Temperature control methods, devices, culture vessels, bioreactors, equipment and media

Abstract

This application relates to the field of biopharmaceuticals, and in particular to a temperature control method, apparatus, culture vessel, bioreactor, computer equipment, and storage medium. The method includes: determining a corresponding temperature control strategy based on a first preset temperature value, a first temperature value, and a preset temperature difference of the culture medium to control the first temperature value to reach the first preset temperature value; when the first preset temperature value is greater than the first temperature value, while executing the corresponding temperature control strategy, controlling the working state of a first heating film and a second heating film based on a second temperature value, a third temperature value, and a second preset temperature value. This invention can determine a corresponding temperature control strategy based on the first preset temperature value, the first temperature value, and the preset temperature difference of the culture medium, enabling rapid and accurate temperature control of the culture medium, and avoiding exceeding the second preset temperature value, which could affect cell culture.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of biopharmaceuticals, and in particular to a temperature control method and device, a culture tank, a bioreactor, a computer device and a storage medium. BACKGROUND

[0002] Bioreactors are suitable for various biological culture process development, testing, medium optimization in the field of biopharmaceuticals, and can be used for the production of biological drugs and vaccines, and have wide application in the fields of suspension culture of mammalian, insect and other cell strains, culture of yeast, bacteria and some molds, and microcarrier adherent cell line culture.

[0003] To maintain normal cell growth, constant and appropriate temperature is required, and different cells have different temperature requirements. If the appropriate temperature is deviated, the normal metabolism of cells will be affected, and even death will occur.

[0004] At present, the common temperature control methods for bioreactors are water bath temperature control and TCU temperature control. The water bath temperature control method can only be used for the jacketed tank body of the stirring type bioreactor, and has the problems of slow temperature control speed and low temperature control precision. The TCU temperature control method also has the problems of slow temperature control speed and low temperature control precision. SUMMARY

[0005] Therefore, it is necessary to provide a temperature control method, device, system, computer device and storage medium to solve the above technical problems.

[0006] In a first aspect, the embodiments of the present application provide a temperature control method applied to a culture tank of a bioreactor, wherein the culture tank comprises a tank body, a first heating film arranged at a bottom wall of the tank body, a second heating film arranged at a side wall of the tank body, a first temperature sensor for detecting a first temperature value of a culture solution, a second temperature sensor for detecting a second temperature value of the first heating film, and a third temperature sensor for detecting a third temperature value of the second heating film. The method comprises the following steps:

[0007] Based on a first preset temperature value of the culture solution, the first temperature value and a preset temperature difference value, a corresponding temperature control strategy is determined to control the first temperature value to reach the first preset temperature value.

[0008] In a case where the first preset temperature value is greater than the first temperature value, when the corresponding temperature control strategy is executed, the working states of the first heating film and the second heating film are controlled based on the second temperature value, the third temperature value and a second preset temperature value.

[0009] In some embodiments, determining the corresponding temperature control strategy based on the first preset temperature value, the first temperature value, and the preset temperature difference value comprises:

[0010] obtaining a difference value between the first preset temperature value and the first temperature value;

[0011] determining the corresponding temperature control strategy based on a size relationship between the first preset temperature value and the first temperature value, and a size relationship between the difference value and the preset temperature difference value.

[0012] In some embodiments, determining the corresponding temperature control strategy based on the size relationship between the first preset temperature value and the first temperature value, and the size relationship between the difference value and the preset temperature difference value comprises:

[0013] if the first preset temperature value is greater than the first temperature value, and the difference value is greater than the preset temperature difference value, executing a first temperature control strategy;

[0014] if the first preset temperature value is greater than the first temperature value, and the difference value is less than or equal to the preset temperature difference value, executing a second temperature control strategy;

[0015] if the first preset temperature value is less than or equal to the first temperature value, executing a third temperature control strategy.

[0016] In some embodiments, when the first preset temperature value is greater than the first temperature value, controlling the working states of the first heating film and the second heating film based on the second temperature value, the third temperature value, and a second preset temperature value when executing the corresponding temperature control strategy comprises:

[0017] when executing the first temperature control strategy, if the second temperature value is less than or equal to the second preset temperature value, outputting a first control signal to control the first heating film to be in a heating state, otherwise, outputting the first control signal to control the first heating film to be in an off state; if the third temperature value is less than or equal to the second preset temperature value, outputting a first control signal to control the second heating film to be in a heating state, otherwise, outputting the first control signal to control the second heating film to be in an off state.

