Plant exosome lyophilization environment control method based on temperature and humidity decoupling

Abstract

The present application relates to the field of plant exosome freeze-drying control and intelligent manufacturing, in particular to a plant exosome freeze-drying environment control method based on temperature and humidity decoupling; applied to a freeze-drying system comprising a refrigeration compressor, a silicone oil circulating pump and a vacuum pump valve group; the system obtains the shelf temperature, the probe impedance and the cavity vacuum degree, divides the pre-freezing, sublimation and desorption drying stages and carries out safety evaluation; the core is to accurately identify the sharp release of latent heat of phase transition according to the temperature and impedance change rate in the pre-freezing stage, and calculate the safety distance value of the operating parameters; when the safety evaluation is not up to standard or latent heat release occurs, the system will adaptively adjust the compressor and pump valve group to make the parameters return to the safety range; the present application realizes accurate capture and rapid response of latent heat of phase transition, can effectively inhibit temperature rebound and avoid abnormal growth of ice crystals.

Description

Technical Field

[0001] This invention relates to the field of plant exosome freeze-drying control and intelligent manufacturing, specifically a plant exosome freeze-drying environmental control method based on temperature and humidity decoupling. Background Technology

[0002] During the freeze-drying process of plant exosomes, it is necessary to simultaneously consider the environmental stability of the freezing and shaping, sublimation and dehydration, and subsequent desorption and drying stages. Only by coordinating the shelf heating, the vacuum state of the chamber, and the internal water loss state of the sample can the sample structure be prevented from becoming unstable and the reconstitution effect after freeze-drying be improved. In the existing technology, freeze-drying control is mostly based on preset temperature curves or single vacuum parameters, which lacks an effective identification mechanism for the release of latent heat of phase change in the pre-freezing stage, the risk of collapse in the sublimation stage, and the risk of excessive dehydration in the desorption and drying stage. Summary of the Invention

[0003] The purpose of this invention is to provide a temperature-humidity decoupling-based method for controlling the freeze-drying environment of plant exosomes, addressing the following technical problems: Existing freeze-drying control technologies for plant exosomes are insufficient in identifying the latent heat release during the pre-freezing stage, as well as the risks of collapse during the sublimation stage and excessive dehydration during the desorption drying stage. This invention provides a temperature-humidity decoupling-based method for controlling the freeze-drying environment of plant exosomes that can accurately identify environmental risks at each stage, dynamically coordinate shelf heating, chamber vacuum status, and internal sample dehydration status to improve sample structural integrity and reconstitution effect. The objective of this invention can be achieved through the following technical solutions: A plant exosome freeze-drying environmental control method based on temperature and humidity decoupling is applied to a freeze-drying control system that includes a refrigeration compressor, a silicone oil circulation pump, and a vacuum pump valve assembly, including: The collapse temperature and freezing temperature of plant exosome samples were obtained, and real-time status data including shelf temperature, probe impedance and cavity vacuum were collected to complete parameter setting. The freeze-drying process is divided into pre-freezing, sublimation drying and desorption drying stages; during the pre-freezing stage, the shelf temperature and probe impedance are extracted, and the temperature change rate and impedance change rate are calculated. During the sublimation drying stage, the current operating parameters are formed by combining the shelf temperature, probe impedance, and cavity vacuum, and the distance between the current operating parameters and the pre-constructed safe range defined by the shelf temperature, cavity vacuum, and probe impedance is calculated. During the analytical drying stage, the fluctuation value of the probe impedance above a preset frequency threshold is obtained, and the variance value of the fluctuation value within a preset specific time window is calculated. A safety assessment is performed based on the temperature change rate, impedance change rate, distance value, and variance value. If the preset safety control requirements are not met, feedback adjustments are made to the refrigeration compressor, silicone oil circulation pump, and vacuum pump valve group respectively to bring the current operating parameters back to the safe range. When the absolute value of the impedance change rate within a consecutive preset time period is less than a preset impedance change threshold, a process judgment value is calculated and compared with a preset reference value; if the process judgment value is less than the preset reference value, a freeze-drying end command is output; otherwise, the current operating state is maintained and the control of the current stage continues.

[0004] Optionally, the parameter setting includes the following steps: The collapse temperature of the plant exosome sample was determined by freeze-drying microscopy, and the freezing temperature of the plant exosome sample was determined by resistivity probe. Historical thermal performance data is obtained, and the impedance parameters measured at the moment of freezing of pure water with the preset freeze-drying protectant formulation are used as reference data. The initial value of the preset reference value is set, and operating parameters including shelf temperature, cavity vacuum degree and probe impedance are established.

[0005] Optionally, the calculation of the rate of temperature change and the rate of impedance change includes: Obtain the shelf temperature and probe impedance for the current control cycle and the previous control cycle, and calculate the rate of temperature change of the shelf temperature over time and the rate of impedance change of the probe impedance over time. The rate of temperature change and the rate of impedance change are compared with the reference data.

[0006] Optionally, the freeze-drying control system further includes an electronic expansion valve; comparing the temperature change rate and impedance change rate with the reference data to obtain an evaluation result, specifically including the following steps: Determine whether the temperature change rate of the previous control cycle is less than zero and whether the temperature change rate of the current control cycle is greater than zero; calculate the absolute value of the difference between the impedance change rate of the current control cycle and the previous control cycle, and determine whether the absolute value of the difference is greater than a preset impedance change threshold. When all the above conditions are met, the full-load operation control command for the refrigeration compressor and the maximum opening pulse command for the electronic expansion valve are output; otherwise, the current operating state is maintained.

