An oxygenation temperature control system and adjusting method of an ex vivo multi-organ combined perfusion system

Abstract

The application discloses an oxygenation temperature control system and a regulating method of an ex vivo multi-organ combined perfusion system, and relates to the field of organ perfusion systems.The system comprises: an organ cabin used for accommodating a multi-organ cluster with natural vascular tissue anatomic connection; a perfusion circuit comprising a magnetic suspension pump, a heat exchanger and a membrane lung; an intra-cabin environment regulating module used for regulating the environment inside the organ cabin and the outer surface of the multi-organ cluster; an airway environment regulating module connected to the lungs in the multi-organ cluster; a sensor group comprising environment parameter sensors and physiological monitoring sensors; and a controller used for controlling the heat exchanger, the intra-cabin environment regulating module and the airway environment regulating module to perform regulation according to the parameters collected by the sensor group.The application integrates oxygenation, temperature and humidity and organ state monitoring in the same control system, realizes the coordinated regulation of multiple environment parameters in the multi-organ combined perfusion process, and is especially suitable for the long-term perfusion maintenance scene of the ex vivo multi-organ cluster with natural vascular anatomic connection, and is convenient for improving the organ function preservation quality.

Description

Technical Field

[0001] This invention relates to the field of medical devices and life support technology, specifically to an oxygenation and temperature control system and adjustment method for an ex vivo multi-organ combined perfusion system, used for oxygenation and temperature control regulation in an ex vivo multi-organ combined perfusion system. Background Technology

[0002] With the rapid development of organ transplantation and extracorporeal life support technologies, mechanical perfusion of ex vivo organs has become a key means of maintaining organ viability, assessing organ function, and carrying out reparative treatments. Traditional extracorporeal life support devices are mainly designed for single organs, such as isolated livers or hearts, and typically only require temperature control and oxygenation regulation through a single channel based on the specific physiological characteristics of that organ.

[0003] However, as cutting-edge medical device technologies evolve towards multi-organ combined support, maintaining combined perfusion of multiple isolated organs in vitro (such as combined perfusion of the heart, liver, lungs, and kidneys) has become an important direction for simulating the interaction of multiple organs in vivo, studying systemic metabolism, and maintaining overall physiological homeostasis. In actual clinical and research scenarios, in order to simulate the real physiological environment in vivo to the greatest extent, multi-organ combined perfusion often adopts an integrated multi-organ cluster scheme that maintains the anatomical connection of the natural blood vessels of each organ without severing or cutting them. In this integrated multi-organ cluster tightly connected by natural blood vessels, different organs have significantly different requirements for temperature and humidity in the in vitro microenvironment due to the heterogeneity of their anatomical structure and physiological metabolic mechanisms. For example, solid organs (such as the heart, liver, and kidneys) have huge blood flow, and their core temperature is highly dependent on the endogenous heat exchange of the perfusion fluid, while the lungs, due to their huge anatomical surface area and the gas filling the interior, exhibit extremely high sensitivity to the air temperature in the organ chamber and the airway ventilation temperature (exogenous heat exchange).

[0004] Existing multi-organ perfusion equipment or simple parallel single-organ temperature control systems face significant technical bottlenecks when dealing with such complex clustered heat conduction. Conventional systems typically only perform single-entry air temperature control or isolated pipeline liquid temperature regulation. When lung temperatures are high while non-lung organs such as the kidneys have normal or low temperatures, simply lowering the cabin air temperature in isolation can easily lead to insufficient perfusion and excessively low core temperatures in temperature-insensitive parenchymal organs due to the simultaneous heat dissipation from uncut large blood vessels in the air. This can trigger organ heat stress, metabolic disorders, or local functional damage. Furthermore, existing systems cannot perform precise dual humidity decoupling control to address the unique anatomical separation between the lung's outer surface and the internal airways. This makes it difficult to maintain surface humidity while simultaneously meeting the high saturation humidity requirements of the alveoli, easily leading to decreased lung compliance or airway dryness damage.

[0005] Meanwhile, conventional systems, in order to obtain accurate physiological feedback, often rely heavily on high-density hardware redundancy, such as expensive online blood gas analyzers. This not only significantly increases the overall complexity and number of tubing interfaces in multi-organ perfusion systems but also increases the risk of mechanical failures and tubing leaks. Therefore, how to achieve dynamic and coordinated temperature control of endogenous and exogenous heat exchange, as well as independent and precise regulation of dual humidity, without relying on high-density redundant hardware, while maintaining natural vascular connections in multi-organ clusters, is a critical technical bottleneck that urgently needs to be addressed in the field of medical devices and life support technology. Summary of the Invention

[0006] To address the aforementioned problems, this invention aims to resolve the issues of differing thermal response characteristics among different organs, difficulty in simultaneously controlling temperature and humidity, and the lack of synergistic regulation based on organ physiological state feedback during isolated multi-organ combined perfusion. Particularly in integrated multi-organ clusters including lungs and non-lung organs, since lungs primarily exchange heat through the gas phase environment while non-lung organs primarily exchange heat through the perfusion fluid, existing systems struggle to simultaneously meet the temperature stability and physiological activity maintenance requirements of different organs. Therefore, an oxygenation and temperature control system and method capable of synergistically regulating organ temperature, oxygen supply, and organ functional status is needed.

[0007] This was achieved through the following technical solutions:

[0008] An oxygenation and temperature control system for an ex vivo multi-organ combined perfusion system includes:

[0009] An organ compartment is used to house a multi-organ cluster consisting of multiple ex vivo organs that maintain natural vascular tissue anatomical connections. The multi-organ cluster includes at least the lungs, kidneys, and at least one non-lung organ.

[0010] The perfusion circuit includes a magnetic levitation pump, a heat exchanger, and a membrane lung connected in sequence. The outlet of the membrane lung is connected to the common artery input of the multi-organ cluster, and the common venous return of the multi-organ cluster returns to the inlet of the magnetic levitation pump.

[0011] The cabin environment regulation module, located inside the organ cabin, is used to regulate the temperature inside the organ cabin and provide a primary humidity environment for the outer surface of the multi-organ cluster.

[0012] The airway environment regulation module is ventilated to the lungs in a multi-organ cluster to provide mechanical ventilation support to the lungs and regulate the secondary humidity environment within the airways inside the lungs.

[0013] The sensor group includes environmental parameter sensors for collecting physical state parameters of the organ chamber and perfusion circuit, and physiological monitoring sensors for collecting physiological index parameters of each ex vivo organ in the multi-organ cluster.

[0014] The controller is electrically connected to the sensor group, the infusion circuit, the cabin environment regulation module, and the airway environment regulation module, respectively. The controller is used to control the heat exchanger and the cabin environment regulation module to coordinately regulate the temperature of the multi-organ cluster according to the parameters collected by the sensor group, and to control the cabin environment regulation module and the airway environment regulation module to independently regulate the first humidity environment and the second humidity environment, respectively.

[0015] Optionally, the controller is also used to: during routine steady-state regulation, coordinate the adjustment of the heat exchanger and the cabin environment regulation module based on the deviation of the current temperature of each organ from its respective target value; when the lung temperature is relatively higher than that of non-lung organs, control the cabin environment regulation module to lower the air temperature inside the organ cabin, and coordinate the control of the heat exchanger to raise or maintain the perfusion fluid temperature.

