A dual circulation closed-loop control method and system for ex vivo organ perfusion

Abstract

This invention discloses a dual-circulation closed-loop control method and system for perfusion of isolated organs. The method includes obtaining an isolated placenta and pre-processing and screening it; connecting a fetal side inflow tube and a fetal side outflow tube to a fetal side arterial-venous circuit, respectively; gradually increasing the perfusion flow rate of the fetal side perfusion circuit and collecting its operating parameters; after confirming that the fetal side perfusion circuit meets preset stability conditions, connecting a maternal side inflow tube to the maternal side perfusion area of ​​the isolated placenta; collecting the operating parameters of both the maternal and fetal side perfusion circuits and transmitting them to a central control unit; and comparing the operating parameters with preset parameter thresholds or target ranges, and adjusting the perfusion flow rate, perfusion pressure, and perfusion temperature of the maternal and / or fetal side perfusion circuits. This invention aims to solve the problems of insufficient stability, control precision, and sustained operation capability in the perfusion process.

Description

Technical Field

[0001] This invention relates to the fields of biomedical engineering and ex vivo organ perfusion technology, and particularly to a closed-loop control method and system for ex vivo organ perfusion based on a maternal-fetal dual-circulation structure of the placenta, and its application in maternal-fetal material exchange studies, transplacental material transport studies, and evaluation of drug permeability across the placenta. Background Technology

[0002] The placenta is a vital temporary organ for substance exchange, hormone secretion, and immune regulation between mother and fetus. It is also an important experimental model for studying maternal-fetal substance transport, drug safety evaluation, and placental-related diseases. With the development of biomedical engineering, regenerative medicine, and tissue engineering, the demand for in vitro maintenance and functional studies using ex vivo placentas is constantly increasing. However, placental tissue has a unique physiological structure with parallel maternal and fetal side circulations, and its activity and function are prone to decline after ex vivo. This places high demands on the construction of perfusion pathways, control of perfusion parameters, and the stability of system operation during in vitro maintenance.

[0003] Most existing organ perfusion techniques are designed for large organs such as the heart, liver, and kidneys, and typically use pumps and pressure feedback to circulate the perfusion fluid. While these techniques can meet the perfusion needs of most organs, they are not directly applicable to the placenta, which has a dual maternal-fetal circulation structure. Furthermore, existing ex vivo placental perfusion protocols often suffer from complex modeling processes, insufficient perfusion stability, imprecise parameter adjustments, and difficulties in long-term in vitro maintenance. Especially during the establishment of bilateral circulation, the lack of specialized control measures for the order of perfusion establishment on the fetal and maternal sides, the determination of operational status, and real-time monitoring and adjustment of operational parameters can easily lead to significant fluctuations in the perfusion process, thus affecting the usability and reproducibility of the experimental model. Summary of the Invention

[0004] The purpose of this application is to propose a dual-circulation closed-loop control method and system for ex vivo organ perfusion, in order to solve the technical problems of existing perfusion systems that are difficult to establish a stable ex vivo perfusion environment for the dual-circulation structure of the placenta on the maternal and fetal sides, and that are difficult to meet the needs of maternal-fetal material exchange research, transplacental material transport research, and drug permeability evaluation across the placenta.

[0005] To address the aforementioned technical problems, this application provides a dual-loop closed-loop control method for ex vivo organ perfusion, employing the following technical solution: An isolated placenta was obtained and pretreated and screened to determine the fetal lateral arterial-venous circuit corresponding to the target perfusion area; The fetal side inflow tube and fetal side outflow tube are respectively connected to the fetal side artery-vein circuit to establish the fetal side perfusion circuit, and the excised placenta is placed in the groove of the perfusion table with the maternal side facing upward. The flow rate of the fetal side perfusion circuit is gradually increased, and the operating parameters of the fetal side perfusion circuit are collected. Based on the operating parameters and the fluid level in the pipeline, it is determined whether the current fetal side arterial-venous circuit meets the preset stability conditions.

[0006] After confirming that the fetal side perfusion circuit meets the preset stability conditions, the maternal side inflow tube is connected to the maternal side perfusion area of ​​the excised placenta to establish the maternal side perfusion circuit and start maternal side perfusion. The operating parameters of the maternal side perfusion circuit and the fetal side perfusion circuit are collected respectively, and the operating parameters are transmitted to the central control unit. The central control unit processes the operating parameters and compares them with preset parameter thresholds or target ranges. When the operating parameters deviate from the preset range, a status determination is made based on the coupling determination result of liquid level change parameters and pressure change parameters. The perfusion flow rate, perfusion pressure and perfusion temperature of the maternal side perfusion circuit and / or the fetal side perfusion circuit are then coordinated and adjusted.

[0007] The central control unit preferably filters the collected operating parameters to reduce the impact of instantaneous fluctuations on control decisions, and dynamically adjusts the maternal and fetal perfusion circuits based on a feedback control strategy. At the same time, it coordinates the bilateral perfusion circuits according to the ratio between the maternal and fetal perfusion flow rates to maintain the flow ratio between the maternal and fetal circulations within a preset range.

[0008] To address the aforementioned technical problems, this application also provides a dual-loop closed-loop control system for ex vivo organ perfusion, employing the following technical solution: It includes an irrigation table body, a groove disposed within the irrigation table body, a maternal-side irrigation circuit, a fetal-side irrigation circuit, a sensor module, and a central control unit; The groove is used to support the detached placenta; The maternal-side perfusion circuit and the fetal-side perfusion circuit are configured to communicate with the maternal side and the fetal side of the detached placenta, respectively, and are independent of each other in terms of fluid path. Both the maternal-side perfusion circuit and the fetal-side perfusion circuit include a perfusion fluid storage container, a drive pump, a perfusion pipeline, and a return channel, which are used to realize the circulation of perfusion fluid in an open circulation state or a closed circulation state, and the perfusion parameters of the two can be set independently. The sensor module is used to detect operating parameters during the perfusion process, including at least flow rate parameters, pressure parameters, temperature parameters, and pipeline liquid level status parameters. The central control unit is connected to the sensor module and is used to receive the operating parameters, process the operating parameters, determine their status, and generate control commands. The central control unit is configured to perform multi-parameter fusion judgment based on flow parameters, pressure parameters, temperature parameters, and pipeline liquid level status parameters, and to perform closed-loop adjustment of the actuators in the maternal side perfusion circuit and the fetal side perfusion circuit according to the judgment results, so as to realize the coordinated control of the dual-circulation perfusion system. The central control unit preferably includes a parameter preprocessing module for filtering the flow parameters, a feedback control module for generating control commands based on control deviations, and a proportional control module for bilateral coordinated adjustment based on the ratio of maternal to fetal perfusion flow.