[0007] Optionally, before calculating the distance between the current operating parameters and a pre-defined safe range defined by the shelf temperature, probe impedance, and cavity vacuum, the method further includes the step of constructing the safe range: Based on the preset empirical dynamic model, the boundary equilibrium equation is calculated, and a safe range is defined in a three-dimensional space with the shelf temperature, cavity vacuum degree and probe impedance as coordinate axes, bounded by the collapse temperature boundary and the hydration layer failure boundary. The safety range is discretized into a boundary data table containing multiple safety nodes and their corresponding boundary directions, and the drying endpoint range is defined in the boundary data table. Extract the current running parameters at the current moment and substitute them into the boundary data table for traversal analysis.

[0008] Optionally, the freeze-drying control system further includes a gas-mixing ratio fine-tuning valve; the logic for calculating the distance between the current operating parameters and the safety range is as follows: Calculate the distance parameter from the current running parameters to the nearest boundary node in the boundary data table, and record it as the distance value; Obtain constant coefficients that characterize the statistical features of the safety boundary distance in the early stage of sublimation for historically normal and compliant batches, and determine the minimum safety distance boundary by combining the preset base parameters with the current probe impedance; when the distance value is less than the minimum safety distance, simultaneously reduce the operating frequency of the silicone oil circulation pump and increase the duty cycle of the gas mixing ratio fine-tuning valve; otherwise, maintain the current operating state.

[0009] Optionally, the fluctuation value of the probe impedance above a preset frequency threshold is obtained, and the variance of the fluctuation value within a preset specific time window is calculated. Specific steps include: During the analytical drying stage, the fluctuation value within the preset specific time window is extracted, and the variance of the fluctuation value is calculated. The variance value is compared with a preset impedance fluctuation threshold; When the variance value is greater than the impedance fluctuation threshold, the upper limit of the heating rate of the shelf temperature is set, and the vacuum pump valve group is controlled to maintain the cavity vacuum degree within the preset micro-increase vacuum degree range; otherwise, the current operating state is maintained.

[0010] Optionally, the calculation process determines the value based on the following logic: When the absolute value of the impedance change rate is less than the preset impedance change threshold within a continuous preset time period, and the current operating parameter is within the drying endpoint range defined by the boundary data table within the continuous preset time period, the operating parameter change curve for the entire cycle is obtained according to the preset control cycle. Obtain a pre-stored standard freeze-drying curve, and extract the deviation between the operating parameter change curve and the standard freeze-drying curve; based on a pre-set control cycle weight allocation model, perform a weighted evaluation on the deviation within each control cycle, and determine the process judgment value.

[0011] Optionally, the process determination value is compared with a preset reference value, and the specific steps include: The reference value obtained under the same conditions as a normal freeze-dried batch is used as the preset reference value; The process determination value is compared with the preset reference value; When the process determination value is less than the preset reference value, the freeze-drying end command is output, and a freeze-drying batch report containing the operating parameter change curves of the entire cycle is generated; otherwise, the control of the current stage continues.

[0012] Compared with the prior art, the present invention has the following beneficial effects: 1. This method calculates the rate of change by extracting shelf temperature and probe impedance during the pre-freezing stage, which can accurately identify the violent release of latent heat of phase change. When it is determined that latent heat release has occurred, it promptly outputs commands for full load of the refrigeration compressor and maximum opening of the electronic expansion valve to absorb heat, effectively suppressing temperature rise and avoiding abnormal ice crystal growth caused by the blind zone of traditional pre-freezing control. 2. In the sublimation drying stage, this method constructs the current operating parameters by combining shelf temperature, probe impedance and cavity vacuum, and calculates the distance between them and the preset safety range. When there is a risk of collapse, the silicone oil circulation pump and the gas mixing ratio fine-tuning valve are adjusted simultaneously to correct the heat input and dehumidification conditions in a timely manner, effectively preventing sample structure instability and hydration layer damage. 3. In the analytical drying stage, this method effectively identifies the critical point of excessive dehydration by calculating the variance of the high-frequency fluctuation value of the probe impedance within a specific time window; combined with limiting the shelf heating rate and controlling the vacuum pump valve group to maintain a slight pressure increase, the moisture diffuses slowly, reducing the risk of vesicle rupture caused by excessive dehydration and improving the resolution effect. 4. When determining the end of freeze-drying, this method not only constrains the rate of impedance change and the range of the drying endpoint, but also extracts the weighted Euclidean distance difference between the full-cycle operating parameter change curve and the standard curve as the process determination value. This mechanism avoids premature determination of end due to fluctuations in a single state, and ensures that the actual operating trajectory is highly consistent with the normal compliant batches. Attached Figure Description

[0013] To more clearly illustrate the technical solutions in this invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of this invention. For those skilled in the art, other drawings can be obtained from these drawings without creative effort.

[0014] Figure 1This is a flowchart illustrating the plant exosome freeze-drying environmental control method based on temperature and humidity decoupling proposed in this application. Detailed Implementation

[0015] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to specific embodiments.

