cell culture, applicable to a perfusion medium replacement system; the perfusion medium replacement system includes: a turbulent reactor, an inlet pipe, an outlet pipe, an inlet peristaltic pump, an outlet peristaltic pump, and a control cabinet. The inlet pipe connects the turbulent reactor and the inlet peristaltic pump, and the outlet pipe connects the turbulent reactor and the outlet peristaltic pump. Both the inlet and outlet peristaltic pumps are connected to the control cabinet; the method includes:

[0007] Based on preset operating parameters, the inlet peristaltic pump and the outlet peristaltic pump are controlled to perform perfusion and fluid exchange operations on the target cells;

[0008] During the perfusion and fluid exchange operation on the target cells, the cumulative influent flow rate of the influent peristaltic pump and the cumulative outfluent flow rate of the effluent peristaltic pump are acquired in real time.

[0009] The cumulative influent flow rate and the cumulative effluent flow rate are compared, and the fluid exchange rate corresponding to the perfusion fluid exchange operation is adjusted in real time based on the comparison result.

[0010] In some embodiments, before controlling the inlet peristaltic pump and the outlet peristaltic pump to perform perfusion and fluid exchange operations on the target cells based on preset operating parameters, the method further includes:

[0011] Based on the characteristics of the target cells, the operating parameters of the inlet peristaltic pump and the outlet peristaltic pump are set for each perfusion and fluid exchange stage, as well as the adjustment range for each perfusion and fluid exchange stage.

[0012] In some embodiments, controlling the inlet peristaltic pump and the outlet peristaltic pump to perform perfusion and fluid exchange operations on the target cells based on preset operating parameters includes:

[0013] Based on the operating parameters corresponding to each perfusion fluid exchange stage, the inlet peristaltic pump and the outlet peristaltic pump are calibrated, and the operating parameters include operating rate and operating time;

[0014] The calibrated inlet and outlet peristaltic pumps are used to perform the perfusion and fluid exchange operation on the target cells.

[0015] In some embodiments, comparing the cumulative influent flow rate and the cumulative effluent flow rate, and adjusting the fluid exchange rate corresponding to the perfusion fluid exchange operation in real time based on the comparison result, includes:

[0016] The difference between the cumulative influent flow rate and the cumulative effluent flow rate is obtained, and the difference is used as the cumulative flow rate deviation value corresponding to the perfusion fluid exchange operation.

[0017] If the cumulative flow deviation value is within the adjustment range, the fluid exchange rate corresponding to the perfusion fluid exchange operation is adjusted in real time based on the cumulative flow deviation value.

[0018] In some embodiments, if the cumulative flow deviation value is within the adjustment range, then based on the cumulative flow deviation value, the fluid exchange rate corresponding to the perfusion fluid exchange operation is adjusted in real time, including:

[0019] When the cumulative flow deviation is less than the lower limit of the adjustment range, the fluid exchange rate corresponding to the perfusion fluid exchange operation is maintained.

[0020] When the cumulative flow deviation value is not less than the lower limit of the adjustment range and the cumulative flow deviation value is less than the upper limit of the adjustment range, the liquid replacement rate corresponding to the perfusion liquid replacement operation is adjusted in real time.

[0021] When the cumulative flow deviation value is greater than the upper limit of the adjustment range, the peristaltic pump with the larger current cumulative flow is turned off, the peristaltic pump with the smaller current cumulative flow is kept running normally, and the alarm mechanism is activated until the cumulative flow deviation value is detected to be less than the lower limit of the adjustment range. Then, the peristaltic pump that was turned off is turned on again, and the alarm mechanism is turned off.

[0022] In some embodiments, adjusting the fluid exchange rate corresponding to the perfusion fluid exchange operation in real time when the cumulative flow deviation value is not less than the lower limit of the adjustment range and the cumulative flow deviation value is less than the upper limit of the adjustment range includes:

[0023] When the cumulative flow deviation value is not less than the lower limit of the adjustment range and the cumulative flow deviation value is less than the upper limit of the adjustment range, it is determined whether the cumulative inlet flow rate is greater than the cumulative outlet flow rate.

[0024] When the cumulative inlet flow rate is greater than the cumulative outlet flow rate, the inlet peristaltic pump is adjusted to reduce its speed based on the cumulative flow rate deviation value.

[0025] When the cumulative inlet flow rate is less than the cumulative outlet flow rate, the outlet peristaltic pump is adjusted to reduce its speed based on the cumulative flow rate deviation value.

[0026] Secondly, this embodiment provides a perfusion medium exchange device for cell culture, suitable for perfusion medium exchange systems; the perfusion medium exchange system includes: a turbulent reactor, an inlet pipe, an outlet pipe, an inlet peristaltic pump, an outlet peristaltic pump, and a control cabinet. The inlet pipe connects the turbulent reactor and the inlet peristaltic pump, and the outlet pipe connects the turbulent reactor and the outlet peristaltic pump. Both the inlet and outlet peristaltic pumps are connected to the control cabinet; the device includes:

[0027] The control module, based on preset operating parameters, controls the inlet peristaltic pump and the outlet peristaltic pump to perform perfusion and fluid exchange operations on the target cells;

[0028] The acquisition module acquires the cumulative influent flow rate of the influent peristaltic pump and the cumulative outfluent flow rate of the effluent peristaltic pump in real time when the perfusion and fluid exchange operation is performed on the target cells.

[0029] The adjustment module compares the cumulative influent flow rate and the cumulative effluent flow rate, and adjusts the fluid exchange rate corresponding to the perfusion fluid exchange operation in real time based on the comparison result.

[0030] Thirdly, this embodiment provides a perfusion system for cell culture, which includes: a turbulent reactor, an inlet pipe, an outlet pipe, an inlet peristaltic pump, an outlet peristaltic pump, and a control cabinet. The inlet pipe connects the turbulent reactor and the inlet peristaltic pump, and the outlet pipe connects the turbulent reactor and the outlet peristaltic pump. Both the inlet and outlet peristaltic pumps are connected to the control cabinet.

[0031] Fourthly, this embodiment provides a computer device including a memory, a processor, and a computer program stored in the memory and executable on the processor, wherein the processor executes the computer program to implement the perfusion medium exchange method for cell culture described in the first aspect above.

