Medical radioactive isotope purification multichannel ionic liquid chromatography system

Abstract

The invention belongs to the technical field of radioactive metal isotope ion chromatographic separation, and discloses a medical radioactive isotope purification multichannel ion liquid chromatography system. The system comprises an automatic sample injection system, a parallel sampling and leaching channel, a parallel multi-column chromatographic structure, an online radiation dose monitoring module, a multi-channel tail end detection system, a recycling structure and a central control system. By adopting a full-automatic sample injection and multi-channel parallel chromatography structure, parallel separation, real-time radiation monitoring, multi-mode online detection and closed-loop recovery are realized, and the problems of insufficient nuclear purity, low separation efficiency, low target recovery rate and high radiation exposure of a traditional method are solved.

Description

Technical Field

[0001] This application belongs to the field of radioactive metal isotope ion chromatography separation technology, and particularly relates to a multi-channel ion liquid chromatography system for medical radioactive isotope purification. Background Technology

[0002] Medical radioactive metal isotopes (such as 225 Ac / 226 Ra、 177 Lu / 176 Yb、 161 Tb / 160 Gd is widely used in tumor therapy and medical imaging. Current separation and purification techniques mainly rely on single-pathway chromatography systems, and routine sample injection is mostly manual, making it impossible to simultaneously address radiation protection, safety, purification efficiency, and production capacity. Currently, existing technologies have the following drawbacks:

[0003] (1) The existing radioactive separation process still involves manual sample introduction, which exposes personnel to the risk of radiation damage;

[0004] (2) Most are single-column elution modes, and isotopes with short half-lives are prone to lose specific activity during the separation process;

[0005] (3) Limited production capacity cannot meet the needs of large-scale clinical use;

[0006] (4) The quality control and testing are limited, mostly offline gamma spectroscopy or ICP-MS detection, which cannot achieve real-time online detection of multiple parameters;

[0007] (5) The efficiency of target material recovery is low and resources are wasted.

[0008] While there are automated or semi-automated nuclide separation devices in the existing technology (such as modular systems for ^99mTc or ^64Cu), most lack the technical integration of parallel structure, real-time online radiation monitoring, and multi-channel detection combination. Summary of the Invention

[0009] The purpose of this application is to provide a multi-channel ion liquid chromatography system for the purification of medical radioisotopes. It adopts a fully automated sample injection and multi-channel parallel chromatographic structure to achieve parallel separation, real-time radiation monitoring, multi-modal online detection and closed-loop recovery, thereby solving the problems of insufficient nuclear purity, low separation efficiency, low target recovery rate and high radiation exposure of traditional methods.

[0010] To achieve the above objectives, this application provides the following technical solution:

[0011] A multi-channel ion-liquid chromatography system for purifying medical radioisotopes, comprising:

[0012] An automated sample loading system is used for quantitative, closed, programmable automated loading of samples containing radioactive isotopes and eluents, avoiding artificial radiation exposure and improving repeatability and accuracy;

[0013] Parallel sampling and rinsing pathways are used for multi-path switching to achieve rapid switching of different eluents and parallel rinsing, thereby improving separation efficiency and process flexibility;

[0014] Parallel multi-column chromatography structure is used to run multiple chromatographic columns simultaneously to increase throughput, shorten separation time, and achieve continuous purification of multiple batches;

[0015] The online radiation dose monitoring module is used to monitor the radiation dose of each pathway and key node in real time to ensure operational safety and process control.

[0016] A multi-channel end-of-line detection system is used to synchronously monitor the eluent of each column in real time and identify the elution behavior of the target nuclide.

[0017] The recycling structure is used to automatically recover unreacted or unadsorbed rare targets and return them to the front-end processing, achieving efficient resource utilization;

[0018] The central control system is used to coordinate the parameters, programs, and safety interlocks of all modules, enabling fully automated operation and data tracking throughout the entire process.

[0019] As an feasible approach, the automated sample injection system uses a precision peristaltic pump or diaphragm pump linked with a multi-position automated sample injection valve to achieve automatic proportional injection of sample solutions containing radioactive isotopes and eluents, with a flow control accuracy of ±0.1%.

