Integrated extracorporeal organ perfusion circuit system and perfusion method

Abstract

The application discloses an integrated extracorporeal organ perfusion loop system and a perfusion method, and relates to the technical field of extracorporeal organ perfusion. The system comprises an organ box, a circulating pipeline, a liquid storage container, an oxygenator, a bile collection container and a controller. The circulating pipeline comprises a main outlet pipeline, a perfusion overflow outlet pipeline, a portal vein perfusion pipeline and a hepatic artery perfusion pipeline. Pressure sensors, flow sensors and blood gas monitoring components are arranged on the hepatic artery perfusion pipeline, the portal vein perfusion pipeline and the main outlet pipeline, respectively. The bile collection container is connected with a force sensor. The oxygenator is provided with a temperature control module, a temperature sensor and an oxygen concentration / flow rate sensor. The liquid storage container is connected with a liquid medicine infusion module. The controller can automatically adjust the oxygen flow of an oxygen generator, the temperature control module of the oxygenator, the flow of the perfusion pipeline and the infusion condition of the liquid medicine infusion module according to blood gas analysis results and multi-parameter monitoring data, realize linkage of blood gas monitoring and regulation, and improve the quality of organ preservation in vitro.

Description

Technical Field

[0001] This invention relates to the field of extracorporeal organ perfusion technology. Background Technology

[0002] Existing extracorporeal liver perfusion technology has the following drawbacks: First, the system components are scattered, with organ connection, perfusion fluid circulation, and parameter monitoring modules mostly being independent devices, leading to complex tubing connections and a high risk of leakage and tubing chaos. Second, parameter coordination is poor; the monitoring and control of parameters such as pressure, flow rate, and temperature are independent and cannot be synchronously adapted to the liver's metabolic state. For example, when the perfusion fluid temperature fluctuates, the oxygenation efficiency fails to adjust accordingly. Third, bile and perfusion fluid management is lacking, with a lack of real-time weight monitoring of bile collection and dynamic early warning of perfusion fluid levels, making it easy for insufficient perfusion fluid to cause liver hypoxia. Finally, blood gas monitoring and control are disconnected; existing circuits do not have dedicated sampling structures in key pipelines, making it difficult to conveniently collect perfusion fluid for blood gas analysis. Furthermore, there is a lack of an automatic control mechanism based on blood gas data, making it difficult to monitor the liver's metabolic state in real time, and making it easy for liver damage to occur due to acid-base imbalance and abnormal oxygen supply. Summary of the Invention

[0003] This invention aims to solve the problems of existing in vitro liver perfusion circuit components being scattered, having poor parameter coordination, lacking fluid management, and lacking blood gas monitoring and linkage control, and provides an integrated circuit device that integrates real-time monitoring of multiple parameters, coordinated control of perfusion fluid / oxygenation / temperature control, and linkage of blood gas analysis.

[0004] A first aspect of the present invention provides an integrated extracorporeal organ perfusion circuit system, comprising: Organ box for storing isolated liver, circulation tubing, fluid storage container, oxygenator, bile collection container, controller; The circulation tubing includes a main outlet tubing, an infusion overflow outlet tubing, a portal vein infusion tubing, and a hepatic artery infusion tubing; The inlet of the main outlet pipeline is connected to the inferior vena cava of the isolated liver, and the outlet of the main outlet pipeline is connected to the liquid storage container and the oxygenator respectively through a diversion component. A first pump body is provided on the main outlet pipeline. The outlet of the oxygenator is connected to the liquid storage container and the hepatic artery perfusion line respectively through a diversion component, and the oxygenator has a temperature control module; The hepatic artery perfusion tubing is connected to the hepatic artery of an isolated liver; The inlet of the perfusion overflow outlet pipeline is connected to the lower part of the organ box, and the outlet of the perfusion overflow outlet pipeline is connected to the liquid storage container. A liquid sensor and a second pump body are provided on the perfusion overflow outlet pipeline. The outlet of the liquid storage container is connected to the portal vein perfusion pipeline. A liquid level sensor is provided on the liquid storage container, and a liquid medicine infusion module is also connected to the liquid storage container; The portal vein perfusion pipeline is connected to the portal vein of the ex vivo liver; Blood gas monitoring components are respectively provided on the main outlet pipeline, the portal vein perfusion pipeline and the hepatic artery perfusion pipeline; The bile collection container is connected to the organ box through a force sensor; A controller controls the device.