[0032] Fifthly, this embodiment provides a storage medium storing a computer program that, when executed by a processor, implements the perfusion medium replacement method for cell culture described in the first aspect above.

[0033] Compared with related technologies, this embodiment provides a perfusion medium exchange method, apparatus, system, and computer equipment for cell culture. Based on preset operating parameters, it controls an inlet peristaltic pump and an outlet peristaltic pump to perform perfusion medium exchange operations on target cells. During the perfusion medium exchange operation, the cumulative inlet flow rate of the inlet peristaltic pump and the cumulative outlet flow rate of the outlet peristaltic pump are acquired in real time. Furthermore, the cumulative inlet and outlet flow rates are compared, and the medium exchange rate corresponding to the perfusion medium exchange operation is adjusted in real time based on the comparison results. This solves the problem of not being able to adjust the medium exchange rate in real time during the perfusion process, and enables reasonable adjustment of the medium exchange rate during cell culture to ensure a stable cell growth environment.

[0034] Details of one or more embodiments of this application are set forth in the following drawings and description to make other features, objects and advantages of this application more readily apparent. Attached Figure Description

[0035] The accompanying drawings, which are included to provide a further understanding of this application and form part of this application, illustrate exemplary embodiments and are used to explain this application, but do not constitute an undue limitation of this application. In the drawings:

[0036] Figure 1 This is a hardware structure block diagram of a terminal device for a perfusion medium exchange method for cell culture provided in an embodiment of this application;

[0037] Figure 2 This is a flowchart of a perfusion medium replacement method for cell culture provided in an embodiment of this application;

[0038] Figure 3 This is a schematic flowchart of a perfusion medium replacement method for cell culture provided in an embodiment of this application;

[0039] Figure 4 This is a preferred flowchart of a perfusion medium replacement method for cell culture provided in an embodiment of this application;

[0040] Figure 5 This is a structural block diagram of a perfusion fluid exchange device for cell culture provided in one embodiment of this application;

[0041] Figure 6 This is a schematic diagram of the structure of a perfusion and medium exchange system for cell culture provided in an embodiment of this application;

[0042] Figure 7 This is a logical schematic diagram of a perfusion fluid exchange system for cell culture provided in one embodiment of this application.

[0043] In the diagram: 102, processor; 104, memory; 106, transmission device; 108, input / output device; 100, control module; 200, acquisition module; 300, adjustment module; 10, turbulent reactor; 20, inlet pipe; 30, outlet pipe; 40, inlet peristaltic pump; 50, outlet peristaltic pump; 60, control cabinet. Detailed Implementation

[0044] To better understand the purpose, technical solution, and advantages of this application, the application is described and illustrated below in conjunction with the accompanying drawings and embodiments.

[0045] Unless otherwise defined, the technical or scientific terms used in this application shall have the general meaning as understood by one of ordinary skill in the art to which this application pertains. Words such as “a,” “an,” “an,” “the,” “the,” and “these,” used in this application, do not indicate quantitative limitation and may be singular or plural. The terms “comprising,” “including,” “having,” and any variations thereof used in this application are intended to cover non-exclusive inclusion; for example, a process, method, system, product, or device that comprises a series of steps or modules (units) is not limited to the listed steps or modules (units) but may include steps or modules (units) not listed, or may include other steps or modules (units) inherent to such processes, methods, products, or devices. The terms “connected,” “linked,” and “coupled,” used in this application, are not limited to physical or mechanical connections but may include electrical connections, whether direct or indirect. The term “multiple” used in this application refers to two or more. The "and / or" operator describes the relationship between related objects, indicating that three relationships can exist. For example, "A and / or B" can represent three cases: A alone, A and B simultaneously, and B alone. Typically, the character " / " indicates that the objects before and after it are in an "or" relationship. The terms "first," "second," and "third," etc., used in this application are merely for distinguishing similar objects and do not represent a specific ordering of the objects.

[0046] The method embodiments provided in this example can be executed on a terminal, computer, or similar computing device. For example, it can run on a terminal. Figure 1 This is a hardware structure block diagram of the terminal of the perfusion medium exchange method for cell culture in this embodiment. Figure 1 As shown, a terminal may include one or more ( Figure 1 Only one is shown in the diagram. A processor 102 and a memory 104 for storing data are also included. The processor 102 may be, but is not limited to, a microprocessor (MCU) or a programmable logic device (FPGA). The terminal may also include a transmission device 106 for communication functions and an input / output device 108. Those skilled in the art will understand that… Figure 1 The structure shown is for illustrative purposes only and does not limit the structure of the terminal described above. For example, the terminal may also include components that are larger than... Figure 1 The more or fewer components shown, or having the same Figure 1 The different configurations shown are illustrated.

[0047] The memory 104 can be used to store computer programs, such as application software programs and modules, like the computer program corresponding to the perfusion and medium exchange method for cell culture in this embodiment. The processor 102 executes various functional applications and data processing by running the computer program stored in the memory 104, thereby implementing the above-described method. The memory 104 may include high-speed random access memory, and may also include non-volatile memory, such as one or more magnetic storage devices, flash memory, or other non-volatile solid-state memory. In some instances, the memory 104 may further include memory remotely located relative to the processor 102, and these remote memories can be connected to the terminal via a network. Examples of such networks include, but are not limited to, the Internet, corporate intranets, local area networks, mobile communication networks, and combinations thereof.

[0048] The transmission device 106 is used to receive or send data via a network. This network includes a wireless network provided by the terminal's communication provider. In one example, the transmission device 106 includes a Network Interface Controller (NIC), which can connect to other network devices via a base station to communicate with the Internet. In another example, the transmission device 106 can be a Radio Frequency (RF) module used for wireless communication with the Internet.

[0049] This embodiment provides a perfusion medium replacement method for cell culture. Figure 2 This is a flowchart of the perfusion medium exchange method for cell culture in this embodiment, as shown below. Figure 2 As shown, the process includes the following steps:

[0050] Step S210: Based on preset operating parameters, control the inlet peristaltic pump and the outlet peristaltic pump to perform perfusion and fluid exchange operations on the target cells.