[0016] Optionally, the controller is used to receive parameters collected by the sensor group and perform data anomaly detection and fault tolerance processing based on physiological rationality verification and historical baseline comparison; and the controller is also used to dynamically calculate multiple derived physiological indicators reflecting the overall oxygen supply status, circulation status, organ function status and temperature regulation status based on the processed parameters.

[0017] Optionally, the multiple derived physiological indicators include one or more of the following:

[0018] The oxygen supply capacity evaluation parameters are calculated based on perfusion flow rate and blood oxygen saturation.

[0019] The circulatory status evaluation parameters are calculated based on at least one of heart rate, systolic blood pressure, mean arterial pressure, perfusion pressure, and blood flow variability.

[0020] The organ function status evaluation parameters are calculated based on at least one of the following: urine volume change rate, bile secretion rate, lactate change rate, glucose metabolism rate, or tissue oxygen uptake rate.

[0021] Organ heat load is calculated based on organ surface temperature and perfusion fluid temperature;

[0022] The parameters for evaluating pulmonary oxygenation status are calculated based on blood oxygen saturation and inhaled oxygen concentration.

[0023] Optionally, the controller is also used to determine whether an emergency exists based on the parameters and derived physiological indicators collected by the sensor group, and to execute a rapid emergency response in descending order of priority for insufficient oxygenation, circulatory instability, and organ dysfunction when an emergency exists; specifically, when the oxygen supply capacity evaluation parameter or blood oxygen saturation is lower than the preset reference range, an insufficient oxygenation response is triggered, controlling the increase of membrane lung oxygen concentration and perfusion flow; when the circulatory status evaluation parameter exceeds the preset reference range, a circulatory instability response is triggered, controlling the increase of perfusion flow; when the organ function status evaluation parameter exceeds the preset reference range, an organ dysfunction response is triggered, and a protective regulation strategy is executed according to the corresponding organ function status.

[0024] Optionally, during the rapid emergency response process, the controller continuously monitors the temperature status and lung oxygenation status of each isolated organ;

[0025] When the actual temperature of any excised organ exceeds the preset upper temperature threshold, the organ overheat response is triggered, controlling the heat exchanger to reduce the perfusion fluid temperature and controlling the cabin environment regulation module to reduce the air temperature inside the organ cabin.

[0026] When the lung oxygenation status evaluation parameters are detected to deviate continuously from the preset reference range, it is determined that there is a risk of lung dysfunction, and the second humidity environment and mechanical ventilation parameters are controlled and adjusted.

[0027] Optionally, the airway environment regulation module includes a ventilator and a ventilator humidifier located on the ventilator's ventilation line. The ventilator humidifier is used to regulate the temperature and humidity of the respiratory gas entering the lungs to change the airway environment inside the lungs. The cabin environment regulation module includes a heating wire, a fan, and a cabin humidifier located in the organ compartment.

[0028] Optionally, the multi-organ cluster includes the heart, liver, lungs, and kidneys, which maintain natural vascular anatomical connections;

[0029] The environmental parameter sensors include an internal temperature and humidity sensor installed in the organ compartment, a pipeline temperature probe installed on the perfusion circuit pipeline, and a flow meter installed at the outlet of the magnetic levitation pump.

[0030] The physiological monitoring sensors include single-point temperature sensors respectively installed on the surface of each organ, blood oxygen saturation sensors installed in the perfusion circuit, electronic weighing modules installed at the kidney excretion collection end, and ECG leads and arterial catheters respectively connected to the heart and the arterial side of the perfusion circuit.

[0031] Optionally, the membrane lung is connected to a membrane lung gas mixer, which is used to regulate the oxygen and carbon dioxide concentrations in the membrane lung.

[0032] Secondly, an adjustment method is proposed for adjusting the aforementioned oxygenation temperature control system. This method includes the following steps:

[0033] S1. The sensor group collects environmental parameters of the organ chamber, perfusion parameters of the perfusion circuit and physiological parameters of each organ in real time. Based on physiological rationality verification and comparison with historical baseline, data anomaly detection and fault tolerance processing are performed to obtain the final parameters and calculate the corresponding derived physiological indicators based on the final parameters.

[0034] S2. Determine whether there is an abnormal state based on the final parameters and derived physiological indicators; generate a steady-state control command when there is no abnormal state, and generate an emergency control command when there is an abnormal state; when generating a steady-state control command, generate a coordinated temperature control command based on the difference between lung temperature and non-lung organ temperature and the deviation between the temperature of each organ and the target value.

[0035] S3. According to the steady-state control command or emergency control command, control the heat exchanger to adjust the temperature of the infusion fluid, control the cabin environment adjustment module to adjust the cabin temperature and the first humidity environment, and control the airway environment adjustment module to adjust the second humidity environment of the airway inside the lungs.

[0036] The beneficial effects of this invention compared to the prior art are:

[0037] 1. This invention relates to an integrated multi-organ cluster oxygenation and temperature control system that maintains the anatomical connection of natural vascular tissue. It utilizes a heat exchanger to regulate the perfusion fluid temperature and an internal environment control module to regulate the air temperature within the organ chamber, achieving coordinated control of the perfusion fluid temperature and the internal air temperature. Since the lungs primarily exchange heat through the gas phase environment, while non-pulmonary organs primarily exchange heat through the perfusion fluid, the combined regulation of the internal air temperature and perfusion fluid temperature enables differentiated thermal management of the lungs and non-pulmonary organs. This maintains stable lung temperature while ensuring adequate heat supply to non-pulmonary organs, thereby improving overall temperature stability and organ viability maintenance during multi-organ combined perfusion.

[0038] 2. This invention establishes a first humidity environment and a second humidity environment. The first humidity environment is used to maintain the moisture state of the outer surface of the detached organ within the organ chamber, while the second humidity environment is used to regulate the humidity of respiratory gases in the airways inside the lungs, achieving independent control of organ surface humidity and lung airway humidity. Compared to existing technologies that employ a single humidity control method, this invention can simultaneously meet the humidity requirements of different tissues, reducing the risk of functional damage caused by organ surface dehydration and lung airway dryness.

[0039] 3. This invention uses a sensor array to collect perfusion parameters, environmental parameters, and organ physiological parameters in real time. Based on the processed data, it dynamically calculates derived physiological indicators such as oxygen supply status, circulation status, organ function status, and temperature regulation status, constructing a closed-loop control mechanism based on physiological feedback. The controller can automatically adjust temperature control, oxygen supply, and perfusion parameters according to changes in organ status, improving the timeliness and accuracy of system regulation and reducing the uncertainty caused by human experience-based adjustments.

[0040] 4. This invention establishes a multi-level emergency response mechanism for conditions such as insufficient oxygenation, circulatory instability, and abnormal organ function, and can continuously monitor organ temperature and lung oxygenation status during the emergency response process. When there is a risk of organ overheating or abnormal lung function, the system can automatically execute corresponding protection strategies, thereby improving the operational safety and organ protection capabilities during multi-organ combined perfusion, and prolonging the stable maintenance time of isolated organs. Attached Figure Description

[0041] Figure 1 A schematic diagram of the oxygenation temperature control system for an ex vivo multi-organ combined perfusion system;

[0042] Figure 2 This is a detailed flowchart of an oxygenation temperature control system from system startup to cycle monitoring and regulation;

[0043] Figure 3 This is a flowchart of an adjustment method. Detailed Implementation

[0044] The technical solutions in the embodiments of the present invention will now be described in detail with reference to the accompanying drawings.

