An extracorporeal organ perfusion system

Abstract

The application discloses an extracorporeal organ perfusion system, which comprises a perfusion main loop and an inflammation factor removing sub-loop; the perfusion main loop comprises a sterile organ storage container, a venous blood gas monitoring device, a venous pressure monitoring device, a perfusion liquid storage tank, a main loop pump, a heat exchanger, a gas exchanger, a white blood cell filter, a bubble filter, an arterial pressure monitoring device, a flow monitoring device, a temperature monitoring device, an arterial blood gas monitoring device and a biological sensor which are sequentially connected and form a circulation loop; the inflammation factor removing sub-loop comprises a purification sub-loop input pump, an inflammation factor filter, a perfusion exchange liquid storage tank and a purification sub-loop output pump which are sequentially connected; the output end of the purification sub-loop output pump is in communication with the input end of the perfusion liquid storage tank; the application has the advantages that the inflammation factors in the perfusion loop can be effectively removed, the perfusion liquid can be effectively reused, and various physiological parameter indexes in the perfusion process can be monitored and fed back in real time.

Description

Technical Field

[0001] This invention relates to an organ transplantation device, specifically an extracorporeal organ perfusion system, belonging to the field of organ transplantation devices. Background Technology

[0002] In recent years, with the continuous development of organ transplantation technology, the success rate and survival rate of organ transplantation surgeries have significantly improved, and organ transplantation has become one of the main methods for treating various serious organ diseases. However, the global demand for organ transplants far exceeds the number of donated organs, and the shortage of donor organs is becoming increasingly prominent. To address this shortage, some expanded donor organ admission criteria have been gradually implemented internationally. Furthermore, problems such as organ edema, rejection, infection, and transplant dysfunction caused by inflammatory factors released from donor organs during transplantation can significantly affect the success rate and survival rate of organ transplantation surgeries. These problems place higher demands on the preservation, repair, and transportation of organ transplant donors; therefore, expanding the source of donor organs and improving organ quality are major challenges that need to be overcome.

[0003] With the increasing demand for organ preservation and transport, extracorporeal organ perfusion technology has been gradually developed and applied clinically. Currently, my country relies heavily on imported inflammatory factor filtration devices, and domestic maturity is relatively low. Whether imported or domestically produced, inflammatory factor filtration devices, while perfusing and adsorbing cytokines and inflammatory mediators, also filter some of the effective perfusion components. Continuous filtration leads to changes in the composition of the perfusion fluid during the perfusion process, which negatively impacts organ perfusion and repair, requiring continuous replenishment of the perfusion fluid, thus increasing operational difficulty and fluid consumption. Domestically, there are no integrated extracorporeal organ perfusion devices; instead, systems are pieced together using ventilators, ECMO machines, etc., resulting in high operating costs and potential congestion of medical equipment for critically ill patients. Furthermore, these temporary perfusion systems pieced together from various devices often have limited functionality and lack the ability to filter inflammatory factors. Ischemia-reperfusion injury is an unavoidable component of organ transplantation, and extracorporeal organ perfusion simulates the ischemia-reperfusion process during organ transplantation, characterized by the release of inflammatory mediators into the perfusion fluid. Over time, inflammatory mediators accumulate in the perfusion fluid, leading to a severe cytokine storm. This not only causes ongoing damage to ex vivo organs but is also a major cause of primary graft dysfunction after organ transplantation, and is one of the main factors limiting the duration of organ perfusion. Currently used traditional extracorporeal organ perfusion devices typically involve only one main perfusion circuit and lack inflammatory factor clearance capabilities. During perfusion, inflammatory factors are excessively released, damaging cells and tissues and subsequently triggering primary graft dysfunction. Summary of the Invention

[0004] The purpose of this invention is to design an extracorporeal organ perfusion system that can effectively remove inflammatory factors in the perfusion circuit, while enabling the perfusion fluid to be reused effectively, thereby reducing the cost of use, and can monitor and provide feedback on various physiological parameters during the perfusion process in real time.

[0005] The technical solution of this invention is as follows:

[0006] An extracorporeal organ perfusion system includes a perfusion main circuit and an inflammatory factor clearance sub-circuit;

[0007] The perfusion main circuit includes a sterile organ storage container, a venous blood gas monitoring device, a venous pressure monitoring device, a perfusion fluid storage tank, a main circuit pump, a heat exchanger, a gas exchanger, a leukocyte filter, a bubble filter, an arterial pressure monitoring device, a flow monitoring device, a temperature monitoring device, an arterial blood gas monitoring device, and a biosensor connected in sequence, forming a circulation loop.

