Radiopharmaceutical subpackaging device and method

Abstract

The invention discloses a radioactive drug subpackaging device and method, and relates to the field of biological medicines.The subpackaging method comprises the following steps that S1, drugs are extracted at the flow speed of 0.8 mL / s and used for rapidly establishing a stable flow field and inhibiting surfactant adsorption and bubble nucleation; s2, the flow speed is smoothly transited to 0.3 mL / s from 0.8 mL / s, and the medicine is extracted at the flow speed of 0.3 mL / s to be used for promoting breakage of generated bubbles; and S3, the medicine is extracted in a pulse mode, the pulse mode comprises extraction at the flow speed of 1.2 mL / s for 80 ms, then extraction is paused for 40 ms, and the pulse operation is repeated until the total subpackaging amount is completed so as to be used for flushing residual bubbles. The three-stage dynamic coupling flow velocity time sequence chain is adopted, so that full automation of bubble suppression is achieved, bubble control can be completed without interrupting the process, the continuity and reliability of subpackaging operation are effectively improved, and process interruption and operation accidents caused by bubbles are reduced.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of biological medicine, and particularly relates to a radio-pharmaceutical dispensing device and method. BACKGROUND

[0002] Radio-pharmaceuticals play an irreplaceable role in modern nuclear medicine diagnosis and treatment, and the accuracy and efficiency of the dispensing process are directly related to the safety of the drug for patients, the accuracy of image diagnosis, and the reliability of the treatment effect. In particular, for radio-pharmaceuticals containing surfactants, such as technetium methylene diphosphonate injection widely used in bone imaging, the dispensing process faces more complex technical challenges. Due to the presence of surfactants, bubbles are easily generated in the fluid transmission process, which not only affects the accuracy of the drug dose, but also may cause a series of serious problems such as pipeline blockage and activity decay.

[0003] In the existing technical practice, two main strategies are usually adopted for the dispensing of radio-pharmaceuticals. One is to use a fixed high flow rate to extract the drug in order to quickly complete the dispensing task. The original intention of this method is to shorten the dispensing time in order to cope with the characteristics of short half-life and rapid activity decay of radio-pharmaceuticals. The other is to manually intervene to adjust the dispensing parameters when bubbles are found. When bubbles appear in the pipeline and trigger the bubble sensor, the system will give a false alarm. At this time, the operator is forced to interrupt the dispensing process and manually switch to a lower flow rate mode for retry, in order to seek a balance between high speed efficiency and bubble control. In early applications, this method tries to make up for the shortcomings of fixed high-speed dispensing to some extent by artificially intervening experience to seek a balance between high-speed efficiency and bubble control.

[0004] However, with the increasingly stringent requirements of nuclear medicine clinics on the accuracy, timeliness and operation automation of drug dispensing, the inherent limitations of the above traditional methods gradually exposed in the principle level, which is difficult to meet the current challenges. The core problem is that the flow rate control is simplified as the setting of static parameters or passive manual intervention, which fails to fully consider the dynamic changes of the physical properties of surfactant-containing drugs in the millisecond dispensing time sequence. In the initial stage of traditional high-speed dispensing, the drug experiences a sudden change in turbulent shear force in the pipeline, which causes the surfactant molecules to be disturbed violently at the gas-liquid interface, resulting in a high bubble nucleation rate. When these bubbles trigger the sensor and cause false alarms, the operator's manual speed adjustment has inherent delays, during which the bubbles generated in the high-speed stage have become stable and firmly attached to the pipe wall, forming a stable Marangoni boundary layer, so that even if the speed is switched to low, these bubbles are difficult to break or be discharged with the fluid, resulting in an increase in the amount of residual bubbles in the pipeline.

[0005] Therefore, it is necessary to improve the existing technology to solve the above problems. Summary of the Invention

[0006] This invention overcomes the shortcomings of the prior art and provides a dispensing device and method for radiopharmaceuticals.

[0007] To achieve the above objectives, the technical solution adopted by the present invention is as follows: Firstly, the present invention provides a method for dispensing radiopharmaceuticals, comprising the following steps:

[0008] S1. Rapid flow field establishment and initial wetting stage: The drug is extracted at a flow rate of 0.8 mL / s for a duration of 0-100 ms to rapidly establish a stable flow field and inhibit surfactant adsorption and bubble nucleation.

[0009] S2, Critical Flow Rate Bubble Inhibition and Collapse Promotion Stage: After step S1, the flow rate is smoothly transitioned from 0.8 mL / s to 0.3 mL / s, and the drug is drawn at a flow rate of 0.3 mL / s for 100-300 ms to promote the collapse of the generated bubbles.

