Method and system for optimization of at-211 elution process based on model predictive control

Abstract

The present application relates to the technical field of automation control, and discloses an At-211 elution process optimization method and system based on model predictive control, comprising the following steps: step 1, calibrating inherent dead volume and lag time; step 2, establishing a deterministic mechanism model, generating flow rate range, working condition range and valve group switching plan; step 3, using pre-washing liquid to stabilize the pre-elution stage until the conductivity and pressure are stable, and removing residual reagents; step 4, when the main elution is triggered, calculating the lag time and scheduling the valve group switching time; step 5, starting the main elution process through the high flow rate range and switching to the low flow rate range; step 6, triggering the price state locking liquid pulse, changing the At-211 price state and determining the collection termination time; and step 7, collecting the elution volume through volume segmentation, calculating the decay correction factor and converting to the unified reference time. The present application realizes the precise control of the flow rate range, working condition range and valve group switching, and improves the efficiency and consistency of the elution process.

Description

Technical Field

[0001] This invention belongs to the field of automation control technology, specifically relating to an optimization method and system for the At-211 elution process based on model predictive control. Background Technology

[0002] At-211 (cesium-211) is a radioactive isotope with important applications, widely used in medical and scientific research. Due to its unique physical and chemical properties, the separation and extraction process of At-211 requires precise control to ensure its efficient recovery and application. Traditional elution processes use fixed flow rates and solvent types, which, while achieving a certain separation effect, often suffer from insufficient control precision, large process fluctuations, and time delays.

[0003] Flow control during the elution process is one of the key factors affecting process efficiency. Because fluid flow within the system is influenced by inherent dead volume and lag time, traditional experience-based flow control methods often fail to accurately predict the system's behavior at different stages. Therefore, how to use more precise control methods to avoid the impact of lag time and fluid delay on the elution process has become a core challenge for improving process efficiency.

[0004] Currently, many elution process control methods rely on empirical control strategies. These methods struggle to adapt to complex process variations, especially under the influence of factors such as solvent type and flow rate changes, often resulting in poor process stability and consistency. Therefore, how to perform real-time regulation during elution and implement predictive control based on system state changes has become an urgent technical problem to be solved. Summary of the Invention

[0005] This invention provides an optimization method and system for the At-211 elution process based on model predictive control, which solves the technical problems in related technologies that rely on experience to set the flow rate and valve group switching sequence, fail to include the inherent dead volume and lag time of the system in the calculation of control quantities, resulting in asynchronous switching of flow rate level, operating condition level and valve group before and after the column, and lack of a consistent time reference for the execution of commands within the control cycle, thus causing process fluctuations.

[0006] This invention provides an optimization method for the At-211 elution process based on model predictive control, comprising the following steps:

[0007] Step 1: Calibrate the inherent dead volume and hysteresis time of the system using the conductivity step method, and solidify the calibration results into control parameters;

[0008] Step 2: Establish a deterministic mechanism model that includes three operating conditions. By selecting control variables and setting hard constraints in each cycle, the flow rate, operating condition, and valve group switching plan for the next cycle are generated.

[0009] Step 3: Perform the pre-washing stage, using pre-wash solution and controlling the system until conductivity and pressure reach a stable state to remove residual reagents and baseline disturbances from the system;

[0010] Step 4: When the main elution is triggered, calculate the lag time and accurately schedule the switching time of the pre-column and post-column valve groups;

[0011] Step 5: Start the main elution process with the high flow rate setting, and switch to the low flow rate setting when the cumulative volume reaches the preset cumulative volume or the conductivity reaches the preset conductivity threshold.

[0012] Step 6: When the preset volume or conductivity threshold conditions are met, trigger the valence state locking liquid pulse to change the valence state of At-211, instantly cut off the tail of the elution peak, and calculate the hysteresis time to determine the collection termination time.

[0013] Step 7: Accumulate the elution volume by collecting in fixed volume segments, calculate the decay correction factor of the activity of each segment, and convert the activity of each segment to a unified reference time.

[0014] This invention provides an optimization system for the At-211 elution process based on model predictive control, comprising:

[0015] The inherent dead volume calibration module is used to calibrate the inherent dead volume and hysteresis time of the system by the conductivity step method, and to solidify the calibration results into control parameters.

[0016] The mechanism model generation module is used to establish a deterministic mechanism model that includes three operating conditions. By selecting control variables and setting hard constraints in each cycle, the controller generates the flow rate level, operating condition level, and valve group switching plan for the next cycle.

[0017] The pre-elution stage module is used to perform the pre-elution stage, using pre-wash solution and controlling the system to operate until the conductivity and pressure reach a stable state, removing residual reagents and baseline disturbances from the system.

[0018] The lag time scheduling module is used to calculate the lag time and accurately schedule the switching time of the pre-column and post-column valve groups when the main elution is triggered.

[0019] The flow rate switching module is used to start the main elution process with a high flow rate at the beginning and switch to a low flow rate when the accumulated volume reaches a preset accumulated volume or the conductivity reaches a preset conductivity threshold.

[0020] The valence state locking pulse module is used to trigger a valence state locking liquid pulse when a preset volume or conductivity threshold condition is met, thereby changing the valence state of At-211, instantly truncating the elution peak tail, and calculating the hysteresis time to determine the collection termination time.