[0009] Compared with the prior art, the embodiments of this application have the following main advantages: This application discloses a dual-circulation closed-loop control method and system for ex vivo organ perfusion. Addressing the structural characteristics of the placenta with parallel maternal and fetal circulation, it employs a control approach that first establishes the fetal perfusion loop and completes stability assessment before introducing the maternal perfusion loop. Combined with independent fluid circuits on both sides and a closed-loop regulation mechanism in the central control unit based on coupled judgment of fluid level and pressure change parameters, multi-parameter fusion analysis, feedback adjustment, and flow ratio coordinated control, this method achieves stable establishment and continuous maintenance of the ex vivo placental dual-circulation perfusion state, thereby improving the stability, control accuracy, and experimental repeatability of the perfusion process. Compared to conventional perfusion systems primarily designed for the preservation or perfusion repair of single-circulation organs such as the liver and kidney, this application is more suitable for simulating the material exchange environment at the placental-maternal interface, providing a stable and reliable ex vivo experimental platform for maternal-fetal material exchange studies, transplacental material transport studies, and drug permeability evaluation via the placenta. The core of this invention lies in constructing a multi-parameter fusion control mechanism based on the coupling determination of liquid level change parameters and pressure change parameters, and combining it with a dual-circulation flow ratio coordinated adjustment strategy to achieve dynamic and stable control of the dual-circulation perfusion process of isolated placenta. Attached Figure Description

[0010] To more clearly illustrate the solutions in this application, the accompanying drawings used in the description of the embodiments of this application will be briefly introduced below. Obviously, the accompanying drawings described below are some embodiments of this application. For those skilled in the art, other drawings can be obtained from these drawings without creative effort.

[0011] Figure 1This is a flowchart of an embodiment of the dual-loop closed-loop control method for ex vivo organ perfusion according to this application; Figure 2 This is a control principle diagram of one embodiment of the dual-loop closed-loop control method for ex vivo organ perfusion according to this application; Figure 3 This is a schematic diagram of one embodiment of the placental cannulation and perfusion circuit according to this application; Figure 4 This is a comparison chart of the success rate of establishing a dual-cycle irrigation model between the traditional method and the method of this invention; Figure 5 This is a comparison chart of the time required to reach steady state between the traditional method and the method of this invention; Figure 6 This is a comparison chart of the accuracy of anomaly identification between the traditional method and the method of this invention during the irrigation establishment stage; Figure 7 This is a schematic diagram of the antipyrine concentration detection results; Figure 8 This is a schematic diagram of the FITC-dextran concentration detection results. Detailed Implementation

[0012] To make the objectives, technical solutions, and advantages of this application clearer, the following detailed description is provided in conjunction with the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the scope of this application.

[0013] It should be noted that this application is not aimed at the preservation or perfusion repair of single-circulation organs such as liver and kidney before transplantation, but rather at the needs of in vitro research on the dual-circulation structure of the placenta on the maternal and fetal sides. Through bilateral independent perfusion and closed-loop parameter control, it provides an experimental basis for maternal-fetal material exchange research, transplacental material transport research, and evaluation of drug permeability across the placenta.

[0014] refer to Figure 1 A flowchart of an embodiment of the dual-loop closed-loop control method for ex vivo organ perfusion according to this application is shown. The dual-loop closed-loop control method for ex vivo organ perfusion includes the following steps: Step S101: Obtain the isolated placenta and preprocess and screen the isolated placenta to determine the fetal lateral arterial-venous circuit corresponding to the target perfusion area; Step S102: Connect the fetal side inflow tube and the fetal side outflow tube to the fetal side artery-vein circuit respectively to establish the fetal side perfusion circuit, and place the excised placenta in the groove of the perfusion table with the maternal side facing upward; Step S103: Control the perfusion flow rate of the fetal side perfusion circuit to gradually increase, and collect the operating parameters of the fetal side perfusion circuit. Based on the operating parameters and the fluid level in the pipeline, determine whether the current fetal side arterial-venous circuit meets the preset stability conditions. Step S104: After determining that the fetal side perfusion circuit meets the preset stability conditions, connect the maternal side inflow tube to the maternal side perfusion area of ​​the excised placenta to establish the maternal side perfusion circuit and start maternal side perfusion. Step S105: Collect the operating parameters of the maternal side perfusion circuit and the fetal side perfusion circuit respectively, and transmit the operating parameters to the central control unit; In step S106, the central control unit processes the operating parameters and compares them with preset parameter thresholds or target ranges. When the operating parameters deviate from the preset range, a status determination is made based on the coupling determination result of the liquid level change parameter and the pressure change parameter. The perfusion flow rate, perfusion pressure, and perfusion temperature of the maternal side perfusion circuit and / or the fetal side perfusion circuit are adjusted in a coordinated manner. At the same time, the bilateral perfusion circuits are controlled in a coordinated manner based on the proportional relationship between the maternal side perfusion flow rate and the fetal side perfusion flow rate.

[0015] In this embodiment, firstly, an isolated placenta is obtained and pre-processed and screened to determine the fetal side arterial-venous circuit corresponding to the target perfusion area. Specifically, the isolated placenta can be placed on an operating platform to observe the maternal side, fetal side, and umbilical cord vessels, excluding samples with large areas of tissue damage, severe lacerations, unclear vascular orientation, or those clearly unsuitable for cannulation, thereby improving the success rate of subsequent dual-circulation perfusion modeling.

[0016] Subsequently, the fetal side inflow and outflow tubes were connected to the fetal side arterial-venous circuit to establish a fetal side perfusion circuit, and the excised placenta was placed in the groove of the perfusion table with the maternal side facing upwards. Figure 3 It is known that the perfusion fluid on the fetal side, driven by the peristaltic pump, enters the placental tissue through the inlet tube on the fetal side, and then flows out through the outlet tube on the fetal side and returns to the corresponding perfusion fluid storage container, thus forming an independent circulating fluid path on the fetal side. The groove of the perfusion stage is set in the stage area to limit and support the placenta, and works with the constant temperature stage to form a suitable experimental environment.