[0018] In some embodiments, when the first preset temperature value is greater than the first temperature value, controlling the working states of the first heating film and the second heating film based on the second temperature value, the third temperature value, and a second preset temperature value when executing the corresponding temperature control strategy comprises:

[0019] In the execution of the second temperature control strategy, if the second temperature value is less than or equal to the second preset temperature value, a second control signal is output to control the first heating film to be in a heating state, otherwise, the second control signal is output to control the first heating film to be in an off state; if the third temperature value is less than or equal to the second preset temperature value, the second control signal is output to control the second heating film to be in a heating state, otherwise, the second control signal is output to control the second heating film to be in an off state, wherein the second control signal is used to adjust the output power of the first heating film or the second heating film.

[0020] In some embodiments, the second control signal is determined by the following formula:

[0021] y = P[(b * S - T1) + 1 / (I * q) * (S - T1) + D * q / (a * D * q + 1) * (c * S - T1)]

[0022] Wherein, y represents the control signal value, P represents the proportional gain, I represents the integral action time, D represents the differential action time, q represents the Laplace operator, S represents the first preset temperature value, T1 represents the first temperature value, a represents the differential delay coefficient, b represents the proportional action weight, and c represents the differential action weight.

[0023] In some embodiments, the method further comprises:

[0024] In the execution of the third temperature control strategy, a third control signal is output to control the first heating film and the second heating film to be in an off state.

[0025] In a second aspect, an embodiment of the present application provides a temperature control device applied to a culture tank of a bioreactor, the culture tank comprising a tank body, a first heating film arranged on a bottom wall of the tank body, a second heating film arranged on a side wall of the tank body, a first temperature sensor for detecting a first temperature value of a culture solution, a second temperature sensor for detecting a second temperature value of the first heating film, and a third temperature sensor for detecting a third temperature value of the second heating film, the device comprising:

[0026] A strategy determination module is configured to determine a corresponding temperature control strategy based on a first preset temperature value of the culture solution, the first temperature value, and a preset temperature difference value, so as to control the first temperature value to reach the first preset temperature value.

[0027] A temperature control module is configured to, in the case that the first preset temperature value is greater than the first temperature value, control working states of the first heating film and the second heating film based on the second temperature value, the third temperature value, and a second preset temperature value in the execution of the corresponding temperature control strategy.

[0028] In a third aspect, an embodiment of the present application provides a culture tank applied to a bioreactor, characterized in that the culture tank comprises a tank body, a first heating film arranged on a bottom wall of the tank body, a second heating film arranged on a side wall of the tank body, a first temperature sensor for detecting a first temperature value of a culture solution, a second temperature sensor for detecting a second temperature value of the first heating film, and a third temperature sensor for detecting a third temperature value of the second heating film, and the culture tank further comprises a temperature control device, which executes the steps of the method of the first aspect.

[0029] In a fourth aspect, an embodiment of the present application provides a bioreactor comprising a base and a culture tank as described in the first aspect arranged on the base.

[0030] In a fifth aspect, an embodiment of the present application provides a computer device comprising a memory and a processor, wherein the memory stores a computer program, and the processor executes the steps of the first aspect.

[0031] In a sixth aspect, an embodiment of the present application provides a computer readable storage medium having a computer program stored thereon, wherein the processor executes the steps of the first aspect when executing the computer program.

[0032] Compared with the prior art, the above method, device, culture tank, bioreactor, computer device and storage medium determine a corresponding temperature control strategy based on a first preset temperature value of a culture solution, a first temperature value and a preset temperature difference value, so as to control the first temperature value to reach the first preset temperature value; in the case where the first preset temperature value is greater than the first temperature value, the working states of the first heating film and the second heating film are controlled based on the second temperature value, the third temperature value and a second preset temperature value when the corresponding temperature control strategy is executed. The present application can determine a corresponding temperature control strategy according to a first preset temperature value of a culture solution, a first temperature value and a preset temperature difference value, and can realize rapid and accurate control of the temperature of the culture solution. When the corresponding temperature control strategy is executed, the working states of the first heating film and the second heating film are controlled considering the second temperature value and the third temperature value, so as to avoid exceeding the second preset temperature value and affecting cell culture. BRIEF DESCRIPTION OF DRAWINGS

[0033] Figure 1 FIG. 1 is a structural schematic diagram of a bioreactor in an embodiment;

[0034] Figure 2 FIG. 3 is a structural schematic diagram of a temperature control device in an embodiment;

[0035] Figure 3 FIG. 5 is a flow schematic diagram of a temperature control method in an embodiment;

[0036] Figure 4 This is a flowchart illustrating a strategy determination method in one embodiment;

[0037] Figure 5 This is a schematic diagram of the overall process of the strategy determination method in one embodiment;