[0020] As an feasible approach, the automated sample introduction system includes a circulation pump, an autosampler, a sample reservoir, an eluent reservoir, a bubble detection sensor, and an infrared bubble trap. The circulation pump draws the sample from the sample reservoir and pushes it into the system's main injection path; the autosampler samples from the sample reservoir, detects bubbles in the tubing via the bubble detection sensor, and removes residual bubbles via the infrared bubble trap before entering the chromatographic separation system; additionally, the automated sample introduction system can switch eluents, drawing them from the eluent reservoir via the circulation pump and switching the eluent into the injection path via a reversing valve, sharing the autosampler's access to the chromatographic inlet.

[0021] As a feasible approach, the parallel sampling and rinsing pathway includes 4 to 8 independent channels. Each channel is equipped with a miniature peristaltic pump, a three-way proportional solenoid valve, a temperature control module, a pressure sensor, and a flow meter, enabling simultaneous injection and constant temperature control across multiple channels. The specific process is as follows: a circulating pump delivers the sample solution or rinsing solution from each storage tank to the miniature peristaltic pump in each channel. After exiting the peristaltic pump, the solution enters the three-way proportional solenoid valve to select the injection, rinsing, or closed state. The outlet of the solenoid valve is sequentially connected to a pressure sensor and a flow meter for real-time monitoring of pressure and flow rate within the channel. Simultaneously, a temperature control module is wrapped around the channel to maintain the target temperature. All pumps, valves, sensors, and temperature control modules in all channels are uniformly scheduled and synchronously activated by a central control system, thereby achieving simultaneous injection and constant temperature control across multiple channels and ensuring that each pathway performs synchronous separation and rinsing operations under identical conditions.

[0022] As an feasible approach, the parallel multi-column chromatography structure includes 2 to 6 ion exchange columns filled with strongly acidic cation exchange resin and connected by a titanium alloy parallel manifold.

[0023] As an feasible approach, the online radiation dose monitoring module includes multiple distributed detectors connected to an FPGA signal processing unit via optical fiber, achieving a dose detection sensitivity of >103 cps / μCi.

[0024] As a feasible approach, the multi-channel end-of-line detection system integrates UV / Vis spectroscopy, atomic absorption, conductivity-voltammetry, radiation, and pH / pKa detection modules. Through Bayesian algorithm fusion analysis, it achieves chemical and radiometric purity ≥99%. In this system, the effluent from each chromatographic channel first enters the fluid distributor via a main manifold, and then is led out to the UV / Vis spectroscopy, atomic absorption, conductivity-voltammetry, radiation, and pH / pKa detection modules, respectively. Each branch is equipped with a dedicated flow cell or probe for measurement. The detection signals from each module are aggregated via a sensor-conversion module to a signal acquisition bus, and then uniformly sent to the central control system for synchronous triggering, data integration, and feedback control. Simultaneously, switching valves are installed at the distributor front end or branch switching points to select or bypass certain modules, thereby enabling parallel, multimodal, and real-time online detection of the effluent from the multi-channel chromatography system.

[0025] As one feasible approach, the collector's inlet is connected to the outlet of the end-of-line detection system via a switching valve, and the outlet is connected to the recovery pump via a corrosion-resistant pipeline.

[0026] As an feasible approach, the central control system uses a PLC or ARM industrial controller to achieve adaptive control of flow, temperature, pressure and radiation parameters through finite state machines and PID algorithms.

[0027] Compared with existing technologies, the multi-channel recovery and recycling structure for purifying medical radioisotopes provided in this application has the following advantages:

[0028] This application includes a product collector, a recovery pump, a nanofiltration membrane module, and an online conductivity / pH sensor. The chromatographic outlet liquid is first collected in the product collector, and then pumped by the recovery pump to the nanofiltration membrane module for concentration or component separation. The liquid at the concentration end of the membrane module is returned to the product collector or a preset position, while the liquid at the permeate end is discharged as waste liquid or further processed. The online conductivity / pH sensor monitors the conductivity and pH of the returned liquid in real time throughout the process and feeds it back to the central control system to determine whether the recovery and concentration conditions are met and to trigger the next operation of the system.