[0017] After the fetal side perfusion circuit is established, the perfusion flow rate of the fetal side perfusion circuit is gradually increased, and the operating parameters of the fetal side perfusion circuit are collected. Based on the operating parameters and the fluid level in the tubing, it is determined whether the current fetal side arterial-venous circuit meets the preset stability conditions. Figure 2The control framework shown includes a sensor module in the fetal side perfusion circuit that can collect flow rate parameter Q(t), pressure parameter P(t), temperature parameter T(t), and pipeline liquid level status parameter H(t) in real time, and transmit the collected results to the central control unit. The central control unit can perform status determination based on the collected parameters; preferably, by calculating the pressure change parameter ΔP and the liquid level change parameter ΔH, a coupled analysis of the current liquid circuit status is performed to identify liquid circuit leakage, abnormal bubble formation, partial blockage, or a combination of abnormal states. Compared to methods that rely solely on a single pressure parameter for judgment, this application can more accurately distinguish different types of abnormalities through the coupled determination of liquid level and pressure, thereby improving the accuracy and reliability of circuit stability determination.

[0018] After confirming that the fetal side perfusion circuit meets the preset stability conditions, the maternal side inflow tube is connected to the maternal side perfusion area of ​​the excised placenta to establish the maternal side perfusion circuit, and maternal side perfusion is initiated. Combined with... Figure 3 It is known that the maternal perfusion fluid enters the placental maternal perfusion area driven by the maternal peristaltic pump and returns to the maternal perfusion fluid storage container through the return channel, thus forming an independent maternal circulating fluid circuit. By first establishing the fetal perfusion circuit and verifying its stability, and then introducing the maternal perfusion circuit, interference in the initial stage of simultaneous dual-circulation modeling can be reduced, which is beneficial to improving the success rate of establishing the overall perfusion model.

[0019] After the bilateral perfusion circuits are established, the operating parameters of the maternal-side and fetal-side perfusion circuits are collected and transmitted to the central control unit. The central control unit processes the operating parameters and compares them with preset parameter thresholds or target ranges. When the operating parameters deviate from the preset range, a control command is generated and the corresponding actuators are driven to dynamically adjust the bilateral fluid circuits, thereby forming a closed control link of parameter acquisition, status determination, execution adjustment, and feedback update.

[0020] In a preferred embodiment, the central control unit filters the collected flow parameters to reduce the impact of pump pulsation, bubble disturbance, or transient noise on control decisions. Preferably, a moving average algorithm can be used, the expression of which is: , in, This represents the average flow rate at the k-th sampling time; Let be the instantaneous flow rate value obtained from the i-th sampling; k represents the current sampling sequence number; i is the sampling sequence number within the sliding window; and n represents the length of the sliding average window, i.e., the number of consecutive sampling points participating in the averaging calculation. This formula represents the averaging of the original flow rate values ​​of the current sampling time and the preceding n consecutive sampling points to reduce the impact of instantaneous pulsations, bubble disturbances, or electrical noise on control decisions.

[0021] Furthermore, the central control unit calculates the pressure change parameter ΔP and the liquid level change parameter ΔH based on the measurement data at adjacent time points, with the following expressions: , Where Δt is the sampling time interval.

[0022] In a preferred embodiment, the central control unit can construct a system state evaluation function S to quantitatively assess the current irrigation state, the expression of which is: , Where S is the system state evaluation index, w1 and w2 are weight coefficients, and P ref and H ref These refer to the range of change in reference pressure and reference liquid level, respectively. Preferably, when S exceeds a preset threshold, the system is determined to be in an abnormal state; and the abnormality type is further identified by combining the relative changes of ΔP and ΔH: when ΔH changes significantly while ΔP remains basically stable, it is determined to be a liquid circuit leakage or bubble abnormality; when ΔP changes significantly while ΔH remains basically stable, it is determined to be a local blockage or vasoconstriction abnormality; when ΔH and ΔP change abnormally at the same time, it is determined to be a complex liquid circuit abnormality.

[0023] After completing the state determination, the central control unit adjusts the irrigation system based on a feedback control strategy. In one implementation, a proportional-integral-derivative (PID) control algorithm can be used, the expression of which is: , in The control quantity output by the central control unit at the k-th sampling time is used to adjust the drive pump speed, valve opening and / or temperature control module output; k represents the control deviation at the k-th sampling time, which is defined as the difference between the target set value and the current measured value; This represents the control deviation at the (k-1)th sampling time; j is the accumulation index in the integral term; Kp, Ki, and Kd are the proportional, integral, and derivative control coefficients, respectively. Preferably, when the controlled object is a flow parameter, ,in, This indicates the preset target traffic value. This represents the current flow rate value after smoothing. Through the aforementioned control algorithm, the central control unit can dynamically adjust the flow rate and pressure of both the maternal and fetal perfusion circuits, ensuring that the bilateral perfusion parameters are stably maintained within a preset range.

[0024] Furthermore, to simulate the physiological characteristics of placental-fetal dual circulation, the central control unit can also base its calculations on the maternal side flow rate Q. m Fetal side flow Q fThe proportional relationship is used for bilateral coordinated control, and its expression is: , Wherein, Qm represents the maternal side perfusion flow rate; Qf represents the fetal side perfusion flow rate. Preferably, the control range of the maternal-fetal flow rate ratio R is 1.5-3.0. When the ratio R deviates from the preset target range, the central control unit adjusts the drive pump speed to compensate for the maternal or fetal side perfusion flow rate, so that the maternal-fetal flow rate ratio is maintained within the preset range, thereby more closely approximating the physiological ratio of placental-fetal circulation in vivo.

[0025] This application establishes a fetal-side perfusion circuit and completes stability assessment before introducing a maternal-side perfusion circuit. Combined with closed-loop regulation of independent fluid circuits on both sides and a central control unit, it can achieve stable establishment and continuous maintenance of the isolated placental dual-circulation perfusion state, thereby improving the stability, control accuracy, and experimental repeatability of the perfusion process, and is more conducive to simulating the physiological environment inside the placenta.

[0026] In one possible implementation of this embodiment, in the steps of obtaining the isolated placenta and preprocessing and screening the isolated placenta, the screening includes: Ex vivo placentas with intact maternal surface morphology and no large-area defects or lacerations were selected, and ex vivo placentas with clearly identifiable umbilical cord vessels on the fetal surface were selected. The arterial-venous circuits that are parallel, single, unbranched, and whose corresponding maternal surface tissues are intact were preferred as the fetal side arterial-venous circuits.

[0027] In this embodiment, the overall morphology and integrity of the maternal surface of the placenta are first observed to confirm whether it provides a basis for the uniform distribution of maternal side perfusion pathways. Then, the visibility and clarity of the umbilical cord vessels on the fetal surface are observed to determine if they facilitate subsequent cannulation. Based on this, a parallel, single, unbranched arterial-venous circuit corresponding to the intact tissue of the maternal surface region is selected as the target vascular circuit. This setup facilitates the stable passage of fetal side perfusion fluid through the selected vascular pathway and also promotes a better structural correspondence between the selected vascular circuit and the maternal side perfusion area.