[0038] Figure 6 This is a flowchart illustrating the execution of a first temperature control strategy in one embodiment;

[0039] Figure 7 This is a flowchart illustrating the execution of a second temperature control strategy in one embodiment;

[0040] Figure 8 This is a flowchart illustrating the execution of a third temperature control strategy in one embodiment;

[0041] Figure 9 This is a schematic diagram of the module connection of the temperature control device in one embodiment;

[0042] Figure 10 This is a schematic diagram of the structure of a computer device in one embodiment. Detailed Implementation

[0043] To more clearly illustrate the technical solutions of the embodiments of the present invention, the accompanying drawings used in the description of the embodiments will be briefly introduced below. Obviously, the drawings described below are merely some examples or embodiments of the present invention. For those skilled in the art, the present invention can be applied to other similar scenarios based on these drawings without creative effort. Unless obvious from the context or otherwise specified, the same reference numerals in the drawings represent the same structures or operations.

[0044] As indicated in this invention and the claims, unless the context clearly indicates otherwise, the words "a," "an," "an," and / or "the" do not specifically refer to the singular and may also include the plural. Generally speaking, the terms "comprising" and "including" only indicate the inclusion of explicitly identified steps and elements, which do not constitute an exclusive list, and the method or apparatus may also include other steps or elements.

[0045] While this invention makes various references to certain modules in systems according to embodiments of the invention, any number of different modules can be used and run on computing devices and / or processors. Modules are merely illustrative, and different aspects of the system and method may use different modules.

[0046] It should be understood that when a unit or module is described as "connected" or "coupled" to other units, modules, or blocks, it may refer to a direct connection or coupling, or communication with other units, modules, or blocks, or the presence of intermediate units, modules, or blocks, unless the context explicitly indicates otherwise. The term "and / or" as used herein may include any and all combinations of one or more of the related listed items.

[0047] Figure 1 This is a schematic diagram of a bioreactor in one embodiment. The bioreactor includes a base 10 and a culture tank 20 disposed on the base 10. The culture tank 20 includes a tank body 202, a temperature control device (not shown in the figure), a first heating film 204 disposed on the bottom wall of the tank body 202, a second heating film 206 disposed on the side wall of the tank body 202, a first temperature sensor 208 for detecting a first temperature value of the culture medium, a second temperature sensor 210 for detecting a second temperature value of the first heating film 204, and a third temperature sensor 212 for detecting a third temperature value of the second heating film 206. A culture bag for holding the culture medium is also provided inside the tank body 202.

[0048] Bioreactors, for example, are turbulent flow bioreactors.

[0049] The bottom wall of tank 202 is, for example, an inverted cone shape or other shapes. The side walls of tank 202 are, for example, cylindrical or other shapes.

[0050] The first temperature sensor 208, the second temperature sensor 210, and the third temperature sensor 212 detect the corresponding temperature values ​​at preset time intervals.

[0051] The temperature control method provided in this application can be applied to the temperature control device described in the above embodiments. For example... Figure 2 As shown, the temperature control device may include a processor 302 and a memory 304 for storing data. The processor 302 may be, but is not limited to, a microprocessor (MCU) or a programmable logic device (FPGA). The temperature control device may also include a transmission device 306 for communication functions and an input / output device 308. Those skilled in the art will understand that... Figure 2 The structure shown is for illustrative purposes only and does not limit the structure of the terminal described above. For example, the temperature control device may also include a... Figure 2 The more or fewer components shown, or having the same Figure 2 The different configurations shown are illustrated.

[0052] The memory 304 can be used to store computer programs, such as application software programs and modules, like the computer program corresponding to the temperature control method in this embodiment. The processor 302 executes various functional applications and data processing by running the computer program stored in the memory 304, thereby implementing the aforementioned method. The memory 304 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 304 may further include memory remotely located relative to the processor 302, 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.

[0053] Transmission device 306 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, transmission device 306 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, transmission device 306 can be a Radio Frequency (RF) module used for wireless communication with the Internet.

[0054] In one embodiment, such as Figure 3 As shown, a temperature control method is provided, which is applied to... Figure 2 Taking the temperature control device in the middle as an example, the following steps are included:

[0055] S302: Based on the first preset temperature value of the culture medium, the first temperature value, and the preset temperature difference, determine the corresponding temperature control strategy to control the first temperature value to reach the first preset temperature value.

[0056] The first preset temperature value is set according to the actual cells being cultured. For example, when culturing CHO cells, the first preset temperature value is usually set to 37°C.

[0057] The preset temperature difference can be set according to the actual volume of the culture medium, for example, 0.4℃.