[0005] The blood gas monitoring component can quickly detect the blood gas indexes of the perfusion fluid and detect core parameters such as HCT, pH, PaO2, and PaCO2. The blood gas analysis result is input into the controller through a data interface, and the controller can automatically adjust the parameters of relevant components based on the blood gas analysis result to realize the linkage of blood gas monitoring and regulation.

[0006] In some preferred embodiments, a pressure sensor, a flow sensor and a clamp valve are provided on the portal vein perfusion pipeline; a pressure sensor, a flow sensor and a clamp valve are provided on the hepatic artery perfusion pipeline. The pressure sensor is used to monitor the perfusion pressure in real time, the flow sensor is used to monitor the perfusion flow in real time, and the clamp valve is used to adjust the perfusion flow, so as to realize the precise control of the perfusion pressure and flow and ensure that the organ obtains appropriate perfusion conditions.

[0007] In some preferred embodiments, the liquid medicine infusion module includes an injection pump and an external liquid medicine and / or perfusion fluid. The injection pump is used to accurately infuse drugs or supplementary fluids, and the infusion rate can be automatically adjusted according to the monitoring results.

[0008] In some preferred embodiments, an oxygen generator is connected to the oxygenator. An oxygen concentration / flow rate sensor is provided at the air outlet of the oxygen generator, and the oxygenator has a temperature sensor. The oxygen generator is used to provide the oxygen required for oxygenation. The oxygen concentration / flow rate sensor is used to monitor the concentration and flow rate of oxygen in real time, and the temperature sensor is used to monitor the temperature of the perfusion fluid in the oxygenator. The controller can automatically adjust the oxygen flow of the oxygen generator and the temperature control module of the oxygenator according to the monitoring results to realize the precise control of the oxygenation parameters and temperature.

[0009] In some preferred embodiments, the first pump body is a centrifugal pump, the second pump body is a roller pump, and the shunt component is a three-way joint. The centrifugal pump has the advantages of large flow rate and small damage to blood cells and is suitable as the main circulation power source. The roller pump has the advantages of precise flow control and good sealing performance and is suitable for recovering the overflow liquid in the organ box. The three-way joint has a simple structure, reliable connection and is convenient for realizing the shunt of the perfusion fluid.

[0010] Another aspect of the present invention provides a perfusion method for an integrated extracorporeal organ perfusion circuit system according to a first aspect of the present invention, the method comprising: The initial filling fluid is injected into the filling circuit through the gravity pre-filling function of the storage container to purge the air from the pipeline; Start the oxygenator's temperature control module to adjust the initial infusion fluid temperature to the target temperature; Start the first and second pumps. The first pump pumps the initial perfusion fluid into the oxygenator and the storage container, and the second pump pumps the secretions and exudates from the isolated liver into the storage container. After the initial perfusion fluid entering the oxygenator is oxygenated, a portion of the oxygenated perfusion fluid enters the storage container, and the remaining oxygenated perfusion fluid is perfused into the hepatic artery through the hepatic artery perfusion tubing. After the secretions and exudates of the isolated liver, the initial perfusion fluid, and the oxygenated perfusion fluid are mixed in the reservoir, the portal vein is perfused through the portal vein perfusion tubing. Blood gas monitoring components are used to monitor blood gas parameters on the main outlet line, portal vein perfusion line, and hepatic artery perfusion line. A force sensor was used to monitor the amount of bile secreted from an isolated liver.

[0011] In some preferred embodiments, blood gas parameters include hematocrit (HCT), pH, PaO2, and PaCO2. HCT, or hematocrit, represents the proportion of red blood cells in the blood and directly determines the blood's actual oxygen-carrying capacity. pH reflects the acid-base balance of the perfusion fluid; too low or too high pH can lead to acidosis or alkalosis. PaO2 represents the partial pressure of oxygen in arterial blood; too low PaO2 indicates insufficient oxygen supply. PaCO2 represents the partial pressure of carbon dioxide in arterial blood; too low or too high PaCO2 indicates inadequate or excessive ventilation.

[0012] In some preferred embodiments, when the hematocrit (HCT) in the blood gas analysis results of the main outlet line and / or portal vein perfusion line is lower than a preset threshold, red blood cell concentrate is infused through the drug infusion module of the reservoir to raise the HCT back above the preset target value. When the HCT is too low, the oxygen-carrying capacity of the perfusion fluid decreases, which may lead to organ hypoxia. By automatically infusing red blood cell concentrate, the problem of low HCT can be corrected in a timely manner, ensuring that the organ receives sufficient oxygen supply.