[0028] This application reduces the probability of subsequent cannulation failure, local leakage, and fluid circuit instability by pre-screening the overall tissue condition of the placenta, the exposure of umbilical cord vessels, and the condition of the target arteriovenous circuit, thereby improving the reliability and repeatability of dual-circulation perfusion modeling from the source.

[0029] In one possible implementation of this embodiment, the pretreatment of the isolated placenta, including the steps of obtaining the isolated placenta and preprocessing and screening it, comprises: The amnion was circumferentially cut 3 cm from the edge of the placenta, the amnion was peeled off, and the umbilical cord was cut 5 cm from the root of the placenta to preserve the length of the umbilical cord vessels for cannulation.

[0030] In this embodiment, the fetal membranes are first circumferentially cut about 3 cm inside the placental edge to separate the outer membranes from the main tissue. Then, the amnion is peeled off to expose the placental surface, which is more suitable for observation and manipulation. Next, the umbilical cord is cut 5 cm from the placental root, leaving a certain length of umbilical cord vessels in the placenta for subsequent arterial and venous cannulation. This pretreatment method makes the fetal vascular pathways clearer while preserving sufficient space for vascular manipulation, facilitating the insertion and fixation of the perfusion needle.

[0031] In one possible implementation of this embodiment, the step of gradually increasing the perfusion flow rate of the fetal side perfusion circuit includes: gradually increasing the fetal side perfusion flow rate to 3-6 mL / min, and continuously observing at this flow rate for 10 minutes to evaluate the sealing and stability of the fetal side perfusion circuit.

[0032] In this embodiment, the fetal perfusion circuit can be started with a low flow rate, then gradually increased to a range of 3-6 mL / min and maintained within this range for 10 minutes. During the observation period, flow rate, pressure, temperature, and fluid level parameters can be recorded simultaneously. Combined with the aforementioned fluid level-pressure coupling judgment logic, it can be determined whether there are obvious leakage, blockage, abnormal air bubbles, or unstable flow problems in the fetal perfusion circuit. Using a gradual increase rather than directly reaching the target flow rate helps to reduce the impact of the initial fluid flow on the fetal vascular access and cannulation connection site.

[0033] In one possible implementation of this embodiment, after determining that the fetal side perfusion circuit meets the preset stability conditions, the six shunt cannulas connected to the maternal side inflow tube are vertically and evenly inserted into the maternal side perfusion area, and the maternal side inflow rate is set to 12 mL / min; after the maternal side perfusion is started, the entire system is monitored for 30 minutes, and when the perfusion pressure and tubing liquid level on both the fetal side and the maternal side remain stable, the dual-circulation perfusion model is determined to have been successfully established.

[0034] In this embodiment, after the fetal-side perfusion circuit has been verified to be stable, maternal-side shunt cannulas are then deployed in the corresponding maternal-side area. Preferably, six shunt cannulas are inserted into the maternal-side perfusion area in a vertical and evenly distributed manner to ensure that the maternal-side perfusion fluid enters the target area relatively uniformly. Subsequently, the maternal-side inflow rate is set to 12 mL / min to maintain suitable fluid turnover rate and hydrostatic pressure conditions in the maternal-side perfusion area. After simultaneous operation on both sides, monitoring continues for 30 minutes. If no significant abnormal fluctuations are observed in the perfusion pressure and tubing fluid level on both sides, the dual-circulation perfusion model is considered successfully established. By introducing maternal-side shunt perfusion on top of fetal-side stability and limiting the maternal-side cannula deployment method, flow rate, and steady-state confirmation time, the uniformity of maternal-side perfusion distribution and the stability of simultaneous operation on both sides can be improved, thereby more effectively establishing an ex vivo placental dual-circulation perfusion model that closely approximates the actual physiological state. Figure 3 It can be seen that the maternal and fetal fluid circuits form independent circulations under the drive of dual pumps; the perfusion stage structure, the loading stage, and the constant temperature stage together provide a stable support environment for the synchronous operation of both sides.

[0035] This application introduces maternal shunt perfusion on the basis of fetal-side stability, and limits the maternal-side cannulation layout, flow rate and steady-state confirmation time, which can improve the uniformity of maternal-side perfusion distribution and the stability of bilateral synchronous operation, thereby more effectively establishing an isolated placental dual-circulation perfusion model that is close to the real physiological state.

[0036] Those skilled in the art will understand that all or part of the processes in the methods of the above embodiments can be implemented by instructing related hardware through computer-readable instructions. These computer-readable instructions can be stored in a computer-readable storage medium. When the program is executed, it can include the processes of the embodiments of the above methods. The aforementioned storage medium can be a non-volatile storage medium such as a magnetic disk, optical disk, or read-only memory (ROM), or random access memory (RAM).

[0037] It should be understood that although the steps in the flowcharts of the accompanying figures are shown sequentially as indicated by the arrows, these steps are not necessarily executed in the order indicated by the arrows. Unless explicitly stated herein, there is no strict order restriction on the execution of these steps, and they can be executed in other orders. Moreover, at least some steps in the flowcharts of the accompanying figures may include multiple sub-steps or multiple stages. These sub-steps or stages are not necessarily completed at the same time, but can be executed at different times, and their execution order is not necessarily sequential, but can be performed alternately or in turn with other steps or at least some of the sub-steps or stages of other steps.

[0038] Further reference Figure 2 As a response to the above Figure 1 To implement the method shown, this application provides an embodiment of a dual-loop closed-loop control system for ex vivo organ perfusion, which is similar to... Figure 1 Corresponding to the method embodiments shown, the system can be specifically applied to various electronic devices.

[0039] A dual-loop closed-loop control system for ex vivo organ perfusion, used to execute the method described in any of the above embodiments, includes a perfusion table body, a groove disposed in the perfusion table body, a maternal side perfusion circuit, a fetal side perfusion circuit, a sensor module, and a central control unit; The groove is used to support the detached placenta; The maternal-side perfusion circuit and the fetal-side perfusion circuit are configured to communicate with the maternal side and the fetal side of the detached placenta, respectively, and are independent of each other in terms of fluid path. Both the maternal-side perfusion circuit and the fetal-side perfusion circuit include a perfusion fluid storage container, a drive pump, a perfusion pipeline, and a return channel, which are used to realize the circulation of perfusion fluid in an open circulation state or a closed circulation state, and the perfusion parameters of the two can be set independently. The sensor module is used to detect operating parameters during the irrigation process, and the operating parameters include at least flow rate, pressure and temperature parameters. The central control unit is connected to the sensor module and is used to receive the operating parameters and control the operating status of the maternal side perfusion circuit and the fetal side perfusion circuit according to the operating parameters.