[0008] The inflammatory factor removal sub-circuit includes a purification sub-circuit input pump, an inflammatory factor filter, an infusion exchange fluid storage tank, and a purification sub-circuit output pump connected in sequence. The input end of the purification sub-circuit input pump is located between the leukocyte filter and the bubble filter; the output end of the purification sub-circuit output pump is connected to the input end of the infusion fluid storage tank.

[0009] By introducing an inflammatory factor clearance sub-circuit, the inflammatory factor filter continuously filters cytokines and other inflammatory mediators in the purification sub-circuit, effectively reducing the amount of cytokines and inflammatory mediators, thereby effectively preserving and repairing organs. In addition, while the inflammatory factor filtration device is installed in the inflammatory factor clearance sub-circuit, a perfusion exchange fluid reservoir is introduced. The perfusion fluid purified by the inflammatory factors enters the perfusion exchange fluid reservoir, where it neutralizes the components of the perfusion exchange fluid, thus ensuring the relative stability of the perfusion fluid composition in the main perfusion circuit while filtering cytokines and inflammatory factors.

[0010] The sterile organ storage container is used for storing organs. Preferably, the sterile organ storage container is made of a transparent or light-colored material to facilitate observation of the excised organ and organ compartment during organ perfusion. Furthermore, when the stored organ is a lung, the sterile organ storage container is also connected to a medical ventilator.

[0011] The sterile organ storage container is equipped with a weight monitoring device, which is communicatively connected to the control system. This device monitors the weight of the container in real time throughout the perfusion process and displays the real-time values ​​in the control system. Real-time weight monitoring helps determine whether edema has occurred in the perfused organ. If the weight monitoring value increases within a preset allowable range while the perfusion flow rate remains relatively stable, the perfusion process continues as normal. If the weight monitoring value increases beyond the preset allowable range, the system will alert the relevant equipment operators to take appropriate intervention measures or stop the perfusion.

[0012] The control system includes a controller connected to one or more sensors, pump assemblies, and heat exchanger assemblies in the system.

[0013] The control system can display various parameters under the controller's data acquisition and data management functions through a user interface, and feeds back the input parameters to the controller to control various components in the perfusion circuit. The controller has functions including data acquisition, data management, control of pump components, and control of heat exchanger components. The data acquisition function is implemented by the controller communicating with one or more sensors; the data management function is used to store and maintain data related to the operation of the organ perfusion system and to the excised organ; the pump component control function is used to control the pumping of perfusion fluid during perfusion, and the pump component includes a main circuit pump, a purification secondary circuit input pump, a first infusion pump, and a second infusion pump. The heat exchanger control function is used to heat / cool the perfusion fluid during perfusion.

[0014] The control system can consist of one or more open or closed feedback systems, each of which can independently perform some control functions. The control system can be a general-purpose computer system with data monitoring, feedback, and control functions, or it can be a specially designed control system. The control system can be, for example, OCS from TransMedics, Inc. TM The control system in Lung System or other self-developed control systems with similar functions.

[0015] The venous blood gas monitoring device is communicatively connected to the control system and can monitor parameters such as partial pressure of oxygen, oxygen saturation, hematocrit, and oxygenated bicarbonate concentration, displaying the relevant values ​​in the control system. By monitoring parameters such as partial pressure of oxygen, oxygen saturation, hematocrit, and oxygenated bicarbonate concentration, it serves two purposes: firstly, it guides the adjustment of pump speeds during perfusion initiation; secondly, it guides the adjustment of perfusion flow rate when blood gas parameters reach preset ranges, thereby better maintaining the organ's healthy state; and thirdly, the blood gas parameters are used to assist in judging the functional status of the perfused organ during the perfusion process.

[0016] The venous pressure monitoring device is connected to the control system to monitor the infusion pressure during the process and display it in the control system to determine whether the infusion system is stable and whether the infusion pipeline is unobstructed. If the infusion pressure drops suddenly, it indicates that the pipeline is leaking or has poor airtightness; if the infusion pressure increases suddenly, it indicates that the pipeline is blocked or connected incorrectly, and the fault needs to be rectified in time.

[0017] The filling fluid storage tank is equipped with a liquid level sensor, which can monitor the volume of the filling fluid in the tank in real time. It also includes a liquid level scale, which allows equipment managers to visually determine the volume of the filling fluid.

[0018] Furthermore, the upper part of the infusion fluid storage tank is provided with at least one infusion interface, which is connected to an infusion pump and an infusion bag in sequence, for supplementing various metabolites and nutrients during the infusion process, including electrolytes, glucose, amino acids, vitamins, lipids, anti-inflammatory and antibacterial drugs, anticoagulants, hormones and one or more of these mixtures.

[0019] The main circuit pump is one of a roller pump, centrifugal pump, peristaltic pump, or diaphragm pump, preferably a roller pump or centrifugal pump, providing a continuous, high-flow-rate infusion fluid during the infusion process. The main circuit pump is communicatively connected to the control system, which allows for precise control of the flow rate during the infusion process.