[0016] like Figure 1 As shown, in this embodiment, the method is jointly executed by the upper-level control unit and the lower-level controller in the freeze-drying control system. The upper-level control unit is used to complete parameter setting, stage division, reference value storage, and termination determination calculation. The lower-level controller is used to receive sensor data and output control commands to the refrigeration compressor, silicone oil circulation pump, and vacuum pump valve group. The shelf temperature is the actual temperature of the shelf in the freeze-drying equipment, which reflects the heat input. The probe impedance is the electrical response obtained by the resistivity probe, which characterizes the freezing and dehydration state inside the sample. The cavity vacuum degree is the pressure state after vacuuming inside the cavity, which reflects the resistance to water vapor escape. All three types of physical quantities are collected by actual hardware. A plant exosome freeze-drying environmental control method based on temperature and humidity decoupling is applied to a freeze-drying control system that includes a refrigeration compressor, a silicone oil circulation pump, and a vacuum pump valve assembly, including: The collapse temperature and freezing temperature of plant exosome samples were obtained, and real-time status data including shelf temperature, probe impedance and cavity vacuum were collected to complete parameter setting. The freeze-drying process is divided into three stages: pre-freezing, sublimation drying, and desorption drying. During the pre-freezing stage, the shelf temperature and probe impedance are extracted, and the rate of temperature change and the rate of impedance change are calculated. During the sublimation drying stage, the current operating parameters are formed by combining the shelf temperature, probe impedance, and cavity vacuum degree, and the distance between the current operating parameters and the pre-constructed safe range defined by the shelf temperature, cavity vacuum degree, and probe impedance is calculated. During the analysis and drying stage, the fluctuation value of the probe impedance above the preset frequency threshold is obtained, and the variance value of the fluctuation value within a preset specific time window is calculated. Safety assessments are conducted based on the rate of temperature change, rate of impedance change, distance value, and variance value. If the preset safety control requirements are not met, feedback adjustments are made to the refrigeration compressor, silicone oil circulation pump, and vacuum pump valve group to bring the current operating parameters back to the safe range. When the absolute value of the rate of change of impedance within a continuously preset time period is less than the preset impedance change threshold, the process judgment value is calculated and compared with the preset reference value; if the process judgment value is less than the preset reference value, the freeze-drying end command is output; otherwise, the current operating state is maintained and the control of the current stage is continued.

[0017] Parameter settings, the specific steps include: The collapse temperature of plant exosome samples was determined by freeze-drying microscopy, and the freezing temperature of plant exosome samples was determined by resistivity probe. Historical thermal performance data is obtained, and the impedance parameters measured at the moment of freezing of pure water with the preset freeze-drying protectant formulation are used as reference data. The initial value of the preset reference value is set, and the operating parameters including shelf temperature, cavity vacuum degree and probe impedance are established.

[0018] Calculations of the rate of temperature change and the rate of impedance change include: Obtain the shelf temperature and probe impedance of the current control cycle and the previous control cycle, and calculate the rate of temperature change of the shelf temperature over time and the rate of impedance change of the probe impedance over time. The rates of temperature change and impedance change were compared with reference data.