[0051] In step S220, during the perfusion and fluid exchange operation on the target cells, the cumulative influent flow rate of the influent peristaltic pump and the cumulative outfluent flow rate of the effluent peristaltic pump are acquired in real time.

[0052] Specifically, the formula for calculating the cumulative flow rate of the peristaltic pump during the perfusion and medium exchange operation of the target cells is as follows:

[0053] F t =F s× N

[0054] Among them, F t F represents the cumulative flow rate of the peristaltic pump. sThis represents the liquid flow rate generated per revolution of the peristaltic pump; N represents the number of revolutions of the peristaltic pump. Based on the above cumulative flow calculation formula, the cumulative inlet flow rate of the inlet peristaltic pump and the cumulative outlet flow rate of the outlet peristaltic pump are obtained in real time.

[0055] Step S230: Compare the cumulative influent flow rate and the cumulative effluent flow rate, and adjust the fluid exchange rate corresponding to the perfusion fluid exchange operation in real time based on the comparison results.

[0056] It is important to know that the difference between the cumulative influent flow rate and the cumulative effluent flow rate is used as the cumulative flow rate deviation value corresponding to the irrigation and fluid exchange operation, and the magnitude of the cumulative flow rate deviation value is used to characterize whether the influent and effluent states in the irrigation and fluid exchange system are balanced in real time.

[0057] Current perfusion culture methods, based on the comparison between preset liquid weight and actual liquid weight, control the operating rate of the peristaltic pump through a weighing system. This ensures that the total amount of culture medium does not decrease during the perfusion process while updating the culture medium. However, this method, while maintaining a constant total amount of cell culture medium, does not consider the adverse effects of an unreasonable perfusion rate on the culture medium. For example, a low perfusion rate can lead to insufficient nutrients for cell growth and rapid accumulation of harmful metabolic waste, thereby reducing the quality of the cell product. This application addresses the issue of maintaining a constant total culture medium volume while effectively preventing adverse effects of unreasonable perfusion rates on the culture medium by adjusting the medium exchange rate in real time during the perfusion process. Specifically, based on preset operating parameters, the inlet and outlet peristaltic pumps are controlled to perform perfusion and medium exchange operations on the target cells. During the perfusion and medium exchange operation, the cumulative inlet flow rate of the inlet peristaltic pump and the cumulative outlet flow rate of the outlet peristaltic pump are acquired in real time. Furthermore, the cumulative inlet and outlet flow rates are compared, and the medium exchange rate corresponding to the perfusion and medium exchange operation is adjusted in real time based on the comparison results. This solves the problem of not being able to adjust the medium exchange rate in real time during the perfusion process, and enables reasonable adjustment of the medium exchange rate during cell culture to ensure a stable cell growth environment.

[0058] In some embodiments, before controlling the inlet and outlet peristaltic pumps to perform perfusion and media exchange operations on the target cells based on preset operating parameters, the following steps are also included:

[0059] Step S201: Based on the characteristics of the target cells, set the operating parameters of the inlet peristaltic pump and the outlet peristaltic pump for each perfusion and fluid exchange stage, as well as the adjustment range for each perfusion and fluid exchange stage.

[0060] Specifically, based on the characteristics of the target cells to be perfused, such as the osmotic pressure and pH required for target cell growth, the operating parameters of the inlet and outlet peristaltic pumps at different perfusion and media exchange stages are preset, as well as the adjustment range for different perfusion and media exchange stages. For different target cell culture processes, there are different numbers of perfusion and media exchange stages, and the number of stages is set according to the characteristics of the target cells.

[0061] It is important to know that the above adjustment range refers to the specific numerical range corresponding to the cumulative flow deviation value. If the real-time cumulative flow deviation value is within this specific numerical range, it indicates that the current liquid exchange rate needs to be adjusted.

[0062] In this embodiment, based on the characteristics of the target cells, the operating parameters of the inlet peristaltic pump and the outlet peristaltic pump are set for each perfusion and fluid exchange stage, as well as the adjustment range for each perfusion and fluid exchange stage. This allows for accurate setting of the inlet and outlet peristaltic pumps at different perfusion and fluid exchange stages, ensuring a relatively stable inlet and outlet state at different perfusion and fluid exchange stages.

[0063] In some embodiments, based on preset operating parameters, the inlet and outlet peristaltic pumps are controlled to perform perfusion and fluid exchange operations on the target cells, including the following steps:

[0064] Step S211: Based on the operating parameters corresponding to each perfusion fluid exchange stage, calibrate the inlet peristaltic pump and the outlet peristaltic pump. The operating parameters include the operating rate and the operating time.

[0065] Step S212: Control the calibrated inlet peristaltic pump and the calibrated outlet peristaltic pump to perform perfusion and fluid exchange operation on the target cells.

[0066] Specifically, for each perfusion media exchange stage, the operating parameters of the inlet and outlet peristaltic pumps are set, including the operating rate and operating time. These parameters then control the calibrated inlet and outlet peristaltic pumps to perform perfusion media exchange on the target cells. For example, based on the characteristics of the target cells, two perfusion media exchange stages are set, where the operating rate of the inlet peristaltic pump in the first perfusion media exchange stage is set to v. 11 The operating speed of the peristaltic pump is v. 12 The running time t1 and the operating rate v of the peristaltic pump during the second perfusion and fluid exchange stage are also considered. 21 The operating speed of the peristaltic pump is v. 22When the irrigation and liquid replacement system is started, the inlet peristaltic pump and the outlet peristaltic pump are controlled to operate with the operating parameters corresponding to the first irrigation and liquid replacement stage, and when the running time reaches t1, the second irrigation and liquid replacement stage begins. The inlet peristaltic pump and the outlet peristaltic pump switch operating speeds, and when the running time reaches t2, the inlet peristaltic pump and the outlet peristaltic pump stop operating.

[0067] It is important to know that before starting the perfusion and fluid exchange system, cell culture is initiated through a turbulent reactor, including the preparation of the appropriate fresh culture medium, cell retention device, and cell harvesting device, and the operating parameters of the perfusion and fluid exchange system are set to the operating parameters corresponding to the first perfusion and fluid exchange stage.

