Laboratory culture medium integrated preparation equipment and self-adaptive control method

Abstract

The invention discloses laboratory culture medium integrated preparation equipment and a self-adaptive control method, and belongs to the technical field of enzymology or microbiology, and the method comprises the following steps: weighing according to a selected culture medium, loading corresponding process parameters from a database, and starting heating and stirring, the database is stirring torque data corresponding to different temperature points in the dissolving process of different culture media; in the heating and dissolving process, monitoring the temperature and the pH value of the culture medium and the torque calculated based on the current of the stirring assembly in real time; when it is monitored that the temperature and the torque meet preset dissolution completion conditions, the stirring rotation speed is switched to a sterilization mode; a database integrating various formula process parameters is constructed, and a personalized self-adaptive control process is driven, so that the database prestores a complete characteristic parameter set including a torque temperature reference curve and a torque threshold value for each culture medium formula.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of enzymology or microbiology, in particular to temperature reaction control, and specifically to a laboratory culture medium integrated preparation device and a self-adaptive control method. BACKGROUND

[0002] Culture medium is a core carrier for supporting the growth and metabolism of living organisms outside the body, and its preparation quality directly determines the reliability and repeatability of subsequent experimental results. Currently, the mainstream integrated culture medium preparation equipment on the market is designed to meet the needs of industrial mass production. The core control logic and equipment scale of these devices are aimed at large-batch, continuous production scenarios, such as thousands of liters of bioreactor liquid preparation systems. These industrial-grade devices emphasize production efficiency and operational stability, but they have large volumes, high energy consumption, huge initial investments, and complex control systems that require professional personnel to operate and maintain. In the laboratory research and quality control scenarios, the demand patterns are completely different. Laboratory environments usually require small-batch, multi-batch culture medium preparation to meet the needs of high-throughput screening, rapid prototyping, and personalized research. The volume of each preparation may vary from a few liters to a few dozen liters, and the formula changes frequently. Industrial-grade large devices cannot adapt to this flexible, small-scale production rhythm. The large system volume will result in serious raw material waste, and the lengthy cleaning and validation period cannot meet the requirements of rapid switching between multiple batches.

[0003] To try to improve efficiency, some laboratories have introduced semi-automatic heating and stirring devices to simplify the control logic of industrial large-scale liquid preparation systems and attempt to achieve an integrated process from dissolution to sterilization. Such improved devices are usually controlled based on pre-set fixed temperature time programs, i.e., maintaining constant heating power and stirring speed for a set time to complete the dissolution of agar and other coagulants and subsequent thermal sterilization process. However, these solutions still essentially follow the rigid control logic suitable for stable mass production and fail to address the core pain points of small-batch, multi-batch preparation in laboratory settings.

[0004] However, the above technical solutions gradually show deeper limitations in response to laboratory actual application scenarios, that is, there is an essential disconnection between the fixed program control logic and the actual physical evolution process of the culture medium, and it cannot adapt to the dynamic characteristics of different formulations and small batch preparation. The typical solid or semi-solid culture medium represented by agar experiences a highly nonlinear and strong dynamic phase change process during heating. In the initial stage, it is a low-viscosity suspension. As the temperature rises to a certain point, the agar molecules rapidly hydrate and swell, and the system viscosity rises sharply, forming a uniform colloid. If the stirring is insufficient or the local temperature is too high, it is easy to cause clumping, charring or uneven dissolution. Once completely dissolved, the system enters a high-viscosity steady state. At this time, if high-intensity stirring is continued, a large amount of foam will be induced, which not only affects the volume accuracy, but also may cause contamination risk due to foam overflow in the subsequent sterilization stage. Correspondingly, the core goal of the sterilization stage has changed from promoting mass transfer to precise temperature control to accumulate effective sterilization value, requiring a highly stable environment. It can be seen that although dissolution and sterilization occur continuously in the same container, their requirements for stirring intensity and heat input strategy are completely opposite, forming a process contradiction that is difficult to reconcile within the integrated equipment. The existing fixed program control method cannot perceive this key physical transition point. Under small batch conditions, the thermodynamic behavior of the material is different from that under large batch conditions, leading to the fact that the general program is more likely to cause incomplete dissolution or excessive stirring, thereby affecting the uniformity and sterility assurance level of the final product. When faced with the differentiated dissolution kinetics exhibited by different formulations, the general program is even more inadequate and must rely on the experience of the operator to repeatedly adjust, which deviates from the original intention of automation and standardization. SUMMARY

[0005] The present application overcomes the shortcomings of the prior art and provides a laboratory culture medium integrated preparation device and a self-adaptive control method.

[0006] To achieve the above-mentioned purpose, the technical scheme adopted by the present application is as follows: a self-adaptive control method for laboratory culture medium integrated preparation, comprising the following steps: S1. After weighing according to the selected culture medium, load the corresponding process parameters from the database, and start heating and stirring, wherein the database is the stirring torque data corresponding to different temperature points in the dissolution process of different culture media; S2. During the temperature rising and dissolution process, the temperature, pH value and torque calculated based on the current of the stirring assembly of the culture medium are monitored in real time; S3. When the temperature and torque meet the preset dissolution completion condition, the stirring speed is switched to the sterilization mode; S4. In the sterilization mode, the target sterilization temperature is maintained and the sterilization value is calculated cumulatively; S5. After sterilization, the culture medium is cooled to 70-80℃ and is divided into small batches.

[0007] In a preferred embodiment of the present application, in step S1, the database comprises a torque-temperature reference curve generated for each medium formula.

