Perfusion repair system for isolated organs

Abstract

The invention relates to an isolated organ perfusion repair system, and belongs to the field of biomedical instruments. The perfusion repair system provided by the invention comprises an organ chamber; a liquid inlet of the perfusate circulating device is communicated with a liquid outlet of the organ chamber, and a liquid outlet of the perfusate circulating device can be communicated with a blood vessel of an isolated organ in the organ chamber; the drug delivery module is connected with the perfusate circulating device and is used for delivering drugs; the monitoring module is used for analyzing the physiological parameters of the perfusate in the isolated organ; the detection module is connected with the perfusate circulation device so as to detect perfusate parameters in the perfusate circulation loop; and the control module is connected with the perfusate circulating device and the detection module and is used for adjusting the working parameters of the perfusate circulating device according to the perfusion parameters. The perfusion repair system provided by the invention is diversified in function, can provide a physiology-imitating preservation and repair environment for isolated organs, and meanwhile, meets various application requirements of organ pathology / physiology, drug research and development, hemodynamics, immune stress and the like.

Description

Technical Field

[0001] The present application relates to the field of biomedical instruments, and in particular to an ex vivo organ perfusion repair system. Background Art

[0002] Mechanical perfusion (MP) technology is a new method for preservation, transportation and evaluation of isolated organs. It can continuously perfuse the isolated organs with perfusion fluid during the organ preservation and transportation stages, while supplying the isolated organs with oxygen, nutrients, etc., providing a physiological environment for the isolated organs.

[0003] At present, mechanical perfusion systems are usually developed and designed according to the needs of application scenarios, with relatively single functions. They are unable to systematically take into account the simulation of the physiological environment of organs, achieve long-term in vitro preservation and repair, and conduct research on organ pathology / physiology, drug development, hemodynamics, immune stress, etc.

[0004] In view of the above, the present invention is proposed. Summary of the invention

[0005] The present application provides an ex vivo organ perfusion repair system to solve the problem that the above-mentioned existing mechanical perfusion systems are unable to systematically take into account the simulation of the physiological environment of the organ, achieve long-term in vitro preservation and repair, and conduct research on organ pathology / physiology, drug development, hemodynamics, immune stress, etc.

[0006] The present application provides a perfusion repair system for an isolated organ, comprising: an organ chamber for accommodating an isolated organ and a perfusion solution; a perfusion solution circulation device, wherein a liquid inlet of the perfusion solution circulation device is connected to a liquid outlet of the organ chamber, and a liquid outlet of the perfusion solution circulation device is used to communicate with a blood vessel of the isolated organ in the organ chamber to form a perfusion solution circulation loop; a drug administration module, connected to the perfusion solution circulation device, and used to supply drugs to the perfusion solution circulation loop; a monitoring module, used to analyze physiological parameters of the perfusion solution in the isolated organ; a detection module, connected to the perfusion solution circulation device, and used to detect perfusion parameters in the perfusion solution circulation loop; and a control module, connected to the perfusion solution circulation device and the detection module, and used to adjust the working parameters of the perfusion solution circulation device according to the perfusion parameters detected by the detection module.

[0007] In some embodiments, the perfusion fluid circulation device includes a perfusion pipeline and a peristaltic pump arranged on the perfusion pipeline; the detection module includes a flow detection unit and a pressure detection unit, the flow detection unit and the pressure detection unit are arranged on the perfusion pipeline between the peristaltic pump and the organ chamber, the flow detection unit is used to detect the flow of the perfusion fluid in the perfusion fluid circulation loop, and the pressure detection unit is used to detect the pressure of the perfusion fluid in the perfusion fluid circulation loop; the control module is connected to the flow detection unit and the pressure detection unit, and is used to adjust the rotation speed of the peristaltic pump according to the flow of the perfusion fluid detected by the flow detection unit and the pressure of the perfusion fluid detected by the pressure detection unit.

[0008] In some embodiments, the control module is configured to increase or decrease the speed of the peristaltic pump based on a preset flow threshold, so as to maintain constant flow perfusion of the perfusion fluid when the flow rate of the perfusion fluid detected by the flow detection unit does not match the preset flow threshold; and / or the control module is configured to increase or decrease the speed of the peristaltic pump based on a preset pressure threshold, so as to maintain constant pressure perfusion of the perfusion fluid when the pressure of the perfusion fluid detected by the pressure detection unit does not match the preset pressure threshold.

[0009] In some embodiments, the perfusion fluid circulation device also includes an oxygenation module, a detoxification module and a buffer box arranged on the perfusion pipeline; the liquid inlet of the oxygenation module is connected to the liquid outlet of the organ chamber, and the liquid outlet of the oxygenation module is connected to the liquid inlet of the peristaltic pump, so as to oxygenate the perfusion fluid in the perfusion fluid circulation loop; the liquid inlet of the detoxification module is connected to the liquid outlet of the peristaltic pump, so as to remove impurities contained in the perfusion fluid in the perfusion fluid circulation loop; the liquid inlet of the buffer box is connected to the liquid outlet of the detoxification module, so as to eliminate bubbles contained in the perfusion fluid in the perfusion fluid circulation loop; the drug administration module is arranged on the perfusion pipeline between the buffer box and the detoxification module.