[0068] In this embodiment, based on the operating parameters corresponding to each perfusion and fluid exchange stage, the inlet peristaltic pump and the outlet peristaltic pump are calibrated. The operating parameters include the operating rate and the operating time. The calibrated inlet peristaltic pump and the calibrated outlet peristaltic pump are controlled to perform perfusion and fluid exchange operations on the target cells.

[0069] In some embodiments, the cumulative influent flow rate and the cumulative effluent flow rate are compared, and the fluid exchange rate corresponding to the perfusion fluid exchange operation is adjusted in real time based on the comparison result, including the following steps:

[0070] Step S231: Obtain the difference between the cumulative influent flow rate and the cumulative effluent flow rate, and use the difference as the cumulative flow rate deviation value corresponding to the perfusion fluid replacement operation;

[0071] Step S232: If the cumulative flow deviation value is within the adjustment range, the liquid exchange rate corresponding to the perfusion liquid exchange operation is adjusted in real time based on the cumulative flow deviation value.

[0072] Specifically, the cumulative influent flow rate and cumulative effluent flow rate acquired in real time are compared, the difference between the cumulative influent flow rate and cumulative effluent flow rate is calculated, and this difference is used as the cumulative flow rate deviation value corresponding to the current perfusion fluid replacement operation.

[0073] Furthermore, determine whether the current cumulative flow deviation value is within the adjustment range corresponding to the current stage. If the cumulative flow deviation value is within the adjustment range, it indicates that the liquid exchange rate corresponding to the perfusion liquid exchange operation needs to be adjusted in real time.

[0074] It is important to know that when the detected cumulative flow deviation value is small, it indicates that the current inlet and outlet liquid status is relatively stable. Conversely, when the detected cumulative flow deviation value is too large, it indicates that the current inlet and outlet liquid status is unbalanced and the liquid exchange rate needs to be fine-tuned. Specifically, the need for fine-tuning the rate is determined by comparing the actual results of the cumulative flow deviation value and the adjustment range.

[0075] In this embodiment, the difference between the cumulative influent flow rate and the cumulative effluent flow rate is obtained. This difference is used as the cumulative flow rate deviation value corresponding to the perfusion and fluid exchange operation. If the cumulative flow rate deviation value is within the adjustment range, the fluid exchange rate corresponding to the perfusion and fluid exchange operation is adjusted in real time based on the cumulative flow rate deviation value. This allows for real-time monitoring of whether the influent and effluent states are balanced, eliminating the need for a separate weighing device to provide feedback on the influent and effluent conditions. This ensures a stable cell growth environment while reducing the production cost of cell products.

[0076] In some embodiments, if the cumulative flow deviation is within the adjustment range, the fluid exchange rate corresponding to the perfusion fluid exchange operation is adjusted in real time based on the cumulative flow deviation, including the following steps:

[0077] When the cumulative flow deviation is less than the lower limit of the adjustment range, maintain the liquid replacement rate corresponding to the perfusion liquid replacement operation;

[0078] When the cumulative flow deviation is not less than the lower limit of the adjustment range and the cumulative flow deviation is less than the upper limit of the adjustment range, the liquid replacement rate corresponding to the perfusion liquid replacement operation is adjusted in real time.

[0079] When the cumulative flow deviation value is greater than the upper limit of the adjustment range, the peristaltic pump with the larger current cumulative flow is turned off, while the peristaltic pump with the smaller current cumulative flow is kept running normally, and the alarm mechanism is activated until the cumulative flow deviation value is detected to be less than the lower limit of the adjustment range. Then, the peristaltic pump that was turned off is turned back on, and the alarm mechanism is turned off.

[0080] Specifically, it is determined whether the current cumulative flow deviation value is within the corresponding adjustment range for the current stage. If the current cumulative flow deviation value is less than the lower limit of the adjustment range, it indicates that the current inlet and outlet liquid status is relatively stable, and the current liquid exchange rate should be maintained. However, if the current cumulative flow deviation value is not less than the lower limit of the adjustment range and the current cumulative flow deviation value is less than the upper limit of the adjustment range, it indicates that the current inlet and outlet liquid status is unbalanced, and therefore, the current liquid exchange rate needs to be adjusted.

[0081] Furthermore, if the current cumulative flow deviation value is greater than the upper limit of the adjustment range, it indicates that the current inflow and outflow state has been severely unbalanced and has damaged the stability of the target cell growth environment. Therefore, it is necessary to shut down the peristaltic pump with the larger current cumulative flow, keep the peristaltic pump with the smaller current cumulative flow running normally, and activate the alarm mechanism until the cumulative flow deviation value is detected to be less than the lower limit of the adjustment range. Then, the peristaltic pump that was shut down should be restarted and the alarm mechanism should be turned off.

[0082] This embodiment determines whether the current cumulative flow deviation value is within the corresponding adjustment range for the current stage, and initiates corresponding operations based on the determination result, thereby maintaining a scientific perfusion and fluid exchange rate and providing a stable growth environment for the target cells.

[0083] In some embodiments, when the cumulative flow deviation is not less than the lower limit of the adjustment range and the cumulative flow deviation is less than the upper limit of the adjustment range, the liquid replacement rate corresponding to the perfusion liquid replacement operation is adjusted in real time, including the following steps:

[0084] When the cumulative flow deviation is not less than the lower limit of the adjustment range and the cumulative flow deviation is less than the upper limit of the adjustment range, determine whether the cumulative inlet flow rate is greater than the cumulative outlet flow rate.

[0085] When the cumulative inlet flow rate is greater than the cumulative outlet flow rate, the inlet peristaltic pump is adjusted to reduce its speed based on the cumulative flow rate deviation.

[0086] When the cumulative inlet flow rate is less than the cumulative outlet flow rate, the outlet peristaltic pump is adjusted to reduce its speed based on the cumulative flow rate deviation.

[0087] Specifically, when the current cumulative flow deviation is not less than the lower limit of the adjustment range and the current cumulative flow deviation is less than the upper limit of the adjustment range, the cumulative flow of the inlet peristaltic pump and the cumulative flow of the outlet peristaltic pump are compared, and the peristaltic pump with the larger cumulative flow is decelerated.