[0013] In some preferred embodiments, when the PaO2 in the blood gas analysis results of the hepatic artery perfusion line or portal vein perfusion line is lower than a preset target value, the oxygen concentrator is activated to increase the oxygen flow rate. Low PaO2 indicates insufficient oxygen supply; by automatically increasing the oxygen flow rate of the oxygen concentrator, the oxygenation level of the perfusion fluid can be improved, ensuring that the organ receives adequate oxygen.

[0014] In some preferred embodiments, when the PaCO2 in the blood gas analysis of the main outlet tubing is higher than a preset target value, and the force sensor detects that the hourly bile secretion is lower than a preset target value, the flow rates of the portal vein perfusion tubing and the hepatic artery perfusion tubing are reduced. A persistently elevated PaCO2 and decreased bile secretion indicate abnormal organ metabolic function; in this case, the perfusion flow rate should be appropriately reduced to alleviate the metabolic burden on the organs and prevent further damage.

[0015] In some preferred embodiments, when the pH value of the blood gas analyzer in the main outlet pipeline is below 7.2, the ventilation flow rate of the oxygenator is increased, and sodium bicarbonate is simultaneously infused through the drug delivery module in the storage container. When the pH value of the blood gas analyzer in the main outlet pipeline is above 7.4, the ventilation flow rate of the oxygenator is decreased. Increasing the ventilation flow rate of the oxygenator accelerates the diffusion of CO2 from the perfusion solution to the gas phase, thereby increasing CO2 emissions and raising the pH. Conversely, decreasing the ventilation flow rate reduces CO2 emissions and lowers the pH.

[0016] In some preferred embodiments, when the force sensor detects that the hourly bile secretion is less than a preset critical value, ursodeoxycholic acid is infused through the drug infusion module of the storage container. Bile secretion is an important indicator for assessing liver function. By monitoring bile secretion in real time, abnormal organ metabolic function can be detected in a timely manner, and corresponding regulatory measures can be taken. Under normal perfusion, a stable bile secretion rate of 10–30 mL / h indicates good hepatocyte function and a balance between oxygen supply and metabolism. If the secretion rate is less than 5 mL / h, it suggests hepatocyte damage (such as ischemia-hypoxia, insufficient perfusion, acid-base imbalance), which is an early warning signal. If the secretion rate drops sharply or stops, it often indicates irreversible liver damage, requiring urgent adjustment of perfusion parameters or discontinuation of treatment. When the bile secretion rate is less than 5 mL / h, drugs such as ursodeoxycholic acid need to be infused to promote bile secretion and protect hepatocytes.

[0017] In some preferred embodiments, the target temperature of the infusion fluid is 32-37°C.

[0018] In some preferred embodiments, the preset threshold value for HCT is 28%, and the preset target value for HCT is 30-35%. If HCT is below 28%, it indicates that the blood's oxygen-carrying capacity is insufficient, which will lead to liver ischemia and hypoxia. The system will automatically trigger the infusion of concentrated red blood cells until it is restored to the target range, ensuring the oxygen supply needs of liver perfusion.

[0019] In some preferred embodiments, the preset target value for PaO2 is 80 mmHg.

[0020] In some preferred embodiments, the preset target value for PaCO2 is 35-45 mmHg.

[0021] In some preferred embodiments, the preset critical value for bile secretion is 5 mL / h, and the preset target value for bile secretion is 10-30 mL / h.

[0022] The above parameter ranges are optimal ranges determined based on extensive clinical practice and experimental studies, which can provide the most suitable in vitro perfusion environment for organs, significantly prolong organ preservation time and improve organ function.

[0023] Compared with the prior art, the present invention has the following advantages: (1) By setting up blood gas monitoring components on the main outlet pipeline, portal vein perfusion pipeline and hepatic artery perfusion pipeline respectively, combined with sensors, the blood oxygenation status, perfusion pressure, perfusion flow rate, perfusion fluid temperature, bile secretion and other comprehensive real-time monitoring is realized, which provides a data basis for multi-parameter coordinated regulation, and can promptly detect abnormal changes in organ metabolic status and take corresponding regulatory measures.