[0008] In a preferred embodiment of the present application, in step S1, the process parameters at least include: target temperature of the dissolution stage, target temperature of the sterilization stage, torque threshold value, and the corresponding torque-temperature reference curve.

[0009] In a preferred embodiment of the present application, in step S2, the torque is obtained by collecting the real-time current signal of the stirring assembly and indirectly calculating based on the pre-calibrated motor torque constant.

[0010] In a preferred embodiment of the present application, in step S3, the dissolution completion condition is that the medium temperature reaches or exceeds 85°C, and the torque continuously reaches or exceeds the preset torque threshold value.

[0011] In a preferred embodiment of the present application, in step S3, when switching to the sterilization mode, the stirring speed is reduced to a lower set value that is sufficient to maintain temperature uniformity but not prone to foam.

[0012] In a preferred embodiment of the present application, in step S4, the sterilization endpoint is determined by real-time monitoring of the sterilization temperature and calculating the cumulative sterilization value F0, and the sterilization is determined to be complete when the F0 value reaches the preset target.

[0013] In a second aspect, the present application provides a laboratory medium integrated preparation device, comprising: A container body, the inner wall of which is used to contain the medium, and the outer wall and the inner wall form a sandwich layer; A stirring assembly fixedly installed at the top of the container body; A dispensing assembly located at the bottom of the container body for dispensing the prepared medium; A detection and control unit for detecting and executing an adaptive control program.

[0014] In a preferred embodiment of the present application, the outer wall of the container body is provided with a heating assembly and a cooling assembly, respectively, and the heating assembly and the cooling assembly are connected in the sandwich layer of the container body; the dispensing assembly includes a connecting channel screw-connected to the bottom of the container body and a valve sleeved on the outer wall of the connecting channel.

[0015] In a preferred embodiment of the present application, the detection control unit comprises a temperature sensor, a torque detection unit and a control unit, the temperature sensor is arranged on the inner wall of the container body for monitoring the temperature of the culture medium; the torque detection unit is used to calculate the torque based on the current signal of the stirring assembly; the control unit is connected with the temperature sensor, the torque detection unit, the stirring assembly, the heating assembly, the cooling assembly and the valve, and the control unit is used to execute the adaptive control program.

[0016] The present application solves the defects in the background art and has the following beneficial effects: (1) By constructing a database integrating multiple formula process parameters and driving personalized adaptive control process, the database pre-stores a complete set of characteristic parameters including torque temperature reference curve and torque threshold for each culture medium formula, and establishes a deep understanding of formula dissolution kinetics and offline calibration. When the user selects a specific formula, the system automatically loads the corresponding parameters, and the preparation process of different formulas can be standardized and reproduced without manual intervention, which meets the flexible production needs of small batch and multiple varieties in the laboratory, realizes the leap from general program to special parameters, and provides a standardized solution that can be selected and used immediately. Compared with the dilemma of relying on operator experience to repeatedly debug different formulas, the database supports online learning function to enable the system to continuously optimize the process model according to actual operation data, so that the device process knowledge can evolve itself.

[0017] (2) By using real-time torque signal as the core process state variable and combining the constructed physical property response type stage recognition and switching mechanism, the system can capture the nonlinear jump of system viscosity caused by hydration swelling of agar and other coagulants during the heating process, which is specifically manifested as a sharp increase in stirring resistance. The system can accurately determine the physical turning point of dissolution completion by continuously comparing the real-time torque with the preset threshold and reference curve, realize adaptive seamless switching between the removal stage and the sterilization stage, and completely avoid incomplete dissolution or excessive stirring caused by fixed time program. Compared with the rigid time control logic, the intelligent decision-making dynamically matches the process essence, and this switching based on physical property signal ensures that the material is in a completely dissolved homogeneous state when sterilization starts, which lays a foundation for subsequent aseptic process.

[0018] (3) The temperature-torque combined constraint strategy is introduced for the culture medium components to achieve active protection of sensitive materials. For formulations marked as heat-sensitive, the system actively limits the heating rate after warming up to the critical temperature range, and simultaneously monitors the torque rate reflecting the viscosity change rate. Once a sharp rise in torque is detected, indicating that the Maillard reaction or protein denaturation may be occurring, the system immediately suspends heating and only maintains stirring, and then resumes gentle warming after the change subsides. This strategy actively inhibits component degradation by controlling heat and mass transfer processes based on chemical reaction kinetics, significantly reducing the destruction rate of easily degradable components at high temperatures, preserving the effectiveness of the culture medium. Compared to the existing treatment of heat-sensitive formulations that ignore the details of physical properties and cause component damage, the system realizes intelligent adaptation and protection of complex formulations, and expands the range of culture medium formulations that can be safely processed by the device. BRIEF DESCRIPTION OF DRAWINGS

[0019] In order to more clearly illustrate the technical solutions in the embodiments of the present application or the prior art, the following will briefly introduce the drawings needed to be used in the embodiments or prior art description. Obviously, the drawings in the following description are only some embodiments of the present application, and other drawings can be obtained by those skilled in the art without creative labor. Figure 1 is a perspective view of a preferred embodiment of the present application; Figure 2 is a circuit principle diagram of a preferred embodiment of the present application; Figure 3 is a flowchart of a preferred embodiment of the present application; Figure 4 is a self-adaptive control principle diagram of a preferred embodiment of the present application; Figure 5 is a torque-temperature characteristic curve diagram of a preferred embodiment of the present application.