[0029] This application avoids manual contact with radioactive samples by using automated sample introduction and a circulation pump, greatly improving safety.

[0030] This application employs a parallel sampling pathway and a parallel multi-column chromatography design to shorten elution time, increase throughput, and process multiple sample solutions simultaneously.

[0031] This application integrates an online radiation dose monitoring module, which can quickly trigger an alarm and isolate the channel in case of abnormalities.

[0032] The end-of-line detection system of this application supports multi-modal detection such as ultraviolet / visible spectroscopy, atomic absorption, conductivity-voltammetry, radiation, and pH / pKa, and can achieve real-time discrimination of chemical and radioactive purity ≥99%.

[0033] The recycling structure of this application forms a closed loop, and the target material recovery rate can reach more than 99%, reducing production costs.

[0034] The system in this application is modular and scalable, easy to maintain and scale up for production, and complies with GMP requirements.

[0035] This application discloses a fully automated, highly safe, and highly efficient medical radioactive metal isotope ion chromatography separation system, specifically designed for processing radionuclides with short half-lives (such as medical radioactive metal isotopes). By integrating multiple functional modules, the system achieves fully automated operation from sample injection, separation and purification, radiation monitoring, end-point detection, and recycling, avoiding direct human contact with radioactive materials and improving operational safety and processing efficiency. The overall system structure adopts a modular design, facilitating assembly, maintenance, and expansion. Attached Figure Description

[0036] To more clearly illustrate the technical solution of this application, the accompanying drawings used in the technical description will be briefly introduced below.

[0037] Figure 1 A block diagram of the multichannel ion liquid chromatography system for purifying medical radioisotopes provided in this application;

[0038] Figure 2 The overall system flowchart provided for this application;

[0039] Figure 3 The control system flowchart provided in this application;

[0040] Figure 4 This is a schematic diagram of the multi-channel end-point detection system provided in this application;

[0041] Figure 5 Parallel elution / chromatographic column layout diagram provided in this application;

[0042] Figure 6 The process flow diagram of the multichannel ion liquid chromatography system for purifying medical radioisotopes provided in this application. Detailed Implementation

[0043] The following detailed description provides further details on specific implementation methods.

[0044] like Figures 1 to 6 As shown, this application provides a multi-channel ion liquid chromatography system for purifying medical radioisotopes, including an automatic sample introduction system, a parallel sampling and elution pathway, a parallel multi-column chromatography structure, an online radiation dose monitoring module, a multi-channel end detection system, a recovery and circulation structure, and a central control system.

[0045] These modules form a tree-like series-parallel fluid network through corrosion-resistant piping, solenoid valves, and standardized quick connectors: parallel input at the front end, confluence and separation in the middle, and branch outputs at the rear end. The central control system connects to various sensors and actuators via an industrial bus to achieve fully automated sequential control. The entire device is installed within a lead-shielded frame (10mm shielding thickness), with a total footprint of less than 2m². 2 .

[0046] The automated sample introduction system includes a circulation pump, an autosampler, a sample reservoir, an eluent reservoir, a bubble detection sensor, and an infrared bubble trap.

[0047] Both the sample storage tank and the eluent storage tank are made of PTFE or PFA, with a volume of 50–500 mL. They are housed in a lead-shielded protective enclosure and equipped with a magnetic stirrer and a PT100 temperature sensor. The liquid level is monitored by a capacitive level gauge. The outlet of the storage tank is connected to the inlet of the sampling circulation pump via a PFA pipeline. The pump outlet is connected to the common port of the injection valve. The multiple outlets of the injection valve are connected to the inlet of the parallel sampling and eluent pathway via PFA branch pipes. The autosampler switches between the sample solution and eluents of different concentrations through its valve core to achieve linear or stepped gradient. The flow rate and switching sequence of the sampling circulation pump and autosampler are controlled by a central control system, with a gradient accuracy of ±0.1%.