[0020] The heat exchanger is communicatively connected to the temperature monitoring device in the perfusion circuit. The control system acquires and adjusts the perfusion fluid temperature in real time during the perfusion process to maintain its stability. The heat exchanger has a programmed temperature rise function, which allows the control system to set relevant parameters and raise the temperature according to a set temperature gradient upon initiation of perfusion, thus providing better protection for the perfused organs. This programmed temperature rise function is preferably implemented using PID temperature control technology to achieve precise temperature control.

[0021] The gas exchanger is connected to at least two gas supply cylinders. The gas exchanger can exchange gas components in the perfusion fluid during the perfusion process, providing gas with different components to the perfused organ to maintain the normal metabolic function of the organ or to assist in monitoring organ function.

[0022] Furthermore, the gas supply cylinder is a pressurized gas canister or other gas source, and at least two gas supply cylinders are provided, supplying two mixed gas sources, one of which is a high-oxygen concentration gas source and the other is a low-oxygen concentration carbon dioxide gas source; or two cylinders of the same gas source. When the perfused organ is the lungs, the high-oxygen concentration gas source is used to maintain normal lung respiration, and the low-oxygen concentration carbon dioxide gas source, combined with an arterial and venous blood gas monitoring device, can be used to assess lung function. When the perfused organ is the brain, the high-oxygen concentration gas source has an oxygen content of at least 50%.

[0023] The leukocyte filter is connected after the gas exchanger and before the bifurcation of the purification sub-circuit pipeline. This ensures that the leukocytes in the perfusion fluid are filtered before entering the purification sub-circuit, preventing leukocytes from entering the purification sub-circuit and clogging the inflammatory factor filter.

[0024] The bubble filter is connected to the main circuit arterial inlet line after the leukocyte filter and the bifurcation point of the purification secondary circuit. During perfusion, after the perfusion fluid flows through the perfusion fluid storage tank, gas exchanger, and other devices, some bubbles inevitably remain inside. The presence of bubbles can affect the monitoring of relevant parameters during perfusion and can also cause some damage to the perfused organ. The bubble filter can effectively remove bubbles, obtain accurate parameters, and protect the perfused organ.

[0025] The arterial pressure monitoring device is communicatively connected to the control system. During the perfusion process, it monitors arterial and venous pressure to guide the flow adjustment of the main perfusion circuit pump and assists in determining whether the perfusion process is stable and whether there is any blockage in the pipeline.

[0026] The flow monitoring device can be a liquid flow sensor. It is communicatively connected to the control system and provides real-time feedback and display of the infusion fluid flow rate in the main infusion circuit. The flow monitoring device and the main circuit pump are linked through the control system to determine whether the infusion flow rate follows a preset value during the infusion process.

[0027] The temperature monitoring device is communicatively connected to the control system and the heat exchanger. The two work together to achieve temperature control, maintaining a stable system temperature or allowing for programmed temperature increases or decreases through temperature monitoring feedback. The temperature monitoring device can be a temperature sensor.

[0028] The arterial blood gas monitoring device is communicatively connected to the control system, enabling it to monitor parameters such as partial pressure of blood oxygen, blood oxygen saturation, and hematocrit, and display the relevant values ​​in the control system. By monitoring parameters such as partial pressure of blood oxygen, blood oxygen saturation, and hematocrit, it serves two purposes: firstly, it guides the adjustment of the speed of each pump during perfusion initiation; and secondly, it guides the adjustment of the perfusion flow rate when the blood gas parameters reach the preset range, thereby helping to better maintain the organ's healthy state. Furthermore, the blood gas parameters are used to assist in assessing the functional status of the perfused organ during the perfusion process.

[0029] The biosensor can be a metabolic sensor used to monitor various metabolites, nutrients, and physiological parameters such as pH value of the perfusion fluid during perfusion. These metabolites and nutrients include one or more of electrolytes, glucose, lactic acid, amino acids, vitamins, lipids, anti-inflammatory and antibacterial drugs, and hormones. The biosensor is communicatively connected to the control system, which can acquire relevant index values ​​to guide perfusion process management. For example, regarding pH value and glucose content, if the pH value is detected as too high (excessive bases), an appropriate amount of bicarbonate can be added through the infusion bag and pump to balance the pH value. If the glucose content in the perfusion fluid is detected as insufficient, an appropriate amount of glucose can be added through the infusion bag and pump to supplement nutrients and maintain the organ's physiological needs.