[0024] (2) An automatic control mechanism based on blood gas analysis was established. The controller can automatically adjust the oxygen flow rate of the oxygen generator, the temperature control module of the oxygenator, the flow rate of the perfusion pipeline and the infusion rate of the drug infusion module according to the blood gas analysis results and multi-parameter monitoring data. This realizes the linkage between blood gas monitoring and control, and can automatically maintain key parameters such as pH, PaO2, PaCO2 and HCT within the optimal range, avoiding organ damage caused by acid-base imbalance, abnormal oxygen supply and low hematocrit.

[0025] (3) The present invention maintains the portal vein oxygen partial pressure PvO2 within the range of 40%-80%, thus avoiding tissue damage caused by hyperoxygenated blood in the portal vein. Attached Figure Description

[0026] Figure 1 This is a schematic diagram of an embodiment of the present invention.

[0027] Figure label: Organ box 1, main outlet line 101, perfusion overflow outlet line 102, portal vein perfusion line 103, hepatic artery perfusion line 104, force sensor 2, level sensors 3 and 21, roller pump 4, centrifugal pump 5, reservoir bag 6, syringe pump 7, tube clamp 8, flow sensors 9-1 and 9-2, clamp valve 10-1 and 10-2, oxygen generator 11, oxygenator 12, variable temperature water tank 13, temperature sensor 14, pressure sensor 15-1 and 15-2, blood gas monitoring components 16-1, 16-2 and 16-3, tee connectors 18-1 and 18-2, bile collection bag 19, oxygen concentration / flow rate sensor 20. Detailed Implementation

[0028] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. However, the embodiments described below are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0029] Figure 1 An integrated ex vivo liver perfusion circuit system is shown, including an organ box 1 for storing the ex vivo liver, circulation tubing, a reservoir bag 6, an oxygenator 12, a bile collection bag 19, and a controller (not shown).

[0030] Organ cartridge 1 is equipped with quick-connect heads for the hepatic artery (HA), portal vein (PV), and inferior vena cava (IVC), allowing for rapid connection to the corresponding vessels in the isolated liver and avoiding time-consuming tubing connections. The bottom of organ cartridge 1 has a fluid collection tank for collecting secretions and exudates from the isolated liver during perfusion.

[0031] The circulation tubing includes a main outlet tubing 101, an infusion overflow outlet tubing 102, a portal vein infusion tubing 103, and a hepatic artery infusion tubing 103.

[0032] The inlet of the main outlet pipe 101 is connected to the inferior vena cava of the isolated liver. The outlet of the main outlet pipe is connected to the reservoir bag 6 and the oxygenator 12 via a three-way connector 18-1. The flow ratio between the flow path to the reservoir bag and the flow path to the oxygenator is controlled at 1:4. A centrifugal pump 5 is installed on the main outlet pipe. The centrifugal pump 5 is used to pump the perfusion fluid into the oxygenator 12 and the reservoir bag 6 to provide circulation power. The centrifugal pump 5 has a speed range of 0-5000 rpm and a flow rate range of 0-5 L / min, which can provide circulation power for the entire perfusion circuit.

[0033] The inlet of the oxygenator 12 is connected to the main outlet pipe 101, and the outlet of the oxygenator 12 is connected to the reservoir bag 6 and the hepatic artery perfusion pipe 104 via a tee connector 18-2. The flow ratio between the flow path to the reservoir bag and the flow path to the hepatic artery perfusion pipe is 1:4, achieving oxygenation of the perfusion fluid. The heat exchange interface of the oxygenator 12 is externally connected to a variable-temperature water tank 13 via inlet and outlet water pipes. The variable-temperature water tank contains circulating water, which exchanges heat with the perfusion fluid through the heat exchange channel of the oxygenator, thereby regulating the temperature of the perfusion fluid. The variable-temperature water tank is equipped with a heater and a cooler, capable of controlling the temperature of the circulating water within the range of 10-40 degrees Celsius, with a temperature control accuracy of ±0.5℃. The outlet of the oxygen generator 11 is connected to the inlet of the oxygenator 12, providing the oxygen required for oxygenation. The oxygen concentrator 11 uses pressure swing adsorption (PSA) technology to generate oxygen, with an oxygen concentration of 90-95% and a maximum oxygen flow rate of 5 liters per minute.

[0034] The hepatic artery perfusion line 104 is connected to the hepatic artery of the isolated liver.