[0048] A bubble detection sensor and an infrared bubble trap are installed in the sample injection line. When the sensor detects a bubble volume exceeding 5 μL, the central control system immediately switches the valve path and drives the trap to vent, preventing bubbles from entering the chromatographic column. The storage tank, pump, and valves are all fixed on a lead-shielded platform. The control interface displays real-time information such as flow rate, pressure, and temperature via a touchscreen, avoiding direct contact between personnel and radioactive samples and reducing operator radiation exposure to below 1 μSv / h.

[0049] Parallel sampling and elution pathways are a key structure for the efficient separation of short-lived nuclides. This pathway comprises 4–8 independent parallel lines, each consisting of a miniature peristaltic pump, a three-way proportional solenoid valve, a temperature control module, a pressure sensor, and a flow meter, connected by quartz or PFA capillary tubes (0.5–1 mm inner diameter, 30–50 cm length). The miniature peristaltic pump (e.g., Harvard PHD ULTRA) in each channel provides synchronous flow control. The three-way proportional valve mixes the sample solution and eluent at a ratio of 1:1 to 1:100. The temperature control module uses a Peltier element (5W power, 20–60°C), and the pressure sensor (0–5 bar range) and thermal flow meter (0.01 mL / min resolution) monitor the fluid status in real time.

[0050] The front end of this pathway is connected to the automated sample injection system via a split tube, while the rear end converges to a parallel multi-column chromatographic structure. The multi-channel design allows multiple sample solutions to be injected simultaneously into different columns. Flow rates and pressures between pathways are balanced in real time by a PID algorithm in the central control system, with flow rate deviations controlled within 2%. A temperature control module ensures a constant eluent temperature, preventing the decay and loss of short-lived nuclides in the pathway. The parallel sampling and elution pathway shortens elution time to 15–25 min per batch, increasing specific activity by more than 20%.

[0051] The parallel multi-column chromatographic structure is the core separation unit of this application, consisting of 2-6 ion exchange columns, a titanium alloy parallel manifold, column shells, a switchable bypass solenoid valve, a column pressure monitoring sensor, and a regeneration and rinsing module. The ion exchange columns are made of glass or PFA (inner diameter 5-20 mm, length 100-500 mm), filled with a strongly acidic cation exchange resin (such as Dowex 50WX8, with an exchange capacity >4 meq / g). Each column is housed in an independent lead-shielded column shell to reduce radiation. The titanium alloy parallel manifold inlet is connected to the parallel sampling and elution pathway via a manifold, and an internal microporous distribution plate ensures uniform fluid distribution with a homogeneity >98%. The column outlet is connected to the multi-channel end-detection system via a reverse manifold, and a UV detection port (wavelength 254 nm) is provided on a branch of the manifold for monitoring the elution peak shape.

[0052] Each column inlet is equipped with a quick-sealing vacuum interface, and a bypass solenoid valve can isolate a single column without affecting the remaining channels when the column pressure exceeds 8 bar. The regeneration and rinsing module is connected to the eluent storage tank via a check valve. After each batch, 0.5M NaOH (approximately twice the column bed volume) is automatically injected for regeneration, followed by equilibration with 0.1M HCl. The entire regeneration process takes less than 10 minutes. The parallel multi-column design can increase the throughput by 2 to 5 times compared to single-column series connection, achieving an annual capacity of 100 to 500 Ci with a separation purity >99.9%.

[0053] The online radiation dose monitoring module is used to monitor and alarm the radiation dose of the entire system in real time, ensuring operational safety. This module includes 12 distributed radiation detectors (3-5 CsI:Tl or α / β / γ composite detectors), a preamplifier, a multi-channel analyzer (MCA), an FPGA processing unit, a fiber optic transmission link, and alarm relays. The detectors are located at the sample inlet (sample reservoir outlet), elution outlet (column outlet), and recovery outlet (product collector inlet), respectively, and are connected to the preamplifier and MCA via BNC or fiber optic cables. The signals are then transmitted to the central control system via fiber optic cables. The system uses... 137 The Cs source is calibrated, and the alarm threshold adopts a two-level design: when the dose rate is >5μSv / h, an audible and visual alarm is issued and the flow rate is reduced; when it is >20μSv / h, all pumps and valves are automatically shut down and the system enters a safe mode.