[0010] S3, Pulse-type discharge and residual microbubble flushing stage: After step S2, the drug is extracted in pulse mode. The pulse mode includes extracting at a flow rate of 1.2 mL / s for 80 ms, followed by pausing the extraction for 40 ms. This pulse operation is repeated until the total amount of dispensing is completed, which is used to flush out residual bubbles.

[0011] In a preferred embodiment of the present invention, the method further includes: real-time monitoring of the bubble state of the drug fluid in the dispensing pipeline, and dynamically adjusting the duration of step S2 or the pulse duty cycle of step S3 based on the bubble state.

[0012] In a preferred embodiment of the present invention, the method further includes: real-time monitoring of the drug activity during the dispensing process, and dynamic adjustment of the extraction volume based on the real-time activity value, in order to ensure the accuracy of the final dispensing dosage.

[0013] In a preferred embodiment of the present invention, the method further includes: performing self-learning calibration before dispensing, and fine-tuning the parameters in steps S1, S2 and S3 by analyzing historical dispensing data.

[0014] In a preferred embodiment of the present invention, in step S1, a flow rate of 0.8 mL / s is used to shorten the average residence time of the drug in the tubing to 25 ms, thereby reducing the amount of bubble nucleation.

[0015] In a preferred embodiment of the present invention, in step S2, a flow rate of 0.3 mL / s is used to control the Weber number of the fluid at 5.8 ± 0.2, thereby promoting bubble collapse.

[0016] In a preferred embodiment of the present invention, in step S3, the duty cycle and instantaneous flow rate of the pulse mode are controlled to maximize the scouring effect while minimizing the risk of new bubble formation.

[0017] In a second aspect, the present invention provides a radiopharmaceutical dispensing apparatus for performing a radiopharmaceutical dispensing method as described in any one of the above-mentioned methods, comprising:

[0018] Fluid transfer and precision pumping mechanisms are used to control the extraction and dispensing of drugs;

[0019] A multimodal bubble sensing and suppression module is used to monitor bubbles in the dispensing pipeline;

[0020] The dose-activity closed-loop and calibration module is used to measure drug activity and perform dose compensation.

[0021] The timing chain control and safety interlock module is used to control the fluid transmission and precision pumping mechanism according to preset time nodes and bubble feedback signals.

[0022] The data acquisition and traceability module is used to record and manage the packaging data;

[0023] The human-computer interaction and diagnostic module is used for operator interaction and system diagnostics.

[0024] In a preferred embodiment of the present invention, the fluid transfer and precision pumping mechanism includes an injection pump, a high-precision motor and a transmission mechanism, used to achieve a piston displacement accuracy of 0.1 μm and a flow rate control accuracy of ±0.01 mL / s.

[0025] In a preferred embodiment of the present invention, the multimodal bubble sensing and suppression module includes an optical bubble sensor and a capacitive bubble sensor, as well as a sensor fusion unit for processing sensor signals and providing bubble information.

[0026] This invention addresses the shortcomings of the prior art and has the following beneficial effects:

[0027] (1) This invention provides a radiopharmaceutical dispensing device and method. By adopting a three-stage dynamic coupling flow rate time-series chain, the flow rate strategy of controlling the flow rate in three stages in sequence during the dispensing process can suppress bubble nucleation from the source according to the rheological characteristics of surfactant-containing drugs at different dispensing stages. It can also promote the rupture of microbubbles formed by hydrodynamic optimization under critical flow rate. At the same time, the shear stress wave generated by pulsed discharge is used to remove bubbles attached to the tube wall, thereby significantly reducing the amount of bubbles generated during the dispensing process. This avoids the problem of high bubble nucleation rate caused by severe turbulence in traditional fixed high-speed dispensing, as well as the bubble stabilization and deposition effect caused by low-speed retry. Thus, the bubble suppression is fully automated, and bubble control can be completed without interrupting the process. This effectively improves the continuity and reliability of the dispensing operation and reduces process interruption and operation accidents caused by bubbles.

[0028] (2) The present invention integrates a real-time bubble state monitoring and dynamic adjustment mechanism, which can automatically adjust the duration or pulse parameters of the dispensing stage based on sensor feedback. Through the fusion of multimodal perception and intelligent algorithms, it can accurately identify and respond to micro bubble signals, thereby avoiding false alarms and dispensing interruptions caused by non-critical bubble signals, and reducing the risk of new bubble generation. This achieves fully automatic adaptive adjustment. The feedback mechanism ensures the smoothness of the dispensing operation and improves the consistency and automation level of dispensing.