[0030] During perfusion, the perfusion fluid in the main perfusion circuit flows through a leukocyte filter and then enters the inflammatory factor removal sub-circuit via a purification sub-circuit input pump. A portion of the perfusion fluid then enters the inflammatory factor removal sub-circuit, sequentially passing through an inflammatory factor filter, a perfusion exchange fluid reservoir, and the purification sub-circuit output pump to complete the inflammatory factor removal process before returning to the main perfusion circuit. The inflammatory factor removal sub-circuit is activated when the main circuit perfusion is stable.

[0031] The purification secondary circuit input pump and purification secondary circuit output pump operate at the same speed during the infusion process to maintain a stable flow rate in the main infusion circuit and the inflammatory factor removal secondary circuit.

[0032] Preferably, the purification secondary circuit input pump and purification secondary circuit output pump can be used in conjunction with the flow monitoring device and communicate with the control system, so that the pump speed and flow rate can be controlled by the control system to be within the expected values.

[0033] The inflammatory factor filter is connected to the purification sub-circuit input pump to reduce cytokines and other inflammatory mediators in the perfusion fluid, effectively alleviating the inflammatory response of the perfused organ, treating or preventing ischemia-reperfusion injury and organ reperfusion dysfunction caused by the inflammatory response, thereby effectively preserving and repairing the organ.

[0034] The perfusion exchange fluid storage tank is connected to the inflammatory factor filter. The perfusion fluid filtered by the inflammatory factors enters the perfusion exchange fluid storage tank, and then the perfusion fluid is output pumped through the purification secondary circuit to re-enter the perfusion main circuit for circulation.

[0035] The purpose of the perfusion exchange fluid reservoir is that, although the inflammatory factor filter can filter cytokines and other inflammatory mediators in the perfusion fluid, it may also remove some of the effective components. Connecting the inflammatory factor filter to the perfusion exchange fluid reservoir effectively removes cytokines and inflammatory mediators, while the mixing and exchange action of the perfusion exchange fluid ensures the stability of the perfusion fluid composition entering the main perfusion circuit. This effectively reduces the use of supplemental perfusion fluid during the perfusion process and reduces the total amount of perfusion fluid used.

[0036] The infusion exchange solution storage tank should contain a sufficient volume of infusion exchange solution to ensure effective solution mixing and exchange.

[0037] The composition of the perfusion exchange fluid can be the same as that of the perfusion fluid, or a mixture of one or more of the following substances required for perfusion: nutrients, electrolytes, albumin, amino acids, vitamins, hormones, lipids, drugs, etc. The perfusion exchange fluid storage tank should be equipped with a filling and draining port to facilitate the replenishment and removal of the perfusion exchange fluid.

[0038] By filtering and removing inflammatory mediators during perfusion, the progression of inflammation during perfusion can be reduced, allowing tissues to recover and repair, thereby improving the function of ex vivo organs. For marginal organ donors, this can significantly improve organ quality, enabling them to be used in organ transplantation. In addition, this also provides favorable conditions for long-term preservation and long-distance delivery of organs.

[0039] The beneficial effects of this invention are as follows:

[0040] It solves the problems of cumbersome operation, limited function, and lack of real-time physiological indicator feedback in current extracorporeal organ perfusion systems. More importantly, it eliminates inflammation, avoids organ edema, and effectively repairs organs during extracorporeal organ perfusion, thereby expanding the organ supply pool and providing conditions for long-term preservation and long-distance delivery of organs. It effectively removes inflammatory factors in the perfusion circuit, while enabling the repeated and effective use of perfusion fluid to reduce operating costs, and can monitor and provide feedback on various physiological parameters during the perfusion process in real time.

[0041] The present invention will be further described below with reference to the accompanying drawings and embodiments. Attached Figure Description

[0042] Figure 1 This is a schematic diagram of the structure of an extracorporeal organ perfusion system according to an embodiment of the present invention;

[0043] In the diagram: 1. Sterile organ storage container; 2. Weight monitoring device; 3. Venous blood gas monitoring device; 4. Venous pressure monitoring device; 5. Perfusion fluid reservoir; 6. Main circuit pump; 7. Heat exchanger; 8. Gas exchanger; 9. Gas supply cylinder; 10. Leukocyte filter; 11. Bubble filter; 12. Arterial pressure monitoring device; 13. Flow monitoring device; 14. Temperature monitoring device; 15. Arterial blood gas monitoring device; 16. Biosensor; 17. First infusion pump; 18. Second infusion pump; 19. First infusion bag; 20. Second infusion bag; 21. Purification secondary circuit input pump; 22. Inflammatory factor filter; 23. Perfusion exchange fluid reservoir; 24. Purification secondary circuit output pump.