[0040] In this embodiment, the main body of the perfusion stage serves as the supporting foundation for the entire system. A groove is provided in the stage area to accommodate the detached placenta. A constant temperature stage is located at the bottom of the main body of the perfusion stage to maintain the temperature of the placenta area and adjacent liquid channels. A dust cover is located above the main body of the perfusion stage to provide a relatively clean and enclosed environment for the experiment. A pipe retainer is used to limit and organize the perfusion pipes on both sides to reduce the impact of pipe swaying on the perfusion stability. A first inlet and a second inlet are used to introduce the corresponding liquids. A drain outlet is used for draining the liquid after the experiment. A constant pressure controller is configured to cooperate with the corresponding liquid channels to help maintain the stability of the liquid channel pressure.

[0041] The maternal-side perfusion circuit and the fetal-side perfusion circuit are configured to communicate with the maternal and fetal sides of the detached placenta, respectively, and are independent of each other in terms of fluid path. Both perfusion circuits include a perfusion fluid storage container, a drive pump, perfusion tubing, and a return channel, used to achieve perfusion fluid circulation in either open or closed loop conditions, and their perfusion parameters can be set independently. A sensor module is used to detect operating parameters during the perfusion process. The central control unit is connected to the sensor module to receive operating parameters and control the operating status of the maternal-side and fetal-side perfusion circuits based on these parameters.

[0042] This application integrates temperature control, load-bearing capacity, fluid circulation, parameter acquisition, and central control into a single system, providing a complete hardware and control foundation for ex vivo placental dual-circulation perfusion. This facilitates experimental operation and helps maintain the stability of temperature, pressure, and flow rate during the perfusion process, thereby improving the overall reliability of the system.

[0043] In one possible implementation of this embodiment, the fetal side perfusion circuit includes a fetal side inflow tube and a fetal side outflow tube, and the ends of the fetal side inflow tube and the fetal side outflow tube are respectively provided with perfusion needles for inserting into the fetal side artery and the fetal side vein; The maternal side irrigation circuit includes a maternal side inflow pipe, which is connected to multiple shunt cannulas for insertion into the maternal side irrigation area.

[0044] In this embodiment, the perfusion needle at the end of the fetal side inlet tube is used to insert into a selected artery, and the perfusion needle at the end of the fetal side outlet tube is used to insert into the corresponding vein, thus forming a fetal side inlet-outlet fluid pathway. On the maternal side, multiple shunt cannulas are connected via the maternal side inlet tube to disperse the perfusion fluid into the maternal side perfusion area. This structural arrangement is consistent with... Figure 3 The corresponding relationship between the two fluid pathways shown is consistent and also compatible with the multi-port layout on the upper part of the perfusion table. Targeted vascular cannulation is used on the fetal side, while multi-point shunt infusion is used on the maternal side. The two are structurally distinct but functionally complementary, working together to achieve dual-circulation perfusion.

[0045] This application, by setting the fetal side as an arteriovenous directional cannulation structure and the maternal side as a multi-shunt cannulation structure, enables the fetal side perfusion to more accurately enter the target vascular pathway, while making the maternal side perfusion more uniformly distributed in the target area, thereby improving the adaptability and perfusion effect of the bilateral perfusion structure.

[0046] In one possible implementation of this embodiment, the central control unit is configured as follows: The system receives the operating parameters collected by the sensor module and compares the operating parameters with a preset parameter threshold or target range. When the operating parameters are within the preset parameter threshold or target range, the current operating state is maintained; when the operating parameters deviate from the preset parameter threshold or target range, a control command is generated. The control command is sent to the actuator in the maternal side perfusion circuit and / or the fetal side perfusion circuit to adjust the perfusion flow rate, perfusion pressure and perfusion temperature.

[0047] Combination Figure 2 The central control unit (CCU) occupies the core of the system control framework, connecting the parameter acquisition layer above and the control decision layer and execution and feedback layer below. Sensor modules in the maternal and fetal perfusion circuits collect operating parameters such as flow rate, pressure, and temperature, and transmit the results to the CCU. The CCU compares the real-time parameters with preset thresholds or target ranges. When the parameters are within the target range, the current operating state is maintained; when the parameters deviate from the target range, control commands are generated for the corresponding fluid circuit and sent to the drive pump, valves, temperature control components, or other actuators to dynamically correct the perfusion flow rate, pressure, and temperature. After correction, the sensor modules continue to collect updated operating parameters and transmit them back, thus forming a complete closed-loop control process.

[0048] This application uses a central control unit to compare and dynamically adjust the operating parameters of both liquid circuits in real time, which can improve the system's response speed and adjustment accuracy to abnormal fluctuations, prevent the irrigation process from deviating from the target operating range for a long time, and thus improve the continuous stability and controllability of the dual-circulation irrigation.

[0049] The technical solution of the present invention will be further described below with reference to specific embodiments. It should be noted that the following embodiments are mainly used to illustrate the implementation process and technical effects of the present invention. The experimental materials, operating conditions, parameter settings, and detection methods involved are merely illustrative examples and do not constitute a limitation on the scope of protection of the present invention. Without departing from the concept of the present invention, those skilled in the art can make conventional adjustments or equivalent substitutions to the relevant experimental conditions, operating steps, and parameters according to actual application scenarios.

[0050] Example 1: Establishment of an in vitro bilateral placental perfusion method 1. Experimental Materials and Equipment Fresh excised human placenta; sterile nursing pad; main body of the perfusion table and perfusion chamber; maternal side perfusion circuit; fetal side perfusion circuit; flow sensor, pressure sensor, temperature sensor; central control unit; constant temperature water bath module; perfusion fluid storage container; perfusion pump; perfusion needle, shunt cannula, connecting tubing, and fixing suture.

[0051] The perfusion fluid can be a placental perfusion fluid system commonly used in the art, such as a culture medium or perfusion fluid containing electrolytes, glucose, buffer salts and protein components, preferably a pre-warmed and defoamed perfusion fluid.

[0052] 2. Methods and Steps 2.1 Placental screening and pretreatment The excised placenta, retrieved after delivery, is placed on a sterile nursing pad, and the morphology of the maternal and fetal surfaces is observed. Placentas with intact maternal surfaces, no obvious lacerations, and clearly visible fetal facial arteries and veins are selected. The amnion is circumferentially cut approximately 3 cm from the placental edge, and the amnion is detached. The umbilical cord is cut approximately 5 cm from the placental root, retaining sufficient length for subsequent cannulation.