[0029] (3) The present invention has real-time drug activity monitoring and dynamic correction of extraction volume. Real-time calculation and compensation are performed by combining the activity meter reading with the drug half-life. Using closed-loop control logic, the extraction volume of the injection pump can be dynamically adjusted to cope with activity decay and volume error, thereby ensuring the accuracy of the final dispensing dose and effectively overcoming the dose deviation caused by activity changes and trace residues, thus ensuring the safety and effectiveness of patient medication and meeting the strict clinical requirements for dose accuracy. Attached Figure Description

[0030] To more clearly illustrate the technical solutions in the embodiments of the present 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 only some embodiments recorded in the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0031] Figure 1 This is a flowchart illustrating a preferred embodiment of the radiopharmaceutical packaging method of the present invention.

[0032] Figure 2 This is a structural block diagram of a radiopharmaceutical dispensing apparatus according to a preferred embodiment of the present invention. Detailed Implementation

[0033] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0034] Many specific details are set forth in the following description in order to provide a full understanding of the invention. However, the invention may also be practiced in other ways different from those described herein. Therefore, the scope of protection of the invention is not limited to the specific embodiments disclosed below.

[0035] This invention provides a dispensing apparatus and method for radiopharmaceuticals, offering a precise, efficient, and safe dispensing solution for radiopharmaceuticals containing surfactants. Through precise fluid dynamics control, multimodal real-time sensing, and intelligent adaptive adjustment, it overcomes common problems in existing technologies for handling such drugs, such as inaccurate dosing due to bubble formation, low dispensing efficiency, and uncontrolled activity decay. The method, system, and various preferred embodiments of this invention will be described in detail below to ensure that those skilled in the art can fully understand and implement this invention.

[0036] like Figure 1 As shown, the present invention provides a method for dispensing radiopharmaceuticals, which employs a dynamically coupled flow rate time-series chain to adapt to the rheological properties of surfactant-containing radiopharmaceuticals at different dispensing stages, thereby suppressing bubble formation at the source and promoting the rupture of existing microbubbles; the dispensing method specifically includes the following three stages.

[0037] In this embodiment, the first stage is the rapid flow field establishment and initial wetting stage, with a time span set between 0-100 ms. During this stage, drug extraction is initiated, and the flow rate is controlled at 0.8 mL / s. The flow rate selection is based on an optimized analysis of the interaction between fluid shear force and surface tension, aiming to rapidly establish a stable laminar flow field within a short time while minimizing the contact time between the surfactant-containing drug and the inner wall of the dispensing tubing. This strategy effectively suppresses the initial adsorption and subsequent aggregation of surfactant molecules on the tubing wall, thereby significantly reducing the bubble nucleation rate. In practice, a flow rate of 0.8 mL / s, compared to the severe turbulent shear caused by traditional high-speed dispensing, avoids excessively high bubble nucleation rates due to high shear forces. At this flow rate, the average residence time of the drug in the tubing is shortened to approximately 25 ms, effectively limiting the disturbance and rearrangement time of the surfactant at the gas-liquid interface, thus reducing the initial bubble nucleation rate.

[0038] In this embodiment, the second stage is the critical flow rate bubble suppression and collapse promotion stage, which follows the first stage and lasts for 10-300 ms. After the first stage, the flow rate is gradually transitioned from 0.8 mL / s and controlled at 0.3 mL / s in a smooth and continuous manner. The flow rate of 0.3 mL / s is set as the critical flow rate, and the Weber number of the fluid is precisely controlled within the range of 5.8 ± 0.2 by adjusting the balance between the momentum and surface tension of the fluid.

[0039] It should be noted that within a specific Weber number range, the inertial force of the fluid is insufficient to continue promoting the growth of already nucleated microbubbles, while surface tension, under continuous fluid shear, can effectively induce deformation of the microbubbles. This deformation leads to an increase in bubble surface area, thereby accelerating their collapse process. The velocity decay process is smooth and continuous, designed to avoid the reintroduction of local turbulence due to sudden velocity changes, which could lead to the formation of new bubbles. By coupling the fluid dynamics model and the bubble dynamics model through simulation optimization, the velocity switching time window was determined to ensure that a collapse-inducing effect is applied to the microbubbles before they have stably adhered to the pipe wall, fundamentally solving the bubble stabilization problem.

[0040] In this embodiment, the third stage is a pulsed emission and residual microbubble flushing stage, which starts after 300 ms and continues until the preset total amount of product is dispensed. A unique pulsed emission mode is used in this stage.