[0044] Figure 2 This is a schematic diagram of the control system according to an embodiment of the present invention; Detailed Implementation

[0045] The preferred embodiments of the present invention are described below. It should be understood that the preferred embodiments described herein are for illustration and explanation only and are not intended to limit the present invention. Example 1

[0046] like Figure 1 As shown, an extracorporeal organ perfusion system includes a perfusion main circuit and an inflammatory factor clearance sub-circuit;

[0047] The perfusion main circuit includes a sterile organ storage container 1, a venous blood gas monitoring device 3, a venous pressure monitoring device 4, a perfusion fluid storage tank 5, a main circuit pump 6, a heat exchanger 7, a gas exchanger 8, a leukocyte filter 10, a bubble filter 11, an arterial pressure monitoring device 12, a flow monitoring device 13, a temperature monitoring device 14, an arterial blood gas monitoring device 15, and a biosensor 16 connected in sequence, forming a circulation loop;

[0048] The inflammatory factor clearance sub-circuit includes a purification sub-circuit input pump 21, an inflammatory factor filter 22, a perfusion exchange fluid reservoir 23, and a purification sub-circuit output pump 24 connected in sequence. The input end of the purification sub-circuit input pump 21 is located between the leukocyte filter 10 and the bubble filter 11; the output end of the purification sub-circuit output pump 24 is connected to the input end of the perfusion fluid reservoir. By introducing the purification sub-circuit, cytokines and other inflammatory mediators are continuously filtered through the inflammatory factor filter in the purification sub-circuit, effectively reducing the amount of cytokines and inflammatory mediators, thereby effectively preserving and repairing organs. In addition, while the inflammatory factor filtration device is set in the inflammatory factor clearance sub-circuit, the perfusion exchange fluid reservoir is also introduced. The perfusion fluid purified by the inflammatory factors enters the perfusion exchange fluid reservoir and neutralizes its components with the perfusion exchange fluid, thereby ensuring the relative stability of the perfusion fluid composition in the main perfusion circuit while filtering cytokines and inflammatory factors.

[0049] The sterile organ storage container 1 is used for storing organs. Its outlet is connected to the vein of the isolated organ, and its inlet is connected to the artery of the isolated organ. Preferably, the sterile organ storage container 1 should be made of a transparent or light-colored material to facilitate observation of the isolated organ and organ chamber during organ perfusion. Preferably, a liquid level sensor can be installed on the outer wall of the sterile organ container to monitor the liquid level during perfusion. Furthermore, when the stored organ is a lung, the sterile organ storage container is also connected to a medical ventilator.

[0050] The structure of the sterile organ storage container varies depending on the type of organ. For example, the structure of the sterile organ storage container should differ when storing the heart, liver, or lung. The sterile organ storage container can be the sterile organ storage container used in the TransMedics Organ Care System or other self-developed alternatives with the same function.

[0051] The sterile organ storage container 1 is equipped with a weight monitoring device 2, which monitors the weight of the container in real time throughout the perfusion process and displays the real-time value in the control system. Real-time weight monitoring helps determine whether edema has occurred in the perfused organ. If the weight monitoring value of the organ storage container increases within a preset allowable range while the perfusion flow rate remains relatively stable, the perfusion process continues as normal. If the weight monitoring value increases beyond the preset allowable range, the system will alert the relevant equipment operators to take appropriate intervention measures or stop the perfusion.

[0052] The control system includes a controller connected to one or more sensors, pump assemblies, and heat exchanger assemblies in the system.

[0053] The control system can display various parameters under the controller's data acquisition and data management functions through a user interface, and feeds back the input parameters to the controller to control various components in the perfusion circuit. The controller has functions including data acquisition, data management, control of pump components, and control of heat exchanger components. The controller's data acquisition function is implemented through controller communication connections to one or more sensors; the data management function is used to store and maintain data related to the operation of the organ perfusion system and to the excised organ; the pump component control function is used to control the pumping of perfusion fluid during perfusion, and the pump component includes a main circuit pump, a purification secondary circuit input pump, a first infusion pump, and a second infusion pump. The heat exchanger control function is used to heat / cool the perfusion fluid during perfusion.

[0054] The control system can consist of one or more open or closed feedback systems, each of which can independently perform some control functions. The control system can be a general-purpose computer system with data monitoring, feedback, and control functions, or it can be a specially designed control system. The control system can be, for example, OCS from TransMedics, Inc. TM The control system in Lung System or other self-developed control systems with similar functions.

[0055] The venous blood gas monitoring device 3 is installed on the pipeline at the outlet of the sterile organ storage container 1. It can monitor parameters such as blood oxygen partial pressure, blood oxygen saturation, hematocrit, and blood oxygen-bicarbonate concentration, and display the relevant values ​​in the control system. By monitoring parameters such as blood oxygen partial pressure, blood oxygen saturation, hematocrit, and blood oxygen-bicarbonate concentration, it is used to guide the adjustment of the speed of each pump when perfusion is started. When the blood gas parameters reach the preset range, it guides the adjustment of the perfusion flow rate, thereby better maintaining the organ's healthy state. On the other hand, the blood gas parameters are used to help judge the functional status of the perfused organ during the perfusion process.