[0035] The inlet of the perfusion overflow outlet pipe 102 is connected to the bottom of the organ box 1, and the outlet of the perfusion overflow outlet pipe is connected to the storage bag 6. A liquid sensor 3 and a ball pump 4 are installed on the perfusion overflow outlet pipe. The ball pump is installed downstream of the liquid sensor. The ball pump is a peristaltic pump with a speed range of 0-200 rpm and a flow rate range of 0-5 L / min. The liquid sensor 3 is used to detect the liquid level in the organ box and control the ball pump 4 to deliver the liquid to the storage bag 6.

[0036] The outlet of the reservoir bag 6 is connected to the portal vein perfusion tubing 103. The reservoir bag has a capacity of 2000-3000 mL. As a buffer storage unit for the perfusion fluid, the reservoir bag 6 is equipped with an ultrasonic level sensor 21 to monitor the remaining perfusion fluid level in real time and trigger an early warning. It also serves as a key component for pre-filling, utilizing gravity for pre-filling to vent air from the perfusion circuit. During pre-filling, the reservoir bag is suspended approximately 1 meter above the organ box, and the outlet valve of the reservoir bag is opened. The perfusion fluid flows into the tubing under gravity, expelling air from the tubing. The reservoir bag contains a mixture of three liquids: a portion of unoxygenated perfusion fluid that has passed through a centrifugal pump, a portion of oxygenated perfusion fluid that has passed through an oxygenator, and overflow fluid recovered by a roller pump.

[0037] The portal vein perfusion line 103 is connected to the portal vein of the isolated liver.

[0038] The controller controls the device and employs a programmable logic controller (PLC).

[0039] Drug infusion module

[0040] A drug infusion module is connected to the reservoir bag 6. The module includes an infusion pump 7, tubing clamps 8, and externally connected drug solutions and / or perfusion solutions. Drug solutions include concentrated erythrocytes, sodium bicarbonate, ursodeoxycholic acid, etc. The infusion pump 7 is connected to the reservoir bag 6 via the tubing clamps 8 and is used to infuse vasoactive drugs, hormones, or nutrients into the perfusion circuit. The infusion rate can be adjusted based on parameter monitoring results. The infusion pump is a plunger-type pump with an injection rate range of 0.1-100 mL / hour. The infusion rate of the drug infusion module can be automatically adjusted based on parameter monitoring results.

[0041] Multi-parameter monitoring module

[0042] Two pressure sensors, 15-1 and 15-2, are installed at the liver inlet of the portal vein perfusion line 103 and the hepatic artery perfusion line 104, respectively, to monitor the inlet pressure in the liver in real time. The pressure sensors are piezoresistive silicon pressure sensors. The target pressure for the hepatic artery perfusion line is 20-40 mmHg (physiological arterial pressure range), the critical pressure is 15-20 mmHg or 40-50 mmHg, and the abnormal pressure is <15 mmHg or >50 mmHg. The target pressure for the portal vein perfusion line is 8-12 mmHg (physiological portal vein pressure range), the critical pressure is 6-8 mmHg or 12-15 mmHg, and the abnormal pressure is <6 mmHg or >15 mmHg.

[0043] Two flow sensors, 9-1 and 9-2, are installed downstream of clamp valves 10-1 and 10-2 in the portal vein perfusion line and hepatic artery perfusion line, respectively, to monitor the influent flow to the liver. Ultrasonic flow meters are used as the flow sensors. The target flow rate for the hepatic artery perfusion line is 250-500 mL / min, the critical flow rate is 150-250 mL / min or 500-600 mL / min, and the abnormal flow rate is <150 mL / min or >600 mL / min. The target flow rate for the portal vein perfusion line is 500-1500 mL / min, the critical flow rate is 300-500 mL / min or 1500-1800 mL / min, and the abnormal flow rate is <300 mL / min or >1800 mL / min.

[0044] Three blood gas monitoring components, 16-1, 16-2, and 16-3, are installed on the main outlet line, portal vein perfusion line, and hepatic artery perfusion line, respectively, to monitor oxygenation and blood status in real time. Blood gas monitoring is performed through periodic sampling and testing, with core parameters including HCT, pH, PaO2, and PaCO2. Blood gas analysis results are automatically entered into the controller via a data interface. The blood gas monitoring components can be configured by combining multiple sensors; for example, a fluorescence optical sensor can be used to detect pH, PaO2, and PaCO2, while an optical reflection / transmission sensor can be used to detect HCT. Alternatively, commercially available testing platforms can be used.