[0053] 2.2 Fetal lateral cannulation Select a well-defined arterial-venous circuit. Insert the end of the fetal inflow tube into the artery and the end of the fetal outflow tube into the corresponding vein, and secure them with sutures to ensure a tight connection and no risk of leakage.

[0054] 2.3 Establishment of fetal lateral circulation Transfer the placenta into the perfusion chamber, keeping the mother's side facing upwards. Start the fetal side perfusion pump, allowing the perfusion fluid to flow in slowly, gradually increasing the flow rate to 3 mL / min and maintaining it for 10 minutes; observe the fluid level changes and backflow. If there are no obvious abnormalities, adjust the flow rate to 6 mL / min and maintain it for another 10 minutes. If there are continuous abnormal fluctuations in the fluid level, replace the circuit and re-insert the cannula.

[0055] 2.4 Establishment of maternal side perfusion After the fetal side circuit is stabilized, the six maternal side shunt cannulas are vertically and evenly inserted into the target maternal surface area, and the maternal side perfusion pump is started, with the flow rate set to 12 mL / min. The maternal side perfusion fluid is returned to the reservoir through the return channel after perfusion through the placental maternal surface.

[0056] 2.5 Steady-state confirmation After the bilateral perfusion was started, it ran continuously for 30 minutes, and the flow rate, pressure, and temperature were monitored in real time using a sensor module. If the parameters on both sides fluctuated within the preset range without significant abrupt changes, the system was determined to have reached steady state, and the formal experiment began.

[0057] 3. Experimental Results After using the bilateral placental perfusion system established in this embodiment, the perfusion on both the maternal and fetal sides can be continuously and stably operated, the fluctuation of perfusion parameters is reduced, and the local tissue condition of the placenta is good, indicating that this method can be used to establish an in vitro bilateral placental perfusion model.

[0058] Example 2: Comparative verification of the effectiveness of the method of the present invention in establishing an isolated placental dual-circulation perfusion model. To verify the technical effectiveness of the method of the present invention based on the coupling determination of liquid level change parameter ΔH and pressure change parameter ΔP, multi-parameter fusion analysis and bilateral flow ratio coordinated control in the process of establishing a dual circulation perfusion model of isolated placenta, a comparative experiment was conducted between the traditional method group and the method group of the present invention.

[0059] 1. Experimental Grouping Traditional methods: The loop status is judged by monitoring a single pressure parameter and manually observing changes in the liquid level. The perfusion parameters are adjusted based on operational experience. The coupling judgment of the liquid level change parameter ΔH and the pressure change parameter ΔP is not used. Multi-parameter fusion analysis of flow rate, pressure, temperature and liquid level status is not performed. Bilateral coordinated control is not based on the ratio of perfusion flow rate between the maternal and fetal sides.

[0060] The method of this invention is as follows: an isolated placental dual-circulation perfusion model is established using the method described in Example 1. The central control unit performs coupled judgment based on the liquid level change parameter ΔH and the pressure change parameter ΔP. Multi-parameter fusion analysis is performed by combining flow rate parameters, pressure parameters, temperature parameters and liquid level state parameters. The dual-circuit perfusion is coordinated and controlled based on the ratio between the maternal side perfusion flow rate and the fetal side perfusion flow rate.

[0061] 2. Experimental conditions Both groups used fresh, excised human placental samples from the same source and conditions, with 12 samples in each group. The same perfusion fluid system, cannulation method, ambient temperature, and observation time window were used in both groups. The perfusion flow rate for the fetal side was set to 3–6 mL / min, and the perfusion flow rate for the maternal side was set to 12 mL / min.

[0062] 3. Evaluation Indicators (1) Success rate of establishing the dual-circulation irrigation model; (2) The time required to reach steady state; (3) Accuracy of abnormal state identification; (4) Fluctuation range of fetal side pressure and flow during steady state; (5) Deviation rate of perfusion flow rate ratio between the maternal side and the fetal side.

[0063] 4. Experimental Results like Figure 4 As shown, the success rate of establishing the dual-circulation perfusion model using the traditional method was 58.3%, while the success rate of establishing the dual-circulation perfusion model using the method of this invention was 91.7%, indicating that the method of this invention can significantly improve the success rate of establishing the dual-circulation perfusion model of the ex vivo placenta.

[0064] like Figure 5As shown, the traditional method group requires 41.8 min to reach steady state, while the method group of the present invention requires 23.6 min to reach steady state, indicating that the method of the present invention can shorten the time required for the dual-circulation irrigation system to reach steady state.

[0065] like Figure 6 As shown, the accuracy rate of anomaly identification in the traditional method group during the irrigation establishment stage is 66.7%, while the accuracy rate of anomaly identification in the method group of the present invention is 83.6%, indicating that the method of the present invention can significantly improve the ability to identify abnormal states such as leakage, abnormal bubbles, and local blockage.

[0066] 5. Results Explanation The above results demonstrate that the method of this invention, by introducing a coupled judgment mechanism of liquid level change parameter ΔH and pressure change parameter ΔP, can more accurately distinguish different types of abnormal states such as fluid leakage, abnormal bubbles, and local blockage, thereby improving the accuracy of abnormality identification. By introducing a multi-parameter fusion analysis and closed-loop adjustment mechanism for flow rate, pressure, temperature, and liquid level status, the method can shorten the time required for the dual-circulation perfusion system to reach steady state. Furthermore, by introducing a coordinated control mechanism for the flow ratio between the maternal and fetal sides, the method can improve the coordination of bilateral perfusion, thereby significantly increasing the success rate of establishing the dual-circulation perfusion model. These performance improvements are mainly attributed to the coupled judgment mechanism of liquid level change parameter and pressure change parameter, the multi-parameter fusion analysis mechanism, and the coordinated control mechanism for the flow ratio between the two sides introduced in this invention. These mechanisms enable the system to accurately identify abnormal states and make timely adjustments in the early stages of perfusion establishment, thus avoiding modeling failures caused by misjudgment or delayed adjustments in traditional methods.

[0067] Example 3: Comparison of perfusion stability under different fetal side flow conditions To verify the rationality of the fetal side perfusion flow rate range, fetal side flow rates of 3 mL / min, 4.5 mL / min, and 6 mL / min were set and compared under the same conditions.

[0068] 1. Experimental Grouping Group A: 3 mL / min; Group B: 4.5 mL / min; Group C: 6 mL / min 2. Observation Indicators Circuit sealing; pressure fluctuation range; liquid level stability; whether there is obvious leakage or abnormal backflow.