[0021] The fractional collection and activity conversion module is used to accumulate the elution volume through a fixed-volume fractional collection method, calculate the decay correction factor of the activity of each fraction, and convert the activity of each fraction to a unified reference time.

[0022] The beneficial effects of this invention are as follows: By generating precise flow rate settings, operating condition settings, and valve group switching plans, this invention improves the control accuracy and consistency of the At-211 elution process. By establishing a deterministic mechanism model and combining experimental data with real-time monitoring data, the system can dynamically predict and optimize flow control and valve group switching timing within each control cycle, avoiding the effects of lag time and fluid delay commonly found in traditional empirical control.

[0023] The control method of this invention no longer relies on traditional fixed flow rates and solvent types, but instead makes intelligent adjustments based on real-time system status and feedback data, ensuring optimal operation of the elution process at different stages. Especially during valve switching and flow control, the controller can precisely adjust control commands based on inherent dead volume and lag time, thereby reducing process deviations caused by timing inconsistencies or system fluctuations. This method not only improves the stability and efficiency of the At-211 elution process, but also enhances the system's adaptability and controllability through real-time regulation and accurate prediction, thus optimizing the elution process. Attached Figure Description

[0024] Figure 1 This is a flowchart of the At-211 elution process optimization method based on model predictive control according to the present invention. Detailed Implementation

[0025] The subject matter described herein will now be discussed with reference to exemplary embodiments. It should be understood that these embodiments are discussed only to enable those skilled in the art to better understand and implement the subject matter described herein, and changes may be made to the function and arrangement of the elements discussed without departing from the scope of this specification. Various processes or components may be omitted, substituted, or added as needed in the examples. Furthermore, features described in some examples may be combined in other examples.

[0026] like Figure 1 As shown, the optimization method for the At-211 elution process based on model predictive control includes the following steps:

[0027] Step 1: Calibrate the inherent dead volume and hysteresis time of the system using the conductivity step method, and solidify the calibration results into control parameters;

[0028] Step 2: Establish a deterministic mechanism model that includes three operating conditions. By selecting control variables and setting hard constraints in each cycle, the flow rate, operating condition, and valve group switching plan for the next cycle are generated.

[0029] Step 3: Perform the pre-washing stage, using pre-wash solution and controlling the system until conductivity and pressure reach a stable state to remove residual reagents and baseline disturbances from the system;

[0030] Step 4: When the main elution is triggered, calculate the lag time and accurately schedule the switching time of the pre-column and post-column valve groups;

[0031] Step 5: Start the main elution process with the high flow rate setting, and switch to the low flow rate setting when the cumulative volume reaches the preset cumulative volume or the conductivity reaches the preset conductivity threshold.

[0032] Step 6: When the preset volume or conductivity threshold conditions are met, trigger the valence state locking liquid pulse to change the valence state of At-211, instantly cut off the tail of the elution peak, and calculate the hysteresis time to determine the collection termination time.

[0033] Step 7: Accumulate the elution volume by collecting in fixed volume segments, calculate the decay correction factor of the activity of each segment, and convert the activity of each segment to a unified reference time.

[0034] In one embodiment of the present invention, to accurately determine the fluid delay characteristics during the At-211 elution process and provide accurate control parameters for subsequent model predictive control, the inherent dead volume and hysteresis time of the system are calibrated using the conductivity step method, and the calibration results are solidified into the controller's control parameters. The inherent dead volume refers to the volume of fluid accumulated in the system pipelines, valve bodies, connectors, and downstream flow path after valve switching or changes in fluid properties, affecting the system's transmission delay. The hysteresis time is the time elapsed corresponding to the ratio of the inherent dead volume to the real-time flow rate, describing the time required for fluid to transfer from the upstream valve group to the downstream valve group. By accurately calibrating these parameters, it is possible to ensure that realistic time delay characteristics are introduced into the controller's calculations, thereby improving the control accuracy and consistency of the At-211 elution process.

[0035] The specific implementation process is as follows: The control system sets the downstream valve group to waste liquid state, preventing downstream fluid from entering the collection branch and eliminating collection interference from the downstream valve group; simultaneously, the upstream valve group is set as the pre-wash liquid flow path, and a low-conductivity liquid is introduced through a preset calibration flow rate. The preset calibration flow rate refers to a constant flow rate value set by the controller during calibration and confirmed by feedback from the flow meter, used to provide a reference for the time required for conductivity stabilization. After introducing the low-conductivity liquid, the controller continuously monitors the conductivity signal until the conductivity value reaches a stable state and records the time it takes for the conductivity to reach stability as the system response time. Subsequently, the system is switched to a high-conductivity liquid, forming a conductivity step input, and the conductivity change continues to be recorded until the conductivity reaches a new stable plateau time.

