Wave reactor reaction bag liquid temperature detection and control method, system and electronic device

By setting up center and platform temperature sensors in the wave reactor and combining them with a PID control algorithm, the temperature of the heating tray can be accurately calculated and controlled, thus solving the temperature difference problem in the detection of liquid temperature in the reaction bag and ensuring the stability of the cell growth environment.

CN122357809APending Publication Date: 2026-07-10APPLITECH BIOLOGICAL TECH CO LTD
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Patent Information

Application Number
CN202610467224.6
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2026-04-09
Publication Date
2026-07-10

AI Technical Summary

Technical Problem

In existing technologies, the temperature difference in the reaction bag liquid of wave reactors is large, which can lead to cell death or slow growth.

Method used

By setting a center temperature sensor in the center of the heating tray and a tabletop temperature sensor in the outer ring, the average value of the center temperature and the tabletop temperature is calculated. Combined with a PID control algorithm, the heating temperature of the heating tray is precisely controlled.

Benefits of technology

It achieves precise detection and control of the liquid temperature inside the reaction bag, with a temperature difference of less than ±0.1℃, which improves the stability and adaptability of temperature control and protects the cell growth environment.

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Abstract

This invention provides a method, system, and electronic device for detecting and controlling the liquid temperature of a wave-shaped reactor reaction bag. The method includes acquiring the center temperature of the reaction bag using a center temperature sensor located at the center of the heating tray, and acquiring the platform temperature of the reaction bag using a platform temperature sensor located on the outer ring of the heating tray. The center temperature is taken as value A, and the platform temperature is taken as value B, and a calculated center temperature value C is obtained, where C = (A + B) / 2. A temperature control module calculates the target platform temperature value using value C. The target platform temperature value is compared with value B to calculate the duty cycle of the heating output, thereby controlling the heating temperature of the heating tray. This invention achieves the effects of small temperature detection difference, low cell death rate, or rapid cell growth.
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Description

Technical Field

[0001] This invention relates to the field of biopharmaceutical technology, and more specifically, to a method for detecting and controlling the liquid temperature in a wave-type reactor reaction bag. Background Technology

[0002] A wave-type bioreactor typically consists of a swaying heating tray and a reaction bag. The reaction bag is placed on the tray, and liquid is injected into the bag. The swaying heating tray evens out the liquid in the reaction bag. Current technology uses a surface-temperature sensor located at the center of the heating tray. The reaction bag is placed on the tray, and heating is achieved through contact between the bag and the tray. Temperature measurement is achieved indirectly through contact between the central temperature sensor and the bag. The temperature sensor detects the surface temperature of the bag and then controls the heating elements on the tray, thus controlling the temperature of the liquid inside the bag.

[0003] However, existing technologies suffer from temperature discrepancies between the sensor and the liquid temperature due to varying liquid volumes in the reaction bag. This discrepancy is particularly pronounced when the reaction bag is filled to its minimum volume, typically reaching ±0.3 degrees Celsius. Consequently, the sensor's temperature readings fail to accurately reflect the actual liquid temperature within the bag, potentially leading to cell death or slow growth. Summary of the Invention

[0004] This invention addresses the shortcomings of existing methods by proposing a method, system, and electronic equipment for detecting and controlling the liquid temperature in a wave-shaped reactor reaction bag, thereby solving the technical problems of large temperature differences, easy cell death, or slow growth in the prior art.

[0005] In a first aspect, embodiments of the present invention provide a method for detecting and controlling the liquid temperature in a wave-shaped reactor reaction bag, characterized in that it includes: The center temperature of the reaction bag is collected by a center temperature sensor located at the center of the heating tray to obtain the center temperature detection value, and the table surface temperature of the reaction bag is collected by a table surface temperature sensor located on the outer ring of the center of the heating tray to obtain the table surface temperature detection value. Take the center temperature detection value as value A and take the table surface temperature detection value as value B, and calculate the center temperature value as value C, where C = (A + B) / 2; The target table temperature is obtained by calculating the C value through the temperature control module. The target table temperature is then compared with the B value to calculate the duty cycle of the heating output, thereby controlling the heating temperature of the heating tray.