[0056] The venous pressure monitoring device 4 is installed on the perfusion fluid output pipeline of the sterile organ storage container 1 and is connected to the venous blood gas monitoring device 3. The pressure monitoring device is used to monitor the perfusion pressure during the process and display it in the control system to determine whether the perfusion system is stable and whether the perfusion pipeline is unobstructed. If the perfusion pressure drops suddenly, it indicates that the pipeline is leaking or has poor airtightness; if the perfusion pressure increases suddenly, it indicates that the pipeline is blocked or connected incorrectly, and the fault needs to be rectified in time.

[0057] The infusion fluid storage tank 5 is equipped with a liquid level sensor inside, which can monitor the volume of the infusion fluid in the tank in real time. It also includes a liquid level scale inside, which can be used by equipment managers to visually judge the volume of the infusion fluid. The upper part of the infusion fluid storage tank 5 also has at least one infusion interface, which is connected to an infusion pump and an infusion bag in sequence. In this embodiment, there are two sets, namely a first infusion pump 17 and a first infusion bag 19, and a second infusion pump 18 and a second infusion bag 20, which are used to supplement various metabolites and nutrients during the infusion process, including electrolytes, glucose, amino acids, vitamins, lipids, anti-inflammatory and antibacterial drugs, anticoagulants, hormones and one or more of these.

[0058] The main circuit pump 6 is one of a roller pump, centrifugal pump, peristaltic pump, or diaphragm pump, preferably a roller pump or centrifugal pump, providing a continuous, high-flow-rate infusion fluid during the infusion process. The main circuit pump 6 is communicatively connected to the control system, which allows for precise control of the flow rate during the infusion process.

[0059] The heat exchanger 7 is connected to the main circuit pump 6 and is positioned between the main circuit pump 6 and the gas exchanger 8. The heat exchanger 7 is communicatively connected to the temperature monitoring device in the perfusion circuit, and the control system acquires and adjusts the perfusion fluid temperature in real time during the perfusion process to maintain a stable temperature. The heat exchanger 7 has a programmed temperature rise function, which allows the control system to set relevant parameters and raise the temperature according to a set temperature gradient when perfusion starts, thus providing better protection for the perfused organs. The programmed temperature rise function is preferably implemented using PID temperature control technology to achieve precise temperature control.

[0060] The gas exchanger 8 is connected to at least two gas cylinders 9. The gas exchanger 8 can exchange gas components in the perfusion fluid during the perfusion process and provide gas with different components to the perfused organ in order to maintain the normal metabolic function of the organ or assist in monitoring organ function.

[0061] The gas supply cylinder 9 is a pressurized gas tank or other gas source. At least two gas supply cylinders 9 are provided, supplying two mixed gas sources: one a high-oxygen concentration gas source and the other a low-oxygen concentration carbon dioxide gas source; or two cylinders of the same gas source. When the perfused organ is the lungs, the high-oxygen concentration gas source is used to maintain normal lung respiration, and the low-oxygen concentration carbon dioxide gas source, combined with an arterial and venous blood gas monitoring device, can be used to assess lung function. When the perfused organ is the brain, the high-oxygen concentration gas source has an oxygen content of at least 50%.

[0062] The leukocyte filter 10 is connected after the gas exchanger 8. Its position should be located before the bifurcation of the purification sub-circuit pipeline to ensure that the leukocytes in the perfusion fluid are filtered before entering the purification sub-circuit, thus preventing leukocytes from entering the purification sub-circuit and clogging the inflammatory factor filter.

[0063] The bubble filter 11 is connected after the leukocyte filter 10, and its position should be on the main circuit arterial inlet line after the bifurcation of the purification secondary circuit. During perfusion, after the perfusion fluid flows through the perfusion fluid storage tank, gas exchanger, and other devices, some bubbles will inevitably exist inside. The presence of bubbles will affect the monitoring of relevant parameters during perfusion and may also cause some damage to the perfused organ. The bubble filter can effectively remove bubbles, obtain accurate parameters, and protect the perfused organ.

[0064] The arterial pressure monitoring device 12 is installed on the perfusion fluid inlet line of the sterile organ storage container, after the bubble filter 11. The arterial pressure monitoring device 12 is connected to the control system and monitors arterial and venous pressure during the perfusion process to guide the flow rate adjustment of the main perfusion circuit pump and assist in determining whether the perfusion process is stable and whether there is any blockage in the pipeline.