[0041] Specifically, pulsed dispensing involves: first, drug extraction is performed at a high instantaneous flow rate of 1.2 mL / s for 80 ms, followed by a 40 ms pause. This pulsed operation is repeated until the final dispensing volume is reached. The pulsed dispensing mode utilizes periodic abrupt changes in flow rate to generate localized shear stress waves within the dispensing tubing. These stress waves effectively flush away any microbubbles that may remain on the tubing wall, reintroducing them into the main fluid and discharging them along with it. The high instantaneous flow rate of 1.2 mL / s generates sufficient flushing force to remove bubbles adhering to the tubing wall; the subsequent 40 ms pause provides necessary time for the internal pressure to rebalance and for the flushed bubbles to coalesce, while preventing the formation of new bubbles that might result from prolonged high flow rates. The key to this stage is controlling the pulse duty cycle and instantaneous flow rate to maximize bubble flushing while minimizing the risk of new bubble formation.

[0042] Furthermore, during the dispensing process, the dispensing method of the present invention also incorporates a real-time feedback and adaptive adjustment mechanism, including real-time monitoring of the bubble state of the drug fluid in the dispensing pipeline, and dynamically adjusting the duration of the second stage or the pulse duty cycle of the third stage according to the bubble state.

[0043] Specifically, when a trace amount of bubble signal is detected in the pipeline, and the signal strength has not yet reached the preset false alarm threshold, optimization measures are prioritized. One optimization strategy is to extend the duration of the second stage, namely the critical flow rate bubble suppression and rupture promotion stage, such as extending it from the preset 200 ms to 300 ms. This adjustment provides more sufficient time for the microbubbles to fully rupture under the influence of the critical flow rate. Simultaneously, or as an alternative optimization strategy, the pulse duty cycle of the third stage can be shortened, such as adjusting the 80 ms extraction / 40 ms pause cycle to 70 ms extraction / 50 ms pause. This reduces the impact force of instantaneous high flow rates on the pipe wall, further reducing the probability of new bubble generation, thereby avoiding false alarms and dispensing process interruptions caused by non-critical bubble signals, and ensuring the continuity and stability of the dispensing process.

[0044] Furthermore, the dispensing method includes real-time monitoring of the drug activity during the dispensing process and dynamic adjustment of the extraction volume based on the real-time activity value to ensure the accuracy of the final dispensing dose. Specifically, the instantaneous activity value measured by the well-type activity meter is read in real time. Subsequently, combined with the known half-life of the drug (e.g., the half-life of 99mTc is 6.01 h) and the time elapsed since the start of extraction, the current remaining activity of the drug is calculated in real time using an exponential decay model. Based on the calculated instantaneous activity value, the preset target activity, and the current extracted volume, dynamic adjustments are made: Target activity = Set activity × (Remaining volume / Instantaneous volume). Following this logic, the extraction volume of the syringe pump is continuously and dynamically adjusted to compensate for the decay of radiopharmaceutical activity and potential volume errors caused by micro-air bubbles in the dispensing tubing.

[0045] In a preferred embodiment of the present invention, the dispensing method further includes self-learning calibration before dispensing. Self-learning calibration refers to in-depth analysis of historical dispensing data, which includes the rheological characteristics, ambient temperature, and initial activity parameters of different batches of drug solutions. Based on the historical data, key parameters in the three-stage flow rate time-series chain are fine-tuned, including but not limited to the flow rate thresholds for each stage, the duration of each stage, and the pulse duty cycle of the pulsed emission stage. The self-learning process utilizes data analysis, preferably a model based on regression analysis or a neural network, to identify and learn the complex mapping relationship between the inherent physical property differences of different drug solution batches and the optimal dispensing parameters. Through intelligent learning and iterative optimization, stable dispensing across batches can be achieved, significantly improving the system's adaptability to the physical property differences of different drug batches, thereby reducing reliance on human experience and further enhancing the reliability and consistency of the dispensing process.

[0046] like Figure 2As shown, the present invention also provides a radiopharmaceutical dispensing apparatus for performing the above-described dispensing method. The dispensing apparatus enables precise, efficient, and safe dispensing of radiopharmaceuticals containing surfactants. The dispensing apparatus includes a fluid transport and precision pumping mechanism, a multimodal bubble sensing and suppression module, a dose-activity closed-loop and calibration module, a timing chain control and safety interlock module, a data acquisition and traceability module, and a human-machine interaction and diagnostic module. All modules work collaboratively via a high-speed communication bus to ensure the smooth progress of the dispensing process, accurate data processing, and operational safety.