[0069] 3. Results Explanation The results showed that fetal side perfusion could be achieved within the range of 3–6 mL / min, but the return flow was more complete and the system steady-state establishment time was shorter at 4.5–6 mL / min; exceeding this range increased the risk of leakage. Therefore, 3–6 mL / min is the optimal range for fetal side perfusion.

[0070] Example 4: Comparative experiment on the transport of antipyrine and FITC-dextran in an isolated bilateral placental perfusion system To verify the applicability of the ex vivo bilateral placental perfusion system described in this invention in transplacental material transport studies, antipyrine and FITC-dextran were used as tracers in bidirectional transport experiments. Antipyrine was added to the maternal perfusion fluid to assess transplacental transport capacity from the maternal side to the fetal side; FITC-dextran was added to the fetal perfusion fluid to assess transport characteristics from the fetal side to the maternal side and the integrity of the system barrier.

[0071] 1. Experimental Materials This embodiment uses the ex vivo bilateral placental perfusion system established according to Embodiment 1, which includes a perfusion table body, a perfusion chamber, a maternal side perfusion circuit, a fetal side perfusion circuit, a sensor module, and a central control unit.

[0072] The experimental materials included: fresh isolated human placenta; maternal side perfusion fluid; fetal side perfusion fluid; antipyrine standard; FITC tracer; sampling tubes and testing consumables. Both the maternal and fetal side perfusion fluids were pre-warmed to physiologically suitable temperatures and defoamed.

[0073] 2. Experimental Methods 2.1 Establishment of the placental perfusion model The isolated placenta was screened, pretreated, and cannulated on the fetal side and maternal side, and a bilateral perfusion circuit was established according to the method in Example 1. After the maternal and fetal perfusion circuits were running stably and the steady-state was confirmed after 30 minutes, the transport experiment was started.

[0074] 2.2 Method of adding tracers After the system reaches steady state: (1) antipyrine is added to the maternal side perfusion fluid reservoir, allowing it to enter the placental maternal perfusion area along with the maternal side perfusion fluid; (2) FITC is added to the fetal side perfusion fluid reservoir, allowing it to enter the placental fetal side vascular pathway along with the fetal side perfusion fluid. This forms a bidirectional tracing pattern of antipyrine transport from the maternal side to the fetal side and FITC transport from the fetal side to the maternal side.

[0075] 2.3 Irrigation Parameters During the experiment, the bilateral irrigation system was maintained under preset steady-state conditions. Preferably: The fetal side perfusion flow rate was maintained at 3–6 mL / min; The maternal perfusion rate was maintained at 8–20 mL / min, preferably about 12 mL / min; The perfusion temperature was maintained within the physiologically suitable range; The sensor module continuously monitors flow, pressure, and temperature parameters, and the central control unit performs closed-loop regulation.

[0076] 2.4 Sampling and Testing After the tracer is added, samples of maternal and fetal reflux fluid are collected at preset time points. The time points can be set to 5 min, 15 min, 30 min, 45 min, 60 min, 90 min, and 120 min after addition, or adjusted according to experimental needs.

[0077] The collected samples were tested: changes in the concentration of antipyrine in the fetal side reflux fluid reflected its transport from the maternal side to the fetal side; changes in the concentration of FITC in the maternal side reflux fluid reflected its transport from the fetal side to the maternal side. Preferably, antipyrine was quantified using ultraviolet spectrophotometry; FITC was quantified using fluorescence detection.

[0078] 3. Application Examples of the Dual-Circulation Closed-Loop Control System for Ex vivo Organ Perfusion in Maternal-Fetal Material Exchange Studies, Transplacental Material Transport Studies, and Drug Transplacental Permeability Evaluation Experimental results show that, Figure 7 and Figure 8 As shown, in the dual-circulation closed-loop control system for ex vivo organ perfusion described in this invention, antipyrine added to the maternal side perfusion fluid gradually appears in the fetal side return fluid as the perfusion time increases, indicating that the system can simulate the transplacental transport process from the maternal side to the fetal side. FITC-dextran added to the fetal side perfusion fluid can be used to observe the transport characteristics and placental barrier status in the fetal-maternal direction. Because this invention employs a dual-circulation structure for both the maternal and fetal sides of the placenta, combined with real-time parameter monitoring and closed-loop control, it can monitor the dynamic changes of tracers in different directions under relatively stable conditions. Therefore, it is not only suitable for establishing ex vivo placental perfusion models, but also provides a stable and reliable experimental platform for maternal-fetal material exchange studies, transplacental material transport studies, and drug permeability evaluation across the placenta. Because the system of this invention adopts an independent structural design for the maternal side perfusion loop and the fetal side perfusion loop, combined with real-time parameter monitoring and closed-loop control, it can monitor the dynamic changes of two types of tracers in opposite directions under relatively stable conditions, thus providing a reliable model for transplacental material exchange studies.

[0079] Furthermore, by comparing the concentration changes of antipyrine and FITC in the reflux fluids on both sides at different time points, the transport capacity, barrier function, and system stability of placental tissue under in vitro perfusion conditions can be evaluated.

[0080] Based on the aforementioned dual-circulation closed-loop control method and system for ex vivo organ perfusion, a stable dual-circulation perfusion environment on both the maternal and fetal sides of the placenta can be established under ex vivo conditions, and continuous control of bilateral perfusion parameters can be achieved under relatively stable operating conditions. Therefore, the technical solution described in this application is not only applicable to the establishment and maintenance of ex vivo placental dual-circulation perfusion models, but also applicable to applications such as maternal-fetal material exchange studies, transplacental material transport studies, and evaluation of drug permeability across the placenta.

[0081] The above are merely preferred embodiments of this application and are not intended to limit this application. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of this application should be included within the protection scope of this application.

Claims

1. A dual-loop closed-loop control method for perfusion of isolated organs, characterized in that, Includes the following steps: An isolated placenta was obtained and pretreated and screened to determine the fetal lateral arterial-venous circuit corresponding to the target perfusion area; The fetal side inflow tube and fetal side outflow tube are respectively connected to the fetal side artery-vein circuit to establish the fetal side perfusion circuit, and the excised placenta is placed in the groove of the perfusion table with the maternal side facing upward. The flow rate of the fetal side perfusion circuit is gradually increased, and the operating parameters of the fetal side perfusion circuit are collected. Based on the operating parameters and the fluid level in the pipeline, it is determined whether the current fetal side arterial-venous circuit meets the preset stability conditions. After confirming that the fetal side perfusion circuit meets the preset stability conditions, the maternal side inflow tube is connected to the maternal side perfusion area of ​​the excised placenta to establish the maternal side perfusion circuit and start maternal side perfusion. The operating parameters of the maternal side perfusion circuit and the fetal side perfusion circuit are collected respectively, and the operating parameters are transmitted to the central control unit. The central control unit processes the operating parameters and compares them with preset parameter thresholds or target ranges. When the operating parameters deviate from the preset range, based on the coupling judgment result of liquid level change parameters and pressure change parameters, it coordinates the perfusion flow rate, perfusion pressure and perfusion temperature of the maternal side perfusion circuit and / or the fetal side perfusion circuit, and coordinates the bilateral perfusion circuits based on the proportional relationship between maternal side perfusion flow rate and fetal side perfusion flow rate.