[0058] In this embodiment, the temperature control strategy is determined based on the first preset temperature value of the culture medium, the first temperature value, and the preset temperature difference. The temperature of the culture medium is adjusted quickly and accurately through the most suitable control strategy.

[0059] S304: When the first preset temperature value is greater than the first temperature value, when executing the corresponding temperature control strategy, based on the second temperature value, the third temperature value, and the second preset temperature value, control the working states of the first heating film and the second heating film.

[0060] The second preset temperature value is the protection temperature of the culture bag. Usually, the protection temperature of the culture bag is 45°C. If the temperature of the heating film exceeds 45°C, it may cause damage to the culture bag.

[0061] In this embodiment, when the first preset temperature value is greater than the first temperature value, the protection temperature of the culture bag is considered. Therefore, when executing the corresponding temperature control strategy, based on the second temperature value, the third temperature value, and the second preset temperature value, control the working states of the first heating film and the second heating film. Therefore, the culture will not fail due to damage to the culture bag.

[0062] In some embodiments, as Figure 4 shown, determining the corresponding temperature control strategy based on the first preset temperature value of the culture solution, the first temperature value, and the preset temperature difference includes:

[0063] S402: Obtain the difference between the first preset temperature value and the first temperature value.

[0064] Assume that the first preset temperature value of the culture solution is S, and the first temperature value of the culture solution is T1.

[0065] Compare the first preset temperature value S and the first temperature value T1 through a comparator, calculate the difference E, and the calculation method is: E = S - T1.

[0066] S404: Based on the magnitude relationship between the first preset temperature value and the first temperature value, and the magnitude relationship between the difference and the preset temperature difference, determine the corresponding temperature control strategy.

[0067] In this embodiment, based on the magnitude relationship between the first preset temperature value and the first temperature value, and the magnitude relationship between the difference and the preset temperature difference, determine the most suitable temperature control strategy for the current first temperature value.

[0068] Assume that the preset temperature difference is F. Compare the difference E, the preset temperature difference F, and the value 0 through a comparator. There are three comparison results, which are: E > 0 and E > F; E > 0 and E < F; E < 0, each corresponding to a temperature control strategy.

[0069] Specifically, as Figure 5As shown, determining the corresponding temperature control strategy based on the relationship between the first preset temperature value and the first temperature value, and the relationship between the difference and the preset temperature difference, includes:

[0070] S502: If the first preset temperature value is greater than the first temperature value, and the difference is greater than the preset temperature difference, then the first temperature control strategy is executed.

[0071] The flowchart for executing the first temperature control strategy is as follows: Figure 6 As shown, assuming the second temperature value is T2, the third temperature value is T3, and the second preset temperature value is D, when executing the first temperature control strategy, if the second temperature value T2 is less than or equal to the second preset temperature value D, then the first control signal is output to control the first heating film to be in a heating state; otherwise, the first control signal is output to control the first heating film to be in a closed state. If the third temperature value T3 is less than or equal to the second preset temperature value D, then the first control signal is output to control the second heating film to be in a heating state; otherwise, the first control signal is output to control the second heating film to be in a closed state.

[0072] After executing the first temperature control strategy, the first, second, and third temperature sensors detect the corresponding temperature values ​​at preset time intervals to determine the corresponding temperature control strategy again, thereby achieving real-time control of the culture medium temperature. For example, if the conditions of the first temperature control strategy are still met, the first temperature control strategy continues to be executed; if the conditions of the second temperature control strategy are met, the second temperature control strategy is executed.

[0073] The first temperature control strategy is generally used in the early stage of culture when the culture medium is first added and the temperature begins to rise, or during the replenishment stage of culture. In this case, the initial temperature of the culture medium is relatively low. When the first and second heating films meet the heating conditions, the first and second heating films are controlled to heat at a higher output power (e.g., rated power), thereby improving the speed of temperature control.

[0074] S504: If the first preset temperature value is greater than the first temperature value, and the difference is less than or equal to the preset temperature difference, then the second temperature control strategy is executed.

[0075] The flowchart for executing the first temperature control strategy is as follows: Figure 7As shown, when executing the second temperature control strategy, if the second temperature value T2 is less than or equal to the second preset temperature value D, a second control signal is output to control the first heating film to be in a heating state; otherwise, a second control signal is output to control the first heating film to be in a closed state. If the third temperature value T3 is less than or equal to the second preset temperature value D, a second control signal is output to control the second heating film to be in a heating state; otherwise, a second control signal is output to control the second heating film to be in a closed state. The second control signal is used to adjust the output power of the first heating film or the second heating film.