[0020] In the figure: 1, container body; 2, stirring assembly; 3, heating assembly; 4, cooling assembly; 5, connecting channel; 6, valve. DETAILED DESCRIPTION

[0021] The technical solutions in the embodiments of the present application will be described clearly and completely below with reference to the drawings in the embodiments of the present application. Obviously, the described embodiments are only some of the embodiments of the present application, not all. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor are within the scope of protection of the present application.

[0022] In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present application. However, it will be recognized by one skilled in the art that the present application can be practiced without the specific details described herein. In other instances, well-known methods, procedures, components and circuits have not been described in detail as not to unnecessarily obscure aspects of the present application.

[0023] In the description of the present application, it needs to be understood that the terms "center", "longitudinal", "transverse", "upper", "lower", "front", "back", "left", "right", "vertical", "horizontal", "top", "bottom", "inner", "outer" and the like indicate the orientation or positional relationship based on the orientation or positional relationship shown in the drawings, and are only for the purpose of facilitating the description of the present application and simplifying the description, and do not indicate or imply that the device or element referred to must have a particular orientation, be constructed and operated in a particular orientation, and therefore cannot be understood as limiting the scope of protection of the present application. In addition, the terms "first", "second" and the like are only for descriptive purposes and cannot be understood as indicating or implying relative importance or implicitly indicating the number of the technical features indicated. Therefore, the features defined with "first", "second" and the like can explicitly or implicitly include one or more features. In the description of the present application, unless otherwise specified, the meaning of "a plurality of" is two or more.

[0024] In the description of the present application, it needs to be understood that unless otherwise explicitly specified and limited, the terms "mounting", "connection", "connection" should be understood broadly, for example, it can be fixed connection, or detachable connection, or integral connection; it can be mechanical connection, or electrical connection; it can be directly connected, or indirectly connected through intermediate medium, or it can be the communication inside two elements. For those skilled in the art, the specific meaning of the above terms in the present application can be understood through specific circumstances.

[0025] SUMMARY As a core material for supporting microorganisms, cell culture and biological reaction, the preparation process of the medium usually covers multiple key steps such as dissolution, sterilization and cooling. Especially for semi-solid or solid medium containing agar and other coagulants, the physical properties show significant nonlinear change during heating process. In the early stage of temperature rise, the system shows low viscosity suspension state; as the temperature rises, the coagulant molecules gradually hydrate and swell, the viscosity of the system rises sharply and finally forms a uniform colloid; if high-intensity stirring is continued thereafter, it is easy to cause foam, affecting the precision of dispensing and increasing the risk of contamination in the sterilization stage, therefore, the requirements of stirring and heating for the two stages of dissolution and sterilization are completely different, and the traditional programmed control method based on fixed time and temperature cannot accurately perceive the physical property transition point, resulting in the disconnection between process control and actual material state.

[0026] Applicants find that the current laboratory commonly used integrated medium preparation equipment is mostly used rigid control logic of industrial mass production, relying on the preset fixed temperature-time program operation; such way can not consider the difference of different formulations in the dissolution kinetics, also can not adapt to the flexible demand of laboratory small batch, multiple batches, frequent change of formula, in the actual application, the fixed program often because of unable to identify the dissolution turning point of agar and other components, resulting in incomplete dissolution, local coking or excessive stirring to produce foam and other problems; especially in the processing of heat-sensitive components, continuous high temperature heating can easily cause Maillard reaction or protein denaturation, reduce the activity of the medium, these control blind area not only affects the uniformity and sterility assurance level of the medium, but also forces the experimental personnel to rely on experience to adjust repeatedly, reduces the preparation efficiency and process repeatability.

[0027] Applicants further realize that the concept of this method is derived from the analysis of the lack of perception of existing equipment, the traditional equipment only monitors the temperature, time and other conventional parameters, but ignores the torque signal which can directly reflect the state change of the material. By introducing torque into the control logic, the equipment is essentially given a sense of touch, which enables it to perceive the key process state of medium viscosity, thereby simulating the experienced judgment of skilled operators, achieving intelligent, adaptive stage switching and process adjustment, and ultimately achieving the goal of high-quality, standardized preparation of small-batch, multi-variety medium.

[0028] In view of the above problems, the core idea of the method is derived from the in-depth observation of the physical nature of the medium dissolution process. The sudden change of the system viscosity directly manifests as a significant increase in stirring resistance, and the current or torque signal of the stirring assembly can indirectly reflect this physical property change in real time. Based on this discovery, the present application establishes a torque-temperature characteristic database for different formulations in advance, and uses the torque, a key physical response signal, as a basis for process state judgment, and tracks it in real time and compares it with the reference curve in the database. When the torque reaches or exceeds the specific threshold value of the formulation as the temperature rises, the system determines that the dissolution is complete, and automatically and smoothly switches to the sterilization stage with accurate temperature control as the core. This method realizes a fundamental change from time program control to physical property response control, enabling the equipment to automatically adapt to the dissolution characteristics of different formulations, ensuring complete dissolution while avoiding excessive stirring, and significantly reducing the dependence on operator experience, providing a reliable technical foundation for the standardization, automation and flexibility of medium preparation in laboratory environment.

[0029] Example 1:

[0030] Exemplary method: As Figure 3 shown, an adaptive control method for laboratory medium integrated preparation includes the following steps: S1, after weighing according to the selected medium, load the corresponding process parameters from the database, and start heating and stirring, wherein the database is the stirring torque data corresponding to different temperature points in the dissolution process of different media; S2, in the process of temperature rising and dissolution, the temperature, pH value and torque calculated based on the current of the stirring assembly of the medium are monitored in real time; S3, when the temperature and torque meet the preset dissolution completion condition, the stirring speed is switched to the sterilization mode; S4, in the sterilization mode, the target sterilization temperature is maintained and the sterilization value is accumulated; S5, after sterilization, the medium is cooled to 70-80 DEG C and is divided into portions.