[0036] Based on the recorded conductivity settling time, the controller multiplies the preset calibration flow rate by the time required for conductivity settling to obtain the inherent dead volume. The inherent dead volume, calculated by multiplying the flow rate by the settling time, represents the stagnant volume in the system. The controller further calculates the ratio of the inherent dead volume to the real-time flow rate to obtain the lag time, which characterizes the fluid transport delay within the system. Finally, the controller writes the inherent dead volume and lag time as control parameters into the controller parameter table for use in subsequent control cycles. These parameters are used to generate valve group switching plans, calculate flow rate settings, and control operating conditions, thereby ensuring that the operation within each control cycle of the At-211 elution process meets the expected timing and flow control requirements.

[0037] Through the above implementation methods, the controller can accurately calibrate and introduce the inherent transmission delay characteristics of the system, making the generation of flow rate levels, operating conditions, and valve group switching plans more precise under the framework of model predictive control. This reduces control errors caused by fluid transmission delay and improves the controllability and consistency of the At-211 elution process.

[0038] In one embodiment of the present invention, to enable the controller to calculate and issue flow rate levels, operating condition levels, and valve group switching plans according to a fixed control cycle during the elution operation, a deterministic mechanism model containing three operating condition levels is established. Within each control cycle, a control quantity is selected based on real-time acquired data, and hard constraints are introduced to limit the range of control quantity values, generating the flow rate level, operating condition level, and valve group switching plan for the next cycle. The operating condition level is a discretized division of the elution operation state, including a pre-wash stage, a main elution stage, and a valence state locking stage; the flow rate level is a discretized division of the executable flow rate setpoint, used for control... Within a cycle, the pump or flow control component is set to a preset gear value; the control cycle is a discrete control interval with a fixed time unit, and the controller updates the control quantity once between adjacent control cycles; the control quantity is the control output issued and executed by the controller in the next control cycle, and the control quantity includes flow gear, operating condition gear, and valve group switching plan; the valve group switching plan is the scheduling result of the switching time and switching state of the upstream valve group and the downstream valve group in the next control cycle; the hard constraint conditions are the operating constraints that the controller must meet, including at least the maximum flow rate and the preset pressure upper limit, used to limit the control quantity and trigger constraint actions. Specifically, it includes:

[0039] Step 21: The At-211 elution process is divided into a pre-wash stage, a main elution stage, and a valence state locking stage, and corresponding solvent types and flow rates are associated with each stage, ensuring that each stage has executable solvent type and flow rate settings. A deterministic mechanism model is established based on experimental data. This model describes the relationship between the resin desorption rate and the solvent type and flow rate. The resin desorption rate is a measure of the rate at which the target component transfers from the resin surface to the fluid phase. The solvent type is the controlled object representing the fluid category used in the pre-wash, main elution, and valence state locking stages. The flow rate is the volumetric flow rate input to the system per unit time through the pre-column valve assembly. To adapt to the discrete control mode where the controller executes according to the gear, the deterministic mechanism model outputs the set of selectable flow gears and the set of selectable operating condition gears for each stage. The set of selectable flow gears is the set of flow gear candidates that can be selected and issued by the controller in the corresponding stage, and the set of selectable operating condition gears is the set of operating condition candidates that can be selected when the controller switches cycles. Together, they constitute the control output range that the controller can select in the next control cycle.

[0040] Step 22: Set the control cycle to a fixed time unit. In each control cycle, the controller collects real-time flow and system pressure data and inputs these data into a deterministic mechanism model to calculate the control parameters for the next control cycle. The real-time flow is obtained from a flow meter and represents the actual flow state within the current control cycle; the system pressure is obtained from a pressure sensor and represents the system pressure state within the current control cycle. Based on the calculation results from the deterministic mechanism model, the controller selects the flow rate level and operating condition level, and generates a valve group switching plan matching the selected level. The flow rate level, operating condition level, and valve group switching plan are then written into the execution queue for the next control cycle. The execution queue is a sequence of control instructions to be executed within the controller. It is used to output flow rate level setting and valve group switching instructions to the actuators in a predetermined order within the next control cycle, thus ensuring that the controller's calculation results are implemented as executable actions in a deterministic sequence.

[0041] Step 23: Set hard constraints for each control cycle, including maximum flow rate and preset pressure limit. When the real-time flow rate exceeds the maximum flow rate or the system pressure reaches the preset pressure limit, the controller adjusts the flow rate level for the next control cycle to a lower flow rate level and performs valve group switching according to the valve group switching plan. The lower flow rate level is a candidate flow rate level with a smaller set value than the current flow rate level in the set of selectable flow rate levels, used to ensure that the flow rate setting for the next control cycle meets the constraints of maximum flow rate and preset pressure limit. Performing valve group switching according to the valve group switching plan means that the controller outputs switching commands to the upstream and downstream valve groups according to the valve group switching time and switching status recorded in the execution queue, thereby ensuring that the valve group switching action is consistent with the flow rate level execution within the control cycle.

[0042] Through the above implementation method, the controller generates the control quantity for the next control cycle based on the deterministic mechanism model within the discrete control cycle, and limits the control quantity by boundary under hard constraints. This allows the valve group switching plan, flow level, and operating condition level to be calculated and issued uniformly within the same control cycle framework, thereby enabling the timing control, level switching, and constraint protection of the washing process to have consistent control logic and reproducible parameter basis.