[0076] After executing the second temperature control strategy, the first, second, and third temperature sensors detect the corresponding temperature values ​​at preset time intervals, and then determine the corresponding temperature control strategy again, thereby achieving real-time control of the culture medium temperature. For example, if the conditions of the second temperature control strategy are still met, the second temperature control strategy continues to be executed; if the conditions of the first temperature control strategy are met, the first temperature control strategy is executed.

[0077] A second temperature control strategy is typically employed during the cultivation process, where the temperature fluctuation of the culture medium is relatively small. Therefore, the output power of the first or second heating film is adjusted by a second control signal to achieve slower heating of the culture medium, thereby improving the accuracy of temperature control.

[0078] In some embodiments, the output power of the first heating film or the second heating film decreases as the difference between the first preset temperature value and the first temperature value decreases. Specifically, the second control signal is determined by the following formula:

[0079] y=P[(b*S-T1)+1 / (I*q)*(S-T1)+D*q / (a*D*q+1)*(c*S-T1)]

[0080] Where y represents the control signal value, P represents the proportional gain, I represents the integral action time, D represents the derivative action time, q represents the Laplace operator, S represents the first preset temperature value, T1 represents the first temperature value, a represents the derivative delay coefficient, b represents the proportional action weight, and c represents the derivative action weight.

[0081] According to the above formula, as the temperature of the culture medium gradually rises during the heating process, the difference between the first preset temperature value and the first temperature value gradually decreases, and at the same time, the control signal value also gradually decreases. Thus, the accuracy of temperature control gradually improves during the temperature control process, so as to achieve more precise temperature control.

[0082] S506: If the first preset temperature value is less than or equal to the first temperature value, then execute the third temperature control strategy.

[0083] The flowchart for executing the first temperature control strategy is as follows: Figure 8 As shown, if the temperature of the culture medium is too high, and the first preset temperature value S is less than or equal to the first temperature value T1, then when the third temperature control strategy is executed, a third control signal is output to control the first heating film and the second heating film to be in the closed state.

[0084] After executing the third temperature control strategy, the first, second, and third temperature sensors detect the corresponding temperature values ​​at preset time intervals, and then determine the corresponding temperature control strategy again, thereby achieving real-time control of the culture medium temperature. For example, if the conditions of the third temperature control strategy are still met, the third temperature control strategy continues to be executed; if the conditions of the first temperature control strategy are met, the first temperature control strategy is executed.

[0085] In one example embodiment, a 50L turbulent flow bioreactor was used to culture CHO cells, and the temperature control process was as follows:

[0086] ① Add culture medium to the 50L turbulent bioreactor culture bag, and then set the first preset temperature value S of the culture medium to 37℃ (based on the actual cultured cells) and the preset temperature difference value F to 0.4℃ (based on the actual culture volume) through the reactor host computer. Set the rotation speed of the turbulent bioreactor to 35rpm, and then switch the temperature control and rotation speed control to automatic mode and start the turbulent bioreactor.

[0087] ② Due to the newly added culture medium, the first temperature value T1 of the culture medium is 25℃. According to the formula E=S-T1, E=12℃, E>0 and E>F. At this time, the second temperature value T2 of the first heating film and the third temperature value T3 of the second heating film are obtained. When T2<45℃, the first control signal is output to turn on the first heating film; otherwise, the first control signal is output to turn off the first heating film. Similarly, when T3<45℃, the first control signal is output to turn on the second heating film; otherwise, the first control signal is output to turn off the second heating film.

[0088] ③ When the first temperature value T1 of the culture medium gradually rises to between 36.6℃ and 37℃, according to the formula E=S-T1, E<=0.4℃, E>0 and E<=F. At this time, the PID controller outputs the second control signal. When the PID controller has a pulse width output, the second temperature value T2 of the first heating film and the third temperature value T3 of the second heating film are checked. When T2<45℃, the second control signal is output to turn on the first heating film; otherwise, the second control signal is output to turn off the first heating film. Similarly, when T3<45℃, the second control signal is output to turn on the second heating film; otherwise, the second control signal is output to turn off the second heating film.

[0089] ④ When the first temperature value T1 of the culture medium rises to 37℃ or above 37.0℃, according to the formula E=S-T1, E<=0℃, at this time the third control signal is output to shut down the first heating film and the second heating film.

[0090] ⑤ As the first and second heating films are closed, the first temperature value T1 of the culture medium will gradually decrease to between 36.6℃ and 37.0℃. At this time, the temperature will be adjusted according to the control logic in ③.