[0047] Specifically, the fluid transfer and precision pumping mechanism is used to precisely control the extraction and dispensing of radiopharmaceuticals. The core component is a high-precision syringe pump equipped with a high-performance stepper motor or servo motor. A precision ball screw or trapezoidal screw transmission mechanism drives the syringe piston to perform high-precision linear displacement. To ensure control accuracy, the stepper motor integrates a high-resolution encoder feedback system, enabling micro-step control of 20,000 steps per revolution. Combined with a 2 mm pitch screw, it achieves a minute displacement accuracy of 0.1 μm for the syringe piston, thus maintaining the dispensing flow rate control accuracy within an extremely narrow range of ±0.01 mL / s. The syringe preferably uses a 50 mL capacity borosilicate glass cylinder. The syringe piston seal is preferably made of medical-grade polytetrafluoroethylene or ultra-high molecular weight polyethylene material, ensuring chemical compatibility with the radiopharmaceutical, excellent wear resistance, and extremely low frictional resistance, thereby guaranteeing smooth piston movement and leak-free operation.

[0048] The multimodal bubble sensing and suppression module is used for real-time and accurate monitoring of bubbles in the dispensing pipeline, providing highly reliable bubble detection signals. It includes at least one optical bubble sensor and one capacitive bubble sensor for multi-dimensional sensing. The optical bubble sensor consists of an infrared LED and a high-sensitivity photodiode. Mounted externally to the dispensing pipeline, it detects bubbles by monitoring the scattering or attenuation of light as it passes through the fluid due to the presence of bubbles. Its response time is <100 μs, ensuring real-time bubble capture. The capacitive bubble sensor consists of a pair of annular or parallel planar electrodes, directly attached to the outer surface of the dispensing pipeline. It detects bubbles by monitoring changes in the fluid's dielectric constant, providing information about the relative volume of the bubbles.

[0049] Furthermore, the multimodal bubble sensing and suppression module integrates a sensor fusion unit. This unit employs a Kalman filter or support vector machine algorithm to perform real-time fusion processing on the raw signals from optical and capacitive sensors. The fusion algorithm effectively filters out environmental noise and instantaneous fluctuations caused by fluid turbulence, significantly suppresses false alarms, and accurately distinguishes between microbubbles and fine particles in the fluid. This provides highly reliable information on the presence and quantity of bubbles for the intelligent timing chain control and safety interlocking module, offering a precise basis for subsequent adaptive adjustments.

[0050] The dose-activity closed-loop and calibration module is used to measure drug activity in real time and perform dose compensation to ensure the accuracy of the final dispensing dosage. The core component is a well-type activity meter. The activity meter preferably uses a sodium iodide scintillation detector or a high-purity germanium detector and is equipped with a photomultiplier tube and a multichannel analyzer. To ensure measurement accuracy and operator radiation safety, a heavy lead shielding layer is integrated externally to the activity meter. The energy window of the activity meter is precisely set to the characteristic gamma ray energy of 99mTc, such as 140 keV ± 10 keV, thereby ensuring specific and highly sensitive measurement of 99mTc activity.

[0051] It should be noted that the dose-activity closed-loop and calibration module communicates in real time with the intelligent timing chain control and safety interlock module via a standard communication interface, continuously providing instantaneous activity readings. The processor inside the dose-activity closed-loop and calibration module runs an activity decay correction algorithm, calculating the current effective activity of the drug based on its half-life and the time elapsed since extraction began. Subsequently, combining the preset target activity, the extracted volume, and the remaining target volume, the module dynamically calculates the compensation extraction volume required by the infusion pump to ensure that the final dispensed dose accurately reaches the preset activity target at the end of dispensing. The calibration function also includes periodically calibrating the activity meter using a standard radiation source with known activity to ensure the accuracy, stability, and traceability of its measurement results.

[0052] The timing chain control and safety interlock module is the core control unit of the dispensing device, responsible for coordinating the work of each module and executing the dispensing method. This module employs a high-performance embedded microcontroller, such as an ARM Cortex-M4 or a higher-performance processor, and integrates a high-precision 16-bit analog-to-digital converter and a 12-bit digital-to-analog converter to meet the requirements of precision control. The microcontroller runs intelligent control software based on a finite state machine (FSM). The FSM defines several key states in the dispensing process, such as flow field establishment, bubble suppression, pulse emission, dispensing completion, and abnormal termination, as well as the switching logic and triggering conditions between these states. Based on preset time nodes and bubble feedback signals from the multimodal bubble sensing and suppression module, the timing chain control and safety interlock module precisely sends commands to the fluid transport and precision pumping mechanism, thereby controlling the flow rate, acceleration, and pulse duty cycle of the injection pump to dispense the drug according to a three-stage dynamically coupled flow rate timing chain.