[0006] Optionally, where: The duration of one swing cycle of the center of the heating tray is set as T1, and the heating cycle of the heating tray is set as T2; in, During the swing cycle of T1, the center temperature sensor repeatedly collects the center temperature of the reaction bag to obtain the center temperature detection value, and calculates the average of the multiple center temperature detection values ​​to obtain the value A; during the heating cycle of T2, the table surface temperature sensor repeatedly collects the table surface temperature of the reaction bag to obtain the multiple table surface temperature detection values, and calculates the average of the multiple table surface temperature detection values ​​to obtain the value B.

[0007] Optionally, the count of the plurality of said tabletop temperature detection values ​​is ten.

[0008] Optionally, the interval between two consecutive samplings of the platform temperature is one second.

[0009] Optionally, the temperature control module calculates the C value using a PID calculation method to obtain the target value of the tabletop temperature.

[0010] Optionally, the temperature control module calculates the first control variable value CV1 using the PID calculation method; The preset target temperature value set by the temperature control module is D, and the target table temperature value is CV1. A+D.

[0011] Optionally, the temperature control module calculates the target temperature of the countertop using a PID calculation method to obtain the duty cycle of the countertop heating output.

[0012] Optionally, the duty cycle of the tabletop heating output is calculated as follows: The temperature control module calculates the second control variable value CV2 using the PID calculation method, and the duty cycle time of the table heating output is equal to CV2. T2.

[0013] Secondly, embodiments of the present invention also provide a wave-type reactor reaction bag liquid temperature detection and control system, including a heating tray, a reaction bag, a center temperature sensor, a table surface temperature sensor, and a temperature control module. The reaction bag is placed on the top surface of the heating tray, the center temperature sensor is placed at the center of the heating tray, and the surface temperature sensor is placed on the heating tray and located outside the center temperature sensor. The heating tray, the center temperature sensor, and the tabletop temperature sensor are respectively connected to the temperature control module.

[0014] Thirdly, embodiments of the present invention also provide an electronic device, including a memory and a processor that executes commands stored in the memory, the processor executing the commands to implement the method described above.

[0015] The beneficial technical effects brought about by the technical solutions provided in the embodiments of the present invention include: First, calculating the liquid temperature inside the reaction bag using the center temperature and the tabletop temperature is more accurate, resulting in a smaller temperature difference between the measured temperature and the liquid temperature inside the reaction bag (which can be controlled to within ±0.1℃). This improved calculation accuracy leads to a more precise tabletop heating output duty cycle, enabling more accurate control over the actual heating temperature of the heating elements in the heating tray.

[0016] Secondly, by adopting an average value algorithm, the problem of fluctuating detection values ​​caused by insufficient liquid volume and poor contact between the bag and the central temperature sensor and the platform due to gas inflation is solved, resulting in better adaptability of temperature control and improved temperature control stability.

[0017] Additional aspects and advantages of the invention will be set forth in part in the description which follows, and will become apparent from the description or may be learned by practice of the invention. Attached Figure Description

[0018] The above and / or additional aspects and advantages of the present invention will become apparent and readily understood from the following description of the embodiments taken in conjunction with the accompanying drawings, wherein: Figure 1 A flowchart of a method for detecting and controlling the liquid temperature in a wave-shaped reactor reaction bag provided in an embodiment of the present invention; Figure 2 for Figure 1 A schematic diagram illustrating the principle of PID control. Detailed Implementation

[0019] The present invention will now be described in detail. Examples of embodiments of the invention are illustrated in the accompanying drawings, wherein the same or similar reference numerals denote the same or similar parts or parts having the same or similar functions throughout. Furthermore, detailed descriptions of known technologies that are unnecessary for the features of the illustrated invention are omitted. The embodiments described below with reference to the accompanying drawings are exemplary and are only used to explain the invention, and should not be construed as limiting the invention.

[0020] It will be understood by those skilled in the art that, unless otherwise defined, all terms used herein (including technical and scientific terms) have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. It should also be understood that terms such as those defined in general dictionaries should be understood to have the same meaning as in the context of the prior art, and should not be interpreted in an idealized or overly formal sense unless specifically defined as herein.