[0091] ⑥ When new culture medium is added to the reactor culture bag during the culture process, the first temperature value T1 of the culture medium will decrease. If the first temperature value T1 of the culture medium decreases to below 36.6℃, the control logic will be adjusted according to ②; if the first temperature value T1 of the culture medium decreases to between 36.6℃ and 37.0℃, the control logic will be adjusted according to ③.

[0092] ⑦ When the culture is finished, turn off the start signal of the equipment, stop temperature adjustment, and stop heating the first and second heating films.

[0093] It should be understood that although the steps in the flowchart above are shown sequentially as indicated by the arrows, these steps are not necessarily executed in the order indicated by the arrows. Unless explicitly stated herein, there is no strict order restriction on the execution of these steps, and they can be executed in other orders. Moreover, at least some steps in the flowchart above may include multiple steps or multiple stages. These steps or stages are not necessarily completed at the same time, but can be executed at different times. The execution order of these steps or stages is not necessarily sequential, but can be performed alternately or in turn with other steps or at least some of the steps or stages in other steps.

[0094] In one embodiment, such as Figure 9 As shown, the present invention provides a temperature control device, the device comprising:

[0095] The strategy determination module 902 is used to determine a corresponding temperature control strategy based on the first preset temperature value of the culture medium, the first temperature value, and the preset temperature difference value, so as to control the first temperature value to reach the first preset temperature value.

[0096] The temperature control module 904 is used to control the working state of the first heating film and the second heating film based on the second temperature value, the third temperature value and the second preset temperature value when executing the corresponding temperature control strategy, when the first preset temperature value is greater than the first temperature value.

[0097] In some embodiments, the strategy determination module is specifically used for:

[0098] Obtain the difference between the first preset temperature value and the first temperature value;

[0099] Based on the relationship between the first preset temperature value and the first temperature value, and the relationship between the difference and the preset temperature difference, a corresponding temperature control strategy is determined.

[0100] In some embodiments, the strategy determination module is specifically used for:

[0101] If the first preset temperature value is greater than the first temperature value, and the difference is greater than the preset temperature difference, then the first temperature control strategy is executed.

[0102] If the first preset temperature value is greater than the first temperature value, and the difference is less than or equal to the preset temperature difference, then the second temperature control strategy is executed.

[0103] If the first preset temperature value is less than or equal to the first temperature value, then the third temperature control strategy is executed.

[0104] In some embodiments, the temperature control module is specifically used for:

[0105] When executing the first temperature control strategy, if the second temperature value is less than or equal to the second preset temperature value, a first control signal is output to control the first heating film to be in a heating state; otherwise, a first control signal is output to control the first heating film to be in a closed state. If the third temperature value is less than or equal to the second preset temperature value, a first control signal is output to control the second heating film to be in a heating state; otherwise, a first control signal is output to control the second heating film to be in a closed state.

[0106] In some embodiments, the temperature control module is specifically used for:

[0107] When executing the second temperature control strategy, if the second temperature value is less than or equal to the second preset temperature value, a second control signal is output to control the first heating film to be in a heating state; otherwise, a second control signal is output to control the first heating film to be in a closed state. If the third temperature value is less than or equal to the second preset temperature value, a second control signal is output to control the second heating film to be in a heating state; otherwise, a second control signal is output to control the second heating film to be in a closed state. The second control signal is used to adjust the output power of the first heating film or the second heating film.

[0108] In some embodiments, the second control signal is determined by the following formula:

[0109] y=P[(b*S-T1)+1 / (I*q)*(S-T1)+D*q / (a*D*q+1)*(c*S-T1)]

[0110] Where y represents the control signal value, P represents the proportional gain, I represents the integral action time, D represents the derivative action time, q represents the Laplace operator, S represents the first preset temperature value, T1 represents the first temperature value, a represents the derivative delay coefficient, b represents the proportional action weight, and c represents the derivative action weight.

[0111] In some embodiments, the temperature control module is specifically used for:

[0112] When executing the third temperature control strategy, a third control signal is output to control the first heating film and the second heating film to be in the off state.

[0113] Specific limitations regarding the temperature control device can be found in the limitations of the temperature control method described above, and will not be repeated here. Each module in the aforementioned temperature control device can be implemented entirely or partially through software, hardware, or a combination thereof. These modules can be embedded in hardware within or independently of the processor in a computer device, or stored in software within the memory of a computer device, so that the processor can call and execute the corresponding operations of each module.

[0114] In one embodiment, a culture vessel is provided for use in a bioreactor. The culture vessel includes a vessel body and a first heating film disposed on the bottom wall of the vessel body, a second heating film disposed on the side wall of the vessel body, a first temperature sensor for detecting a first temperature value of the culture medium, a second temperature sensor for detecting a second temperature value of the first heating film, and a third temperature sensor for detecting a third temperature value of the second heating film. The culture vessel also includes a temperature control device that performs the steps of the above-described temperature control method.