[0045] like Figure 1 The diagram shown is a framework diagram of the oxygenation and temperature control system for an isolated multi-organ combined perfusion system; as shown... Figure 2 The diagram shows a detailed flowchart of an oxygenation and temperature control system from system startup to cycle monitoring and regulation, illustrating the detailed process of monitoring and regulation of each part of the system. This system mainly includes an organ chamber, a perfusion circuit, an internal environment regulation module, an airway environment regulation module, a sensor group, and a controller. It is used to maintain the combined perfusion of multiple organs such as the heart, liver, lungs, and kidneys under in vitro conditions. Through precise oxygenation and temperature control strategies, it achieves the maintenance of the physiological functions of each organ in the in vitro environment.

[0046] The organ compartment is a sealed, insulated chamber with multiple organ fixation supports to house and secure the heart, liver, lungs, and kidneys. The compartment walls are made of insulating material to minimize heat exchange between the interior and the external environment. Multiple access points are provided for the entry and exit of perfusion tubing, the routing of sensor cables, and the connection of gas channels. The internal space of the organ compartment is divided into zones according to the physiological needs of each organ. The lung area is connected to the ventilator tubing of the airway environment regulation module, while the heart, liver, and kidney areas have their environmental parameters uniformly regulated by the internal environment regulation module.

[0047] In this embodiment, the perfusion circuit is the core circulation pathway of the system, comprising a magnetic levitation pump, a heat exchanger, and a membrane lung connected in sequence. A flow meter is installed at the outlet of the magnetic levitation pump for real-time monitoring of the perfusion flow rate. The magnetic levitation pump employs a non-contact magnetic drive method, avoiding mechanical damage to blood cells in the perfusion fluid, while also featuring precisely adjustable flow rate, covering the physiological flow range required for combined perfusion of various organs.

[0048] A heat exchanger is positioned between the magnetic levitation pump and the membrane lung to regulate the temperature of the perfusion fluid. The heat exchanger employs a highly efficient heat exchange structure, and the temperature of its heat exchange medium is dynamically adjusted by a controller based on temperature feedback from each organ. The heat exchanger can precisely control the perfusion fluid temperature within the target range, with single adjustments not exceeding preset temperature limits (e.g., 0.3°C to avoid drastic temperature changes that could cause organ stress), thus preventing thermal damage from sudden temperature fluctuations.

[0049] The membrane lung is connected after the heat exchanger. Its inlet receives the temperature-controlled perfusion fluid, and its outlet connects to the perfusion inlet used by all organs in the organ chamber. The membrane lung is responsible for gas exchange in the perfusion fluid, that is, dissolving oxygen into the perfusion fluid and removing carbon dioxide. The membrane lung is connected to a membrane lung gas mixer, which is used to adjust the oxygen and carbon dioxide concentrations in the membrane lung, thereby precisely controlling the partial pressure of oxygen and carbon dioxide in the perfusion fluid to meet the oxygenation requirements of different organs under different physiological conditions.

[0050] The perfusion outlets used by each organ are collected through the return pipeline and returned to the inlet of the magnetic levitation pump, forming a complete circulation path. The return pipeline is equipped with a bubble detection device, a filter, and a blood leakage sensor to detect the presence of blood leakage, ensuring the continuity and safety of the perfusion fluid return.

[0051] The internal environment control module includes heating wires, a fan, and a humidifier located within the organ chamber to regulate the temperature and humidity. The heating wires are evenly distributed along the inner walls of the organ chamber or positioned in dedicated heating areas to provide a heat source for the air inside when heating is required. The fan is positioned appropriately within the chamber to promote uniform airflow, ensuring even distribution of temperature and humidity throughout the chamber. The heating wires and fan work together to achieve bidirectional temperature control: when heating is needed, the controller simultaneously activates both the heating wires and the fan, evenly dispersing hot air throughout the chamber; when cooling is needed, the controller deactivates the heating wires while keeping the fan running, accelerating heat dissipation through airflow and utilizing the chamber's cooling system to achieve cooling, thus meeting the system's temperature regulation needs for the organ chamber.

[0052] The humidity control requirements for isolated multi-organ clusters are shown in the table below:

[0053] lung Airway environment regulation module (ventilator humidifier) 95-100%RH Protect airways and alveoli, prevent dryness damage heart In-cabin environment control module (in-cabin humidifier) 50-80%RH Avoid surface drying, but it is not strictly required. liver In-cabin environment control module (in-cabin humidifier) 50-80%RH Avoid surface drying kidney In-cabin environment control module (in-cabin humidifier) 50-80%RH Avoid surface drying

[0054] Table 1

[0055] In this embodiment, the first humidity environment (provided by the in-cabin humidifier) ​​and the second humidity environment (provided by the ventilator humidifier, controlling temperature and humidity) operate as two independent subsystems, each independently adjusted by the controller based on corresponding feedback, without interference. This dual humidity regulation architecture satisfies both the need for external surface moisturizing and stress prevention, and also takes into account the protection of the physiological barrier inside the airway, effectively avoiding decreased lung compliance or airway dryness damage caused by humidity confusion. The controller independently controls the in-cabin humidifier to maintain the first humidity environment inside the organ chamber at a normal moderate relative humidity (50%~80%RH) to ensure that the external surfaces of the heart, liver, kidneys, and lungs exposed in the chamber space remain moist, preventing tissue dehydration. At the same time, the controller independently controls the ventilator humidifier in the airway environment regulation module to maintain the second humidity environment entering the airway inside the lungs at a physiologically high saturation humidity (95%~100%RH), specifically protecting the alveoli and internal airway mucosa. The heating wire and fan work together to achieve bidirectional temperature regulation within the chamber: when heating is needed, the controller simultaneously activates both the heating wire and the fan; the heating wire provides heat, and the fan evenly distributes hot air throughout the chamber. When cooling is needed, the controller deactivates the heating wire while keeping the fan running, accelerating heat dissipation through airflow and utilizing the chamber's cooling system to achieve cooling. This design eliminates the need for additional refrigeration equipment, simplifying the system structure while meeting the precise temperature control requirements during organ maintenance.

[0056] In this embodiment, a ventilator is connected to the lungs within the organ chamber to provide mechanical ventilation support to the lungs in an isolated state, simulating the respiratory movements of the lungs in vivo. The ventilator can be set with ventilation parameters such as tidal volume, respiratory rate, inspiratory-to-expiratory ratio, and positive end-expiratory pressure to maintain lung ventilation function and alveolar tension. The ventilator is equipped with an independent humidifier to humidify the gas output by the ventilator, providing a second humidity environment with saturated humidity for the lungs. In this embodiment, the ventilator humidifier is used not only to regulate the humidity of the inhaled gas entering the lungs but also to regulate the temperature of the inhaled gas. By changing the temperature and humidity conditions of the inhaled gas, the heat exchange environment of the airways and alveolar regions within the lungs can be adjusted, thereby assisting in the regulation and maintenance of lung temperature. The second humidity environment typically requires close to 100% saturated humidity to simulate the humid environment of the lungs in vivo, preventing alveolar drying and surfactant inactivation.