[0054] This module has a measurement sensitivity >10. 3 With a dose accuracy of ±5% and coverage of over 95% of the total tubing length, the system utilizes Poisson statistics combined with energy dispersive spectroscopy analysis to plot attenuation curves in real time and compensate for background noise, ensuring accurate monitoring even in high-background environments. This architecture can keep operator exposure below 1 μSv / h.

[0055] The multi-channel end-of-line detection system is used for multimodal online quality control of elution products, determining chemical and radiological purity and deciding the split direction. The system includes a parallel flow cell manifold, a UV / Vis spectroscopy module, an atomic absorption spectroscopy module, a conductivity-voltammetry module, a CsI:Tl radiation detection module, a pH / pKa measurement module, an automatic calibration unit, a software processing platform, and a power supply module. These modules can be freely combined via the main manifold and multi-position switching valves (such as the Cheminert CV-4000, 4–6 channels) to adapt to the detection needs of different nuclides.

[0056] The parallel flow cell manifold consists of a main manifold and several branches. The main manifold has an inner diameter of 1–2 mm and a length of <10 cm, and connects to the column outlet manifold via a Swagelok quick connector. Each branch is equipped with an independent quartz flow cell (volume 20–50 μL, optical path 1–10 mm), featuring an optical window, electrochemical electrode interface, and radiation detection interface. The flow cell outlet connects to either the product collector (qualified path) or the waste tank (unqualified path) via a three-way valve, with a check valve preventing backflow. The control line of the switching valve is connected to the central controller for rapid flow splitting based on detection results.

[0057] The UV / Vis spectroscopy module includes a spectrometer (such as the Ocean Optics USB2000+, 1 nm resolution, wavelength range 190–800 nm), a deuterium / tungsten halide light source (5 W power, ±0.5% stability), and a fiber optic probe (200 μm core diameter) for identifying impurity peaks such as those from organic chelating agents. The atomic absorption spectroscopy module uses a PinAAcle 900AAS or similar device, equipped with a hollow cathode lamp (e.g., Ga lamp, 240.0 nm wavelength) and a 5 mL nebulizer for the target metal, enabling quantitative analysis of metal impurities down to 0.01 ppm. The conductivity-voltammetry module includes an electrochemical workstation (such as the Metrohm 858), a conductivity cell (1 mm electrode spacing), a voltage scanner (–2 to +2 V, scan rate 50 mV / s), and a 24-bit ADC data acquisition card, capable of analyzing ion concentration and redox behavior. The radiation detection module uses a CsI:Tl scintillation crystal (5×5×10mm) coupled to a SiPM, achieving a counting efficiency >90%. The signal is preamplified and sent to the MCA, sharing a data link with the online monitoring module. The pH / pKa module consists of a high-precision glass electrode (accuracy ±0.01pH), an ion-selective electrode, and an automatic titration pump, used to determine the dissociation constant of the complexing agent.

[0058] The aforementioned submodules are connected to the software processing platform via a local area network. The platform uses a Bayesian algorithm to fuse multi-source data and automatically generate a purity report (impurity peak area <1%, metal concentration at the ppm level, radioactive purity >99%). Based on the report results, the control system drives a switching valve to send qualified products to the product collector, while unqualified products are discharged into the waste liquid tank, and the upstream column is notified to regenerate. The system also has an automatic calibration function: a standard solution is injected for calibration before each batch operation, and the correlation coefficient R of the calibration curve is... 2 >0.999. This module is compact, with each detection unit having a volume of <30cm². 3 It can be maintained by hot-swapping without affecting the operation of other channels.

[0059] The recycling structure is used for closed-loop recovery of product liquid, enabling the reuse of the target material. This structure includes a product collector, a recovery pump, a return pipeline, a nanofiltration membrane module, a check valve, and an online conductivity / pH sensor. The product collector is a multi-chamber stainless steel tank with a volume of 100–1000 mL, lined with lead to reduce radiation. The inlet of the collector is connected to the qualified outlet of the end-of-line detection system via a switching valve, and the outlet is connected to the recovery pump via corrosion-resistant piping. The recovery pump is a precision gear pump with a flow rate of 0.1–5 mL / min, capable of both forward and reverse operation; its outlet is connected to a nanofiltration membrane module (such as Millipore Amicon, with a pore size <1 nm, capable of selectively recovering >98% of metal ions), and after HEPA filtration, the product is returned to the eluent storage tank, forming a closed loop.