[0021] Those skilled in the art will understand that, unless specifically stated otherwise, the singular forms “a,” “an,” “the,” and “the” used herein may also include the plural forms. It should be further understood that the term “comprising” as used in this specification means the presence of the stated features, integers, steps, operations, elements, and / or components, but does not exclude the presence or addition of one or more other features, integers, steps, operations, elements, components, and / or groups thereof. It should be understood that when we say an element is “connected” or “coupled” to another element, it can be directly connected or coupled to the other element, or there may be intermediate elements. Furthermore, “connected” or “coupled” as used herein can include wireless connections or wireless coupling. The term “and / or” as used herein includes all or any units and all combinations of one or more associated listed items.

[0022] The method for detecting and controlling the liquid temperature in a wave-shaped reactor reaction bag provided by this invention aims to solve the above-mentioned technical problems in the prior art.

[0023] The technical solution of the present invention and how the technical solution of the present invention solves the above-mentioned technical problems are described in detail below with specific embodiments.

[0024] This invention provides a method for detecting and controlling the liquid temperature in the reaction bag of a wave-shaped reactor, as illustrated in the schematic diagram below. Figure 1 As shown, it includes: The center temperature of the reaction bag is collected by a center temperature sensor located at the center of the heating tray to obtain the center temperature detection value. The table surface temperature of the reaction bag is collected by a table surface temperature sensor located on the outer ring of the center of the heating tray to obtain the table surface temperature detection value. The center temperature detection value is taken as value A and the table surface temperature detection value is taken as value B. The calculated center temperature value is C, where C = (A + B) / 2. The table surface temperature target value is obtained by calculating value C through the temperature control module. The table surface temperature target value is compared with value B to calculate the table surface heating output duty cycle, thereby controlling the heating temperature of the heating tray.

[0025] According to existing technology, a heating element is installed inside the heating tray to heat the tray, which then transfers heat to the reaction bag. This will not be elaborated further here.

[0026] In this embodiment, the specific range of the center temperature is the central area with a radius of 1 cm, centered on the center of the heating tray. The center temperature sensor is located in this central area. The outer area of ​​the heating tray, excluding the central area, is used to house the table surface temperature sensor.

[0027] The key advantage lies in the greater accuracy of calculating the liquid temperature inside the reaction bag using both the center temperature and the tabletop temperature. The final temperature reflected in this method deviates less from the actual liquid temperature within the reaction bag (controllable to within ±0.1℃). Furthermore, while controlling the heating tray temperature via the tabletop heating output duty cycle, this method continuously monitors the center and tabletop temperatures using both sensors. The temperature control module then continuously adjusts the tabletop heating output duty cycle, creating a dynamic, cyclical monitoring and control system that enhances temperature control accuracy.

[0028] The extended heating tray can be equipped with multiple tabletop temperature sensors arranged sequentially in the opposite direction from the center outwards. The temperature data from these multiple sensors can be used to average the calculations, which can further reduce deviations.

[0029] Optionally, the duration of one swing cycle of the center of the heating tray is set as T1, and the heating cycle of the heating tray is T2; in, During the swing cycle of T1, the center temperature sensor repeatedly collects the center temperature of the reaction bag to obtain the center temperature detection value, and calculates the average of the multiple center temperature detection values ​​to obtain the value A; during the swing cycle of T2, the table surface temperature sensor repeatedly collects the table surface temperature of the reaction bag to obtain the multiple table surface temperature detection values, and calculates the average of the multiple table surface temperature detection values ​​to obtain the value B.

[0030] In this embodiment, for example, the duration of one oscillation cycle T1 at the center of the heating tray is 60 seconds. Therefore, it can be known that T2 is greater than or equal to 60 seconds, meaning that one heating cycle has at least one oscillation cycle (T2). Generally, the center temperature sensor and the tabletop temperature sensor take the temperature value of their corresponding points once per second, thus completing the average calculation.