[0057] The sensor array primarily includes cabin temperature and humidity sensors, pipeline temperature probes, flow meters, organ temperature sensors, blood oxygen saturation sensors, electronic weighing modules, ECG leads, and arterial catheters. Table 2 shows the types of parameters acquired by the sensor array, their corresponding hardware sources, and the multi-timescale fusion sampling frequencies.

[0058] Environmental parameters Organ compartment temperature and relative humidity In-cabin temperature and humidity sensor 1Hz Infusion parameters Injection temperature, injection flow rate Pipeline temperature probe + magnetic levitation pump outlet flow meter 1Hz Organ temperature Temperature of organs such as the heart, liver, lungs, and kidneys Organ surface / core single-point temperature sensor (1 per organ) 1Hz Heart function ECG (heart rate), blood oxygen saturation ECG lead + blood oxygen saturation sensor 250Hz→1Hz / 1Hz Hemodynamics Invasive blood pressure (systolic blood pressure, diastolic blood pressure, mean arterial pressure MAP) ductus arteriosus 50Hz→1Hz Kidney function Weighing of kidney metabolites (urine volume / dialysis fluid volume) Electronic weighing module 0.1Hz Respiratory support <![CDATA[Ventilator parameters (FiO2, tidal volume, respiratory rate, minute ventilation MV, ventilator output humidity)]]> ventilator data interface 0.5Hz Membrane lung gas <![CDATA[membrane lung O2 concentration, CO2 concentration, air ratio (adjustable)]]> Membrane lung gas mixer control signal (feedback optional) —

[0059] Table 2

[0060] Temperature and humidity sensors are installed inside the organ chamber to collect real-time data on the temperature and humidity of the air. Pipeline temperature probes are installed in key sections of the perfusion circuit to monitor the temperature of the perfusion fluid at various points during circulation. A flow meter is installed at the outlet of the magnetic levitation pump to monitor the flow rate of the perfusion fluid in real time.

[0061] The organ temperature sensor includes individual temperature sensors located on the surfaces of the heart, liver, lungs, and kidneys, which are used to directly monitor the surface temperature of each organ and provide direct basis for the controller's temperature control decisions.

[0062] A blood oxygen saturation sensor is installed in the perfusion circuit to monitor the blood oxygen saturation in the perfusion fluid in real time, reflecting the oxygenation status of various organs. An electronic weighing module is located below the urine collection container to monitor the urine output of the kidneys in real time through weight changes, thereby assessing the perfusion and functional status of the kidneys.

[0063] The ECG lead is connected to the heart to collect electrophysiological signals, including heart rate and rhythm. An arterial catheter is placed on the arterial side of the perfusion circuit to monitor perfusion pressure and arterial waveforms, providing a basis for assessing circulatory status.

[0064] It should be noted that the controller is the core processing unit of this system, connected to the sensor group, perfusion circuit, cabin environment regulation module, and airway environment regulation module, and is responsible for data acquisition, data processing, status judgment, and control command generation. After receiving multi-source heterogeneous data collected by the sensor group, the controller adopts a multi-timescale fusion strategy due to the large differences in sampling frequencies among the sensors. First, it performs time alignment processing on the multi-source heterogeneous data: slow variables (kidney weighing) are downsampled to 1 point every 60 seconds, and denoising is performed using exponentially weighted moving average (EWMA) with a weighting coefficient α=0.2; medium-speed variables (temperature and humidity, perfusion parameters, organ temperature, SpO2, heart rate, MAP) are uniformly resampled to 1Hz, and linear interpolation is used to fill in brief packet loss (packet loss <5 seconds); fast variables (ECG, blood pressure waveform) have feature values ​​extracted (heart rate, systolic / diastolic blood pressure, MAP), and downsampled to 1Hz. Because different types of sensors have different sampling frequencies and response delays, the controller uses timestamp alignment and interpolation algorithms to unify the data from each sensor to the same time base, ensuring the temporal consistency of subsequent analysis.

[0065] After time alignment, the controller performs anomaly detection and processing based on physiological rationality verification and historical baseline comparison. Physiological rationality verification involves checking the range of collected data to determine whether it falls within a physiologically reasonable range. For example, blood oxygen saturation should not exceed 100% or fall below a certain limit, and organ temperature should not deviate excessively from the physiological range. Data outside the reasonable range is marked as anomalous by the controller and filtered or removed. Historical baseline comparison involves comparing current data with historical baseline data accumulated during system operation to identify abrupt changes or drift trends, thereby proactively detecting potential sensor malfunctions or organ abnormalities.

[0066] Since each parameter is configured with only a single sensor (no hardware redundancy), the following software fault-tolerance strategy is adopted: historical baseline comparison, each parameter maintains the median and standard deviation of the past 5 minutes; if the current value deviates from the median by more than 3σ, it is marked as suspicious. Physiological rationality verification: organ temperature, 30~40℃; SpO2, 50~100% (<80% triggers oxygenation enhancement alarm); systolic blood pressure, 30~200mmHg; heart rate, 30~200bpm; urine output change rate, 0~500 mL / h. When handling abnormal values, for values ​​marked as suspicious, if the duration is <3 seconds, it is regarded as spike noise and the value is directly discarded and replaced by the previous valid value (keeping the value of the previous moment); if the duration is ≥3 seconds, it is determined to be a sensor failure or a real physiological event, triggering an alarm and suspending the automatic control of the parameter, prompting the operator to check the sensor status, and the system temporarily uses the control command of the previous cycle to maintain operation.

[0067] For cases where there may be missing data in the collected data, imputation is required: for short-term missing data (e.g., <10 seconds), the most recent valid value is used to fill the gap (keeping the value from the previous moment). If the missing data exceeds 10 seconds, an alarm is triggered, prompting the operator to check the sensor connection.

[0068] After completing data preprocessing, the controller calculates multiple indirect parameters using the directly acquired parameters, collectively referring to these indirect parameters as derived physiological indicators to reflect overall oxygen supply, circulatory status, organ function, and temperature regulation. These derived physiological indicators include:

[0069] 1) Oxygen delivery capacity evaluation parameters: The oxygen delivery index (DO2I) is calculated using perfusion flow rate and blood oxygen saturation. This index reflects the total amount of oxygen delivered to the organ per unit time and is a key indicator for assessing the oxygen supply status of the organ.

[0070] 2) Circulatory status evaluation parameters: The shock index (SI = heart rate / systolic blood pressure) is calculated using heart rate collected from ECG leads and systolic blood pressure collected from arterial catheters. This index is used to assess the stability of the circulatory system.

[0071] 3) Organ Functional Status Evaluation Parameters: The urine volume change rate is calculated using weight change and time information collected by the electronic weighing module. This indicator is used to assess the adequacy of renal perfusion and functional status. In other embodiments, this parameter may also be characterized by bile secretion, lactate change rate, glucose metabolism rate, or tissue oxygen uptake rate. The controller determines the functional status of the corresponding organ based on the changing trend of the organ functional status evaluation parameters and executes corresponding adjustment strategies.

[0072] 4) Organ heat load: Calculated based on the difference between the actual temperature collected by a single-point temperature sensor on the organ surface and the temperature of the perfusion fluid collected by the tubing temperature probe. It is used to assess the local metabolic heat production and heat conduction deviation of a single organ and is the core control basis for the system to perform daily steady-state coordinated regulation.