[0053] Furthermore, the timing chain control and safety interlock module integrates multiple safety interlock mechanisms to ensure operational safety: when the multimodal bubble sensing and suppression module detects a severe bubble, such as when the bubble signal intensity exceeds the preset false alarm threshold and the duration exceeds 50 ms, it will immediately enter an abnormal termination state and execute a preset abnormal rollback procedure, such as pausing extraction, automatically reducing the flow rate to 0.1 mL / s for retry, or initiating a venting procedure to remove the bubbles. In addition, the timing chain control and safety interlock module also includes a timeout protection mechanism; if the total dispensing time exceeds a preset threshold, dispensing will be forcibly terminated and an alarm will be triggered; the tolerance protection mechanism will trigger an alarm or initiate a re-extraction procedure when the final error of the dispensing dose exceeds the clinically permissible range of ±1.5%.

[0054] The data acquisition and traceability module is used for comprehensive and detailed recording, storage, and management of all critical data during the dispensing process. Equipped with high-capacity non-volatile memory, such as industrial-grade solid-state drives or high-reliability flash memory, it stores all relevant data, including patient information, drug batch parameters, initial activity, real-time activity / volume change curves, flow rate change curves, bubble detection logs, alarm logs, and operator operation records. To ensure data integrity and security, all data is precisely timestamped during storage and encrypted using the AES-256 encryption algorithm to prevent unauthorized access and tampering. The data acquisition and traceability module has a built-in data analysis engine capable of statistically analyzing massive amounts of historical dispensing data, generating detailed dispensing reports, and providing the data input required for self-learning by the timing chain control and safety interlock modules, continuously optimizing system performance.

[0055] The Human-Machine Interface (HMI) and Diagnostic Module serves as the intuitive interface between the operator and the entire dispensing unit, including a high-resolution color TFT LCD screen. The HMI and Diagnostic Module's software interface is designed according to ergonomic principles and medical equipment operating procedures, providing an intuitive graphical display that allows the operator to quickly grasp the system's status and perform necessary operations. Furthermore, the HMI and Diagnostic Module offers comprehensive self-diagnostic capabilities, enabling real-time monitoring of the operational status of each hardware module, the health of communication links, and the integrity of the system software. Upon detecting any anomalies, the operator will be promptly notified via audible and visual alarms and on-screen prompts, along with troubleshooting guidance or suggestions to contact professional maintenance personnel, ensuring the system's continuous and stable operation and rapid fault response.

[0056] In a preferred embodiment of the present invention, the injection pump is electrically connected to the timing chain control and safety interlock module via a servo motor driver or a stepper motor driver, thereby achieving precise motion control. The well-type activity meter is connected to the dose-activity closed-loop and calibration module via an RS-232 serial communication interface or a CAN bus for real-time transmission of activity data. Optical bubble sensors and capacitive bubble sensors are connected to the multimodal bubble sensing and suppression module via dedicated signal acquisition circuits, providing raw bubble detection signals. The human-machine interaction and diagnostic module is connected to the timing chain control and safety interlock module via an LVDS (Low Voltage Differential Signaling) interface, enabling high-speed transmission of displayed data and touch events.

[0057] Example 1: Smart dispensing of radiopharmaceuticals containing surfactant 99mTc-MDP

[0058] This embodiment aims to demonstrate in detail the performance of the dispensing device and method of the present invention in processing specific surfactant-containing radiopharmaceuticals. A commonly used radiopharmaceutical, namely technetium [99mTc]methylene bisphosphonate (99mTc-MDP) injection, is selected, containing 0.05% (w / v) polysorbate 80 as a surfactant. The target dispensing dose is set at 370 MBq, and the target volume is 10.0 mL. The initial drug activity is 400 MBq, and the drug temperature is 25°C.

[0059] The packaging process is executed according to the three-stage dynamically coupled flow velocity timing chain described in this invention:

[0060] Rapid flow field establishment and initial wetting stage (0-100 ms): The syringe pump is started, and the flow rate is controlled at 0.8 mL / s. During this stage, the device rapidly establishes a stable laminar flow field, ensuring that the average residence time of the drug solution in the tubing is approximately 25 ms. Optical and capacitive bubble sensors detect extremely low bubble nucleation signals. Real-time data shows that the bubble nucleation rate during this stage is reduced by 25.3% compared to traditional fixed high-speed dispensing.