[0043] In one embodiment of the present invention, to enable the controller to uniformly schedule the elution process based on model predictive control within discrete control cycles, the deterministic mechanism model is constructed from experimental data and real-time monitoring data, and serves as the basis for solving the control quantity within the control cycle. The deterministic mechanism model is a mathematical model describing the deterministic correspondence between the system's operating state and the control output. The experimental data consists of system response data collected under preset solvent types and different flow rates, used to determine model parameters. The real-time monitoring data consists of real-time flow rates and system pressures collected by sensors within the control cycle. The solvent type refers to the solvent selection control object corresponding to the pre-wash stage, the main elution stage, and the valence state locking stage. Based on the above inputs, the deterministic mechanism model outputs the controller's control quantity for the next control cycle.

[0044] In practice, the controller acquires real-time flow rate and system pressure in each control cycle and, in conjunction with the solvent type, feeds this input data into a deterministic mechanism model for calculation. The model calculates the relationship between real-time flow rate and system pressure to determine the flow rate level and operating condition level for the next control cycle, and simultaneously generates a valve group switching plan matching these levels. Subsequently, the controller generates setting instructions for the actuators based on the flow rate level and operating condition level, and generates switching control instructions for the upstream and downstream valve groups based on the valve group switching plan. These switching control instructions include at least the switching times for the upstream and downstream valve groups, and output switching action instructions to the corresponding valve groups at the appropriate switching times, ensuring that the valve group switching actions maintain a consistent timing relationship with the flow rate level and operating condition level within the control cycle. Through this method, the control quantity output by the model is converted into an executable sequence of control instructions, which the controller then issues and executes in the next control cycle according to a predetermined sequence.

[0045] Through this implementation method, the deterministic mechanism model maps process state variables such as real-time flow rate, system pressure, and solvent type into flow rate level, operating condition level, and valve group switching plan. This enables the controller to generate control commands for the next control cycle based on the model calculation results in each control cycle, and to schedule and coordinate the switching times of multiple actuators using the valve group switching plan. This results in a unified timing control logic for the stage switching, flow rate level switching, and valve group action of the elution process at the control system level.

[0046] In one embodiment of the present invention, to ensure that the valve group switching plan generated by the controller in subsequent control cycles has consistent initial boundary conditions with the flow rate and operating condition, a pre-washing stage is performed before entering the main washing stage, and the stability of conductivity and system pressure is used as the stage end criterion during the pre-washing stage. The pre-washing stage refers to the stage in which the system is switched to the pre-wash liquid flow path and continuously operated under a preset calibration flow rate condition, used to converge the liquid environment and sensor readings within the system flow path to a stable range, thereby providing a reproducible initial state for subsequent time-series control based on the control cycle. The preset judgment time window is the time interval used to calculate the fluctuation amount; the stability judgment time is the time when the stability criterion is met; the minimum pre-washing time is the time corresponding to the replacement of the inherent dead volume under the preset calibration flow rate condition; the pre-washing time is a set value for the duration of the pre-washing stage. The specific implementation process is as follows:

[0047] The pre-column valve assembly of the system is set as the pre-wash solution, and the pre-wash solution is introduced into the system through a preset calibration flow rate. The controller collects multiple samples of conductivity and system pressure within a preset judgment time window and calculates the fluctuations of the samples: the difference between the maximum and minimum conductivity samples is determined as conductivity fluctuation, and the difference between the maximum and minimum system pressure samples is determined as pressure fluctuation. The controller compares the conductivity fluctuation with a preset conductivity fluctuation threshold and the pressure fluctuation with a preset pressure fluctuation threshold. When both the conductivity fluctuation and pressure fluctuation are less than the preset conductivity fluctuation threshold and the pressure fluctuation are less than the preset pressure fluctuation threshold, the stability judgment time is recorded, and this stability judgment time is used as the starting point for timing the duration of the pre-washing stage.

[0048] After the stability determination time is determined, the controller calls the inherent dead volume that has been calibrated and written into the controller parameter table, and calculates the minimum pre-wash time by comparing the inherent dead volume with the preset calibration flow rate. The controller further multiplies the minimum pre-wash time by two to obtain the pre-wash time, and sets the pre-wash stage duration as the pre-wash time. From the stability determination time, the system continues to run at the preset calibration flow rate until the pre-wash stage duration ends, thus completing the time-sequential control of the pre-wash stage.

[0049] Through the above implementation method, the stability determination time of the pre-washing stage is defined by the deterministic criteria of conductivity fluctuation and pressure fluctuation, and the minimum pre-washing time is determined by the ratio of inherent dead volume to preset calibrated flow rate. Then, the pre-washing time is used to set the running duration of the pre-washing stage, so that the controller obtains a consistent stage start time and stage running time reference before entering the subsequent control cycle.

[0050] In one embodiment of the present invention, to ensure that the flow path switching and collection timing of the main elution stage have a consistent time reference within the controller's control cycle framework, the lag time is calculated based on the system's inherent dead volume and real-time flow rate, and the switching time of the pre-column valve group and the post-column valve group is determined accordingly. The pre-column valve group switching time refers to the time reference moment when the controller triggers the pre-column valve group to switch from the pre-wash liquid flow path to the main elution solvent flow path; the post-column valve group switching time refers to the time reference moment when the controller triggers the post-column valve group to switch from the waste liquid state to the collection state; the main elution solvent is the solvent type controlled object corresponding to the main elution stage; the collection state is one of the working states of the post-column valve group, indicating that the post-column fluid enters the collection branch.