[0019] Before the start of freeze-drying, the upper control unit first executes parameter settings; the plant exosome sample is first tested by a freeze-drying microscope to obtain the collapse temperature; the collapse temperature refers to the temperature boundary at which the structure of the sample begins to destabilize during the freeze-drying heating process, and the control of the subsequent sublimation drying stage must not exceed this boundary; the freezing temperature is measured using a resistivity probe; the freezing temperature is the characteristic temperature at which the sample changes from liquid to solid, and is used to delineate the range of interest in the pre-freezing stage. Meanwhile, the upper control unit retrieves historical thermal performance data and extracts reference data from the impedance parameters of pure water at the moment of freezing under the same freeze-drying protectant formulation. The reference data is preferably the change value of impedance derivative in adjacent control cycles before and after pure water freezing. The reference data is used to characterize the basic amplitude of impedance change during phase transition. The upper control unit writes the reference data into the parameter table of this batch and stores the initial value of the reference value obtained under normal freeze-drying batch for subsequent process judgment and comparison. After completing the above processing, a set of operating parameters including shelf temperature, cavity vacuum degree and probe impedance is established as the input for subsequent stage control. When dividing the process into stages, the upper-level control unit divides the entire freeze-drying process into three stages according to the sample's freezing state and drying task: pre-freezing stage, sublimation drying stage, and desorption drying stage. The pre-freezing stage corresponds to the process of the sample changing from liquid to solid and forming ice crystals. The sublimation drying stage corresponds to the process of ice phase water being directly converted into vapor and then removed. The desorption drying stage corresponds to the process of further removing bound water. After this division is completed, the lower-level controller calls the corresponding judgment logic in each stage. During the pre-freezing stage, the bottom-level controller continuously collects the shelf temperature and probe impedance of the current control cycle, and calculates the temperature change rate and impedance change rate respectively; the control cycle is the time interval between two consecutive sampling and processing operations under discrete control. Therefore, the temperature change rate is obtained by dividing the shelf temperature difference between adjacent control cycles by the specific duration of that control cycle, for example, 2 seconds, and the impedance change rate is obtained by dividing the probe impedance difference between adjacent control cycles by the specific duration of that control cycle. The upper control unit further compares the temperature change rate and impedance change rate of this batch with the reference data. If the comparison results show that the current temperature change trend and impedance change trend are close to the characteristic changes of pure water freezing instant, it indicates that a significant liquid-solid phase transition has occurred inside the sample, and the latent heat release is increasing. The rate of temperature change and the rate of impedance change are used together for joint judgment to identify the moment of latent heat release; In the safety assessment at each stage, the assessment results of the pre-freezing stage mainly come from the rate of temperature change and the rate of impedance change. If both are within the preset safety control requirements, the bottom controller maintains the current operating status of the refrigeration compressor and the silicone oil circulation pump. If the assessment results indicate that there is a trend of excessive latent heat release in the pre-freezing stage, the bottom controller sends a control command to the refrigeration compressor to increase the cooling capacity and adjusts the operating status of the silicone oil circulation pump to suppress the temperature rise around the shelf. The intermediate state change at this time is that the heat around the sample is removed more quickly, and the rate of temperature change of the shelf returns to the allowable range, thereby avoiding a sudden increase in ice crystal size. During the sublimation drying stage, the bottom controller combines the shelf temperature, probe impedance, and cavity vacuum level of the current control cycle into the current operating parameters; the current operating parameters are three-dimensional state points that reflect the current heat input, dehumidification resistance, and the degree of dryness inside the sample; The system calculates the distance between the current state point and the safe range. If the distance is within the safe control requirements, it indicates that the current heating and dehumidification relationship is matched, and the current operating state is maintained. If the distance deviates from the safe range, it indicates that the heat and mass transfer in the sublimation stage is unbalanced. The system adjusts the silicone oil circulation pump and vacuum pump valve group to change the shelf temperature and the cavity vacuum degree in the safe direction. Through the above adjustment, the current operating parameters are restored to the safe range, preventing the local temperature of the sample from exceeding the collapse boundary and causing structural collapse. During the desorption drying stage, the bottom-level controller extracts fluctuation values ​​above a preset frequency threshold from the probe impedance signal and calculates the variance of these fluctuation values ​​within a preset specific time window. The fluctuation value is the high-frequency variation part of the probe impedance, used to reflect the instability of the bound water state on the sample surface. The larger the variance value, the stronger the impedance fluctuation within that time window, and the closer the sample is to an over-dehydrated state. If the variance value meets the safety control requirements, the current heating and vacuum state is maintained. If the variance value exceeds the safety control requirements, the bottom-level controller reduces the dehydration driving force through the vacuum pump valve assembly and limits and adjusts the shelf temperature to slow down the bound water removal rate. This stabilizes the environment during the desorption drying stage and reduces the risk of vesicle rupture. When the system enters the end determination section, the upper control unit continuously monitors the absolute value of the impedance change rate; if the absolute value is always less than the preset impedance change threshold within a continuous preset time period, it indicates that the amount of water migration inside the sample is lower than the preset threshold, and the freeze-drying process is close to completion. At this point, the system does not terminate directly, but further calculates the process judgment value. The process judgment value is used to evaluate the similarity between the current batch's running trajectory and that of a normal freeze-dried batch. Then, this value is compared with a preset reference value. If the process judgment value is less than the reference value, a freeze-drying termination command is output. If it is not less than the reference value, the current running state is maintained, and the current stage of control is continued. Through the above methods, the pre-freezing stage uses the rate of temperature change and the rate of impedance change to identify the release of latent heat of phase change; the sublimation drying stage uses the distance between the current operating parameters and the safe range to limit the risk of collapse; the analytical drying stage uses the variance of high-frequency impedance fluctuations to identify the trend of excessive dehydration; and finally, the process judgment value is used to complete the end judgment. The whole method directly acts on the refrigeration compressor, silicone oil circulation pump and vacuum pump valve group, which can make the shelf temperature and the cavity vacuum degree always change around the safe range of the sample, thereby improving the structural integrity and reconstitution activity retention rate of plant exosomes after freeze-drying. This implementation method is used to intercept the latent heat release during the pre-freezing stage and to construct and control the safety range during the sublimation drying stage. In addition to the refrigeration compressor, silicone oil circulation pump and vacuum pump valve group, the freeze-drying control system also includes an electronic expansion valve and a gas mixing ratio fine-tuning valve. The electronic expansion valve is used to quickly adjust the refrigerant flow rate to cooperate with the compressor to improve the instantaneous cooling capacity. The gas mixing ratio fine-tuning valve is used to introduce a controlled amount of gas into the cavity to change the cavity vacuum degree and local dehumidification state. The freeze-drying control system also includes an electronic expansion valve; the evaluation results are obtained by comparing the rate of temperature change and the rate of impedance change with reference data, and the specific steps include: Determine whether the temperature change rate of the previous control cycle is less than zero and whether the temperature change rate of the current control cycle is greater than zero; calculate the absolute value of the difference between the impedance change rate of the current control cycle and the previous control cycle, and determine whether the absolute value of the difference is greater than the preset impedance change threshold. When all the above conditions are met, the system outputs a full-load operation control command for the refrigeration compressor and a pulse command for the maximum opening of the electronic expansion valve; otherwise, it maintains the current operating state.

[0020] Before combining shelf temperature, probe impedance, and cavity vacuum to form the current operating parameters, and calculating the distance between the current operating parameters and the pre-established safe range defined by shelf temperature, cavity vacuum, and probe impedance, the process also includes the step of establishing the safe range: Based on the preset empirical dynamic model, the boundary equilibrium equation is calculated, and a safe range is defined in a three-dimensional space with shelf temperature, cavity vacuum degree and probe impedance as coordinate axes, bounded by the collapse temperature boundary and the hydration layer failure boundary. The safety range is discretized into a boundary data table containing multiple safety nodes and their corresponding boundary directions, and the drying endpoint range is defined within the boundary data table. Extract the current running parameters at the current moment and substitute them into the boundary data table for traversal analysis.