[0031] The core of the application is that by monitoring the torque change in the medium dissolution process in real time, intelligent switching in the preparation stage is realized; in view of the defect that the prior art cannot accurately perceive the material state, a torque-temperature characteristic database is established for different formulations in advance; during actual preparation, the system compares the real-time torque signal with the reference curve and threshold value in the database, and once the signal indicates that the dissolution is completed, it is automatically switched from the dissolution mode to the sterilization mode. This realizes the transformation from fixed program control to physical property response adaptive control, effectively ensures the product quality and process stability.

[0032] Each step will be described in detail below.

[0033] In S1 step, the database is built to realize the physical property response type adaptive control in the medium preparation process, and the dissolution characteristics of different formulations are converted into process parameters that can be recognized and called by the equipment, and the knowledge base of torque-temperature characteristic curve, key threshold value and process condition is integrated.

[0034] Specifically, the dissolution behavior of each medium formulation under standardized experimental conditions is systematically collected, and during the experiment, under the controlled heating and stirring conditions, the corresponding relationship between the medium temperature and the stirring assembly current is continuously recorded, forming the original data sequence of the torque change with temperature in the dissolution process of the formulation.

[0035] Further, by smoothing, denoising and feature extraction of the original data, a torque-temperature reference curve representing the typical dissolution behavior of the formulation is generated; from the curve, further key process parameters are calibrated, including the torque threshold value of dissolution completion, the target temperature of the dissolution stage, the target temperature of the sterilization stage, and the temperature rising rate limit and torque change rate warning value for heat-sensitive formulations, etc. These parameters are stored together with the corresponding formulation identification, constituting a record of the database.

[0036] Further, when the user selects a certain formula, the system automatically loads the corresponding reference curve and parameter set from the database, and makes real-time judgment based on this; in the dissolution stage, the system continuously monitors the actual temperature and torque signals, and compares them with the reference curve in the database; when the measured torque reaches or exceeds the preset threshold value of the formula and the temperature meets the conditions, the system determines that the dissolution is complete, and automatically switches to the sterilization stage; for formulas marked as heat-sensitive, the database also stores protective strategy parameters, and the system will dynamically adjust the heating behavior according to the torque change rate during the heating process to avoid degradation of the ingredients.

[0037] It should be noted that the target temperature in the dissolution stage refers to a specific temperature set value determined by experiment according to the physical and chemical properties of the coagulant and other components in the medium formula, which is used to achieve the full dissolution and homogenization of the components. This parameter ensures that the system can reach the thermodynamic conditions required for complete hydration, swelling and formation of a uniform colloidal solution of solid components during the heating process, providing a reliable temperature benchmark for physical property judgment based on torque monitoring.

[0038] It should be noted that the target temperature in the sterilization stage is a constant temperature maintenance value set based on the thermal death kinetics parameters of the target microorganism, which is used to achieve effective sterilization; this temperature is designed to ensure that the sterilization value can be accumulated at a rate that meets the specifications during the sterilization stage, and its stable control is directly related to the reliability and reproducibility of the microorganism killing effect, which is a key process parameter to ensure the sterile state of the final product.

[0039] It should be noted that the torque threshold is a critical value representing the stirring resistance corresponding to the expected viscosity, obtained by experimental calibration of the rheological properties of a specific formula in a fully dissolved state; this threshold is one of the criteria for determining the completion of the dissolution stage, when the real-time monitored torque continuously reaches or exceeds this value and the temperature conditions are met simultaneously, the system determines that the physical property transition is complete, and triggers the process stage switching.

[0040] It should be noted that the torque-temperature reference curve is a characteristic curve representing the relationship between viscosity and temperature of a specific formula, established by collecting torque data at different temperature points during the standard dissolution process of the formula; this curve serves as a comparison benchmark for process state, to determine whether the dissolution process meets the expected trajectory in real time, and provides process context for the application of torque threshold, thereby realizing the transition from fixed program control to physical property response adaptive control (as shown in Figure 5 ).

[0041] Specifically, after selecting the target medium formula, the control unit immediately loads the corresponding complete process parameter set from the database, which includes the target sterilization F0 value , the target temperature in the dissolution stage , and the target temperature in the sterilization stage , torque threshold , torque-temperature reference curve , and stirring speed upper limit , etc. Key process parameters, wherein the target temperature of the dissolution stage is usually set to 92-98℃, the target temperature of the sterilization stage is fixed to 121℃, and the torque threshold is determined in the range of 0.8-3.2 N·m according to the agar content.

[0042] Further, the system performs hardware self-diagnosis procedures, including motor stall test, temperature sensor detection and heating loop verification, to ensure that each component is working properly. After initialization is completed, the system starts the heating module and controls the temperature rise according to the PID algorithm, and at the same time, starts the stirring module and runs at an initial speed usually set to 60% of the maximum speed. The preparation process of the medium is officially started.

[0043] During the temperature rise and dissolution process in S2 step, the system implements multi-dimensional real-time monitoring. The torque signal is obtained by collecting the three-phase current of the brushless direct current motor, and after Clarke transformation and Park transformation, the q-axis current component is calculated, and then the real-time torque value is indirectly obtained by combining the pre-calibrated motor torque constant. The specific calculation formula is: is the motor torque constant.