[0031] It should be noted that by adopting an average value algorithm, the problem of fluctuating detection values ​​caused by insufficient liquid volume and poor contact between the bag and the central temperature sensor and the platform due to gas inflation is solved, resulting in better adaptability of temperature control and improved temperature control stability.

[0032] Extended, the preferred relationship between T2 and T1 is T2 ≥ T1, for example T2 = nT1 (n = 1, 1.5, 2.0, etc.). The significance of this setting is that the heating cycle T2 at least covers the entire swing cycle T1. Firstly, this can effectively ensure that all the liquid in the bag can be heated, greatly avoiding the situation where some liquid in the bag is not heated. Secondly, the heating tray continuously heats during the entire swing cycle in the center of the heating tray, which can avoid sudden temperature changes in the liquid in the reaction bag. As a result, the temperature uniformity of the liquid in the bag will be better, avoiding too many variables from having a positive or negative impact on the detection, and ensuring the detection accuracy.

[0033] In addition, the time point for measuring both the center temperature and the countertop temperature can be arbitrarily selected within their respective cycles, and no restrictions are imposed here.

[0034] Optionally, the count of multiple countertop temperature readings is ten.

[0035] In this embodiment, ten tabletop temperature values ​​are detected during the heating cycle of T2. Therefore, the value of B is the average of the sum of the ten tabletop temperature values.

[0036] Optionally, the interval between two consecutive table surface temperature measurements is one second.

[0037] In this embodiment, it is known that the outer periphery of the reaction bag is more prone to fluctuations or undulations closer to the outer edge of the heating tray. Taking values ​​in one-second increments increases the data collection base and improves the accuracy of the collected data. Similarly, the center temperature sensor can also take values ​​in one-second increments to improve data accuracy. However, in this embodiment, the center temperature sensor typically takes temperature values ​​every five seconds.

[0038] To understand the overall detection logic of the center temperature and tabletop temperature detection values, for example, T2=T1=10 seconds (n is 1), and both the center temperature and tabletop temperature detection values ​​are taken at one-second intervals. If both the temperature readings are counted ten times, then both will start taking readings from the first second, and both will complete the taking of ten temperature readings by the tenth second. If one or both of the temperature readings are counted five times, then the time point for taking the five readings can be any five seconds within the ten-second timeframe.

[0039] Other embodiments can arbitrarily adjust the duration of the T2 and T1 cycles, as well as the count and interval of the center temperature detection value and the table surface temperature detection value, which will not be described in detail here.

[0040] Optionally, the temperature control module calculates the target tabletop temperature by using the PID calculation method to calculate the C value.

[0041] As is known from existing technology, the PID calculation method is proportional-integral-derivative control, which will not be elaborated further. The key point is that the two PID controls in this embodiment can be set individually or simultaneously. Specifically, by using a dual-loop PID (the first PID loop is formed by the preset temperature target value, C value, and the platform temperature target value; the second PID loop is formed by the platform temperature target value, B value, and the heating element) with stroke-based double-comparison adjustment, the problem of large heating fluctuations on the heating tray platform is solved, suppressing excessively high platform temperatures and creating a suitable environment for cell growth in the liquid. It should be noted that in the PID calculation of the platform temperature target value, existing technologies typically set a preset temperature target value in the temperature control module, performing a difference calculation between the preset temperature target value and the C value; this will not be elaborated upon here.

[0042] For ease of understanding, combined with Figure 2 The real-time target temperature value is y(t) or u(t); the set temperature target value is r(t); the set temperature target value is the deviation value between the real-time target temperature value and e(t) = r(t) - y(t) or e(t) = r(t) - u(t). The PID calculates the output value as u(t), which is also known as CV. Additionally, the controlled object in the diagram refers to the aforementioned heating element.

[0043] Optionally, the temperature control module calculates the first control variable value CV1 using a PID calculation method; the preset target temperature value set by the temperature control module is D, and the table surface temperature target value = CV1. A+D.