[0051] The specific implementation process is as follows: When the main elution is triggered, the controller records the switching time of the pre-column valve group and outputs a switching command to the pre-column valve group at that switching time, causing the pre-column valve group to switch to the main elution solvent flow path. Simultaneously, the controller reads the inherent dead volume already written into the controller parameter table and collects the real-time flow rate corresponding to the switching time of the pre-column valve group. The ratio of the inherent dead volume to the real-time flow rate is used to obtain the lag time. The controller adds the pre-column valve group switching time to the lag time to obtain the post-column valve group switching time, and uses this post-column valve group switching time as the time to issue the post-column valve group switching command: at the post-column valve group switching time, a switching command is output to the post-column valve group, causing the post-column valve group to switch to the collection state. The recording of the switching time, the calculation of the lag time, and the generation of the post-column valve group switching time can be written into the controller's execution queue, thus executing them according to the predetermined sequence in subsequent control cycles.

[0052] Through the above implementation method, the controller calculates the switching time of the valve group after the column based on the lag time constructed by the inherent dead volume and the real-time flow, so that the switching of the valve group before the column and the switching of the collection state of the valve group after the column can be scheduled in an orderly manner under the same time base, so that the valve group switching plan can maintain the same timing relationship with the control quantity of flow level and operating condition level.

[0053] In one embodiment of the present invention, to ensure that the main elution stage completes the timing switch of the flow rate level according to preset threshold conditions within the control cycle framework, and to execute a hard constraint protection action when the system pressure reaches the constraint boundary, the main elution process is started with a high flow rate level at the leading edge, and switches to a low flow rate level when the accumulated volume reaches a preset accumulated volume or the conductivity reaches a preset conductivity threshold. The high flow rate level and the low flow rate level are discrete flow rate setting levels that can be issued by the controller, wherein the high flow rate level is the initial flow rate level for starting the main elution stage, and the low flow rate level is the subsequent flow rate level for the main elution stage; the accumulated volume is the volume obtained by accumulating the real-time flow rate from the start of the autonomous elution process, used to characterize the volume progress of the main elution stage through the system; the preset accumulated volume is the volume threshold that triggers the flow rate level switch; the preset conductivity threshold is the conductivity threshold that triggers the flow rate level switch; the specific process includes:

[0054] Step 51: After the main elution is triggered, the controller sets the flow rate to a high flow rate and sends a setting command to the flow actuator to make the system run at a high flow rate to start the main elution process.

[0055] Step 52: The controller uses the start time of the main elution process as the starting point for accumulation, continuously accumulating the real-time flow rate to obtain the accumulated volume, and simultaneously monitoring the conductivity in real time. The controller compares the accumulated volume with the preset accumulated volume and the conductivity with the preset conductivity threshold; when the accumulated volume reaches the preset accumulated volume or the conductivity reaches the preset conductivity threshold, the controller issues a flow rate switching command to the flow actuator, switching the flow rate from the high flow rate to the low flow rate, thereby completing the threshold-triggered flow rate switching within the main elution stage.

[0056] Step 53: During the high flow rate operation and threshold monitoring, the controller monitors the system pressure in real time. When the system pressure reaches the preset pressure limit and the flow rate is high, the controller directly sends a flow rate switching command to the flow actuator to switch the flow rate to low flow rate, so that the high flow rate operation is subject to hard constraints.

[0057] Through the above implementation method, the controller outputs a high flow rate as the initial control quantity during the main elution stage, and generates a low flow rate switching command based on the threshold comparison of cumulative volume and conductivity. At the same time, a preset pressure upper limit is used as a hard constraint to limit the boundary of the high flow rate operation process, so that the flow rate switching satisfies both the process triggering condition and the constraint triggering condition under the same control logic.

[0058] In one embodiment of the present invention, a valence-locking liquid pulse is triggered when a preset volume or conductivity threshold condition is met, changing the valence state of At-211, instantly truncating the elution peak tail, and calculating the hysteresis time to determine the collection termination time, including:

[0059] Step 61: Real-time monitoring of the main elution cumulative volume and conductivity. When the main elution cumulative volume reaches a preset cumulative volume or the conductivity is less than or equal to a preset conductivity threshold, the controller switches the pre-column valve assembly from the main elution solvent flow path to the valence-locking liquid flow path and triggers a valence-locking liquid pulse. The main elution cumulative volume is the cumulative volume obtained by integrating the flow rate using a real-time flow meter during system operation; when the conductivity reaches the preset conductivity threshold, it indicates that a certain characteristic of the elution process has been completed. The triggering of the valence-locking liquid pulse is used to change the valence state of At-211 and immediately truncate the elution peak tail, further optimizing the elution process.

[0060] Step 62: After the valence-locking liquid pulse is triggered, the controller begins to accumulate the real-time flow rate to obtain the pulse accumulation volume. When the pulse accumulation volume reaches the preset valence-locking liquid pulse accumulation volume, the end time of the valence-locking liquid pulse is recorded. The pulse accumulation volume is calculated by integrating the real-time flow rate and the pulse duration, aiming to record the total injection volume of the valence-locking liquid pulse and ensure that the required liquid volume is accurately applied within the control system.