[0073] 5) Lung oxygenation status evaluation parameters: These parameters are calculated based on the current actual inhaled oxygen concentration obtained from the blood oxygen saturation and airway environment regulation module. They are used to reflect the changing trend of oxygenation status in isolated lungs and provide a reference for lung status monitoring and abnormal early warning.

[0074] Since this solution does not use a conventional high-precision online blood gas analyzer with redundant tubing, in order to reduce hardware complexity and minimize the physical interfaces of the extracorporeal circulation tubing, the controller of this invention uses a built-in soft measurement method to infer five derived physiological indicators reflecting the overall and local metabolism of the cluster in real time using direct physical quantities collected by the basic sensor group. The specific calculation formulas and corresponding Chinese physiological meanings of the derived physiological indicators are as follows:

[0075] The oxygen supply capacity evaluation parameter DO2 = Q × SpO2; where Q is the real-time perfusion flow rate and SpO2 is the blood oxygen saturation. This parameter reflects the overall oxygen supply capacity change trend of the system and provides a reference for the controller to assess the oxygen supply status.

[0076] Circulatory status evaluation parameters are used to reflect the circulatory stability during multi-organ combined perfusion. In one embodiment, the circulatory status evaluation parameter can be characterized by the shock index SI: Shock index SI = HR / SBP; where SI is the heart rate acquired through the ECG lead, and SBP is the systolic blood pressure acquired through the ductus arteriosus. In other embodiments, the circulatory status evaluation parameter can also be characterized by mean arterial pressure, perfusion pressure, blood flow variability, pressure change rate, or a combination thereof. The controller determines the stability of the circulatory system based on the circulatory status evaluation parameters and adjusts the perfusion flow rate, pump rate, or oxygen supply parameters accordingly.

[0077] Organ function status evaluation parameters are used to reflect the physiological activity status of the corresponding isolated organs. When a multi-organ cluster includes the kidney, the organ function status evaluation parameter can be characterized by the rate of change in urine volume: ΔU = ΔW / Δt; ΔW is the weight change of urine collected by the electronic weighing module per unit time, and Δt is the corresponding time interval. In other embodiments, organ function status evaluation parameters can also be characterized by bile secretion, lactate change rate, glucose metabolism rate, tissue oxygen uptake rate, or other parameters that can reflect organ function status. The controller determines the functional status of the corresponding organ based on the changing trend of the organ function status evaluation parameters and executes corresponding regulatory strategies.

[0078] Organ heat load ΔT i = T organ _i - T per f; where T organ _i T represents the actual temperature collected by a single-point temperature sensor located on the surface of the i-th organ, where i is a positive integer. per f represents the temperature of the perfusion fluid collected by the pipeline temperature probe. The Chinese physiological meaning of organ heat load is explained as follows: It is used to assess the degree of local metabolic heat production and heat conduction deviation in a single heterogeneous organ. This indicator is used to accurately quantify the dynamic temperature difference generated by the heat production of a specific organ's own cells and the heat exchange with the exogenous environment. It is the core control basis for the system to perform daily steady-state coordinated regulation and heterogeneous temperature difference countermeasures under normal conditions.

[0079] The lung oxygenation status evaluation parameter O / S = SpO2 / FiO2; where SpO2 is the perfusion oxygen saturation and FiO2 is the current actual inhaled oxygen concentration obtained from the ventilator data interface. This parameter reflects the changing trend of the oxygenation status of isolated lungs, providing a reference for lung status monitoring and abnormal early warning. In this embodiment, the system also includes an emergency judgment and rapid emergency response mechanism. The controller determines whether an emergency exists based on the collected direct parameters and calculated indirect parameters. If an emergency exists, a rapid emergency response is executed; otherwise, routine steady-state regulation is performed. To achieve refined maintenance of high-value multi-organ clusters, the core control parameter range managed by the controller and the corresponding physical actuator mapping relationship are shown in Table 3 below:

[0080] Injection fluid temperature 34.0~39.0℃ heat exchanger cabin temperature 34.0~38.0℃ Heated fan cabin humidity 40~90%RH In-cabin humidifier Infusion flow rate 0.5~4.0 L / min magnetic levitation pump membrane lung oxygen concentration 21~100% Membrane lung gas mixer membrane lung carbon dioxide concentration 0~10% Membrane lung gas mixer ventilator oxygen concentration 21~100% Ventilator mechanical ventilation 2~15 L / min Ventilator ventilator humidity 30~100%RH ventilator humidifier

[0081] Table 3

[0082] The rapid emergency response, prioritized from highest to lowest, is as follows: hypoxia, circulatory instability, and organ dysfunction. When oxygen delivery capacity assessment parameters (such as the oxygen delivery index) or blood oxygen saturation are below a preset reference range (e.g., 90%), the controller determines hypoxia and triggers the hypoxia response. This response includes increasing the oxygen concentration setpoint of the membrane lung gas mixer to increase the oxygen content of the perfusion fluid; simultaneously, appropriately increasing the perfusion flow rate of the magnetic levitation pump to increase the oxygen delivery per unit time. When circulatory status assessment parameters (such as the shock index) are above a preset reference range (e.g., 0.9), the controller determines circulatory instability and triggers the circulatory instability response. This response includes increasing the perfusion flow rate of the magnetic levitation pump to improve circulatory perfusion and restore blood supply to various organs. When organ function status assessment parameters (such as urine output change rate) are below a preset threshold (e.g., 30 mL / h), the controller determines organ dysfunction (e.g., oligouria) and triggers the organ dysfunction response. The response executes protective regulation strategies based on the functional status of the corresponding organ, specifically including: First, checking whether the oxygen delivery index is sufficient; if the oxygen delivery index is low, prioritizing increasing the perfusion flow rate to improve renal oxygen supply; if the oxygen delivery index is normal, appropriately increasing the perfusion flow rate to improve renal perfusion pressure and promote urine production. In other embodiments, if the organ functional status evaluation parameters are abnormal (e.g., bile secretion, lactate change rate, glucose metabolism rate, or tissue oxygen uptake rate), the controller executes corresponding protective perfusion flow rate adjustment or temperature compensation strategies based on the metabolic characteristics of the corresponding organ.

[0083] When multiple physiological parameters or derived physiological indicators deviate from the safety threshold and meet the corresponding emergency triggering conditions, the controller activates a rapid emergency response mechanism. The specific emergency situation classification and emergency response priority are shown in Table 4 below:

[0084] Oxygen deficiency <![CDATA[SpO2< 90%]]> Immediately increase the oxygen concentration in the membrane lung by 10-20%; if still insufficient, increase the perfusion flow rate. Unstable cycle Shock index > 0.9 Increase the infusion flow rate by 0.1~0.2 L / min Insufficient urine output Urine output <0.3 mL / kg / h Check oxygen delivery; if normal, increase the infusion flow rate. Lung abnormalities Decreased lung compliance Reduce ventilator humidity and ventilation volume to increase oxygenation sharing in membrane lungs. Organ overheating Temperature of any organ exceeding the upper limit Lower the temperature of the infusion fluid, and simultaneously turn off the heating element and turn on the fan to cool it down.