[0021] The freeze-drying control system also includes a gas-mixing ratio fine-tuning valve; it calculates the distance between the current operating parameters and the safe range, based on the following logic: Calculate the distance parameter from the current running parameters to the nearest boundary node in the boundary data table, and record it as the distance value; Obtain constant coefficients that characterize the statistical features of the safety boundary distance in the early stage of sublimation for historically normal and compliant batches, and determine the minimum safety distance boundary by combining the preset base parameters with the current probe impedance; when the distance value is less than the minimum safety distance, simultaneously reduce the operating frequency of the silicone oil circulation pump and increase the duty cycle of the gas mixing ratio fine-tuning valve; otherwise, maintain the current operating state.

[0022] During the pre-freezing stage, the bottom controller first reads the temperature change rate and impedance change rate from the adjacent control cycle; then performs a two-step joint judgment; the first step is to determine whether the temperature change rate of the previous control cycle is less than zero and whether the temperature change rate of the current control cycle is greater than zero; this condition indicates that the shelf temperature has changed from a downward trend to an upward trend, indicating that the sample is experiencing a warming phenomenon. The second step is to calculate the absolute value of the difference between the impedance change rate of the current control cycle and the previous control cycle, and compare this value with the impedance mutation threshold. The impedance mutation threshold is preferably taken from the range of impedance derivative difference at the moment when pure water freezes, in order to eliminate misjudgments caused by ordinary temperature disturbances or probe noise. Only when the above two conditions are met at the same time will the bottom controller determine that a strong latent heat of phase change has been released. Once a strong release of latent heat from phase change is identified, the underlying controller bypasses the conventional regulation loop and directly outputs a high-frequency full-load operation control command to the refrigeration compressor. Simultaneously, based on preset compressor anti-liquid slugging protection parameter thresholds, it outputs a matching maximum safe opening command to the electronic expansion valve. The former puts the compressor into its highest refrigeration output state, while the latter rapidly increases the refrigerant flow rate. The heat absorption rate on the evaporator side increases, and the conduction and dissipation rate of the heat released from phase change also increases, suppressing the temperature rise near the shelf. If either of the aforementioned two judgment conditions is not met, the system determines that the current situation is not a typical release of latent heat from phase change and only maintains the current operating state without triggering forced full load. This eliminates the interference of normal temperature disturbances on phase change determination and limits the overload output of the subsequent refrigeration system. Before the sublimation drying stage begins, the upper control unit first establishes a safety range. During the establishment, the shelf temperature, cavity vacuum degree, and probe impedance are used as three-dimensional coordinate axes to unify the sample heat input, dehumidification resistance, and internal drying degree into the same coordinate space. The heat and mass transfer balance equations are calculated based on a multiphase flow model, and a safe range is defined in this three-dimensional space. The multiphase flow model uses the current probe impedance, which characterizes the content of remaining bound water and ice crystals, to represent the current probe impedance. The cavity vacuum degree characterizes the environmental pressure resistance encountered by water vapor escape. As a conditional input, based on the formula Calculate the theoretical upper limit temperature of the input allowed under this specific combination of states. This forms a collapse temperature boundary, in which These are the system dynamic constants; At the same time, according to the formula Calculate the theoretical lower limit temperature This forms the boundary of the hydration layer destruction, in which The lower limit kinetic constant is preset; the safety range is enclosed by the collapse temperature boundary and the hydration layer failure boundary, where the collapse temperature boundary is used to limit the structural instability of the sample during the sublimation stage, and the hydration layer failure boundary is used to limit the surface damage caused by excessive subsequent water loss. After completing the continuous spatial calculation, the upper control unit discretizes the safety range and generates a boundary data table. The boundary data table stores multiple safety nodes and their corresponding boundary directions, and marks the drying endpoint range in it. The boundary direction is used to indicate the outward change direction of the dangerous boundary at each boundary node, so that the lower controller can determine the degree of proximity between the current state point and the dangerous boundary. After entering the sublimation drying stage, the bottom-level controller obtains the current shelf temperature, cavity vacuum, and probe impedance from the sensors to form the current operating parameters. Based on the preset physical limit ranges of the shelf temperature, cavity vacuum, and probe impedance, the bottom-level controller maps them uniformly to a dimensionless normalization process within the 0-1 range. The dimensionless normalization process sets separate lower limit extreme values ​​for the shelf temperature, cavity vacuum, and probe impedance. and the upper limit of operation Through mapping formula Set the current value Convert to normalized values This avoids orders-of-magnitude interference. The underlying controller synchronously substitutes this parameter into the boundary data table that has already undergone the same dimensionless processing and traverses and analyzes it. During the traversal, the controller compares the correspondence between the normalized current operating parameters and each normalized boundary node in turn, finds the nearest boundary node, and then calculates the spatial Euclidean distance from the current operating parameters to the nearest boundary node and records it as the distance value. The smaller the distance value, the closer the current operating state is to the collapse boundary or the hydration layer failure boundary. The upper control unit extracts constant coefficients from historical thermal performance data in advance and constructs the minimum safety distance according to the negative probe impedance power of the preset base; The constant coefficient is derived from the statistical average of the maximum safety boundary Euclidean distance of historically compliant batches in the early stages of sublimation; based on the constant coefficient... Preset base greater than 1 and the normalized probe impedance value The minimum safe distance was calculated. The minimum safe distance decreases exponentially as the probe impedance increases; the underlying controller compares the distance value with this minimum safe distance in each control cycle. When the distance value is less than the minimum safe distance, the bottom controller determines that there is a risk of collapse in the current sample environment and performs two actions simultaneously: first, it reduces the operating frequency of the silicone oil circulation pump to reduce the heat transferred from the shelf to the sample; second, it increases the duty cycle of the gas mixing ratio fine-tuning valve to adjust the vacuum state in the cavity and promote the faster dissipation of local water vapor. Specific step size for increasing the duty cycle of the gas mixing ratio fine-tuning valve The specific step size for reducing the operating frequency of the silicone oil circulation pump All are proportional to the difference between the current distance value and the safety boundary, respectively according to the formula and formula Dynamic output adjustment amount, where This is the valve proportional gain coefficient. This is the frequency-adjustable gain coefficient. The calculated Euclidean distance value is used; the synchronous action corrects the current operating parameters from both the heat input and dehumidification conditions. After execution, the intermediate state is characterized by a weakening trend in shelf temperature rise and improved steam discharge state corresponding to cavity vacuum, ultimately bringing the current operating parameters back to the safe range defined by the boundary data table; if the distance value is not less than the minimum safe distance, it indicates that the current state is still within the acceptable range, and the system maintains the current operating state. This embodiment is used to analyze the excessive dehydration control during the drying stage and to determine the end of freeze-drying. The drying stage corresponds to the process of further removing bound water from the sample. If the heating rate and vacuum level are continuously increased to increase the dehydration rate, the rate of peeling off the hydration layer on the surface of plant exosomes will exceed the safety threshold. Therefore, it is necessary to use the fluctuation characteristics of the probe impedance for identification. The steps include: acquiring the fluctuation value of the probe impedance above a preset frequency threshold, and calculating the variance of the fluctuation value within a preset specific time window. During the analysis and drying stage, the fluctuation values ​​within a preset specific time window are extracted, and the variance of the fluctuation values ​​is calculated. The variance value is compared with a preset impedance fluctuation threshold. When the variance value is greater than the impedance fluctuation threshold, the upper limit of the shelf temperature rise rate is set, and the vacuum pump valve group is controlled to maintain the cavity vacuum degree within the preset micro-volume range; otherwise, the current operating state is maintained.