[0088] Furthermore, after identifying the target peristaltic pump requiring rate adjustment, the specific formula is as follows, based on the current cumulative flow deviation and the operating time of the target peristaltic pump since the last rate adjustment in the current stage:

[0089] V1=(F1-F2) / T, V3=V2-V1;

[0090] Wherein, V1 represents the target peristaltic pump's operating rate adjustment value; V2 represents the target peristaltic pump's current operating rate; V3 represents the target peristaltic pump's adjusted operating rate; F1 represents the target peristaltic pump's cumulative flow rate; F2 represents the non-target peristaltic pump's cumulative flow rate; T represents the target peristaltic pump's operating time since the last rate adjustment in the current stage. If this adjustment is the first adjustment, then T represents the target peristaltic pump's operating time in the current stage. Based on a preset time interval, the target peristaltic pump's operating rate is adjusted according to the above operating rate adjustment value until the inflow and outflow liquid states reach equilibrium, and this target peristaltic pump is the target of each subsequent rate adjustment.

[0091] In this embodiment, when the cumulative flow deviation value is not less than the lower limit of the adjustment range and the cumulative flow deviation value is less than the upper limit of the adjustment range, it is determined whether the cumulative influent flow rate is greater than the cumulative effluent flow rate, and the peristaltic pump with the larger cumulative flow rate is decelerated and adjusted, thereby enabling accurate fine-tuning of the peristaltic pump rate to provide a scientific irrigation rate.

[0092] Figure 3This is a schematic flowchart of the perfusion medium replacement method for cell culture in this embodiment, as shown below. Figure 3 As shown, the specific process of this perfusion medium exchange method for cell culture is as follows:

[0093] When the irrigation and fluid replacement system is started (S301), the first irrigation and fluid replacement stage is started (S302). The inlet peristaltic pump and the outlet peristaltic pump are controlled to work according to the operating parameters corresponding to the first irrigation and fluid replacement stage (S303). When the preset running time is reached, the first irrigation and fluid replacement stage ends (S304). Then the second irrigation and fluid replacement stage is started (S305). The inlet peristaltic pump and the outlet peristaltic pump are controlled to work according to the operating parameters corresponding to the second irrigation and fluid replacement stage (S306). When the preset running time is reached, the second irrigation and fluid replacement stage ends (S307). Then the irrigation and fluid replacement process ends (S308).

[0094] During the operation of the inlet peristaltic pump and the outlet peristaltic pump, the cumulative inlet flow rate of the inlet peristaltic pump and the cumulative outlet flow rate of the outlet peristaltic pump are acquired in real time. The cumulative inlet flow rate and the cumulative outlet flow rate are compared to obtain the cumulative flow deviation value S309 corresponding to the current operation process.

[0095] Further, it is determined whether the current cumulative flow deviation value is within the adjustment range corresponding to the current stage. Specifically, when the cumulative flow deviation value is less than the lower limit of the adjustment range (S310), the liquid replacement rate corresponding to the perfusion liquid replacement operation is maintained (S311). When the cumulative flow deviation value is not less than the lower limit of the adjustment range and the cumulative flow deviation value is less than the upper limit of the adjustment range (S312), the cumulative flow of the inlet peristaltic pump and the cumulative flow of the outlet peristaltic pump are compared, and the target peristaltic pump with the larger cumulative flow is decelerated and adjusted. This target peristaltic pump is the target of subsequent rate adjustments (S313). When the cumulative flow deviation value is greater than the upper limit of the adjustment range (S314), the peristaltic pump with the larger current cumulative flow is turned off, the peristaltic pump with the smaller current cumulative flow is kept running normally, and the alarm mechanism is activated until the cumulative flow deviation value is detected to be less than the lower limit of the adjustment range. Then, the peristaltic pump that was turned off is turned on again, and the alarm mechanism is turned off (S315).

[0096] The present embodiment will now be described and illustrated through preferred embodiments.

[0097] Figure 4 This is a preferred flowchart of the perfusion medium exchange method for cell culture in this embodiment, as shown below. Figure 4 As shown, the perfusion medium exchange method for cell culture includes the following steps:

[0098] Step S410: Based on the characteristics of the target cells, set the operating parameters of the inlet peristaltic pump and the outlet peristaltic pump for each perfusion and fluid exchange stage, as well as the adjustment range for each perfusion and fluid exchange stage.

[0099] Step S420: Based on the operating parameters corresponding to each perfusion fluid exchange stage, calibrate the inlet peristaltic pump and the outlet peristaltic pump. The operating parameters include the operating rate and the operating time.

[0100] Step S430: Control the calibrated inlet peristaltic pump and the calibrated outlet peristaltic pump to perform perfusion and fluid exchange operation on the target cells;

[0101] Step S440: When performing perfusion and fluid exchange on the target cells, the cumulative influent flow rate of the influent peristaltic pump and the cumulative outfluent flow rate of the effluent peristaltic pump are acquired in real time.

[0102] Step S450: When the cumulative flow deviation value is less than the lower limit of the adjustment range, maintain the liquid replacement rate corresponding to the perfusion liquid replacement operation;

[0103] Step S460: When the cumulative flow deviation value is not less than the lower limit of the adjustment range and the cumulative flow deviation value is less than the upper limit of the adjustment range, compare the cumulative flow of the inlet peristaltic pump and the cumulative flow of the outlet peristaltic pump, and reduce the speed of the target peristaltic pump with the larger cumulative flow.

[0104] Step S470: When the cumulative flow deviation value is greater than the upper limit of the adjustment range, shut down the peristaltic pump with the larger current cumulative flow, keep the peristaltic pump with the smaller current cumulative flow running normally, and start the alarm mechanism until the cumulative flow deviation value is detected to be less than the lower limit of the adjustment range, then restart the peristaltic pump that was in the off state and shut down the alarm mechanism.