[0060] Online conductivity and pH sensors are installed on the reflux line to monitor the quality of the recovered solution (range 0–2000 μS / cm, accuracy ±0.05 pH). When the conductivity exceeds 500 μS / cm or the pH deviates from the set range, the central control system triggers a distillation or nanofiltration regeneration program to discharge waste liquid and replenish fresh eluent, thereby maintaining the purity of the recovered solution. Based on the mass conservation principle calculation η = (Vrec × Crec) / (Vin × Cin) × 100%, the measured recovery rate is ≥99%, and the target material utilization rate is increased to over 95%.

[0061] The central control system coordinates the operation of all modules, achieving full-process automation. It includes a PLC controller (such as a Siemens S7-1200 or an industrial PC with an ARM processor), a touchscreen human-machine interface, a database, a PID feedback algorithm unit, and finite state machine (FSM) software. The system connects to all sensors, pumps, and valves via Ethernet, Modbus, or other industrial buses, achieving 100% coverage. The touchscreen displays parameters such as flow rate, pressure, temperature, radiation, and purity in real time, supporting remote APP monitoring and data logging. The database records batch operation logs, sensor data, decay curves, and purity reports, meeting GMP traceability requirements.

[0062] Control process reference Figure 3 The state machine model shown includes a preparation phase, an injection and rinsing phase, a separation and monitoring phase, a detection and diversion phase, and a recovery and regeneration phase. Each phase has defined trigger conditions, execution actions, key component interactions, and output verification. Flow rate, temperature, and pressure are adjusted in real time through a PID loop, and safety is ensured by radiation monitoring priority interrupts. Typical batch processing time is less than 45 minutes, and it can be operated in batch or continuous mode.

[0063] Furthermore, the following separation is achieved through ion exchange. 225 Ac and 226 Taking Ra as an example, the various stages will be explained. Other metal isotopes (such as...) 68Ga) allows for adjustment of the elution gradient and detection combination based on ionic properties.

[0064] (1) Preparation phase: After the system is powered on, the PLC initializes all sensors and actuators, and calibrates the radiation detector (using...). 137 Cs source), pressure sensor and flow meter; containing 226 The sample solution to be separated (concentration 0.1–10 mCi / mL, volume 1–100 μL, dissolved in 0.01 M HNO3) is added to the sample solution storage tank, and 0.01–1 M HNO3 or HCl gradient eluent is added to the eluent storage tank. A magnetic stirrer and temperature controller are used to maintain uniform mixing. Once the sensor displays normal readings, proceed to the next stage.

[0065] (2) Injection and elution stage: The PLC controls the injection circulation pump and six-way valve to draw in the sample solution and eluent at a set ratio, and injects them synchronously into each chromatographic column through a miniature peristaltic pump connected in parallel sampling and elution pathways. The injection flow rate is usually 0.01–10 mL / min, with the gradient gradually increasing from a low concentration of 0.01 M to 0.5 M. The Peltier module heats the solution to 40 °C at a rate of 0.5 °C / min to improve the equilibrium rate between metal ions and resin; the bubble detector monitors the tubing in real time, and if bubbles are detected, it controls the bubble trap to vent.

[0066] (3) Separation and monitoring stage: After the sample solution enters the ion exchange column, the system switches to elution mode: the micro-pumps in each channel maintain a flow rate of approximately 1 mL / min, and the concentration of nitric acid or hydrochloric acid increases linearly. Due to 226 Ra(II) has a weak affinity for the resin, and its distribution coefficient Kd < 10, so it is eluted first. 225 Ac(III) has a Kd > 10³, resulting in a longer residence time and elution at high concentrations. Parallel manifolds ensure uniform flow rates in each column, and column pressure sensors monitor pressure and automatically bypass and isolate individual columns when it exceeds 8 bar. A radiation monitoring module records the count rate and dose rate in real time at the elution end, generating a decay curve, and fine-tunes the gradient based on the peak shape at the UV port.