[0023] The calculation process and the logic it is based on include: When the absolute value of the impedance change rate is less than the preset impedance change threshold within a continuous preset time period, and the current operating parameters are within the drying endpoint range defined by the boundary data table within a continuous preset time period, the operating parameter change curve for the entire cycle is obtained according to the preset control cycle. Obtain the pre-stored standard freeze-drying curve and extract the deviation between the operating parameter change curve and the standard freeze-drying curve; based on the pre-set control cycle weight allocation model, perform weighted evaluation on the deviation within each control cycle and determine the process judgment value.

[0024] The process judgment value is compared with the preset reference value. The specific steps include: Obtain the reference value obtained under the same conditions as the normal freeze-dried batch as the preset reference value; Compare the process judgment value with the preset reference value; When the process judgment value is less than the preset reference value, a freeze-drying end command is output, and a freeze-drying batch report containing the change curve of the operating parameters throughout the entire cycle is generated; otherwise, the control of the current stage continues.

[0025] During the analytical drying stage, the underlying controller continuously reads the impedance sequence output by the resistivity probe and extracts the fluctuation values ​​above a preset frequency threshold. The preset frequency threshold is used to separate the slow-changing and fast-changing parts of the impedance signal. For example, the preset frequency threshold can be set to a fixed frequency value between 0.5 Hz and 2.0 Hz. The signal part above the preset frequency threshold is identified as the fast-changing part. The slow-changing part mainly reflects the overall drying process, while the fast-changing part is more likely to reflect local disturbances when the bound water state is unstable. In each control cycle, the underlying controller extracts data including current and historical data. Fluctuation value sequence within a sliding time window of a control cycle And according to the formula Calculate the high-frequency variance of impedance fluctuations within this window. ,in This is the arithmetic mean of the fluctuation values ​​within this time window. The number of periods is fixed; the larger the variance value, the stronger the high-frequency impedance fluctuation within the window, and the more unstable the hydration layer state on the sample surface. The underlying controller compares the variance value with a preset impedance fluctuation threshold. The impedance fluctuation threshold is used to distinguish between normal desorption drying fluctuations and abnormal fluctuations when approaching over-dehydration. When the variance value is not greater than the impedance fluctuation threshold, it indicates that the current desorption drying is still within an acceptable range, and the system maintains its current operating state. When the variance value is greater than the impedance fluctuation threshold, the system determines that the current freeze-drying environment is approaching the critical point of over-dehydration. At this time, the underlying controller performs two control actions: one is to set the upper limit of the shelf temperature rise rate so that the shelf temperature no longer rises rapidly; the other is to control the vacuum pump valve group to maintain the cavity vacuum degree within the vacuum degree range corresponding to the slight pressure rise. A slight increase in pressure corresponds to a vacuum range indicating that the absolute pressure inside the cavity is moderately increased, causing water migration to change from rapid extraction to a more gradual diffusion. After these two actions, the rate of removal of bound water from the sample surface decreases, and the high-frequency impedance fluctuations weaken, thereby reducing the risk of vesicle rupture. In the freeze-drying end determination section, the upper control unit does not use the impedance change rate at a single moment as the end criterion, but uses a combination of continuous time period conditions and curve comparison conditions to make a judgment; the upper control unit checks whether the absolute value of the impedance change rate is always less than the preset impedance change threshold within a continuous preset time period; this condition indicates that the probe impedance change has tended to stabilize within multiple consecutive control cycles, and the internal moisture migration of the sample has basically ended. The upper control unit also checks whether the current operating parameters are within the drying endpoint range defined by the boundary data table within the above-mentioned continuous preset time period; only when both of these prerequisites are met will the system enter the process judgment value calculation step; this can avoid premature determination of termination when the sample has not yet entered the safe endpoint area, even though the impedance change has decreased in a short time. When calculating the determination value, the upper control unit obtains the operating parameter change curve of the whole cycle according to the preset control cycle; the operating parameter change curve is composed of the shelf temperature, cavity vacuum degree and probe impedance of each control cycle in chronological order, which is used to reflect the overall trajectory of the freeze-drying process of this batch; the upper control unit uses the extreme value mapping method to convert the three types of parameter data at each point of the whole cycle into a dimensionless numerical sequence distributed in