[0085] Table 4

[0086] During rapid emergency response, if the temperature of any organ exceeds the corresponding preset upper limit threshold (e.g., 38.5℃), the controller triggers the organ overheat protection, forcibly controlling the heat exchanger to reduce the perfusion fluid temperature, and controlling the cabin environment control module to shut off the heating wires and turn on the fan at full speed for forced convection cooling until the temperature meets safety requirements. When the ventilator airway pressure and volume feedback calculates a decrease in lung compliance (indicating a possible trend towards pulmonary edema), the controller actively reduces the relative humidity of the secondary humidity environment and decreases mechanical ventilation, while simultaneously controlling and increasing the oxygenation sharing ratio of the membrane lung to reduce the physiological load on the isolated lung.

[0087] Under normal conditions, all physiological indicators of the system remain within safe ranges. During routine steady-state regulation, unless there is an emergency, the controller performs routine steady-state regulation. The core strategy of routine steady-state regulation is based on the deviation between the current feedback values ​​of single-point temperature sensors on the surface of each organ and their respective preset target temperature ranges. Specifically, the target temperature range for the heart is 37.2±0.3℃, for the liver it is 37.2±0.2℃, for the lungs it is 35.5±0.5℃, and for the kidneys it is 36.8±0.3℃. Based on the deviation between the current temperature of each organ and its respective target temperature, the controller comprehensively generates regulation commands for the heat exchanger and the cabin environment regulation module, achieving coordinated control of the perfusion fluid temperature and the cabin air temperature.

[0088] In this embodiment, the lungs and non-lung organs employ different primary heat exchange pathways. The lungs, with their open airway structure and continuous mechanical ventilation, are affected not only by the perfusion fluid but also by the gaseous environment within the organ chamber and the environment of the respiratory gases entering the lungs. Specifically, the chamber environment control module alters the heat exchange conditions on the lung's outer surface by regulating the air temperature within the organ chamber; the ventilator humidifier in the airway environment control module regulates the temperature and humidity of the respiratory gases entering the lungs, thereby altering the heat exchange conditions within the alveoli and regulating the lung temperature. Therefore, the lungs can simultaneously regulate their temperature through gaseous heat exchange between the lung surface and the organ chamber environment, as well as through gaseous heat exchange between the alveoli and the respiratory gases. In contrast, non-lung organs such as the heart, liver, and kidneys primarily rely on the perfusion fluid to transfer heat to the tissues via the vascular system; their temperature is mainly affected by the temperature of the perfusion fluid and therefore primarily exchanges heat through the liquid phase environment. Based on the above differences, this embodiment uses a heat exchanger to adjust the temperature of the perfusion fluid to control the temperature of non-lung organs, an in-cabin environment control module to adjust the air temperature inside the organ chamber, and a ventilator humidifier to adjust the temperature of the inhaled gas to control the temperature of the lungs, thereby achieving differentiated temperature management between the lungs and non-lung organs.

[0089] When the temperature of most organs is low, the controller prioritizes increasing the set temperature of the heat exchanger to raise the temperature of the perfusion fluid. In the multi-organ cluster of this invention, the lungs are extremely sensitive to the air temperature inside the chamber (exogenous heat exchange), while the core temperature of the heart, liver, and kidneys, as non-pulmonary parenchymal organs, is almost entirely determined by the perfusion fluid (endogenous heat exchange). Therefore, the term "most organs" specifically refers to the majority of non-pulmonary parenchymal organs. That is, when the actual temperature of any two or three of the three non-pulmonary parenchymal organs (heart, liver, and kidneys) is lower than the preset target value, it is determined that the temperature of most organs is low, and the controller adjusts the heat exchanger fluid temperature to precisely achieve the technical objective of using fluid temperature to support the core temperature of non-pulmonary parenchymal organs.

[0090] When a non-uniform, heterogeneous temperature difference occurs, where the lung temperature is relatively higher than that of non-lung organs, the controller directs the internal environment regulation module to lower the air temperature within the organ compartment (e.g., by reducing the heating wire power or increasing the fan speed). This uses cool air to quickly remove excess heat from the lung surface, thus cooling the lungs. Simultaneously, it coordinates with the heat exchanger to raise or maintain the perfusion fluid temperature. At this time, the perfusion fluid, carrying higher heat, continuously flows into the cluster from the main artery inlet, prioritizing the replenishment of heat to the cardiac, hepatic, and renal vascular beds, which have extremely high blood flow. This utilizes the blood flow barrier within the blood vessels to counteract and offset the exogenous heat loss caused by the cooling of the organ compartment to the solid organs and naturally connected large blood vessels. Through this dynamic counterbalancing of "cold and hot," a precise temperature balance is achieved between the heterogeneous organs within the same space.

[0091] Based on the above system configuration and adjustment method, this invention verifies and illustrates the system's temperature control, oxygenation, and emergency control effects through the following three typical application examples.

[0092] Example 1: Daily homeostasis coordination and maintenance

[0093] Before the experiment, all system parameters were at initial unsteady-state values. Controller monitoring revealed that kidney temperature and urine output were low, lung temperature was high, and the overall oxygen delivery index was insufficient. After system startup (0-5 minutes), the controller performed routine steady-state coordinated regulation: based on temperature deviations, a gradual adjustment strategy was adopted, with single-time fine-tuning of the heat exchanger setpoint (+0.3℃) and cabin air temperature (-0.2℃) to dynamically counteract and balance the heterogeneous temperature difference through a "cold-hot" dynamic process; simultaneously, overall oxygen delivery was compensated by increasing perfusion flow rate and membrane lung oxygen concentration. After 30 minutes of operation, the system entered a fully steady state and exhibited extremely high control stability during subsequent continuous perfusion of up to 240 minutes. The specific operating results and parameter compliance rates for Example 1 are shown in Table 5.

[0094]

[0095] Table 5

[0096] Example 2: Rapid Emergency Response to Sudden Decline in Oxygenation

[0097] During the steady-state operation of the ex vivo multi-organ combined perfusion system, a sudden drop in membrane lung efficiency (t=0) was artificially simulated, causing the arterial oxygen saturation (SpO2) in the perfusion circuit to plummet from 96% to 82% in a short period. This was accompanied by a compensatory increase in heart rate (reaching 110 beats / min) and a drop in blood pressure (systolic blood pressure dropping to 62 mmHg). After removing abnormal data and aligning with the time, the controller detected the trigger condition of SpO2 < 90% in real time, immediately determining that there was a high-priority "insufficient oxygenation" emergency, and instantly triggering the emergency response chain: automatically increasing the membrane lung oxygen concentration from 55% to 75% and compensatorily increasing the basic perfusion flow rate of the magnetic levitation pump from 2.5 L / min to 2.8 L / min. Experimental results showed that after the system performed rapid emergency adjustments, SpO2 was successfully pulled back to the safe physiological range of over 90% within 90 seconds. All circulatory and kinetic indicators of the system were fully restored to baseline steady state within 10 minutes. During this period, due to the use of blood flow barrier countermeasure technology, the core temperature of each isolated organ was not affected by any temperature control overshoot or fluctuation.