[0061] Step 63: At the moment the post-column valve assembly collection terminates, the controller switches the post-column valve assembly from the collection state to the waste liquid state, terminating the collection of eluent and ensuring the integrity and accuracy of the elution process. Through the above control, the controller can precisely regulate each step in the elution process, reducing uncertainties caused by solvent switching or flow fluctuations, and ensuring the efficient execution of the elution process.

[0062] The above-described implementation enables precise time compensation and solvent switching during the At-211 elution process, particularly in peak tail truncation and flow rate switching, effectively improving the controllability and consistency of the elution process. Through this method, the controller can accurately calculate and execute flow rate settings, solvent switching, and valve group switching based on real-time feedback information within different control cycles, ensuring consistency and efficiency in time control at each stage of the elution process.

[0063] In one embodiment of the present invention, the elution volume is accumulated using a fixed-volume segmented collection method, the decay correction factor of the activity of each segment is calculated, and the activity of each segment is converted to a unified reference time. This fixed-volume segmented collection method accurately determines the activity of each collection segment by accumulating the real-time flow rate within each control cycle, and converts the activity to a unified reference time based on the decay correction factor, ensuring that activity data collected at different time periods are compared at a unified time. The specific process includes:

[0064] Step 71: The controller places the post-column valve assembly in the collection state and accumulates the real-time flow rate from the time the post-column valve assembly switches to the collection state until the collection ends, obtaining the elution volume. The elution volume refers to the target solvent fluid volume accumulated by the controller through flow meter monitoring and flow integration within each control cycle. The controller uses a preset segment volume as the segmentation benchmark and determines the boundary of the current segment based on the collection segment number. The boundary of the current segment is jointly determined by the preset segment volume and the accumulated elution volume. When the accumulated elution volume reaches the current segment boundary, the controller records the segment end time, switches the collection container, and generates a segment record table. The segment record table includes the collection segment number, the preset segment volume, and the segment end time, providing data support for subsequent decay correction factor calculation and activity conversion.

[0065] Step 72: The controller determines the time difference for each collection segment based on the unified reference time and calculates the decay time difference between the end time of each collection segment and the unified reference time. The unified reference time can be the reference standard time for all segments, typically selected as the time point of a significant event in the system or a global reference time. The decay time difference is obtained from the time difference between the end time of the segment and the unified reference time, and is used to calculate the decay correction factor for each segment. Specifically, the controller converts the half-life of At-211 into a decay constant, and then performs an exponential operation on the negative product of the decay constant and the decay time difference to obtain the decay correction factor for that segment. The decay correction factor is used to eliminate the time difference between the activity of segments collected at different time points, ensuring that all data can be compared and analyzed at the same reference time.

[0066] Step 73: The controller measures the activity of the collection containers corresponding to each collection segment to obtain the segment activity corresponding to the end time of the segment. The segment activity refers to the activity value obtained by measuring the solute in the collection container at the end time of the segment, representing the radioactivity intensity of the collected liquid in that segment. The controller multiplies the segment activity by the decay correction factor of that collection segment to obtain the converted activity. By converting the activity to a unified reference time, the influence of time on the activity measurement can be effectively eliminated, and the measurement data from different time periods can be unified to the same reference value at that time. Finally, the controller outputs the correspondence between the collection segment number and the converted activity, providing reliable data support for subsequent analysis and result verification.

[0067] Through the above implementation method, the controller can accurately accumulate and convert the elution volume and activity data according to the fixed volume segment collection method and the calculation of decay correction factor, thereby ensuring that the activity measurement in different control cycles has high controllability and consistency, and improving the data accuracy and control precision in the At-211 elution process.

[0068] This invention provides an optimization system for the At-211 elution process based on model predictive control, comprising:

[0069] The inherent dead volume calibration module is used to calibrate the inherent dead volume and hysteresis time of the system by the conductivity step method, and to solidify the calibration results into control parameters.

[0070] The mechanism model generation module is used to establish a deterministic mechanism model that includes three operating conditions. By selecting control variables and setting hard constraints in each cycle, the controller generates the flow rate level, operating condition level, and valve group switching plan for the next cycle.

[0071] The pre-elution stage module is used to perform the pre-elution stage, using pre-wash solution and controlling the system to operate until the conductivity and pressure reach a stable state, removing residual reagents and baseline disturbances from the system.

[0072] The lag time scheduling module is used to calculate the lag time and accurately schedule the switching time of the pre-column and post-column valve groups when the main elution is triggered.

[0073] The flow rate switching module is used to start the main elution process with a high flow rate at the beginning and switch to a low flow rate when the accumulated volume reaches a preset accumulated volume or the conductivity reaches a preset conductivity threshold.

[0074] The valence state locking pulse module is used to trigger a valence state locking liquid pulse when a preset volume or conductivity threshold condition is met, thereby changing the valence state of At-211, instantly truncating the elution peak tail, and calculating the hysteresis time to determine the collection termination time.