[0115] In one embodiment, a bioreactor is provided, comprising a base, characterized in that it further comprises a culture tank as described in the above embodiment disposed on the base.

[0116] In one embodiment, a computer device is provided, which may be a server, and its internal structure diagram may be as follows: Figure 10As shown. The computer device includes a processor, memory, and a network interface connected via a system bus. The processor provides computing and control capabilities. The memory includes a non-volatile storage medium and internal memory. The non-volatile storage medium stores an operating system, computer programs, and a database. The internal memory provides an environment for the operation of the operating system and computer programs in the non-volatile storage medium. The database stores motion detection data. The network interface communicates with external terminals via a network connection. When the computer program is executed by the processor, it implements the steps in any of the above-described temperature control method embodiments.

[0117] Those skilled in the art will understand that Figure 10 The structure shown is merely a block diagram of a portion of the structure related to the present application and does not constitute a limitation on the computer device to which the present application is applied. Specific computer devices may include more or fewer components than those shown in the figure, or combine certain components, or have different component arrangements.

[0118] In one embodiment, a computer-readable storage medium is provided having a computer program stored thereon, which, when executed by a processor, implements the steps in any of the above-described temperature control method embodiments.

[0119] Those skilled in the art will understand that all or part of the processes in the methods of the above embodiments can be implemented by a computer program instructing related hardware. The computer program can be stored in a non-volatile computer-readable storage medium. When executed, the computer program can include the processes of the embodiments of the above methods. Any references to memory, storage, databases, or other media used in the embodiments provided in this application can include at least one of non-volatile and volatile memory. Non-volatile memory can include read-only memory (ROM), magnetic tape, floppy disk, flash memory, or optical storage, etc. Volatile memory can include random access memory (RAM) or external cache memory. By way of illustration and not limitation, RAM can be in various forms, such as static random access memory (SRAM) or dynamic random access memory (DRAM), etc.

[0120] The technical features of the above embodiments can be combined in any way. For the sake of brevity, not all possible combinations of the technical features in the above embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0121] The above embodiments merely illustrate 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 the invention patent. 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 protection scope of this application. Therefore, the protection scope of this patent application should be determined by the appended claims.

Claims

1. A temperature control method applied to a culture tank of a bioreactor, the culture tank comprising a tank body and a first heating film arranged at a bottom wall of the tank body, a second heating film arranged at a side wall of the tank body, a first temperature sensor for detecting a first temperature value of a culture solution, a second temperature sensor for detecting a second temperature value of the first heating film, and a third temperature sensor for detecting a third temperature value of the second heating film, characterized in that, The method comprises: determining a corresponding temperature control strategy based on the first preset temperature value of the culture solution, the first temperature value, and a preset temperature difference value, so as to control the first temperature value to reach the first preset temperature value; in the case where the first preset temperature value is greater than the first temperature value, when the corresponding temperature control strategy is executed, the working states of the first heating film and the second heating film are controlled based on the second temperature value, the third temperature value, and a second preset temperature value; determining a corresponding temperature control strategy based on the first preset temperature value of the culture solution, the first temperature value, and a preset temperature difference value comprises: obtaining the difference value between the first preset temperature value and the first temperature value; determining a corresponding temperature control strategy based on the size relationship between the first preset temperature value and the first temperature value, and the size relationship between the difference value and the preset temperature difference value; determining a corresponding temperature control strategy based on the size relationship between the first preset temperature value and the first temperature value, and the size relationship between the difference value and the preset temperature difference value comprises: if the first preset temperature value is greater than the first temperature value, and the difference value is greater than the preset temperature difference value, a first temperature control strategy is executed; if the first preset temperature value is greater than the first temperature value, and the difference value is less than or equal to the preset temperature difference value, a second temperature control strategy is executed; if the first preset temperature value is less than or equal to the first temperature value, a third temperature control strategy is executed; in the case where the first preset temperature value is greater than the first temperature value, when the corresponding temperature control strategy is executed, the working states of the first heating film and the second heating film are controlled based on the second temperature value, the third temperature value, and a second preset temperature value, which comprises: when the first temperature control strategy is executed, if the second temperature value is less than or equal to the second preset temperature value, a first control signal is output to control the first heating film to be in a heating state, otherwise, the first control signal is output to control the first heating film to be in a closed state; if the third temperature value is less than or equal to the second preset temperature value, a first control signal is output to control the second heating film to be in a heating state, otherwise, the first control signal is output to control the second heating film to be in a closed state; when the second temperature control strategy is executed, if the second temperature value is less than or equal to the second preset temperature value, a second control signal is output to control the first heating film to be in a heating state, otherwise, the second control signal is output to control the first heating film to be in a closed state; if the third temperature value is less than or equal to the second preset temperature value, a second control signal is output to control the second heating film to be in a heating state, otherwise, the second control signal is output to control the second heating film to be in a closed state, wherein the second control signal is used to adjust the output power of the first heating film or the second heating film; when the third temperature control strategy is executed, a third control signal is output to control the first heating film and the second heating film to be in a closed state.