the interval of 0 to 1; This mapping method uses the upper and lower envelope boundaries of the historical normal operation corresponding to each parameter as extreme value reference points for linear conversion, thereby obtaining a relative displacement value between 0 and 1 that reflects the relative deviation. The upper control unit retrieves the pre-stored standard freeze-drying curve, which has also undergone dimensionless processing, and calculates the spatial Euclidean distance between the real-time discrete point of the current dimensionless curve and the corresponding point in the three-dimensional coordinate space of the standard freeze-drying curve at the same time node corresponding to each control cycle. This Euclidean distance difference is recorded as the Euclidean distance difference. This Euclidean distance difference can accurately represent the multidimensional comprehensive deviation of the current batch of curves from the standard operating trajectory in each time segment. The upper-level control unit further acquires pre-set weighting coefficients corresponding to each control cycle; in terms of time distribution, the weighting coefficients do not use a single fixed value, but are determined based on a time proportion allocation rule: assuming that the entire cycle includes For the discrete control cycle, for the first One control cycle, of which From 1 to A positive integer, whose corresponding weighting coefficient According to the formula Calculated; The weighting rule increases linearly with the drying process while ensuring that the sum of the weights for all cycles is 1; the Euclidean distance difference within each control cycle is compared with the corresponding weighting coefficient. Multiply them, then sum the products corresponding to all control cycles, and finally record the weighted result as the process judgment value; After the process judgment value is calculated, the upper control unit obtains the reference value obtained under the same conditions as the normal freeze-drying batch as the preset reference value. The preset reference value is not a single fixed empirical value, but is determined by retrieving the weighted process judgment values ​​of freeze-drying batches with the same protective agent formula that have passed the standard at least three times in the historical database, calculating the arithmetic mean, and then multiplying it by the preset safety tolerance coefficient to determine the scale limit value. The system compares the current batch's process judgment value with the reference value. When the process judgment value is less than the reference value, it indicates that the deviation between the current batch's operating trajectory and the normal compliant batch is within the preset tolerance range. The system determines that the freeze-drying process meets the control target and is compliant, outputs a freeze-drying end command, and generates a freeze-drying batch report containing the full-cycle operating parameter change curve. The freeze-drying batch report is used to record the operating status of each stage of the current batch, facilitating the subsequent retrieval of similar samples. If the process judgment value is not less than the reference value, it indicates that although the impedance change has weakened, the overall operating trajectory still deviates from the normal compliant batch. The system continues to execute the current stage control without outputting an end command.

[0026] It should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit it. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can be made to the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention.

Claims

1. A method for controlling the freeze-drying environment of plant exosomes based on temperature and humidity decoupling, applied to a freeze-drying control system including a refrigeration compressor, a silicone oil circulating pump, and a vacuum pump valve assembly, characterized in that... include: The collapse temperature and freezing temperature of plant exosome samples were obtained, and real-time status data including shelf temperature, probe impedance and cavity vacuum were collected to complete parameter setting. The freeze-drying process is divided into pre-freezing, sublimation drying and desorption drying stages; during the pre-freezing stage, the shelf temperature and probe impedance are extracted, and the temperature change rate and impedance change rate are calculated. During the sublimation drying stage, the current operating parameters are formed by combining the shelf temperature, probe impedance, and cavity vacuum degree, and the distance between the current operating parameters and the pre-constructed safety range defined by the shelf temperature, cavity vacuum degree, and probe impedance is calculated. During the analytical drying stage, the fluctuation value of the probe impedance above a preset frequency threshold is obtained, and the variance value of the fluctuation value within a preset specific time window is calculated. A safety assessment is performed based on the temperature change rate, impedance change rate, distance value, and variance value. If the preset safety control requirements are not met, feedback adjustments are made to the refrigeration compressor, silicone oil circulation pump, and vacuum pump valve group to bring the current operating parameters back to the safe range. When the absolute value of the impedance change rate within a continuous preset time period is less than a preset impedance change threshold, the calculation process determines the value and compares it with a preset reference value. If the process determination value is less than the preset reference value, a freeze-drying end command is output; otherwise, the current operating state is maintained and the control of the current stage continues.