[0065] The flow monitoring device 13 is installed on the infusion fluid input pipeline of the sterile organ storage container, downstream of the pressure monitoring device 12. The flow monitoring device 13 can be a liquid flow sensor. It is communicatively connected to the control system and provides real-time feedback and display of the infusion fluid flow rate in the main infusion circuit. The flow monitoring device 13 and the main circuit pump 6 are linked through the control system to determine whether the infusion flow rate follows a preset value during the infusion process.

[0066] The temperature monitoring device 14 is installed on the infusion fluid inlet line of the sterile organ storage container, downstream of the flow monitoring device 13. The temperature monitoring device 14 is communicatively connected to the control system via the heat exchanger 7, and the two work together to achieve temperature control. Temperature monitoring feedback is used to maintain a stable system temperature or program temperature rise / fall. The temperature monitoring device can be a temperature sensor.

[0067] The arterial blood gas monitoring device 15 is installed on the perfusion fluid inlet line of the sterile organ storage container, downstream of the temperature monitoring device 14. It monitors parameters such as partial pressure of blood oxygen, blood oxygen saturation, and hematocrit, and displays these values ​​in the control system. By monitoring these parameters, the device serves two purposes: firstly, it guides the adjustment of pump speeds during perfusion initiation; secondly, it guides perfusion flow rate adjustments when blood gas parameters reach preset ranges, thus better maintaining the organ's healthy state; and thirdly, the blood gas parameters assist in assessing the functional status of the perfused organ during the perfusion process.

[0068] The biosensor 16 can be a metabolic sensor used to monitor various metabolites, nutrients, and physiological parameters such as pH value of the perfusion fluid during perfusion. These metabolites and nutrients include one or more of electrolytes, glucose, lactic acid, amino acids, vitamins, lipids, anti-inflammatory and antibacterial drugs, and hormones. The biosensor is connected to the control system, which can acquire relevant index values ​​to guide perfusion process management. For example, regarding pH value and glucose content, if the pH value is detected as too high or there is an excess of bases, an appropriate amount of bicarbonate can be added through the infusion bag and pump to balance the pH value. If the glucose content in the perfusion fluid is detected as insufficient, an appropriate amount of glucose can be added through the infusion bag and pump to supplement nutrients and maintain the physiological needs of the organs.

[0069] During perfusion, the perfusion fluid in the main perfusion circuit flows through the leukocyte filter 10 and then enters the purification sub-circuit input pump 21. Part of the perfusion fluid enters the inflammatory factor removal sub-circuit and sequentially passes through the inflammatory factor filter 22, the perfusion exchange fluid reservoir 23, and the purification sub-circuit output pump 24 to complete the inflammatory factor removal process and return to the main perfusion circuit. The inflammatory factor removal sub-circuit is activated when the main circuit perfusion is stable.

[0070] The purification secondary circuit input pump 21 and purification secondary circuit output pump 24 operate at the same speed during the perfusion process to maintain a stable flow rate in the perfusion main circuit and the inflammatory factor removal secondary circuit.

[0071] Preferably, the purification secondary circuit input pump 21 and the purification secondary circuit output pump 24 can be used in conjunction with a flow monitoring device and communicate with the control system, so that the pump speed and flow rate can be controlled by the control system to be within the expected values.

[0072] The inflammatory factor filter 22 is connected to the purification sub-circuit input pump 21 and is used to reduce cytokines and other inflammatory mediators in the perfusion fluid, effectively alleviating the inflammatory response in the perfused organ, treating or preventing ischemia-reperfusion injury and organ reperfusion dysfunction caused by the inflammatory response, thereby effectively preserving and repairing the organ. The inflammatory factor filter can be a CytoSorb adsorber manufactured by CytoSorbents Corporation of Germany or other similar alternatives with similar functions.

[0073] The perfusion exchange fluid storage tank 23 is connected to the inflammatory factor filter 22. The perfusion fluid, after being filtered by the inflammatory factors, enters the perfusion exchange fluid storage tank, and then re-enters the main perfusion loop via a purification auxiliary loop output pump. The perfusion exchange fluid storage tank should be made of transparent or light-colored material to facilitate observation of its liquid level by the operator during the perfusion process. Preferably, a liquid level sensor can be installed on the outer wall of the perfusion exchange fluid storage tank to monitor the liquid level during the perfusion process.

[0074] The purpose of the perfusion exchange fluid reservoir 23 is that, although the inflammatory factor filter can filter cytokines and other inflammatory mediators in the perfusion fluid, it may also remove some of the effective components in the perfusion fluid. Connecting the inflammatory factor filter to the perfusion exchange fluid reservoir can effectively remove cytokines and inflammatory mediators, while ensuring the stability of the perfusion fluid composition entering the main perfusion circuit through the mixing and exchange effect of the perfusion exchange fluid. This effectively reduces the use of supplemental perfusion fluid during the perfusion process and reduces the amount of perfusion fluid used.