[0061] Critical flow rate bubble suppression and rupture promotion stage (100-300 ms): The device smoothly transitions and stabilizes the flow rate from 0.8 mL / s to 0.3 mL / s at 100 ms. At this critical flow rate, the Weber number is controlled within the range of 5.75 ± 0.05. During this stage, the bubble sensor continuously monitors microbubble signals, but the signal intensity gradually decreases, indicating that the bubbles are undergoing deformation and rupture. Analysis of the sensor data confirms that the rupture rate of nucleated microbubbles is increased by 92.1%.

[0062] Pulsed Emission and Residual Microbubble Flushing Stage (300 ms until dispensing completion): The device enters pulse mode, pumping at a flow rate of 1.2 mL / s for 80 ms, followed by a 40 ms pause. This cycle is repeated. During dispensing, the multimodal bubble sensing and suppression module does not detect bubble signals exceeding the false alarm threshold. When approximately 8 mL has been dispensed, the bubble sensor detects a trace bubble signal (signal strength below the false alarm threshold but above background noise), and the timing chain control and safety interlock module immediately initiates adaptive adjustment: extending the duration of the second stage from 200 ms to 250 ms to provide a longer bubble breakage time. Simultaneously, the pulse duty cycle of the third stage is fine-tuned, the pumping time is shortened to 75 ms, and the pause time is extended to 45 ms to further reduce the impact of instantaneous high flow rates on the tube wall.

[0063] Dynamic Activity and Volume Correction: Throughout the dispensing process, the dose-activity closed-loop and calibration module reads the instantaneous activity data from the well-type activity meter in real time and performs decay correction based on the half-life of 99mTc (6.01 h) and elapsed time. Assuming that the real-time activity is slightly lower than expected when dispensed to 9.5 mL, the device dynamically fine-tunes the final extraction volume of the syringe pump by slightly increasing it by 0.03 mL, based on the logic of target activity = set activity × (remaining volume / instantaneous volume), to compensate for activity decay and unavoidable trace residues in the tubing.

[0064] Results Analysis: The total dispensing time was 55 seconds, far below the clinically required 60 seconds. The final dispensing volume was 10.03 mL, with an actual activity of 370.2 MBq and an activity-dose error of only +0.05%, significantly better than the expected target of ±0.9% and the clinically acceptable range of ±1.5%. Monitoring logs via a bubble sensor showed that the cumulative bubble occurrence rate (volume percentage) was only 4.1% throughout the dispensing process, far lower than the 37% of traditional methods. No interruptions or abnormal alarms occurred during the dispensing process.

[0065] Comparative Example 1: Conventional repackaging of radiopharmaceuticals containing surfactant 99mTc-MDP

[0066] This comparative experiment used a fixed high-flow-rate dispensing method commonly used in existing technologies. The same 99mTc-MDP injection solution (containing 0.05% polysorbate 80) was used, with a target dispensing dose of 370 MBq and a target volume of 10.0 mL. The initial drug activity was 400 MBq, and the drug temperature was 25 ℃.

[0067] The dispensing process used a fixed flow rate of 1.2 mL / s for extraction until the preset volume was reached. No real-time monitoring of air bubbles or dynamic adjustment of the flow rate was performed, nor was closed-loop correction for activity and volume applied.

[0068] Results and Analysis: During the dispensing process, a large number of bubbles were observed to form due to the high flow rate and the presence of surfactants. At approximately 7.5 mL, bubble accumulation resulted in visible bubble clusters larger than 1 mm in diameter in the dispensing tubing. Dispensing was manually paused, and attempts were made to vent the air by slow extraction and tapping the tubing, a process that took approximately 15 seconds. Dispensing was restarted after venting, but new bubbles continued to form, causing intermittent dispensing. The final total time reached 72 seconds, exceeding the clinically required time of 60 seconds. The final dispensing volume was 9.85 mL, the actual activity was 364.5 MBq, and the activity-dose error was -1.49%, close to the clinically acceptable upper limit of error, and there was a risk of underdosing. The overall bubble incidence rate (volume percentage) was as high as 35.8%.

[0069] In summary, the radiopharmaceutical dispensing apparatus and method provided by this invention effectively overcomes the problems faced by existing technologies in processing surfactant-containing radiopharmaceuticals through its unique dynamic coupling flow rate timing chain, real-time multimodal bubble sensing and intelligent adaptive adjustment, and dose-activity closed-loop correction. The proposed method, by suppressing bubble generation at the source, improving dispensing dosage accuracy, shortening dispensing time, and ensuring operational continuity and safety, can provide a more reliable, efficient, and intelligent radiopharmaceutical dispensing solution for the nuclear medicine field.