[0045] A bile collection bag 19 is attached to the hook of the force sensor 2 to monitor the weight of bile secretion in real time. The force sensor is a strain gauge type. The bile collection bag is connected to the bile duct connector inside the organ box via a thin tube, allowing bile secreted by the liver to flow into the bile collection bag through the tube. The force sensor transmits the weight signal of the bile collection bag to the controller in real time, and the controller calculates the bile secretion volume based on the weight change. The target secretion volume is 10-30 mL / h, the critical secretion volume is 5-10 mL / h or 30-40 mL / h, and the abnormal secretion volume is <5 mL / h or >40 mL / h.

[0046] Temperature sensor 14 is installed at the outlet end of oxygenator 12 to monitor the temperature of the infusion fluid, with a target temperature of 32-37℃.

[0047] The oxygen concentration / flow rate sensor 20 is installed at the outlet of the oxygen generator 11 to monitor the oxygen concentration and flow rate in real time.

[0048] The controller connects all sensors and actuators via data cables, including centrifugal pump 5, roller pump 4, pressure sensors 15-1 and 15-2, flow sensors 9-1 and 9-2, pinch valves 10-1 and 10-2, blood gas monitoring components 16-1, 16-2 and 16-3, temperature sensor 14, level sensors 3 and 21, force sensor 2, oxygen concentration / flow rate sensor 20, syringe pump 7, variable temperature water tank 13, oxygen generator 11, and oxygenator 12. The controller is based on a PID control algorithm and automatically adjusts the operating parameters of each actuator according to the monitoring results of multiple parameters. The controller's control logic includes: automatically adjusting the opening of clamp valves 10-1 and 10-2 based on the monitoring results of pressure sensors 15-1 and 15-2 to maintain the perfusion pressure of the portal vein and hepatic artery within the target range; automatically adjusting the speed of centrifugal pump 5 based on the monitoring results of flow sensors 9-1 and 9-2 to maintain the perfusion flow rate of the hepatic artery and portal vein within the target range; automatically adjusting the heater or cooler of the variable temperature water tank 13 based on the monitoring results of temperature sensor 14 to maintain the perfusion fluid temperature within the target range; and regulating the drug infusion module, perfusion flow rate, oxygen generator 11 output, and oxygenator 12 output based on the monitoring results of blood gas monitoring components 16-1, 16-2, and 16-3.

[0049] Pre-charge and infusion start-up

[0050] The reservoir bag has a capacity of 2000mL. For the initial pre-fill, use 500ml of 5% human serum albumin, filling the disposable perfusion circuit by gravity until the reservoir bag reaches the bottom one-third level. After albumin pre-fill, add 3 units of leukocyte-reduced packed red blood cells matched to the donor's blood type through the interface on the reservoir bag. After this, the reservoir should reach at least three-quarters full. If the level is insufficient, add an additional 5% human serum albumin until the target level is reached. During pre-filling, open all vent valves on the tubing to ensure complete removal of air. After pre-filling, close all vent valves. Start the variable temperature water tank and adjust the perfusion fluid temperature to 37℃; start the oxygen generator and adjust the oxygen saturation at the oxygenator outlet to 97%; start the centrifugal pump and roller pump, and adjust the corresponding flow rate and pressure to the target range with the clamp valve. The portal vein flow rate is 1000mL / min and the pressure is 10mmHg; the hepatic artery flow rate is 300mL / min and the pressure is 30mmHg.

[0051] Real-time control during infusion

[0052] After pre-charging and startup are completed, the filling and real-time monitoring phase begins.

[0053] Two flow sensors monitor the perfusion flow rate of the portal vein and hepatic artery in real time, with data updated every 200 ms. Two pressure sensors monitor the perfusion pressure of the portal vein and hepatic artery in real time, with data updated every 200 ms. A temperature sensor monitors the temperature of the perfusion fluid in real time, with data updated every 200 ms. A level sensor monitors the remaining perfusion fluid level in the reservoir bag in real time, with data updated every 200 ms. A force sensor monitors the weight of the bile collection bag in real time, with data updated every 200 ms. Three blood gas monitoring components collect blood gas samples from the perfusion fluid every 2 seconds for analysis, detecting HCT, pH, PaO2, and PaCO2. All monitoring data is automatically transmitted to the controller.

[0054] When the injection pressure exceeds or falls below the target pressure, the injection pressure is brought back to the target pressure by reducing or increasing the flow rate.

[0055] When the temperature of the injection fluid exceeds or falls below the target temperature, the temperature of the circulating water is adjusted by regulating the heater or cooler of the variable temperature water tank to raise or lower the temperature, thereby bringing the temperature of the injection fluid back to the target temperature range.