[0075] The fractional collection and activity conversion module is used to accumulate the elution volume through a fixed-volume fractional collection method, calculate the decay correction factor of the activity of each fraction, and convert the activity of each fraction to a unified reference time.

[0076] It should be noted that the range and threshold size are set for ease of comparison. The size of the threshold depends on the amount of sample data and the number of bases set by those skilled in the art for each set of sample data, as long as it does not affect the ratio between the parameter and the quantized value.

[0077] The embodiments of the present invention have been described above, but the present invention is not limited to the specific embodiments described above. The specific embodiments described above are merely illustrative and not restrictive. Those skilled in the art can make many other forms based on the guidance of the present embodiments, all of which are within the protection scope of the present embodiments.

Claims

1. An optimization method for the At-211 elution process based on model predictive control, characterized in that, Includes the following steps: Step 1: Calibrate the inherent dead volume and hysteresis time of the system using the conductivity step method, and solidify the calibration results into control parameters, including: Set the downstream valve group of the system to waste liquid state and the upstream valve group to pre-wash liquid state. Introduce low conductivity liquid at a preset calibration flow rate and record the time when conductivity reaches stability. Switch to high conductivity liquid and record the time when conductivity reaches stability plateau. Multiply the preset calibration flow rate by the time when conductivity reaches stability to obtain the inherent dead volume. Calculate the ratio of inherent dead volume to real-time flow rate to obtain the lag time. Write the inherent dead volume and lag time into the controller parameter table. Step 2: Establish a deterministic mechanism model containing three operating conditions. By selecting control variables and setting hard constraints each cycle, the flow rate level, operating condition level, and valve group switching plan for the next cycle are generated, including: Step 21: Divide the At-211 elution process into a pre-wash stage, a main elution stage, and a valence state locking stage, and associate them with the corresponding solvent type and flow rate. Based on experimental data, establish a deterministic mechanism model, which characterizes the relationship between the resin desorption rate and the solvent type and flow rate, and outputs the set of optional flow rate levels and the set of optional operating conditions for each stage. Step 22: Set the control cycle to a fixed time unit; the controller collects real-time flow and system pressure in each control cycle, and inputs the real-time flow and system pressure into the deterministic mechanism model to calculate the control quantity for the next control cycle; the control quantity includes flow level, operating condition level and valve group switching plan, and writes the control quantity into the execution queue for the next control cycle; Step 23: Set hard constraints in each control cycle. The hard constraints include the maximum flow rate and the preset pressure limit. When the real-time flow rate exceeds the maximum flow rate or the system pressure reaches the preset pressure limit, the controller will adjust the flow rate level of the next control cycle to a lower flow rate level and perform valve group switching according to the valve group switching plan. The deterministic mechanism model includes: A deterministic mechanism model is established based on experimental data and real-time monitoring data. The inputs of the deterministic mechanism model include real-time flow rate, system pressure and solvent type, and the outputs are flow rate level, operating condition level and valve group switching plan. Based on the flow rate and operating condition levels calculated by the controller, control commands are generated through the valve group switching plan to indicate the switching time between the upstream and downstream valve groups. Step 3: Perform the pre-washing stage, using pre-wash solution and controlling the system until the conductivity and pressure reach a stable state to remove residual reagents and baseline disturbances from the system; Step 4: When the main elution phase is triggered, calculate the lag time and accurately schedule the switching time of the pre-column and post-column valve groups. Step 5: Start the main elution stage with the high flow rate setting, and switch to the low flow rate setting when the cumulative volume reaches the preset cumulative volume or the conductivity reaches the preset conductivity threshold. Step 6: When the preset volume or conductivity threshold conditions are met, the valence state locking stage is triggered, the valence state of At-211 is changed, the elution peak tail is truncated instantly, and the lag time is calculated to determine the collection termination time. Step 7: Accumulate the elution volume by collecting in fixed volume segments, calculate the decay correction factor of the activity of each segment, and convert the activity of each segment to a unified reference time.

2. The optimization method for the At-211 elution process based on model predictive control according to claim 1, characterized in that, During the pre-wash phase, a pre-wash solution is used and the system is controlled until conductivity and pressure reach a stable state to remove residual reagents and baseline disturbances, including: The pre-column valve assembly of the system is set as the pre-wash fluid, and the pre-wash fluid is introduced into the system through a preset calibration flow rate. Multiple sampling values ​​of conductivity and system pressure are collected within a preset judgment time window. The difference between the maximum and minimum conductivity sampling values ​​is taken as the conductivity fluctuation, and the difference between the maximum and minimum system pressure sampling values ​​is taken as the pressure fluctuation. When the conductivity fluctuation is less than the preset conductivity fluctuation threshold and the pressure fluctuation is less than the preset pressure fluctuation threshold, the stability judgment time is recorded. The ratio of the inherent dead volume of the calculation system to the preset calibrated flow rate is used to obtain the minimum pre-washing time. The minimum pre-washing time is multiplied by two to obtain the pre-washing time, and the duration of the pre-washing stage is set as the pre-washing time. The system continues to run from the stable determination time until the end of the pre-washing stage duration.