[0098] Example 3: Rapid Emergency Response to Sudden Renal Insufficiency and Functional Decline

[0099] During multi-organ cluster perfusion, a sudden insufficiency of perfusion in an isolated kidney was simulated by artificially adjusting the resistance of local branch tubing in the kidney (t=0). The system exhibited a sharp decrease in urine output from 48 mL / h to 25 mL / h, accompanied by a drop in the single-point surface temperature of the kidney from 36.8℃ to 36.4℃, while the physiological parameters of other organs (heart, liver, and lungs) remained normal. The controller detected an emergency trigger threshold of 30 mL / h in real time. After determining that the current system oxygen delivery index was normal (DO2 > 200), it accurately identified the decrease in excretion and metabolism caused by insufficient local perfusion pressure. The controller then executed corresponding emergency adjustments: prioritizing an increase in total perfusion flow rate (+0.2 L / min) to enhance local perfusion pressure in the kidney, and simultaneously increasing the set temperature of the heat exchanger (+0.2℃) for local heat compensation. Experimental results showed that the renal urine output recovered to the physiological standard of over 35 mL / h within 30 minutes, and the renal surface temperature fully recovered to the normal steady state of 36.8℃ within 40 minutes, successfully eliminating the risk of acute termination of renal function. Moreover, during this process, no negative cross-interference was caused to the homeostatic environment of other organs such as the heart, liver, and lungs, verifying that this control method has extremely high efficiency and local decoupling regulation capability when facing local solid organ pathological events.

[0100] In this embodiment, after the system starts, the perfusion fluid is first driven by a magnetic levitation pump to circulate in the perfusion circuit. After being heated and oxygenated by the membrane lung via a heat exchanger, the perfusion fluid enters the organ chamber to perfuse each organ. Simultaneously, the chamber environment control module starts working, with heating wires, a fan, and a chamber humidifier working together to adjust the chamber environment to preset temperature and humidity target values. The airway environment control module starts synchronously, providing saturated humidity ventilation support to the lungs through the ventilator and its ventilation tubing humidifier.

[0101] The sensor array continuously collects various parameters and transmits them to the controller. After time alignment, anomaly detection and processing, the controller calculates derived physiological indicators (such as oxygen delivery index, shock index, and urine output change rate) to comprehensively assess the oxygenation, circulatory, and functional status of each organ. Based on the assessment results, the controller dynamically generates control commands to adjust the operating parameters of the heat exchanger, heating wire, fan, in-cabin humidifier, ventilator humidifier, magnetic levitation pump, and membrane lung gas mixer, ensuring the system always operates at its optimal perfusion state.

[0102] In addition, refer to Figure 3 The flowchart shown illustrates an adjustment method for an oxygenation temperature control system. This application also proposes an adjustment method for adjusting the aforementioned oxygenation temperature control system, comprising the following steps:

[0103] S1. Parameter Acquisition and Data Preprocessing:

[0104] The controller collects environmental parameters from the organ chamber, perfusion parameters from the perfusion circuit, and physiological parameters of each isolated organ in the multi-organ cluster in real time using a sensor array. Environmental parameters may include chamber temperature, humidity, and perfusion circuit temperature; perfusion parameters may include perfusion flow rate, perfusion pressure, and blood oxygen saturation; physiological parameters may include organ surface temperature, electrocardiogram signals, changes in urine weight, and other parameters reflecting organ status. Upon receiving these parameters, the controller first verifies the validity of the collected data based on preset physiological rationality rules. For example, if blood oxygen saturation exceeds the normal measurement range or an abnormal jump occurs within adjacent sampling periods, the corresponding data is marked as abnormal. Subsequently, the controller performs trend analysis based on historical baseline data and corrects or removes abnormal data using filtering, interpolation, redundant data comparison, or other fault-tolerant processing methods to obtain the corresponding final parameters, thereby improving the reliability of subsequent control decisions. After completing data preprocessing, the controller further calculates the corresponding derived physiological indicators based on the final parameters, including one or more of the following: oxygen supply capacity evaluation parameters, circulatory status evaluation parameters, organ function status evaluation parameters, organ heat load, and lung oxygenation status evaluation parameters.

[0105] S2. Status Judgment and Control Command Generation:

[0106] The controller determines whether the system is in an abnormal state based on the final processed parameters and derived physiological indicators obtained in step S1. When all monitored parameters and derived physiological indicators are within the corresponding reference range, the system is determined to be in normal operation, and a steady-state control command is generated. When generating the steady-state control command, the controller performs a comprehensive analysis based on the difference between lung temperature and non-lung organ temperature, as well as the deviation between the temperature of each organ and the target temperature, and generates a coordinated temperature control command. For example, when the lung temperature is higher than the corresponding target temperature and relatively higher than the non-lung organ temperature, the controller controls the cabin environment conditioning module to lower the air temperature inside the organ cabin, and simultaneously controls the heat exchanger to increase or maintain the perfusion fluid temperature, so as to use the lower cabin air temperature to promote heat dissipation from the lungs, while using the perfusion fluid to continuously replenish heat to the non-lung organs, thereby achieving differentiated thermal management of the lungs and non-lung organs.

[0107] When an abnormal state is detected, the controller generates an emergency control command.

[0108] Preferably, the controller judges and executes corresponding emergency response strategies in descending order of priority for insufficient oxygenation, circulatory instability, and abnormal organ function. Specifically, when the oxygen supply capacity evaluation parameter or blood oxygen saturation is lower than the preset reference range, an insufficient oxygenation response is triggered; when the circulatory status evaluation parameter exceeds the preset reference range, a circulatory instability response is triggered; and when the organ function status evaluation parameter exceeds the preset reference range, an abnormal organ function response is triggered.

[0109] S3, Control Command Execution:

[0110] The controller controls each execution unit of the system according to the steady-state control command or emergency control command generated in step S2. Specifically, the controller controls the heat exchanger to adjust the perfusion fluid temperature; controls the chamber environment regulation module to adjust the air temperature and primary humidity environment inside the organ chamber; and controls the airway environment regulation module to adjust the secondary humidity environment inside the lung airway. During the execution of emergency control, the controller continuously monitors the temperature status of each isolated organ and the oxygenation status of the lungs. When the actual temperature of any isolated organ exceeds the preset upper temperature threshold, the controller triggers an overheat response, controls the heat exchanger to lower the perfusion fluid temperature, and controls the chamber environment regulation module to lower the air temperature inside the organ chamber. When the lung oxygenation status evaluation parameters continuously deviate from the preset reference range, it is determined that there is a risk of lung dysfunction, and the controller controls the airway environment regulation module to adjust the secondary humidity environment and mechanical ventilation parameters to maintain the normal physiological state of the lungs. After completing this round of regulation, the controller re-enters step S1 to continuously collect parameters, judge the status, and regulate the control, thereby forming a closed-loop feedback control process to achieve dynamic and coordinated regulation of the oxygen supply environment, temperature environment, and humidity environment during multi-organ combined perfusion.

[0111] In summary, this invention integrates oxygenation control, temperature control, humidity control, and organ status monitoring into a single control system, achieving coordinated regulation of oxygen supply, thermal, and humidity environments during multi-organ combined perfusion. It is particularly suitable for long-term perfusion maintenance of ex vivo multi-organ clusters while maintaining natural vascular anatomical connections, which is beneficial for improving the quality of organ function preservation and its value for subsequent research and application.

[0112] The above embodiments are merely illustrative of the technical concept of the present invention and should not be construed as limiting the scope of protection of the present invention. Any modifications made to the technical solutions based on the technical concept proposed in this invention shall fall within the scope of protection of this invention.