[0056] When the blood gas monitoring module of the main outlet line or the portal vein perfusion line detects that the hematocrit (HCT) has dropped to 28%, erythrocyte concentrate is infused via the infusion pump to raise the HCT back to 32%. The controller automatically starts the infusion pump to infuse the erythrocyte concentrate at a controlled rate. During the infusion, the controller continuously monitors changes in HCT, and automatically stops the infusion pump when the HCT rises to 32%.

[0057] When the force sensor detects an increase of less than 5 mL in bile weight within 1 hour, ursodeoxycholic acid is infused via an injection pump to stimulate bile secretion. Once the bile secretion rate reaches more than 5 mL / hour, the infusion is stopped.

[0058] If the blood gas monitoring components of the portal vein perfusion line or the hepatic artery perfusion line detect that the PaO2 of the blood entering the liver is lower than 80 mmHg, the controller will immediately drive the oxygen generator to increase the oxygen flow rate. At the same time, it will check the perfusion flow rate of the portal vein perfusion line and the hepatic artery perfusion line. If the flow rate is lower than the target lower limit, it may lead to insufficient oxygen supply, and the flow rate should be increased first.

[0059] If the blood gas monitoring component of the main outlet line detects a pH below 7.2 (acidosis) in the liver gas output, the controller simultaneously increases the CO2 output of the oxygenator by 20%, and precisely infuses sodium bicarbonate via an infusion pump to correct the acid-base imbalance, raising the pH back above 7.2. Specifically, the infusion pump infuses 8.4% sodium bicarbonate at a rate of 1-2 ml / min, monitoring pH changes every 30 seconds during the infusion. Once the pH rises to 7.25-7.3, the CO2 output can be adjusted back to 110% of the baseline value. If the pH is above 7.4 (alkalosis), the CO2 output of oxygenator 12 is reduced by 15%, lowering the pH below 7.4. Specifically, no additional acidic solution infusion is required; adjustment is achieved solely through CO2 output. The pH is monitored every minute, and once the pH falls to 7.35-7.4, the CO2 output is restored to the baseline value.

[0060] If the blood gas monitoring component of the main outlet line detects that PaCO2 is consistently higher than 45 mmHg, combined with bile secretion of less than 10 mL / h, it indicates abnormal liver metabolic function. At this time, the system will automatically reduce the perfusion flow rate of the hepatic artery and portal vein by 10-15% gradient. After reducing the perfusion flow rate, the metabolic burden on the liver is reduced, and PaCO2 returns to the normal range.

[0061] This invention can achieve real-time monitoring and risk warning of liver status based on blood gas analysis results, combined with data such as pressure, flow rate, and bile secretion, thus ensuring the viability of ex vivo livers.

Claims

1. An integrated extracorporeal organ perfusion circuit system, characterized in that, include: Organ box for storing isolated liver (1), circulation tubing, liquid storage container (6), oxygenator (12), bile collection container (19), controller; The circulation pipeline includes a main outlet pipeline (101), an infusion overflow outlet pipeline (102), a portal vein infusion pipeline (103), and a hepatic artery infusion pipeline (104); The inlet of the main outlet pipeline (101) is connected to the inferior vena cava of the isolated liver, and the outlet of the main outlet pipeline (101) is connected to the liquid storage container (6) and the oxygenator (12) respectively through the diversion assembly (18-1). A first pump body (5) is provided on the main outlet pipeline (101). The outlet of the oxygenator (12) is connected to the liquid storage container (6) and the hepatic artery perfusion line (104) respectively through the diversion assembly (18-2), and the oxygenator (12) has a temperature control module; The hepatic artery perfusion line (104) is connected to the hepatic artery of the isolated liver; The inlet of the perfusion overflow outlet pipe (102) is connected to the lower part of the organ box (1), and the outlet of the perfusion overflow outlet pipe (102) is connected to the liquid storage container (6). A liquid sensor (3) and a second pump body (4) are provided on the perfusion overflow outlet pipe (102). The outlet of the liquid storage container (6) is connected to the portal vein infusion line (103). A liquid level sensor (21) is provided on the liquid storage container (6). A drug infusion module is also connected to the liquid storage container (6). The portal vein perfusion line (103) is connected to the portal vein of the isolated liver; The main outlet pipeline (101), the portal vein perfusion pipeline (103), and the hepatic artery perfusion pipeline (104) are respectively equipped with blood gas monitoring components (16-1, 16-2, 16-3); The bile collection container (19) is connected to the organ box (1) via a force sensor (2); Controller, which controls the device.