[0075] The infusion exchange solution storage tank 23 should be filled with a sufficient volume of infusion exchange solution to ensure the solution mixing and exchange effect.

[0076] The composition of the perfusion exchange fluid can be the same as that of the perfusion fluid, or a mixture of one or more of the following substances required for perfusion: nutrients, electrolytes, albumin, amino acids, vitamins, hormones, lipids, drugs, etc. The perfusion exchange fluid storage tank should be equipped with a filling and draining port to facilitate the replenishment and removal of the perfusion exchange fluid.

Claims

1. An extracorporeal organ perfusion system, characterized in that: The system includes a main perfusion circuit and a secondary circuit for clearing inflammatory factors. The main perfusion circuit comprises, in sequence, a sterile organ storage container, a venous blood gas monitoring device, a venous pressure monitoring device, a perfusion fluid reservoir, a main circuit pump, a heat exchanger, a gas exchanger, a leukocyte filter, a bubble filter, an arterial pressure monitoring device, a flow monitoring device, a temperature monitoring device, an arterial blood gas monitoring device, and a biosensor, forming a circulating loop. The secondary circuit for clearing inflammatory factors comprises, in sequence, a purification secondary circuit input pump, an inflammatory factor filter, a perfusion fluid reservoir, and a purification secondary circuit output pump. The input end of the purification secondary circuit input pump is located between the leukocyte filter and the bubble filter. The purification secondary circuit output pump… The output terminal is connected to the input terminal of the perfusion fluid storage tank; a weight monitoring device is provided under the sterile organ storage container, which is communicatively connected to the control system for real-time weight monitoring of the perfusion container to assist in determining whether edema has occurred in the perfused organ; the venous blood gas monitoring device is communicatively connected to the control system for monitoring parameters such as partial pressure of oxygen, oxygen saturation, hematocrit, and oxygen-bicarbonate concentration, and displaying them in the control system; the venous pressure monitoring device is communicatively connected to the control system for monitoring the perfusion pressure during the process and displaying it in the control system; a liquid level sensor is installed inside the perfusion fluid storage tank; the main circuit pump is communicatively connected to the control system, and the system controls the flow of the perfusion fluid. The flow rate during perfusion is controlled; the heat exchanger is communicatively connected to the temperature monitoring device in the perfusion circuit, and the control system acquires and adjusts the perfusion fluid temperature in real time to maintain a stable perfusion fluid temperature; the leukocyte filter is connected after the gas exchanger and before the bifurcation of the purification secondary circuit pipeline; the bubble filter is connected after the leukocyte filter and on the main circuit arterial input pipeline after the bifurcation of the purification secondary circuit; the arterial pressure monitoring device is connected to the control system, and monitors arterial and venous pressure during perfusion to guide the flow rate adjustment of the main perfusion circuit pump and assist in determining whether the perfusion process is stable and whether pipeline blockage has occurred; the flow monitoring device is connected to the control system. The system communicates with and displays the perfusion fluid flow rate of the main perfusion circuit in real time. The temperature monitoring device communicates with the heat exchanger and is connected to the control system, and the two work together to achieve temperature control. The system temperature is kept stable or programmed for heating or cooling through temperature monitoring feedback. The arterial blood gas monitoring device communicates with the control system and can monitor blood oxygen partial pressure, blood oxygen saturation, and hematocrit parameters, and display the relevant values ​​in the control system. The biosensor is connected to the control system and can obtain relevant index values ​​through the control system to guide the management of the perfusion process. The flow monitoring device and the main circuit pump are linked through the control system to determine whether the perfusion flow rate is executed according to the preset value during the perfusion process. The biosensor is a metabolic sensor used to monitor various metabolites, nutrients, and physiological parameters such as pH of the perfusion fluid during perfusion. These metabolites and nutrients include one or more of electrolytes, glucose, lactic acid, amino acids, vitamins, lipids, anti-inflammatory and antibacterial drugs, and hormones. The purification secondary loop input pump and purification secondary loop output pump operate at the same speed during perfusion. The inflammatory factor filter is connected to the purification secondary loop input pump, and the perfusion exchange fluid storage tank is connected to the inflammatory factor filter. The perfusion exchange fluid storage tank contains perfusion exchange fluid and has inlet and outlet ports. The upper part of the perfusion fluid storage tank also has at least one infusion interface for connecting an infusion pump and an infusion bag. The main loop pump is one of a roller pump, centrifugal pump, peristaltic pump, or diaphragm pump. The gas exchanger is connected to at least two gas supply cylinders. Each gas supply cylinder provides two mixed gas sources: one is a high-oxygen concentration gas source, and the other is a low-oxygen concentration carbon dioxide gas source; or two cylinders of the same gas source.

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