[0067] (4) Detection and Splitting Stage: The eluent is drawn into the terminal detection system, where each detection module operates in parallel: UV-Vis determines the peak area of ​​organic impurities (<0.1%), AAS quantifies metal impurities (<0.01ppm), conductivity-voltammetry curves identify ion types (conductivity <100μS / cm), pH / pKa module verifies the stability of the complexing agent, and radiation module determines radiometric purity. The software platform uses a Bayesian algorithm to synthesize data from each channel. When the calculated purity is ≥99%, the valve is controlled to guide the product collector; if the purity is insufficient or impurities are detected, the eluent is directed to the waste tank and upstream column regeneration is initiated. The entire stage lasts approximately 2–5 minutes.

[0068] (5) Recycling and regeneration stage: Qualified 225 The Ac solution is pumped by a recycling pump, passes through a nanofiltration membrane and an ion exchange pre-column to remove particles and residual impurities, and then returns to the eluent storage tank to achieve a closed-loop circulation of the target material. At the same time, an on-line conductivity / pH sensor monitors the quality of the recycled liquid. If the conductivity > 500 μS / cm or the pH exceeds the range, distillation regeneration is started to restore the purity. The central control system calculates the recovery rate η. If the recovery rate < 99%, maintenance is reminded. After the end of each batch, the chromatographic column automatically executes a regeneration process: inject 0.5M NaOH to wash twice the column bed volume, and then balance with 0.1M HCl. The entire regeneration process takes 5 - 10 minutes. All data is recorded in the database for quality traceability and parameter optimization.

[0069] The working principle of this application is:

[0070] The separation principle of this system is based on the electrostatic adsorption difference between radioactive metal cations and ion exchange resins. For example, according to the Langmuir isothermal adsorption model q = qmKC / (1 + KC), the adsorption capacity qm of the resin > 4 meq / g, and the affinity constant K can reach more than 103. The hydrodynamic design of parallel multi-columns makes the fluid in each column in a laminar flow state (Reynolds number < 2000). Synchronously processing multiple batches of sample liquids can control the time window within one-tenth of the half-life, thereby reducing decay losses, and the specific activity is increased by more than 20%.

[0071] The control principle manages the switching of each stage through a PLC state machine and uses a PID feedback regulator for the actuator. The error e = SP - PV, and the control output is calculated according to u = Kpe + Ki∫edt + Kdde / dt. For example, the pressure feedback loop maintains the chromatographic column pressure at about 2 bar, and the flow feedback maintains the channel deviation less than 2%. The radiation safety principle is based on Poisson statistics and energy spectrum analysis. Using a CsI:Tl scintillator, γ / β rays are converted into optical signals, and the MCA integrates to obtain a dose rate curve. The alarm threshold is set according to the standards of the International Commission on Radiological Protection (ICRP).

[0072] Optical, electrochemical, and atomic spectral detections in multimodal detection are respectively based on basic principles such as the Beer–Lambert law, the Randles–Sevcik equation, atomic absorption resonance transitions, and the Henderson–Hasselbalch equation. Multisource data is integrated through a Bayesian network algorithm. When the posterior probability P(purity|data) > 0.99, the product is determined to be qualified. The mass conservation calculation of the recycling closed-loop is η ≈ 1 - loss rate. The nanofiltration selectivity makes the loss < 1%. The overall flux improvement of the system is related to the parallelism n. According to Amdahl's law, the speedup ratio ≈ 1 / (1 - p + p / n), where p is the proportion of the series part. The proportion of the series part of this system is about 0.2, and the speedup ratio can reach 3 - 5 when the number of channels is 4 - 8.

[0073] In summary, the multi-channel ion liquid chromatography system for purifying medical radioisotopes provided in this application achieves high-efficiency, high-purity, high-safety, and high-economic production of medical radioisotopes through a comprehensive design that integrates automatic sample introduction, parallel chromatography, real-time radiation monitoring, multimodal detection, and closed-loop recovery. This system is not only suitable for… 225 The separation of Ac can also be achieved by adjusting the gradient and detection module as needed. 68 Ga、 177 Large-scale preparation of Lu and other medical radionuclides. Examples show that the system's batch processing time is less than 45 minutes, target recovery rate is ≥99%, purity is ≥99.5%, and operator radiation exposure is less than 0.1 μSv / batch, demonstrating significant potential for industrial application.