[0044] Specifically, the theoretically optimal temperature required for the liquid inside the reaction bag is set as the preset target temperature D. The actual measured value (i.e., the C value calculated from the center temperature and tabletop temperature measurements) is then compared with the preset target temperature D to calculate the target tabletop temperature. Figure 1 In step a, the strategy for calculating the target table temperature is as follows: the preset target temperature values ​​D and C, along with the target table temperature, form the first PID loop; the controlled object is the heating element, where the upper limit of the table temperature of the heating tray is set to the sum of the preset target temperature value and the value D, and the target table temperature = CV1. A+ sets the target temperature.

[0045] Specifically, in the calculation of the first PID loop mentioned above: the preset target temperature target value D is r(t), and the calculated center temperature value C is y(t).

[0046] Optionally, the temperature control module calculates the target value of the tabletop temperature using a PID calculation method to obtain the duty cycle of the tabletop heating output.

[0047] Furthermore, the calculation method for the duty cycle of the tabletop heating output is as follows: The temperature control module calculates the second control variable value CV2 using the PID calculation method. The duty cycle time of the tabletop heating output is equal to CV2. T2.

[0048] This embodiment demonstrates the first PID loop. Based on the aforementioned calculation approach, the target value for the platform temperature is r(t), and the detected value for the platform temperature is y(t) based on B. Furthermore, T2 is determined based on the specific time period and is not limited here.

[0049] Therefore, the above demonstrates the calculation process of CV2 and CV2. Combining the calculations, the duty cycle of the table heating output can be obtained.

[0050] Based on the same inventive concept, the present invention provides a wave-type reactor reaction bag liquid temperature detection and control system, including a heating tray, a reaction bag, a center temperature sensor, a platform temperature sensor, and a temperature control module; the reaction bag is placed on the top platform of the heating tray, the center temperature sensor is placed at the center of the heating tray, and the platform temperature sensor is placed on the heating tray and located outside the center temperature sensor; the heating tray, the center temperature sensor, and the platform temperature sensor are respectively connected to the temperature control module.

[0051] As mentioned above, the center temperature sensor and the tabletop temperature sensor detect the temperature at their respective points in real time. The detected data is then processed by the temperature control module and used to control the temperature of the heating elements in the heating tray. Furthermore, multiple tabletop temperature sensors can be installed extending outwards from the center of the heating tray to detect the tabletop temperature at even more points.

[0052] An electronic device includes a memory and a processor that executes commands stored in the memory, the processor executing the commands to implement the method described above.

[0053] The memory includes at least one disk storage device; In this embodiment, it can be understood that the temperature control module in the above system processes data from the central temperature sensor, the table surface temperature sensor, etc., and the resulting executable commands are stored in the memory. The processor processes the executable commands to implement the above method.

[0054] Those skilled in the art will understand that the steps, measures, and schemes in the various operations, methods, and processes discussed in this invention can be alternated, modified, combined, or deleted. Furthermore, other steps, measures, and schemes in the various operations, methods, and processes discussed in this invention can also be alternated, modified, rearranged, decomposed, combined, or deleted. Furthermore, steps, measures, and schemes in the prior art that are similar to those disclosed in this invention can also be alternated, modified, rearranged, decomposed, combined, or deleted.

[0055] In the description of this invention, it should be understood that the terms "center", "upper", "lower", "front", "rear", "left", "right", "vertical", "horizontal", "top", "bottom", "inner", "outer", etc., indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings. They are only for the convenience of describing this invention and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation. Therefore, they should not be construed as limitations on this invention.

[0056] The terms "first" and "second" are used for descriptive purposes only and should not be construed as indicating or implying relative importance or implicitly specifying the number of technical features indicated. Thus, a feature defined as "first" or "second" may explicitly or implicitly include one or more of that feature. In the description of this invention, unless otherwise stated, "a plurality of" means two or more.

[0057] In the description of this invention, it should be noted that, unless otherwise explicitly specified and limited, the terms "installation," "connection," and "joining" should be interpreted broadly. For example, they can refer to a fixed connection, a detachable connection, or an integral connection; they can refer to a direct connection or an indirect connection through an intermediate medium; and they can refer to the internal communication between two components. Those skilled in the art can understand the specific meaning of the above terms in this invention based on the specific circumstances.