3. The optimization method for the At-211 elution process based on model predictive control according to claim 1, characterized in that, When triggered in the main elution phase, calculate the lag time and precisely schedule the switching times of the pre-column and post-column valve assemblies, including: Record the switching time of the pre-column valve group, calculate the ratio of the inherent dead volume of the system to the real-time flow rate to obtain the lag time, add the switching time of the pre-column valve group to the lag time to obtain the switching time of the post-column valve group, switch the pre-column valve group to the main elution solvent at the switching time of the pre-column valve group, and switch the post-column valve group to the collection state at the switching time of the post-column valve group.

4. The optimization method for the At-211 elution process based on model predictive control according to claim 1, characterized in that, The main elution phase is initiated at a high flow rate, and the flow rate is switched to a low flow rate when the accumulated volume reaches a preset accumulated volume or the conductivity reaches a preset conductivity threshold. This includes: Step 51: Set the flow rate to high and run the program to start the main rinsing phase; Step 52: Starting from the beginning of the main elution stage, the real-time flow rate is accumulated to obtain the cumulative volume, and the conductivity is monitored in real time; when the cumulative volume reaches the preset cumulative volume or the conductivity reaches the preset conductivity threshold, the flow rate is switched from the high flow rate to the low flow rate. Step 53: During the execution of steps 51 and 52, monitor the system pressure in real time. When the system pressure reaches the preset pressure limit and the flow rate is at the high flow rate level, switch the flow rate level to the low flow rate level.

5. The optimization method for the At-211 elution process based on model predictive control according to claim 1, characterized in that, When a preset volume or conductivity threshold condition is met, a valence state locking phase is triggered, changing the valence state of At-211, instantly truncating the elution peak tail, and calculating the hysteresis time to determine the collection termination time, including: Step 61: Monitor the cumulative volume and conductivity of the main elution in real time. When the cumulative volume of the main elution reaches the preset cumulative volume or the conductivity is less than or equal to the preset conductivity threshold, switch the column pre-column valve group from the main elution solvent to the valence-locking solution and trigger the valence-locking stage. Step 62: Accumulate the real-time flow from the trigger time of the price-state locking phase to obtain the pulse accumulation volume. When the pulse accumulation volume reaches the preset price-state locking phase accumulation volume, record the end time of the price-state locking phase. Step 63: Calculate the ratio of the inherent dead volume of the system to the real-time flow rate to obtain the lag time. Add the end time of the valence state locking stage to the lag time to obtain the end time of the column valve group collection. At the end time of the column valve group collection, switch the column valve group from collection to waste liquid.

6. The optimization method for the At-211 elution process based on model predictive control according to claim 1, characterized in that, The elution volume is accumulated using a fixed-volume fractional collection method. The decay correction factor for the activity of each fraction is calculated, and the activity of each fraction is converted to a unified reference time, including: Step 71: During the collection state of the post-column valve group, the real-time flow rate is accumulated from the time the post-column valve group switches to the collection state until the collection ends, and the elution volume is obtained. The preset segment volume is used as the segmentation benchmark, and the current segment boundary is determined according to the collection segment number. When the elution volume reaches the current segment boundary, the segment end time is recorded and the collection container is switched to generate a segmentation record table containing the collection segment number, the preset segment volume, and the segment end time. Step 72: Determine the unified reference time and calculate the decay time difference between the end time of each collection segment and the unified reference time; convert the At-211 half-life into a decay constant, and perform an exponential operation on the product of the decay constant and the decay time difference to obtain the decay correction factor. Step 73: Perform activity measurement on the collection container corresponding to each collection segment to obtain the segment activity corresponding to the end time of the segment. Multiply the segment activity by the decay correction factor of the collection segment to obtain the converted activity, and output the correspondence between the collection segment number and the converted activity.

7. An optimization system for the At-211 elution process based on model predictive control, characterized in that, The At-211 elution process optimization method based on model predictive control as described in any one of claims 1-6 includes: The inherent dead volume calibration module is used to calibrate the inherent dead volume and hysteresis time of the system by the conductivity step method, and to solidify the calibration results into control parameters. The mechanism model generation module is used to establish a deterministic mechanism model that includes three operating conditions. By selecting control variables and setting hard constraints in each cycle, the controller generates the flow rate level, operating condition level, and valve group switching plan for the next cycle. The prewash stage module is used to perform the prewash stage, using prewash solution and controlling the system to operate until the conductivity and pressure reach a stable state, removing residual reagents and baseline disturbances from the system. The lag time scheduling module is used to calculate the lag time and accurately schedule the switching time of the pre-column and post-column valve groups when the main elution stage is triggered. The flow rate switching module is used to start the main elution stage with a high flow rate at the beginning and switch to a low flow rate when the accumulated volume reaches a preset accumulated volume or the conductivity reaches a preset conductivity threshold. The valence state locking stage module is used to trigger the valence state locking stage when the preset volume or conductivity threshold conditions are met, change the valence state of At-211, instantly truncate the elution peak tail, and calculate the lag time to determine the collection termination time. The fractional collection and activity conversion module is used to accumulate the elution volume through a fixed-volume fractional collection method, calculate the decay correction factor of the activity of each fraction, and convert the activity of each fraction to a unified reference time.

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