2. The method of claim 1, wherein, The second control signal is determined by the following formula: y = P[(b*S-T1)+1 / (I*q)*(S-T1)+D*q / (a*D*q+1)*(c*S-T1)] wherein y represents a control signal value, P represents a proportional gain, I represents an integral action time, D represents a differential action time, q represents a Laplace operator, S represents a first preset temperature value, T1 represents a first temperature value, a represents a differential delay coefficient, b represents a proportional action weight, and c represents a differential action weight.

3. A temperature control device applied to a culture tank of a bioreactor, the culture tank comprising a tank body and a first heating film arranged at a bottom wall of the tank body, a second heating film arranged at a side wall of the tank body, a first temperature sensor for detecting a first temperature value of a culture solution, a second temperature sensor for detecting a second temperature value of the first heating film, and a third temperature sensor for detecting a third temperature value of the second heating film, characterized in that, The device comprises: a strategy determination module configured to determine a corresponding temperature control strategy based on a first preset temperature value of a culture solution, the first temperature value, and a preset temperature difference value, so as to control the first temperature value to reach the first preset temperature value; a temperature control module configured to, when the first preset temperature value is greater than the first temperature value, control working states of the first heating film and the second heating film based on the second temperature value, the third temperature value, and a second preset temperature value when the corresponding temperature control strategy is executed. The strategy determination module is specifically configured to: obtain a difference value between the first preset temperature value and the first temperature value; determine the corresponding temperature control strategy based on a size relationship between the first preset temperature value and the first temperature value and a size relationship between the difference value and the preset temperature difference value; if the first preset temperature value is greater than the first temperature value and the difference value is greater than the preset temperature difference value, execute a first temperature control strategy; if the first preset temperature value is greater than the first temperature value and the difference value is less than or equal to the preset temperature difference value, execute a second temperature control strategy; and if the first preset temperature value is less than or equal to the first temperature value, execute a third temperature control strategy. The temperature control module is specifically configured to: when the first temperature control strategy is executed, if the second temperature value is less than or equal to the second preset temperature value, output a first control signal to control the first heating film to be in a heating state, otherwise, output the first control signal to control the first heating film to be in a closed state; and if the third temperature value is less than or equal to the second preset temperature value, output the first control signal to control the second heating film to be in the heating state, otherwise, output the first control signal to control the second heating film to be in the closed state. When the second temperature control strategy is executed, if the second temperature value is less than or equal to the second preset temperature value, output a second control signal to control the first heating film to be in the heating state, otherwise, output the second control signal to control the first heating film to be in the closed state; and if the third temperature value is less than or equal to the second preset temperature value, output the second control signal to control the second heating film to be in the heating state, otherwise, output the second control signal to control the second heating film to be in the closed state, wherein the second control signal is used to adjust output power of the first heating film or the second heating film; and when the third temperature control strategy is executed, output a third control signal to control the first heating film and the second heating film to be in the closed state.

4. A culture tank applied to a bioreactor, characterized by, The culture tank comprises a tank body, a first heating film arranged at a bottom wall of the tank body, a second heating film arranged at a side wall of the tank body, a first temperature sensor for detecting a first temperature value of a culture solution, a second temperature sensor for detecting a second temperature value of the first heating film, and a third temperature sensor for detecting a third temperature value of the second heating film. The culture tank further comprises a temperature control device, which performs the steps of the method according to any one of claims 1 to 2.

5. A bioreactor comprising a base, characterized in that, The culture tank according to claim 4 is further arranged on the base. 6.A computer device, comprising a memory and a processor, wherein the memory stores a computer program, and the computer device is configured to perform the method according to any one of claims 1-5 when the computer program is executed by the processor. The processor, when executing the computer program, implements the steps of the method according to any one of claims 1 to 2.

7. A computer-readable storage medium having stored thereon a computer program, characterized in that The computer program, when executed by the processor, implements the steps of the method according to any one of claims 1 to 2.

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