2. The method according to claim 1, characterized in that, In the steps of obtaining an isolated placenta and preprocessing and screening the isolated placenta, the screening includes: Ex vivo placentas with intact maternal surface morphology and no large-area defects or lacerations were selected, and ex vivo placentas with clearly identifiable umbilical cord vessels on the fetal surface were selected. The arterial-venous circuits that are parallel, single, unbranched, and whose corresponding maternal surface tissues are intact were preferred as the fetal side arterial-venous circuits.

3. The method according to claim 2, characterized in that, In the steps of obtaining isolated placentas and preprocessing and screening them, the preprocessing includes: The amnion was circumferentially cut 3 cm from the edge of the placenta, the amnion was peeled off, and the umbilical cord was cut 5 cm from the root of the placenta to preserve the length of the umbilical cord vessels for cannulation.

4. The method according to claim 1, characterized in that, The steps for determining whether the current fetal arterial-venous circuit meets the preset stability conditions based on the operating parameters and the fluid level in the pipeline include: The determination is based on the coupling of pressure change parameter ΔP and pipeline liquid level change parameter ΔH. An abnormality in the current fetal arterial-venous circuit is determined when any of the following conditions are met: When ΔH exceeds the preset threshold and ΔP does not change accordingly, it is determined to be a liquid leakage or abnormal bubble. When ΔP exceeds the preset threshold and ΔH remains stable, it is determined to be a local blockage or abnormal vasoconstriction. When ΔH and ΔP change abnormally at the same time, it is determined to be an abnormality in the composite fluid circuit; If an abnormality is detected, the vascular circuit is replaced and cannulation is performed again.

5. The method according to claim 4, characterized in that, If the fluid level on the maternal or fetal side rises or falls rapidly and continuously within a short period of time, it is determined that there is significant leakage in the current fetal arterial-venous circuit, and the cannulation is reinserted after replacing it with another vascular circuit.

6. The method according to claim 4, characterized in that, The steps for gradually increasing the perfusion flow rate of the fetal side perfusion circuit include: The fetal side perfusion flow rate was gradually increased to 3-6 mL / min, and the flow rate was continuously observed for 10 minutes to evaluate the sealing and stability of the fetal side perfusion circuit.

7. The method according to claim 1, characterized in that, After confirming that the fetal side perfusion circuit meets the preset stability conditions, the six shunt cannulas connected to the maternal side inflow tube are arranged in an array in the maternal side perfusion area, and the maternal side inflow rate is set to 12 mL / min. After the maternal side perfusion was started, the entire system was monitored for 30 minutes. The dual-circulation perfusion model was confirmed to have been successfully established when the perfusion pressure and fluid level in the tubing remained stable on both the fetal and maternal sides.

8. A dual-loop closed-loop control system for ex vivo organ perfusion, for executing the method as described in any one of claims 1 to 7, characterized in that, It includes an irrigation table body, a groove disposed within the irrigation table body, a maternal-side irrigation circuit, a fetal-side irrigation circuit, a sensor module, and a central control unit; The groove is used to support the detached placenta; The maternal-side perfusion circuit and the fetal-side perfusion circuit are configured to communicate with the maternal side and the fetal side of the detached placenta, respectively, and are independent of each other in terms of fluid path. Both the maternal-side perfusion circuit and the fetal-side perfusion circuit include a perfusion fluid storage container, a drive pump, perfusion tubing, and a return channel. The sensor module is used to detect operating parameters during the perfusion process, including at least flow rate parameters, pressure parameters, temperature parameters, and pipeline liquid level status parameters. The central control unit is connected to the sensor module and is used to receive the operating parameters, and to process the operating parameters, determine their status, and generate control commands. The central control unit is configured as follows: The operating parameters are filtered to reduce the impact of instantaneous fluctuations on control decisions; Feedback adjustment is performed on the maternal-side perfusion circuit and the fetal-side perfusion circuit based on control deviation; Based on flow rate, pressure, temperature, and pipeline liquid level parameters, a multi-parameter fusion judgment is performed to achieve closed-loop regulation of the actuators in the maternal-side perfusion circuit and the fetal-side perfusion circuit, thereby realizing the coordinated control of the dual-circulation perfusion system.

9. The system according to claim 8, characterized in that, The fetal side perfusion circuit includes a fetal side inlet tube and a fetal side outlet tube, and the ends of the fetal side inlet tube and the fetal side outlet tube are respectively provided with perfusion needles for inserting fetal side artery and fetal side vein; The maternal side irrigation circuit includes a maternal side inflow pipe, which is connected to multiple shunt cannulas for insertion into the maternal side irrigation area to form a distributed irrigation structure. The central control unit is configured as follows: Receive the operating parameters collected by the sensor module, and compare the operating parameters with a preset parameter threshold or target range; The determination is based on the coupling of pressure change parameter ΔP and liquid level change parameter ΔH, and multi-parameter fusion determination is performed by combining flow rate parameter, pressure parameter, temperature parameter and pipeline liquid level state parameter. When the operating parameters deviate from the preset parameter threshold or target range, a control command is generated, and coordinated adjustment is performed based on the ratio between the maternal side perfusion flow and the fetal side perfusion flow. The control command is sent to the execution component in the maternal side perfusion circuit and / or the fetal side perfusion circuit to coordinately regulate the perfusion flow rate, perfusion pressure and perfusion temperature; When the liquid level change parameter ΔH exceeds the preset threshold and the pressure change parameter ΔP does not change accordingly, it is determined to be a liquid circuit leakage or abnormal bubble. When the pressure change parameter ΔP exceeds the preset threshold and the liquid level change parameter ΔH remains stable, it is determined to be a local blockage or abnormal vasoconstriction. When both the liquid level change parameter ΔH and the pressure change parameter ΔP change abnormally at the same time, it is determined to be a composite liquid circuit abnormality.

10. The application of the dual-circulation closed-loop control method for ex vivo organ perfusion as described in any one of claims 1 to 7 in maternal-fetal material exchange studies, transplacental material transport studies, and evaluation of drug transplacental permeability.

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