[0044] is the q-axis current component at the moment.

[0045] The initial stirring speed is set to , and the heating power is adjusted according to the proportional integral differential (PID) algorithm, aiming to make the medium temperature approach at a set slope. During this process, the control unit collects the temperature and torque at a period of 100ms, and executes the following judgment logic: if the current temperature and torque are greater than or equal to the torque threshold for 5 consecutive sampling periods, it is determined that the agar has been completely dissolved, and the stage switching preparation state is entered; otherwise, the current control strategy is maintained. In addition, in order to prevent local overheating from causing carbonization, the system compares the difference between the bottom temperature and the body temperature in real time , if , the heating power is automatically reduced by 10%, and the stirring speed is increased to , until , and then the original strategy is restored.

[0046] When the dissolution completion condition in S3 step is met, the central control unit immediately executes the control strategy switching: first, the stirring speed is linearly reduced to ​​= 30 rpm, a speed sufficient to maintain temperature uniformity but insufficient to induce significant foaming; second, the heating target temperature is switched from 121 °C to 121 °C, and the sterilization F0 value accumulation algorithm is enabled. The F0 value is calculated in real time according to the following formula: ; The cumulative sterilization value is calculated in real time, where for Bacillus stearothermophilus, 10 °C, and during the switching process, the system also references the signal of the foam optical monitoring subsystem for redundant verification. If an abnormality in the foam is detected, the switching is delayed and the foam problem is prioritized, ensuring the rationality and safety of the stage switching.

[0047] In the sterilization mode of S4, the system adopts a feedforward-feedback composite control strategy to maintain precise temperature control. The feedforward part is based on the container heat capacity model to estimate the basic heating power, and the feedback part adopts an incremental PID algorithm, whose control law is: ; wherein, , , are the adjusted control parameters. This control strategy ensures the 121 °C sterilization temperature; at the same time, the system calculates the cumulative F0 value in real time with a step size of 1 s, accurately reflecting the actual sterilization effect through the integral formula; when the cumulative F0 value reaches the target value set by the formula, the system determines that the sterilization is complete. This judgment method based on the kinetics of microbial heat-induced death is more scientific and reliable than fixed-time control.

[0048] In S5, after sterilization is complete, the system immediately turns off the heating module and starts the cooling module, and maintains stirring at 30 rpm until the medium temperature drops below 80 °C, which can prevent the container from deforming due to thermal stress or agar precipitation.

[0049] It should be noted that after preparation is complete, the system automatically records complete operation data and generates a standard audit tracking log, providing a basis for product quality traceability. At the same time, it also calculates the mean square error: ; according to the degree of agreement between this run data and the reference curve, in order to evaluate whether the parameters need to be self-optimized, which embodies the intelligent characteristics of the system.

[0050] Example 2: Exemplary system: This embodiment is further refined on the basis of Example 1, with respect to the construction of the database, self-optimization, and protection strategy for heat-sensitive formulations.

[0051] Specifically, the predetermined experimental conditions use a fixed volume of solvent in a geometrically standardized container, with a constant initial stirring speed (30 rpm) and a constant initial temperature (20 °C). ), and constant heating power ( Heating is performed; the mathematical significance of this standardized condition is that it ensures the heat input ( ), and fluid shear conditions ( To ensure consistency across different experimental batches, thus ensuring the collected torque-temperature data sequence. It possesses strict comparability, laying the foundation for subsequent establishment of reliable statistical models and data fusion. Represents time.

[0052] Specifically, after obtaining the original data sequence, the core task is to generate a smooth torque-temperature reference curve that represents the typical dissolution behavior of the formulation. This process includes data smoothing and curve fitting.

[0053] It should be noted that the data smoothing uses the moving average method. To suppress sampling noise and random fluctuations, the original torque data sequence is first smoothed. Smoothing is performed. This invention uses a window size of [size missing]. A simple moving average method. For temperature indexes. The smoothed torque value at the data point. Calculated using the following formula: ; in, This algorithm effectively filters out high-frequency noise, resulting in a smoother data sequence that better reflects the trend. .

[0054] It should be noted that the feature extraction process is based on the continuous monitoring of the first derivative of the data and the threshold judgment logic to identify the starting point of rise. This feature point is defined as the inflection point temperature at which the torque signal leaves the baseline noise band and begins to show significant nonlinear growth. Its identification logic relies on setting a slope threshold. When the average slope of multiple consecutive data points continues to exceed this threshold, it is determined as a physical sign that the dissolution process has started, indicating that the coagulant molecules have begun to enter the hydration and swelling stage.

[0055] Furthermore, the maximum slope point is located by using an extreme value search algorithm. This point corresponds to the temperature position where the first derivative of the torque-temperature curve reaches its maximum value. Mathematically, it is represented as the inflection point of the curve, and physically, it reflects the core stage of the phase transition where the viscosity of the system increases at the maximum rate.

[0056] Furthermore, by identifying a continuous data range in which the absolute value of the first derivative of torque with respect to temperature remains consistently below a preset tolerance close to zero, it is determined that the dissolution kinetics process is essentially complete and the system has reached viscous-fluid equilibrium. The statistically average torque calculated based on this plateau period data is then directly used as the threshold for determining the completion of dissolution. The core parameters of the system ensure the physical accuracy and reliability of the stage switching criterion.