[0058] In the description of this specification, specific features, structures, materials, or characteristics may be combined in any suitable manner in one or more embodiments or examples.

[0059] It should be understood that although the steps in the flowcharts of the accompanying figures 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 flowcharts of the accompanying figures may include multiple sub-steps or multiple stages. These sub-steps or stages are not necessarily completed at the same time, but can be executed at different times, and their execution order is not necessarily sequential, but can be performed alternately or in turn with other steps or at least some of the sub-steps or stages of other steps.

[0060] The above description is only a partial embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A method for detecting and controlling the liquid temperature in a wave-shaped reactor reaction bag, characterized in that, include: The center temperature of the reaction bag is collected by a center temperature sensor located at the center of the heating tray to obtain the center temperature detection value, and the table surface temperature of the reaction bag is collected by a table surface temperature sensor located on the outer ring of the center of the heating tray to obtain the table surface temperature detection value. Take the center temperature detection value as value A and take the table surface temperature detection value as value B, and calculate the center temperature value as value C, where C = (A + B) / 2; The target tabletop temperature is obtained by calculating the C value through the temperature control module. The target tabletop temperature is then compared with the B value to calculate the tabletop heating output duty cycle, thereby controlling the heating temperature of the heating tray.

2. The method for detecting and controlling the liquid temperature in the reaction bag of a wave-shaped reactor according to claim 1, characterized in that, in: The duration of one swing cycle of the center of the heating tray is set as T1, and the heating cycle of the heating tray is set as T2; in, During the swing cycle of T1, the center temperature sensor repeatedly collects the center temperature of the reaction bag to obtain the center temperature detection value, and calculates the average of the multiple center temperature detection values ​​to obtain the value A; during the heating cycle of T2, the table surface temperature sensor repeatedly collects the table surface temperature of the reaction bag to obtain the multiple table surface temperature detection values, and calculates the average of the multiple table surface temperature detection values ​​to obtain the value B.

3. The method for detecting and controlling the liquid temperature in the reaction bag of a wave-shaped reactor according to claim 2, characterized in that, The count of the multiple table surface temperature readings is ten.

4. The method for detecting and controlling the liquid temperature in the reaction bag of a wave-shaped reactor according to claim 2 or 3, characterized in that, The interval between two consecutive temperature measurements of the platform is one second.

5. The method for detecting and controlling the liquid temperature in the reaction bag of a wave-shaped reactor according to claim 1, characterized in that, The temperature control module calculates the C value using the PID calculation method to obtain the target value of the tabletop temperature.

6. The method for detecting and controlling the liquid temperature in the reaction bag of a wave-shaped reactor according to claim 1 or 5, characterized in that, The temperature control module calculates the first control variable value CV1 using the PID calculation method; The preset target temperature value set by the temperature control module is D, and the target table temperature value is CV1. A+D.

7. The method for detecting and controlling the liquid temperature in the reaction bag of a wave-shaped reactor according to claim 2, characterized in that, The temperature control module calculates the target temperature of the countertop using a PID calculation method to obtain the duty cycle of the countertop heating output.

8. The method for detecting and controlling the liquid temperature in the reaction bag of a wave-shaped reactor according to claim 7, characterized in that, The calculation method for the duty cycle of the tabletop heating output is as follows: The temperature control module calculates the second control variable value CV2 using the PID calculation method, and the duty cycle time of the table heating output is equal to CV2. T2.

9. A liquid temperature detection and control system for a wave-shaped reactor reaction bag, characterized in that, Includes a heating tray, reaction bag, center temperature sensor, tabletop temperature sensor, and temperature control module; The reaction bag is placed on the top surface of the heating tray, the center temperature sensor is placed at the center of the heating tray, and the surface temperature sensor is placed on the heating tray and located outside the center temperature sensor. The heating tray, the center temperature sensor, and the tabletop temperature sensor are respectively connected to the temperature control module.

10. An electronic device, characterized in that, The method includes a memory and a processor that executes commands stored in the memory, the processor executing the commands to implement the method as described in any one of claims 1-5 above.