[0074] The above description is only a specific embodiment of this application, but the protection scope of this application is not limited thereto. Any changes or substitutions that can be easily conceived by those skilled in the art within the scope of the technology disclosed in this application should be included within the protection scope of this application.

Claims

1. A multi-channel ion liquid chromatography system for purifying medical radioisotopes, characterized in that, include: An automated sample loading system is used for quantitative, closed, and programmed automated sample loading of samples containing radioactive isotopes and eluents. Parallel sampling and rinsing pathways are used for multi-channel switching to achieve rapid switching of different elution solutions and parallel rinsing; Parallel multi-column chromatography structure is used to run multiple chromatographic columns simultaneously to increase throughput, shorten separation time, and achieve continuous purification of multiple batches; An online radiation dose monitoring module is used to monitor the radiation dose of each pathway and key node in real time. A multi-channel end-of-line detection system is used to synchronously monitor the eluent of each column in real time and identify the elution behavior of the target nuclide. The recycling structure is used to automatically recover unreacted or unadsorbed rare targets and return them to the front-end processing. The central control system coordinates the parameters, programs, and safety interlocks of all modules to achieve fully automated operation and data tracking.

2. The multi-channel ion liquid chromatography system for purifying medical radioisotopes according to claim 1, characterized in that, The automated sample injection system uses a precision peristaltic pump or diaphragm pump linked with a multi-position automated sample injection valve to achieve automatic proportional injection of sample solutions containing radioactive isotopes and eluents, with a flow control accuracy of ±0.1%.

3. The multi-channel ion liquid chromatography system for purifying medical radioisotopes according to claim 1, characterized in that, The automated sample introduction system includes a circulation pump, an autosampler, a sample reservoir, an eluent reservoir, a bubble detection sensor, and an infrared bubble trap.

4. The multi-channel ion liquid chromatography system for purifying medical radioisotopes according to claim 1, characterized in that, The parallel sampling rinsing pathway includes 4 to 8 independent channels. Each channel is equipped with a miniature peristaltic pump, a three-way proportional solenoid valve, a temperature control module, a pressure sensor, and a flow meter to achieve synchronous injection and constant temperature control across multiple channels.

5. The multi-channel ion liquid chromatography system for purifying medical radioisotopes according to claim 1, characterized in that, The parallel multi-column chromatography structure includes 2 to 6 ion exchange columns, filled with strongly acidic cation exchange resin, and connected by a titanium alloy parallel manifold.

6. The multi-channel ion liquid chromatography system for purifying medical radioisotopes according to claim 1, characterized in that, The online radiation dose monitoring module includes multiple distributed detectors connected to the FPGA signal processing unit via optical fiber, achieving a dose detection sensitivity of >103 cps / μCi.

7. The multi-channel ion liquid chromatography system for purifying medical radioisotopes according to claim 1, characterized in that, The multi-channel end-of-line detection system integrates ultraviolet / visible spectroscopy, atomic absorption, conductivity-voltammetry, radiation, and pH / pKa detection modules. Through Bayesian algorithm fusion analysis, it achieves chemical and radioactive purity ≥99%.

8. The multi-channel ion liquid chromatography system for purifying medical radioisotopes according to claim 1, characterized in that, The recycling structure includes a product collector, a recycling pump, a nanofiltration membrane module, and an online conductivity / pH sensor.

9. The multi-channel ion liquid chromatography system for purifying medical radioisotopes according to claim 8, characterized in that, The collector's inlet is connected to the outlet of the end-of-line detection system via a switching valve, and the outlet is connected to the recovery pump via a corrosion-resistant pipeline.

10. The multi-channel ion liquid chromatography system for purifying medical radioisotopes according to claim 1, characterized in that, The central control system uses a PLC or ARM industrial controller to achieve adaptive control of flow, temperature, pressure and radiation parameters through finite state machines and PID algorithms.

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