[0057] It should be noted that the curve fitting adopts the least square method, and then the smoothed discrete data points are fitted into a continuous reference curve, and the present application adopts the polynomial least square method for fitting. The goal is to find a quadratic polynomial function, the formula is as follows: ; So that the sum of squares of the difference between the fitting value of the polynomial at all data points and the actual smoothed value (i.e. residual sum of squares) is minimized. Mathematically, the coefficient vector is solved to minimize the objective function, the formula is as follows: ; By solving this optimization problem, the optimal coefficient can be obtained, and thus the unique torque-temperature reference model of the formula is established From the model curve, the key torque threshold can be directly calibrated. For example, take 95% of the average torque after the curve enters the platform region.

[0058] Further, the self-learning optimization compares the real-time torque-temperature data sequence collected during each preparation task with the reference curve stored in the database; calculate the mean square error (MSE) of the measured data points and the reference curve at the same temperature interval. If three batches are successfully completed in succession, and the average MSE is lower than the preset learning trigger threshold (for example, 0.05 N 2 ·m 2 ), the system determines that the current operation is stable and well matched with the model. Subsequently, the system starts the learning algorithm, uses the torque data of the three batches to update the torque value of the corresponding temperature point on the original reference curve using the moving average method, and adjusts the torque threshold correspondingly, thereby realizing the progressive optimization of the process model and enabling the control strategy to be self-adaptive to small changes in equipment state and raw material batches.

[0059] Example 3: Exemplary method: This embodiment is based on embodiment 1, and focuses on supplementing the calibration method of torque calculation and the control strategy of the cooling stage.

[0060] Specifically, the pre-calibration method of the motor torque constant is as follows: during the equipment debugging stage, temporarily couple the stirring assembly with a high-precision offline torque sensor. Make the motor run at a plurality of different constant speeds under no load, record the corresponding q-axis current at this time, and record the stable value under each load. The torque constant The ratio of the load torque increment to the q-axis current increment is calculated, and the average value is obtained, that is, This method effectively eliminates the influence of motor friction and no-load loss, ensuring the accuracy of torque conversion.

[0061] It should be noted that in step S6, after sterilization is completed, the system turns off the heating module and starts the cooling module control unit to set a target cooling rate. The system monitors the medium temperature in real time and dynamically adjusts the power of the cooling module using the PID algorithm to make the actual cooling rate follow the target value. The medium is cooled from the sterilization temperature to the set dispensing temperature range smoothly; this controlled cooling strategy avoids damage to the container due to excessive cooling stress or abnormal agar gel structure, and also prevents degradation of active ingredients due to slow cooling, further ensuring product quality.

[0062] Example 4: The device of the present application is used to prepare, and the LB agar medium formula is selected for preparation. The corresponding parameters are loaded from the database: the target sterilization F0 value ( ) is 15.0 min, the target temperature during the dissolution stage ( ) is 95℃, the target temperature during the sterilization stage ( ) is 121℃, the torque threshold ( ) is 2.56N·m, and the upper limit of the stirring speed ( ) is 200rpm.

[0063] After the system is started, it enters the self-adaptive control of the dissolution stage, and the initial stirring speed is set to 120rpm. The heating module is controlled to increase the temperature using the PID algorithm, and the target temperature is 95℃. During the temperature increasing process, the control unit continuously monitors the body temperature and the stirring torque. When the monitored body temperature reaches 85℃ and the real-time torque is continuously not lower than 2.56N·m for 5 consecutive sampling periods, the system determines that the agar has been completely dissolved, and immediately triggers the stage switching. During the switching process, the stirring speed is linearly reduced to 30rpm within 2s, the heating target temperature is switched to 121℃, and the F0 value accumulation algorithm is started. During the entire dissolution stage, the system effectively prevents local overheating by monitoring the bottom and body temperature difference ( ), and no coking phenomenon occurs.

[0064] After entering the sterilization stage, the system uses a feedforward-feedback composite control strategy to accurately maintain a constant temperature of 121℃. When the calculated F0 value accumulation reaches 15.0min, the system determines that the sterilization is complete, automatically turns off the heating and enters the cooling program, maintains low-speed stirring until the temperature drops to below 80℃, and finally prompts the preparation to be completed.

[0065] Comparative Example 1: LB agar medium of the same formulation was prepared using a commercially available fixed time program control device. The device was set to dissolve phase fixed heating for 10 minutes (95°C) and sterilization phase fixed maintaining 121°C constant temperature for 15 minutes.

[0066] Comparative Example 2: LB agar medium of the same batch was prepared using the device of the present application without using its torque feedback function, only relying on temperature and time parameters for phase control.

[0067] The results are as follows:

[0068] By comparing Example 4 and Comparative Example 1, it can be seen that Comparative Example 1 uses fixed time program control, with a dissolve phase fixed heating for 10 minutes and a sterilization phase fixed maintaining 121°C constant temperature for 15 minutes. This rigid control method completely relies on pre-set time and cannot sense the actual physical state of the medium. Agar and other polysaccharides undergo a dynamic process of hydration, swelling, and dissolution during heating, and their viscosity changes have formulation specificity and batch volatility. Fixed time control often ends heating too early when agar has not completely dissolved (viscosity has not reached a stable plateau), resulting in incomplete hydration of some agar molecules, forming microscopic gel particles and affecting medium uniformity. On the contrary, it may continue to stir strongly after the dissolution is completed, causing mechanical shear fracture of high molecular chains and excessive foaming, denaturing and aggregating of surfactants such as proteins at the gas-liquid interface, increasing the risk of foam overflow during the sterilization phase. In addition, fixed sterilization time cannot adaptively compensate for temperature fluctuations, which may result in insufficient F0 value accumulation (such as 83.3% compliance rate in the table), incomplete killing of microbial spores, and reduced sterile pass rate. Local overheating can also cause Maillard reaction between reducing sugars and amino acids, producing brown substances and inhibitors, affecting medium pH and cell growth performance.