[0105] In this embodiment, based on the characteristics of the target cells, the operating parameters of the inlet and outlet peristaltic pumps are set for each perfusion and media exchange stage, along with the adjustment range for each stage. Based on these operating parameters, the inlet and outlet peristaltic pumps are calibrated. The calibrated pumps are then controlled to perform perfusion and media exchange operations on the target cells. During the perfusion and media exchange operation, the cumulative inlet flow rate of the inlet pump and the cumulative outlet flow rate of the outlet pump are acquired in real time. When the cumulative flow rate deviation is less than the lower limit of the adjustment range, the media exchange rate is maintained. Furthermore, when the cumulative flow rate deviation is not less than the lower limit of the adjustment range and is less than the adjustment range... When the upper limit is reached, the cumulative flow rates of the inlet and outlet peristaltic pumps are compared. The target peristaltic pump with the larger cumulative flow rate is decelerated. When the cumulative flow deviation exceeds the upper limit of the adjustment range, the peristaltic pump with the larger cumulative flow rate is shut down, while the peristaltic pump with the smaller cumulative flow rate continues to operate normally, and an alarm mechanism is activated. This continues until the cumulative flow deviation is detected to be less than the lower limit of the adjustment range. Then, the peristaltic pump that was shut down is restarted, and the alarm mechanism is deactivated. This allows for real-time monitoring of the inlet and outlet status of the system and dynamic adjustment of the peristaltic pump's operating rate based on the real-time monitoring results. This solves the problem of not being able to adjust the fluid exchange rate during perfusion in real time, and enables reasonable adjustment of the fluid exchange rate during cell culture to ensure a stable cell growth environment.

[0106] It should be noted that the steps shown in the above process or in the flowchart of the accompanying figures can be executed in a computer system such as a set of computer-executable instructions, and 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.

[0107] This embodiment also provides a perfusion medium exchange device for cell culture, which is used to implement the above embodiments and preferred embodiments; details already described will not be repeated. The terms "module," "unit," "subunit," etc., used below refer to combinations of software and / or hardware that achieve 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.

[0108] Figure 5 This is a structural block diagram of the perfusion and medium exchange device for cell culture in this embodiment, as shown below. Figure 5 As shown, the device includes: a control module 100, an acquisition module 200, and an adjustment module 300;

[0109] The control module 100, based on preset operating parameters, controls the inlet peristaltic pump and the outlet peristaltic pump to perform perfusion and fluid exchange operations on the target cells;

[0110] The acquisition module 200 acquires the cumulative influent flow rate of the influent peristaltic pump and the cumulative outfluent flow rate of the effluent peristaltic pump in real time when performing perfusion and fluid exchange operations on the target cells.

[0111] The adjustment module 300 compares the cumulative influent flow rate and the cumulative effluent flow rate, and adjusts the fluid exchange rate corresponding to the perfusion fluid exchange operation in real time based on the comparison results.

[0112] The device provided in this embodiment controls the inlet and outlet peristaltic pumps to perform perfusion and media exchange operations on target cells based on preset operating parameters. During the perfusion and media exchange operation, the cumulative inlet flow rate of the inlet peristaltic pump and the cumulative outlet flow rate of the outlet peristaltic pump are acquired in real time. Furthermore, the cumulative inlet and outlet flow rates are compared, and the media exchange rate corresponding to the perfusion and media exchange operation is adjusted in real time based on the comparison results. This solves the problem of not being able to adjust the media exchange rate in real time during the perfusion process, and realizes the reasonable adjustment of the media exchange rate during cell culture to ensure a stable cell growth environment.

[0113] In some of these embodiments, Figure 5 Based on this, the device also includes a setting module, which is used to set the operating parameters of the inlet peristaltic pump and the outlet peristaltic pump for each perfusion and fluid exchange stage, as well as the adjustment range for each perfusion and fluid exchange stage, based on the characteristics of the target cells.

[0114] In some of these embodiments, Figure 5 In addition, the device also includes a calibration module, which is used to calibrate the inlet peristaltic pump and the outlet peristaltic pump based on the operating parameters corresponding to each perfusion and fluid exchange stage. The operating parameters include the operating rate and the operating time. The device controls the calibrated inlet peristaltic pump and the calibrated outlet peristaltic pump to perform perfusion and fluid exchange operations on the target cells.

[0115] In some of these embodiments, Figure 5 Based on this, the device also includes a judgment module, which is used to obtain the difference between the cumulative influent flow rate and the cumulative effluent flow rate, and use the difference as the cumulative flow deviation value corresponding to the irrigation and fluid replacement operation; if the cumulative flow deviation value is within the adjustment range, the fluid replacement rate corresponding to the irrigation and fluid replacement operation is adjusted in real time based on the cumulative flow deviation value.

[0116] In some of these embodiments, Figure 5Based on this, the device also includes a first processing module, used to maintain the liquid replacement rate corresponding to the irrigation liquid replacement operation when the cumulative flow deviation value is less than the lower limit of the adjustment range; to adjust the liquid replacement rate corresponding to the irrigation liquid replacement operation in real time when the cumulative flow deviation value is not less than the lower limit of the adjustment range and the cumulative flow deviation value is less than the upper limit of the adjustment range; and to shut down the peristaltic pump with the larger current cumulative flow when the cumulative flow deviation value is greater than the upper limit of the adjustment range, keep the peristaltic pump with the smaller current cumulative flow running normally, and activate the alarm mechanism until the cumulative flow deviation value is detected to be less than the lower limit of the adjustment range, then restart the peristaltic pump that was in the off state and deactivate the alarm mechanism.

[0117] In some of these embodiments, Figure 5 Based on this, the device also includes a second processing module, used to determine whether the cumulative inlet flow rate is greater than the cumulative outlet flow rate when the cumulative flow rate deviation value is not less than the lower limit of the adjustment range and the cumulative flow rate deviation value is less than the upper limit of the adjustment range; when the cumulative inlet flow rate is greater than the cumulative outlet flow rate, the inlet peristaltic pump is decelerated based on the cumulative flow rate deviation value; when the cumulative inlet flow rate is less than the cumulative outlet flow rate, the outlet peristaltic pump is decelerated based on the cumulative flow rate deviation value.

[0118] Figure 6 This is a schematic diagram of the perfusion media exchange system for cell culture in this embodiment, as shown below. Figure 6 As shown, the system includes: a turbulent reactor 10, an inlet pipe 20, an outlet pipe 30, an inlet peristaltic pump 40, an outlet peristaltic pump 50, and a control cabinet 60. The turbulent reactor 10 and the inlet peristaltic pump 40 are connected through the inlet pipe 20, and the turbulent reactor 10 and the outlet peristaltic pump 50 are connected through the outlet pipe 30. Both the inlet peristaltic pump 40 and the outlet peristaltic pump 50 are connected to the control cabinet 60.