2. The method for controlling the freeze-drying environment of plant exosomes based on temperature and humidity decoupling according to claim 1, characterized in that, The parameter setting process includes the following steps: The collapse temperature of the plant exosome sample was determined by freeze-drying microscopy, and the freezing temperature of the plant exosome sample was determined by resistivity probe. Historical thermal performance data is obtained, and the impedance parameters measured at the moment of freezing of pure water with the preset freeze-drying protectant formulation are used as reference data. The initial value of the preset reference value is set, and operating parameters including shelf temperature, cavity vacuum degree and probe impedance are established.

3. The method for controlling the freeze-drying environment of plant exosomes based on temperature and humidity decoupling according to claim 2, characterized in that, Calculations of the rate of temperature change and the rate of impedance change include: Obtain the shelf temperature and probe impedance for the current control cycle and the previous control cycle, and calculate the rate of temperature change of the shelf temperature over time and the rate of impedance change of the probe impedance over time. The rate of temperature change and the rate of impedance change are compared with the reference data.

4. The method for controlling the freeze-drying environment of plant exosomes based on temperature and humidity decoupling according to claim 3, characterized in that, The freeze-drying control system also includes an electronic expansion valve; the temperature change rate and impedance change rate are compared with the reference data to obtain an evaluation result, and the specific steps include: Determine whether the temperature change rate of the previous control cycle is less than zero and whether the temperature change rate of the current control cycle is greater than zero; calculate the absolute value of the difference between the impedance change rate of the current control cycle and the previous control cycle, and determine whether the absolute value of the difference is greater than a preset impedance change threshold. When all the above conditions are met, the full-load operation control command for the refrigeration compressor and the maximum opening pulse command for the electronic expansion valve are output; otherwise, the current operating state is maintained.

5. The method for controlling the freeze-drying environment of plant exosomes based on temperature and humidity decoupling according to claim 1, characterized in that, Before calculating the distance between the current operating parameters and a pre-defined safe range defined by the shelf temperature, probe impedance, and cavity vacuum, the process further includes the step of constructing the safe range: Based on the preset empirical dynamic model, the boundary equilibrium equation is calculated, and a safe range is defined in a three-dimensional space with the shelf temperature, cavity vacuum degree and probe impedance as coordinate axes, bounded by the collapse temperature boundary and the hydration layer failure boundary. The safety range is discretized into a boundary data table containing multiple safety nodes and their corresponding boundary directions, and the drying endpoint range is defined in the boundary data table. Extract the current running parameters at the current moment and substitute them into the boundary data table for traversal analysis.

6. The method for controlling the freeze-drying environment of plant exosomes based on temperature and humidity decoupling according to claim 5, characterized in that, The freeze-drying control system also includes a gas-mixing ratio fine-tuning valve; the logic for calculating the distance between the current operating parameters and the safety range is as follows: Calculate the distance parameter from the current running parameters to the nearest boundary node in the boundary data table, and record it as the distance value; Obtain constant coefficients that characterize the statistical features of the safety boundary distance in the early stage of sublimation for historically normal and compliant batches, and determine the minimum safety distance boundary by combining the preset base parameters with the current probe impedance; When the distance value is less than the minimum safe distance, the operating frequency of the silicone oil circulation pump is reduced and the duty cycle of the gas mixing ratio fine-tuning valve is increased simultaneously; otherwise, the current operating state is maintained.

7. The method for controlling the freeze-drying environment of plant exosomes based on temperature and humidity decoupling according to claim 1, characterized in that, The steps include: obtaining the fluctuation value of the probe impedance above a preset frequency threshold, and calculating the variance of the fluctuation value within a preset specific time window. During the analytical drying stage, the fluctuation value within the preset specific time window is extracted, and the variance of the fluctuation value is calculated. The variance value is compared with a preset impedance fluctuation threshold; When the variance value is greater than the impedance fluctuation threshold, the upper limit of the heating rate of the shelf temperature is set, and the vacuum pump valve group is controlled to maintain the cavity vacuum degree within the preset micro-increase vacuum degree range; otherwise, the current operating state is maintained.

8. The method for controlling the freeze-drying environment of plant exosomes based on temperature and humidity decoupling according to claim 5, characterized in that, The calculation process and the logic it is based on include: When the absolute value of the impedance change rate is less than the preset impedance change threshold within a continuous preset time period, and the current operating parameter is within the drying endpoint range defined by the boundary data table within the continuous preset time period, the operating parameter change curve for the entire cycle is obtained according to the preset control cycle. Obtain a pre-stored standard freeze-drying curve, and extract the deviation between the operating parameter change curve and the standard freeze-drying curve; based on a pre-set control cycle weight allocation model, perform a weighted evaluation on the deviation within each control cycle, and determine the process judgment value.

9. The method for controlling the freeze-drying environment of plant exosomes based on temperature and humidity decoupling according to claim 8, characterized in that, The process determination value is compared with a preset reference value. Specific steps include: The reference value obtained under the same conditions as a normal freeze-dried batch is used as the preset reference value; The process determination value is compared with the preset reference value; When the process determination value is less than the preset reference value, the freeze-drying end command is output, and a freeze-drying batch report containing the operating parameter change curves of the entire cycle is generated; otherwise, the control of the current stage continues.

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