Claims

1. An oxygenation and temperature control system for an isolated multi-organ combined perfusion system, characterized in that, include: An organ compartment is used to accommodate a multi-organ cluster consisting of multiple ex vivo organs that maintain natural vascular tissue anatomical connections, the multi-organ cluster including at least a lung, a kidney and at least one non-lung organ. The perfusion circuit includes a magnetic levitation pump, a heat exchanger, and a membrane lung connected in sequence. The outlet of the membrane lung is connected to the common arterial inlet of the multi-organ cluster, and the common venous return outlet of the multi-organ cluster returns to the inlet of the magnetic levitation pump. An internal environment regulation module is located inside the organ chamber and is used to regulate the temperature inside the organ chamber and provide a primary humidity environment for the outer surface of the multi-organ cluster. An airway environment regulation module is ventilated to the lungs in the multi-organ cluster to provide mechanical ventilation support to the lungs and regulate the secondary humidity environment within the airways of the lungs. The sensor group includes environmental parameter sensors for collecting physical state parameters of the organ chamber and perfusion circuit, and physiological monitoring sensors for collecting physiological index parameters of each ex vivo organ in the multi-organ cluster. The controller is electrically connected to the sensor group, the infusion circuit, the cabin environment regulation module, and the airway environment regulation module, respectively. The controller is used to control the heat exchanger and the cabin environment regulation module to coordinately regulate the temperature of the multi-organ cluster according to the parameters collected by the sensor group, and to control the cabin environment regulation module and the airway environment regulation module to independently regulate the first humidity environment and the second humidity environment, respectively.

2. The oxygenation and temperature control system of the isolated multi-organ combined perfusion system according to claim 1, characterized in that, The controller is also used to: during routine steady-state regulation, adjust the heat exchanger and the cabin environment regulation module in coordination based on the deviation between the current temperature of each organ and its respective target value; when the temperature of the lung is relatively higher than that of the non-lung organs, control the cabin environment regulation module to lower the air temperature inside the organ cabin, and coordinately control the heat exchanger to raise or maintain the perfusion fluid temperature.

3. The oxygenation and temperature control system of the isolated multi-organ combined perfusion system according to claim 1, characterized in that, The controller is used to receive parameters collected by the sensor group and perform data anomaly detection and fault tolerance processing based on physiological rationality verification and historical baseline comparison; and the controller is also used to dynamically calculate multiple derived physiological indicators reflecting the overall oxygen supply status, circulation status, organ function status and temperature regulation status based on the processed parameters.

4. The oxygenation and temperature control system of the isolated multi-organ combined perfusion system according to claim 3, characterized in that, The multiple derived physiological indicators include one or more of the following: The oxygen supply capacity evaluation parameters are calculated based on perfusion flow rate and blood oxygen saturation. The circulatory status evaluation parameters are calculated based on at least one of heart rate, systolic blood pressure, mean arterial pressure, perfusion pressure, and blood flow variability. The organ function status evaluation parameters are calculated based on at least one of the following: urine volume change rate, bile secretion rate, lactate change rate, glucose metabolism rate, or tissue oxygen uptake rate. Organ heat load is calculated based on organ surface temperature and perfusion fluid temperature; The parameters for evaluating pulmonary oxygenation status are calculated based on blood oxygen saturation and inhaled oxygen concentration.

5. The oxygenation and temperature control system of the ex vivo multi-organ combined perfusion system according to claim 4, characterized in that, The controller is also used to determine whether there is an emergency based on the parameters collected by the sensor group and the derived physiological indicators, and to execute a rapid emergency response in the order of priority from high to low when there is an emergency, namely, insufficient oxygenation, unstable circulation, and abnormal organ function. Specifically, when the oxygen supply capacity evaluation parameter or blood oxygen saturation is lower than the preset reference range, an oxygenation deficiency response is triggered, which controls the increase of membrane lung oxygen concentration and perfusion flow rate; when the circulatory status evaluation parameter exceeds the preset reference range, a circulatory instability response is triggered, which controls the increase of perfusion flow rate; when the organ function status evaluation parameter exceeds the preset reference range, an organ function abnormality response is triggered, and a protective regulation strategy is executed according to the corresponding organ function status.

6. The oxygenation and temperature control system of the isolated multi-organ combined perfusion system according to claim 5, characterized in that, During the rapid emergency response, the controller continuously monitors the temperature and lung oxygenation status of each isolated organ; When the actual temperature of any excised organ exceeds the preset upper temperature threshold, the organ overheating response is triggered, controlling the heat exchanger to reduce the perfusion fluid temperature and controlling the cabin environment regulation module to reduce the air temperature inside the organ cabin. When the lung oxygenation status evaluation parameters are detected to deviate continuously from the preset reference range, it is determined that there is a risk of lung dysfunction, and the second humidity environment and mechanical ventilation parameters are controlled and adjusted.

7. The oxygenation and temperature control system of the isolated multi-organ combined perfusion system according to claim 1, characterized in that, The airway environment regulation module includes a ventilator and a ventilator humidifier installed on the ventilator's ventilation line. The ventilator humidifier is used to regulate the temperature and humidity of the respiratory gas entering the lungs to change the airway environment inside the lungs. The cabin environment regulation module includes a heating wire, a fan, and a cabin humidifier installed in the organ cabin.

8. The oxygenation and temperature control system of the isolated multi-organ combined perfusion system according to claim 1, characterized in that, The multi-organ cluster includes the heart, liver, lungs, and kidneys, which maintain natural vascular anatomical connections. The environmental parameter sensors include an interior temperature and humidity sensor installed in the organ compartment, a pipeline temperature probe installed on the perfusion circuit pipeline, and a flow meter installed at the outlet of the magnetic levitation pump. The physiological monitoring sensors include single-point temperature sensors respectively disposed on the surface of each organ, blood oxygen saturation sensors disposed in the perfusion circuit, electronic weighing modules disposed at the kidney excretion collection end, and ECG leads and arterial catheters respectively connected to the heart and the arterial side of the perfusion circuit.

9. The oxygenation and temperature control system of the isolated multi-organ combined perfusion system according to claim 8, characterized in that, The membrane lung is connected to a membrane lung gas mixer, which is used to regulate the oxygen and carbon dioxide concentrations in the membrane lung.

10. An adjustment method for adjusting the oxygenation temperature control system according to any one of claims 1-9, characterized in that, Includes the following steps: S1. The sensor group collects environmental parameters of the organ chamber, perfusion parameters of the perfusion circuit and physiological parameters of each organ in real time. Based on physiological rationality verification and comparison with historical baseline, data anomaly detection and fault tolerance processing are performed to obtain the final parameters and calculate the corresponding derived physiological indicators based on the final parameters. S2. Determine whether there is an abnormal state based on the final parameters and derived physiological indicators; When there is no abnormal state, a steady-state control command is generated; when there is an abnormal state, an emergency control command is generated. When generating a steady-state control command, a coordinated temperature control command is generated based on the difference between lung temperature and non-lung organ temperature and the deviation between the temperature of each organ and the target value. S3. According to the steady-state control command or emergency control command, control the heat exchanger to adjust the temperature of the infusion fluid, control the cabin environment adjustment module to adjust the cabin temperature and the first humidity environment, and control the airway environment adjustment module to adjust the second humidity environment of the airway inside the lungs.

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