[0119] Specifically, based on preset operating parameters, the operating rate and operating time of the peristaltic pump are calibrated through the control cabinet 60, and the calibrated inlet peristaltic pump 40 and outlet peristaltic pump 50 are controlled to perform perfusion and liquid exchange operations on the target cells in the turbulent reactor 10. During the perfusion and liquid exchange operation on the target cells, the cumulative inlet flow rate of the inlet peristaltic pump 40 and the cumulative outlet flow rate of the outlet peristaltic pump 50 are acquired in real time.

[0120] Furthermore, the cumulative inlet flow rate and the cumulative outlet flow rate are compared to determine the difference between them. This difference is then used as the current cumulative flow rate deviation value. When the current cumulative flow rate deviation value is within the adjustment range, the cumulative flow rate of the inlet peristaltic pump 40 and the cumulative flow rate of the outlet peristaltic pump 50 are compared. The target peristaltic pump with the larger cumulative flow rate is decelerated and adjusted until the inlet and outlet states are balanced.

[0121] It is important to know that, such as Figure 7 As shown, the logic execution unit of the perfusion fluid exchange system includes a judgment and control unit and a perfusion fluid exchange execution unit. The judgment and control unit includes a perfusion fluid exchange control module and a pulse output module. The perfusion fluid exchange execution unit includes a perfusion inlet peristaltic pump and a perfusion outlet peristaltic pump. The turbulent reactor and the cell harvesting device are both connected to the perfusion fluid exchange execution unit. During the perfusion fluid exchange process, if the judgment and control unit detects that the cumulative flow deviation value is within the adjustment range, it adjusts the operating rate of the peristaltic pump in the perfusion fluid exchange execution unit through the pulse output module. This provides a scientific perfusion rate for the turbulent reactor, thereby enabling the acquisition of high-quality cells in the cell harvesting device.

[0122] The system provided in this embodiment uses real-time cumulative flow deviation values ​​to fine-tune the operating rates of the inlet peristaltic pump 40 and the outlet peristaltic pump 50 via the control cabinet 60. This enables the cell to have a stable culture environment without the need for a separate weighing device to provide feedback on the inlet and outlet conditions. This not only reduces the production cost of cell products but also ensures stable cell growth with a scientific perfusion rate.

[0123] It should be noted that the above modules can be functional modules or program modules, and can be implemented through software or hardware. For modules implemented through hardware, the above modules can reside in the same processor; or the above modules can be located in different processors in any combination.

[0124] This embodiment also provides a computer device, including a memory and a processor, wherein the memory stores a computer program and the processor is configured to run the computer program to perform the steps in any of the above method embodiments.

[0125] Optionally, the computer device may further include a transmission device and an input / output device, wherein the transmission device is connected to the processor and the input / output device is connected to the processor.

[0126] It should be noted that the specific examples in this embodiment can refer to the examples described in the above embodiments and optional implementations, and will not be repeated in this embodiment.

[0127] Furthermore, in conjunction with the perfusion medium replacement method for cell culture provided in the above embodiments, this embodiment can also provide a storage medium for implementation. This storage medium stores a computer program; when executed by a processor, the computer program implements any of the perfusion medium replacement methods for cell culture described in the above embodiments.

[0128] It should be understood that the specific embodiments described herein are merely illustrative of the application and not intended to limit it. All other embodiments derived by those skilled in the art based on the embodiments provided in this application without inventive effort are within the scope of protection of this application.

[0129] Obviously, the accompanying drawings are merely some examples or embodiments of this application. Those skilled in the art can apply this application to other similar situations based on these drawings without any creative effort. Furthermore, it is understood that although the work done in this development process may be complex and lengthy, for those skilled in the art, certain design, manufacturing, or production modifications made based on the technical content disclosed in this application are merely conventional technical means and should not be considered as insufficient disclosure of this application.

[0130] The term "embodiment" in this application refers to a specific feature, structure, or characteristic described in connection with an embodiment that may be included in at least one embodiment of this application. The appearance of this phrase in various places in the specification does not necessarily imply the same embodiment, nor does it imply that it is mutually exclusive with or independent of other embodiments. It will be clearly or implicitly understood by those skilled in the art that the embodiments described in this application may be combined with other embodiments without conflict.

[0131] The embodiments described above are merely illustrative of several implementation methods of this application, and while the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of patent protection. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of this application, and these all fall within the scope of protection of this application. Therefore, the scope of protection of this application should be determined by the appended claims.

Claims

1. A perfusion medium exchange method for cell culture, characterized in that, This method is applicable to perfusion fluid exchange systems. The perfusion fluid exchange system includes: a turbulent flow reactor, an inlet pipe, an outlet pipe, an inlet peristaltic pump, an outlet peristaltic pump, and a control cabinet. The inlet pipe connects the turbulent flow reactor and the inlet peristaltic pump, and the outlet pipe connects the turbulent flow reactor and the outlet peristaltic pump. Both the inlet and outlet peristaltic pumps are connected to the control cabinet. Based on preset operating parameters, the inlet peristaltic pump and the outlet peristaltic pump are controlled to perform perfusion and fluid exchange operations on the target cells; During the perfusion and fluid exchange operation on the target cells, the cumulative influent flow rate of the influent peristaltic pump and the cumulative outfluent flow rate of the effluent peristaltic pump are acquired in real time. The cumulative influent flow rate and the cumulative effluent flow rate are compared, and the fluid exchange rate corresponding to the perfusion fluid exchange operation is adjusted in real time based on the comparison result. The step of comparing the cumulative influent flow rate and the cumulative effluent flow rate, and adjusting the fluid exchange rate corresponding to the irrigation fluid exchange operation in real time based on the comparison result, includes: obtaining the difference between the cumulative influent flow rate and the cumulative effluent flow rate, and using the difference as the cumulative flow rate deviation value corresponding to the irrigation fluid exchange operation; determining whether the cumulative flow rate deviation value is within the adjustment range corresponding to the current irrigation fluid exchange stage; if the cumulative flow rate deviation value is within the adjustment range, then adjusting the fluid exchange rate corresponding to the irrigation fluid exchange operation in real time based on the cumulative flow rate deviation value. Wherein, if the cumulative flow deviation value is within the adjustment range, the liquid replacement rate corresponding to the irrigation liquid replacement operation is adjusted in real time based on the cumulative flow deviation value, including: maintaining the liquid replacement rate corresponding to the irrigation liquid replacement operation when the cumulative flow deviation value is less than the lower limit of the adjustment range; adjusting the liquid replacement rate corresponding to the irrigation liquid replacement operation in real time when the cumulative flow deviation value is not less than the lower limit of the adjustment range and the cumulative flow deviation value is less than the upper limit of the adjustment range; and shutting down the peristaltic pump with the larger current cumulative flow when the cumulative flow deviation value is greater than the upper limit of the adjustment range, keeping the peristaltic pump with the smaller current cumulative flow running normally, and activating an alarm mechanism until the cumulative flow deviation value is detected to be less than the lower limit of the adjustment range, then restarting the peristaltic pump that was in the off state, and deactivating the alarm mechanism.