[0070] The above description is based on the preferred embodiments of the present invention. It will be apparent to those skilled in the art that the present invention is not limited to the details of the exemplary embodiments described above, and that the invention can be implemented in other specific forms without departing from its spirit or essential characteristics. Therefore, the embodiments should be considered exemplary and non-limiting in all respects. The scope of the invention is defined by the appended claims rather than the foregoing description, and all variations falling within the meaning and scope of equivalents of the claims are intended to be included within the present invention. No reference numerals in the claims should be construed as limiting the scope of the claims.

[0071] Furthermore, it should be understood that although this specification describes embodiments, not every embodiment contains only one independent technical solution. This narrative style is merely for clarity. Those skilled in the art should consider the specification as a whole, and the technical solutions in each embodiment can also be appropriately combined to form other embodiments that can be understood by those skilled in the art.

Claims

1. A method for dispensing radiopharmaceuticals, characterized in that, Includes the following steps: S1. Rapid flow field establishment and initial wetting stage: The drug is extracted at a flow rate of 0.8 mL / s for a duration of 0-100 ms to rapidly establish a stable flow field and inhibit surfactant adsorption and bubble nucleation. S2, Critical Flow Rate Bubble Inhibition and Collapse Promotion Stage: After step S1, the flow rate is smoothly transitioned from 0.8 mL / s to 0.3 mL / s, and the drug is drawn at a flow rate of 0.3 mL / s for 100-300 ms to promote the collapse of the generated bubbles. S3, Pulse-type discharge and residual microbubble flushing stage: After step S2, the drug is extracted in pulse mode. The pulse mode includes extracting at a flow rate of 1.2 mL / s for 80 ms, followed by pausing the extraction for 40 ms. This pulse operation is repeated until the total amount of dispensing is completed, which is used to flush out residual bubbles.

2. The method for dispensing a radiopharmaceutical according to claim 1, characterized in that: Also includes: The bubble state of the drug fluid in the dispensing pipeline is monitored in real time, and the duration of step S2 or the pulse duty cycle of step S3 is dynamically adjusted according to the bubble state.

3. The method for dispensing a radiopharmaceutical according to claim 1, characterized in that: Also includes: The activity of the drug is monitored in real time during the dispensing process, and the extraction volume is dynamically adjusted based on the real-time activity value to ensure the accuracy of the final dispensing dosage.

4. The method for dispensing a radiopharmaceutical according to claim 1, characterized in that: Also includes: Before dispensing, a self-learning calibration is performed, and the parameters in steps S1, S2 and S3 are fine-tuned by analyzing historical dispensing data.

5. The method for dispensing a radiopharmaceutical according to claim 1, characterized in that: In step S1, a flow rate of 0.8 mL / s is used to reduce the average residence time of the drug in the tubing to 25 ms, thereby reducing the amount of bubble nucleation.

6. The method for dispensing a radiopharmaceutical according to claim 1, characterized in that: In step S2, a flow rate of 0.3 mL / s is used to control the Weber number of the fluid at 5.8 ± 0.2, promoting bubble collapse.

7. The method for dispensing a radiopharmaceutical according to claim 1, characterized in that: In step S3, the duty cycle and instantaneous flow rate of the pulse mode are controlled to maximize the scouring effect while minimizing the risk of new bubble formation.

8. A radiopharmaceutical dispensing apparatus for performing a radiopharmaceutical dispensing method according to any one of claims 1-7, characterized in that, include: Fluid transfer and precision pumping mechanisms are used to control the extraction and dispensing of drugs; A multimodal bubble sensing and suppression module is used to monitor bubbles in the dispensing pipeline; The dose-activity closed-loop and calibration module is used to measure drug activity and perform dose compensation. The timing chain control and safety interlock module is used to control the fluid transmission and precision pumping mechanism according to preset time nodes and bubble feedback signals. The data acquisition and traceability module is used to record and manage the packaging data; The human-computer interaction and diagnostic module is used for operator interaction and system diagnostics.

9. A dispensing apparatus for a radiopharmaceutical according to claim 8, characterized in that: The fluid transfer and precision pumping mechanism includes an injection pump, a high-precision motor, and a transmission mechanism, which are used to achieve piston displacement accuracy of 0.1 μm and flow rate control accuracy of ±0.01 mL / s.

10. A dispensing apparatus for a radiopharmaceutical according to claim 8, characterized in that: The multimodal bubble sensing and suppression module includes an optical bubble sensor and a capacitive bubble sensor, as well as a sensor fusion unit for processing sensor signals and providing bubble information.

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