2. The integrated extracorporeal organ perfusion circuit system according to claim 1, characterized in that, The portal vein perfusion line (103) is equipped with a pressure sensor (15-1), a flow sensor (9-1), and a clamp valve (10-1); the hepatic artery perfusion line (104) is equipped with a pressure sensor (15-2), a flow sensor (9-2), and a clamp valve (10-2).

3. The integrated extracorporeal organ perfusion circuit system according to claim 1, characterized in that, The drug infusion module includes an injection pump (7) and an external drug solution and / or infusion solution.

4. The integrated extracorporeal organ perfusion circuit system according to claim 1, characterized in that, The oxygenator (12) is connected to an oxygen generator (11), and the oxygen generator (11) is equipped with an oxygen concentration / flow rate sensor (20) at its outlet. The oxygenator (12) is equipped with a temperature sensor (14).

5. The integrated extracorporeal organ perfusion circuit system according to claim 1, characterized in that, The first pump body (5) is a centrifugal pump, the second pump body (4) is a roller pump, and the flow splitting components (18-1, 18-2) are tee connectors.

6. A perfusion method for an integrated extracorporeal organ perfusion circuit system according to any one of claims 1-5, the method comprising: The initial injection fluid is injected into the injection circuit through the gravity pre-filling function of the liquid storage container (6) to purge the air from the pipeline; Start the temperature control module of the oxygenator (12) to adjust the temperature of the initial infusion fluid to the target temperature; Start the first pump (5) and the second pump (4). The first pump (5) pumps the initial perfusion fluid into the oxygenator (12) and the storage container (6). The second pump (4) pumps the secretions and exudates from the isolated liver into the storage container (6). After the initial perfusion fluid entering the oxygenator (12) is oxygenated, a portion of the oxygenated perfusion fluid enters the storage container (6), and the remaining oxygenated perfusion fluid is perfused into the hepatic artery through the hepatic artery perfusion line (104). The secretions and exudates of the isolated liver, the initial perfusion fluid and the oxygenated perfusion fluid are mixed in the storage container (6) and then perfused into the portal vein through the portal vein perfusion line (103); Blood gas monitoring components (16-1, 16-2, 16-3) on the main outlet line, portal vein perfusion line, and hepatic artery perfusion line are used to monitor blood gas parameters; The control force sensor (2) monitors the amount of bile secreted from the isolated liver.

7. The infusion method according to claim 6, characterized in that, The blood gas parameters include HCT, pH, PaO2, and PaCO2.

8. The infusion method according to claim 7, characterized in that: When the hematocrit (HCT) in the blood gas analysis results of the main outlet line (101) and / or the portal vein perfusion line (103) is lower than the preset threshold, concentrated red blood cells are infused through the drug infusion module of the reservoir (6) to raise the HCT back to the preset target value; and / or, When the PaO2 in the blood gas analysis results of the portal vein perfusion line (103) or the hepatic artery perfusion line (104) is lower than the preset target value, the oxygen generator (11) is activated to increase the oxygen flow rate; and / or, When the PaCO2 in the blood gas analysis of the main outlet line (101) is higher than the preset target value, and the force sensor (2) detects that the hourly bile secretion is less than the preset target value, the flow rates of the portal vein perfusion line (103) and the hepatic artery perfusion line (104) are reduced; and / or, When the pH of the blood gas test result from the main outlet pipeline (101) is lower than 7.2, the ventilation flow rate of the oxygenator (12) is increased, and sodium bicarbonate is simultaneously infused through the drug delivery module of the storage container (6). When the pH of the blood gas test result from the main outlet pipeline (101) is higher than 7.4, the ventilation flow rate of the oxygenator (12) is decreased; and / or, When the force sensor (2) detects that the hourly bile secretion is less than the preset critical value, ursodeoxycholic acid is infused through the drug infusion module of the storage container (6).

9. The perfusion method of the integrated extracorporeal organ perfusion circuit system according to claim 8, characterized in that, The target temperature for the infusion fluid is 32-37℃; The preset threshold value for HCT is 28%, and the preset target value for HCT is 30-35%. The preset target value for PaO2 is 80 mmHg; The preset target value for PaCO2 is 35-45 mmHg; The preset critical value for bile secretion is 5 mL / h, and the preset target value for bile secretion is 10-30 mL / h.

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