2. The perfusion medium replacement method for cell culture according to claim 1, characterized in that, Before controlling the inlet peristaltic pump and the outlet peristaltic pump to perform perfusion and fluid exchange operations on the target cells based on preset operating parameters, the method further includes: Based on the characteristics of the target cells, the operating parameters of the inlet peristaltic pump and the outlet peristaltic pump are set for each perfusion and fluid exchange stage, as well as the adjustment range for each perfusion and fluid exchange stage.

3. The perfusion medium replacement method for cell culture according to claim 2, characterized in that, The process of controlling the inlet and outlet peristaltic pumps to perform perfusion and fluid exchange operations on the target cells based on preset operating parameters includes: Based on the operating parameters corresponding to each perfusion fluid exchange stage, the inlet peristaltic pump and the outlet peristaltic pump are calibrated, and the operating parameters include operating rate and operating time; The calibrated inlet and outlet peristaltic pumps are used to perform the perfusion and fluid exchange operation on the target cells.

4. The perfusion medium replacement method for cell culture according to claim 1, characterized in that, The step of adjusting the fluid exchange rate corresponding to the perfusion fluid exchange operation in real time when the cumulative flow deviation value is not less than the lower limit of the adjustment range and the cumulative flow deviation value is less than the upper limit of the adjustment range includes: When the cumulative flow deviation value is not less than the lower limit of the adjustment range and the cumulative flow deviation value is less than the upper limit of the adjustment range, it is determined whether the cumulative inlet flow rate is greater than the cumulative outlet flow rate. When the cumulative inlet flow rate is greater than the cumulative outlet flow rate, the inlet peristaltic pump is adjusted to reduce its speed based on the cumulative flow rate deviation value. When the cumulative inlet flow rate is less than the cumulative outlet flow rate, the outlet peristaltic pump is adjusted to reduce its speed based on the cumulative flow rate deviation value.

5. A perfusion medium exchange device for cell culture, characterized in that, This device is suitable for perfusion fluid exchange systems. The perfusion fluid exchange system includes: a turbulent flow reactor, an inlet pipe, an outlet pipe, an inlet peristaltic pump, an outlet peristaltic pump, and a control cabinet. The inlet pipe connects the turbulent flow reactor and the inlet peristaltic pump, and the outlet pipe connects the turbulent flow reactor and the outlet peristaltic pump. Both the inlet and outlet peristaltic pumps are connected to the control cabinet. The device includes: The control module, based on preset operating parameters, controls the inlet peristaltic pump and the outlet peristaltic pump to perform perfusion and fluid exchange operations on the target cells; The acquisition module acquires the cumulative influent flow rate of the influent peristaltic pump and the cumulative outfluent flow rate of the effluent peristaltic pump in real time when the perfusion and fluid exchange operation is performed on the target cells. The adjustment module compares the cumulative influent flow rate and the cumulative effluent flow rate, and adjusts the fluid exchange rate corresponding to the perfusion fluid exchange operation in real time based on the comparison result. The adjustment module is further configured to obtain the difference between the cumulative influent flow rate and the cumulative effluent flow rate, and use the difference as the cumulative flow rate deviation value corresponding to the irrigation and fluid replacement operation; determine whether the cumulative flow rate deviation value is within the adjustment range corresponding to the current irrigation and fluid replacement stage; if the cumulative flow rate deviation value is within the adjustment range, then adjust the fluid replacement rate corresponding to the irrigation and fluid replacement operation in real time based on the cumulative flow rate deviation value. The adjustment module is further configured to: maintain the fluid exchange rate corresponding to the perfusion fluid exchange operation when the cumulative flow deviation value is less than the lower limit of the adjustment range; adjust the fluid exchange rate corresponding to the perfusion fluid exchange operation in real time when the cumulative flow deviation value is not less than the lower limit of the adjustment range and the cumulative flow deviation value is less than the upper limit of the adjustment range; and shut down the peristaltic pump with the larger current cumulative flow when the cumulative flow deviation value is greater than the upper limit of the adjustment range, keep the peristaltic pump with the smaller current cumulative flow running normally, and activate the alarm mechanism until the cumulative flow deviation value is detected to be less than the lower limit of the adjustment range, then restart the peristaltic pump that was in the off state and deactivate the alarm mechanism.

6. A perfusion medium exchange device for cell culture, characterized in that, The perfusion media exchange device includes: a turbulent reactor, an inlet pipe, an outlet pipe, an inlet peristaltic pump, an outlet peristaltic pump, and a control cabinet. The inlet pipe connects the turbulent reactor and the inlet peristaltic pump, and the outlet pipe connects the turbulent reactor and the outlet peristaltic pump. Both the inlet and outlet peristaltic pumps are connected to the control cabinet. The perfusion media exchange device is used to perform the steps of the perfusion media exchange method for cell culture according to any one of claims 1 to 4.

7. A computer device, comprising a memory and a processor, characterized in that, The memory stores a computer program, and the processor is configured to run the computer program to perform the steps of the perfusion medium exchange method for cell culture as described in any one of claims 1 to 4.

8. A computer-readable storage medium having a computer program stored thereon, characterized in that, When the computer program is executed by the processor, it implements the steps of the perfusion medium exchange method for cell culture as described in any one of claims 1 to 4.

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