[0069] It can be seen from the comparison of Example 4 and Comparative Example 2 that: although Comparative Example 2 uses the hardware of the present application, the torque feedback function is disabled, and only relies on temperature and time parameters for control, the appropriate torque feedback mechanism in Example 5 can capture the viscosity jump in real time, and switch to the low stirring speed sterilization stage at the moment when the agar is completely dissolved, which not only ensures the completeness of the dissolution, but also avoids excessive stirring; and Comparative Example 2 lacks torque signal and can only rely on temperature threshold (such as 85℃) for judgment, but temperature is only a necessary condition for dissolution but not a sufficient condition. In the actual heating process, the agar may not have been completely dissolved when the temperature reaches 85℃ (especially in small batch preparation, heat transfer is faster, but the dissolution kinetics is not synchronized), at this time, the premature switching will lead to incomplete dissolution, and there are incomplete hydration of agar micelles in the medium, which will form local hardness difference after cooling, affecting the surface flatness. On the contrary, if the dissolution has actually been completed but the system has not sensed it, continued strong stirring will promote air entrainment, forming stable foam, increasing the risk of contamination in the sterilization stage, and possibly causing degradation of heat-sensitive components (such as vitamins, growth factors) due to mechanical shear and oxidation; Therefore, although Comparative Example 2 is better than Comparative Example 1 in F0 value compliance rate, surface flatness, pH stability and sterility qualification rate, it is still significantly lower than Example 1, which reflects the irreplaceable role of torque as a direct representation of physical properties in adaptive control.

[0070] As shown in Figure 1 , Figure 2 and Figure 4 , the present application provides a laboratory medium integrated preparation equipment, specifically, the container body 1 adopts a double-layer jacket structure, the inner wall forms a medium containing cavity, the outer wall and the inner wall form a interlayer for installing the coil for circulating cooling medium, the top is provided with a feeding port for feeding medium dry powder or liquid raw material; the bottom is designed as a cone or arc shape to facilitate complete discharge of the material.

[0071] Specifically, the stirring assembly 2 is fixedly installed at the top center position of the container body 1 and is sealed and fixed by threaded connection, including a brushless DC motor, a speed reduction mechanism, a stirring shaft and stirring blades, the motor drives the stirring shaft to rotate the blades to realize mixing, dissolution and temperature homogenization of the medium.

[0072] Specifically, the sub-packaging assembly is bolted to the container body 1 through the connecting channel 5 at the bottom of the container body 1, the outer wall of which is sleeved with the valve 6, which is preferably a diaphragm valve controlled by an electric valve controlled by the control unit signal to open and close, for sub-packaging the prepared medium cooled to a set temperature into a culture dish or a liquid storage bottle, and the end of the connecting channel 5 away from the container body 1 is provided with a sterile interface.

[0073] It should be noted that the sterile interface is preferably an α-β type sterile interface, the α component of which is fixedly installed at the outlet of the connecting channel 5, and the β component is pre-installed at the inlet of the receiving container.

[0074] It can be understood that the valve 6 is located upstream of the sterile interface, when the valve 6 is opened, the culture medium is transferred to the receiving container through the established sterile flow channel under the action of gravity, after the dispensing, the valve 6 is closed, and the α-β interface can be safely disconnected, the whole process is completed in a closed system under the protection of a clean environment, and the risk of environmental microbial contamination is eliminated.

[0075] Preferably, a conveying mechanism can be arranged at the bottom of the discharge faucet according to requirements, and a capacity tank with different capacities is placed on the conveying mechanism to realize automatic dispensing.

[0076] Specifically, the heating assembly 3 is externally connected to a circulating heat medium, and the circulating heat medium is preferably heat conducting oil. After being heated in an external heating device, the heat conducting oil is pumped into the inner wall jacket of the container body 1 through the injection pipe driven by a circulating pump; when the heat conducting oil flows in the jacket cavity, the heat is conducted to the culture medium in the tank through the metal tank wall, thereby achieving uniform heating of the culture medium.

[0077] Specifically, the cooling assembly 4 is externally connected to circulating cooling water driven by an external circulating pump, and a closed circulating coil pipe is formed between the injection pipe and the container body 1 interlayer to rapidly reduce the temperature of the culture medium after sterilization is completed.

[0078] It should be noted that the cooling assembly 4 integrates a circulating coil pipe made of metal pipes with good heat conduction performance, which is installed in the interlayer inner wall of the container body 1 in a coaxial winding structure and is continuously wound in a spiral shape.

[0079] Specifically, the temperature sensor is a platinum resistance installed on the top and bottom inner walls of the container to monitor the temperature of the culture medium in real time.

[0080] Specifically, the weight sensor is integrated at the bottom of the container body 1 and used to weigh the dry powder or liquid raw material of the culture medium in the initial preparation stage.

[0081] Specifically, the pH probe is installed on the inner wall of the container body 1, and the probe part is immersed below the liquid level of the culture medium to monitor the pH value change of the culture medium in the heating and dissolving and sterilization process in real time and online.

[0082] Specifically, the torque detection unit indirectly calculates the real-time torque by collecting the three-phase current of the stirring assembly 2, calculating the q-axis current through Clarke-Park transformation, and combining the pre-calibrated motor torque constant, and the signal directly reflects the viscosity change of the culture medium, thereby providing a key judgment basis for stage switching.

[0083] Specifically, the control unit is a PLC, which receives temperature and torque signals, outputs control instructions to the stirring assembly 2 to adjust the rotating speed, and outputs control instructions to the heating assembly 3 and the cooling assembly 4 to adjust the power, and controls the opening and closing of the valve 6, and has a built-in adaptive control program to realize the full-process automation from dissolving, sterilizing to cooling.

[0084] When the application is used, first, the corresponding process parameters are loaded from the pre-built database according to the selected medium formula, including the torque-temperature reference curve, the dissolving target temperature and the torque threshold, etc. Then, the system starts the heating assembly 3 and the stirring assembly 2 to start warming and dissolving the medium. During this process, the control unit monitors the temperature of the medium in real time, and indirectly calculates the real-time torque by processing the current signal of the stirring assembly 2. When it is monitored that the temperature reaches or exceeds 85℃ and the real-time torque continuously reaches or exceeds the preset torque threshold of the formula, the system determines that the dissolving stage is completed, and immediately switches the control mode to the sterilization mode. In the sterilization mode, the stirring rotating speed is automatically reduced to the minimum rotating speed required to maintain uniform temperature, while the system accurately controls the temperature at a constant sterilization target temperature, and calculates the accumulated sterilization value in real time until the set requirement is met. After sterilization, the system starts the cooling assembly 4 to cool the medium to 70-80℃, and through the connecting channel 5 and the valve 6 of the bottom dispensing assembly, the sterile dispensing of the medium is completed through the α-β type sterile interface in the A-level clean environment, so as to realize the full-process adaptive integrated preparation from dissolving, sterilizing to cooling and dispensing.

[0085] According to the ideal embodiments of the application, through the above description, relevant personnel can make various changes and modifications without deviating from the technical idea of the application. The technical scope of the application is not limited to the content in the specification, and must be determined according to the scope of claims.

Claims

1. A self-adaptive control method for integrated preparation of laboratory media, characterized in that, The method comprises the following steps: S1, after weighing according to the selected medium, load the corresponding process parameters from the database, and start heating and stirring, wherein the database is the stirring torque data corresponding to different temperature points in the dissolution process of different media; S2, during the temperature rising dissolution process, the temperature, pH value and torque calculated based on the current of the stirring assembly of the medium are monitored in real time; S3, when the temperature and torque meet the preset dissolution completion condition, the stirring speed is switched to the sterilization mode; S4, in the sterilization mode, the target sterilization temperature is maintained and the sterilization value is accumulated; S5, after sterilization, the medium is cooled to 70-80℃ and is divided into small parts.

2. The adaptive control method for integrated preparation of laboratory media according to claim 1, characterized in that: In step S1, the database includes a torque-temperature reference curve generated for each medium formula.

3. The adaptive control method for integrated preparation of laboratory media according to claim 2, wherein: In step S1, the process parameters at least include: target temperature in the dissolution stage, target temperature in the sterilization stage, torque threshold value and the corresponding torque-temperature reference curve.

4. The adaptive control method for integrated preparation of laboratory media according to claim 1, wherein: In step S2, the torque is obtained by collecting the real-time current signal of the stirring assembly and indirectly calculating based on the pre-calibrated motor torque constant.

5. The adaptive control method for integrated preparation of laboratory media according to claim 1, wherein: In step S3, the dissolution completion condition is that the medium temperature reaches or exceeds 85℃, and the torque continuously reaches or exceeds the preset torque threshold value.

6. The adaptive control method for integrated preparation of laboratory media according to claim 1, wherein: In step S3, when switching to the sterilization mode, the stirring speed is reduced to a set value of 30rpm to maintain temperature uniformity and avoid foam generation.

7. The adaptive control method for integrated preparation of laboratory media according to claim 1, wherein: In step S4, the sterilization endpoint is determined by monitoring the sterilization temperature in real time and calculating the accumulated sterilization value F0, and the sterilization is determined to be completed when the F0 value reaches the preset target.

8. A laboratory medium integrated preparation device based on the self-adaptive control method of the laboratory medium integrated preparation of any one of claims 1-7, characterized in that, It comprises: A container body (1) having an inner wall for containing medium and an outer wall forming a sandwich layer between the inner wall and the outer wall; A stirring assembly (2) fixedly installed at the top of the container body (1); A dispensing assembly located at the bottom of the container body for dispensing the prepared medium; A detection control unit for detecting and executing an adaptive control program.

9. The laboratory media integrated preparation apparatus according to claim 8, characterized in that: The outer wall of the container body (1) is provided with a heating assembly (3) and a cooling assembly (4), respectively, and the heating assembly (3) and the cooling assembly (4) are connected in the sandwich layer of the container body; the dispensing assembly comprises a connecting channel (5) screwed on the bottom of the container body (1) and a valve (6) sleeved on the outer wall of the connecting channel (5).

10. The laboratory media integrated preparation apparatus according to claim 9, wherein, The detection control unit comprises: a temperature sensor, a weight sensor, a pH probe, a torque detection unit and a control unit, the temperature sensor is arranged on the inner wall of the bottom of the container body (1) for monitoring the temperature of the medium; the torque detection unit is used for calculating the torque based on the current signal of the stirring assembly (2); the control unit is signal connected with the temperature sensor, the weight sensor, the pH probe, the torque detection unit, the stirring assembly (2), the heating assembly (3), the cooling assembly (4) and the valve (6), and the control unit is used for executing the adaptive control program.

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