[0010] In some embodiments, the perfusion repair system also includes a temperature control module and a stimulation module; the temperature control module includes a temperature control container and a heat exchange unit, the temperature control container is filled with a heat exchange medium, the heat exchange unit is connected to the temperature control container, the organ chamber is arranged in the temperature control container, and the temperature control module is used to adjust the temperature of the organ chamber; the stimulation module is connected to the organ chamber, and is used to apply physical or chemical stimulation to the ex vivo organ.

[0011] In some embodiments, the organ chamber is a closed cavity, and the liquid outlet of the organ chamber is arranged at the bottom of the organ chamber.

[0012] In some embodiments, the temperature control module has a temperature adjustment range of 4°C-37°C; and / or the stimulation module stimulates the isolated organ by at least one of mechanical injury, drug injection, controlled hypoxia, or providing an oxygen-rich environment.

[0013] In some embodiments, the oxygenation module includes an oxygenator and a gas supply unit; the liquid inlet of the oxygenator is connected to the liquid outlet of the organ chamber, and the liquid outlet of the oxygenator is connected to the liquid inlet of the peristaltic pump; the gas supply unit is connected to the oxygenator to provide a gas source to the oxygenator.

[0014] In some embodiments, the gas source includes at least one of oxygen, carbon dioxide, or hydrogen.

[0015] In some embodiments, the perfusion repair system is used to perform perfusion repair on an isolated liver, and the liquid outlet of the perfusion fluid circulation device can be connected to the portal vein of the isolated liver, so that the perfusion fluid flows out into the organ chamber through the vena cava of the isolated liver, and circulates and perfuses through the liquid inlet of the perfusion fluid circulation device.

[0016] In summary, the perfusion repair system for isolated organs provided by the present application has at least the following beneficial effects compared with the prior art:

[0017] The present application designs the structure of the perfusion repair system, which is mainly composed of an organ chamber, a perfusion fluid circulation device, a drug administration module, a monitoring module, a detection module and a control module; wherein the organ chamber is used to provide a closed and sterile environment to accommodate the isolated organ and the perfusion fluid, so as to simulate the physiological conditions in vivo for the isolated organ, so as to support the basic physiological functions of the isolated organ; the liquid inlet of the perfusion fluid circulation device is connected with the liquid outlet of the organ chamber, so that the perfusion fluid can flow into the perfusion fluid circulation device, and at the same time, the liquid outlet of the perfusion fluid circulation device is used to directly connect with the blood vessels of the isolated organ in the organ chamber to form a perfusion fluid circulation loop, and the perfusion fluid is continuously transported to the blood vessels of the isolated organ. After flowing through the isolated organ, the perfusion fluid is directly poured into the organ chamber, and circulated to the perfusion fluid circulation device again, so as to realize the simulation of the blood circulation of the isolated organ, so as to facilitate the long-term in vitro preservation and repair of the isolated organ.

[0018] In particular, the drug administration module is connected to the perfusion fluid circulation device to supply the drug into the perfusion fluid circulation loop, so that the perfusion fluid carries the drug to act on the isolated organ, so as to support the functional recovery of the isolated organ, reduce damage or conduct drug development experiments; the monitoring module can be connected to the perfusion fluid circulation device, collect the perfusion fluid in the perfusion fluid circulation loop, analyze the physiological parameters such as the oxygen concentration and metabolite content of the perfusion fluid, so as to evaluate the functional state and metabolic activity of the organ, guide the adjustment of the perfusion conditions, and optimize the effect of organ preservation and repair; the detection module is connected to the perfusion fluid circulation device, and can detect the perfusion parameters such as flow rate and pressure in the perfusion fluid circulation loop in real time, so as to provide support for hemodynamic research; the control module is connected to the perfusion fluid circulation device and the detection module, and can automatically adjust the working parameters of the perfusion fluid circulation device according to the perfusion parameters detected by the detection module, so as to facilitate dynamic adjustment according to the state and needs of the isolated organ, and improve the adaptability of the perfusion repair system.

[0019] Therefore, the perfusion repair system provided in the present application has a high degree of integration and diversified functions. It can provide a physiological preservation and repair environment for ex vivo organs while taking into account various application needs such as organ pathology / physiology, drug development, hemodynamics, and immune stress.

[0020] Other features and advantages of the perfusion repair system for isolated organs provided by the present application will be further described in the subsequent specific embodiments. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] In order to more clearly illustrate the specific implementation of the present application or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the specific implementation or the prior art description. Obviously, the drawings described below are some implementations of the present application. For those skilled in the art, other drawings can be obtained based on these drawings without creative work.

[0022] Figure 1 A schematic diagram of the overall structure of the perfusion repair system provided in an embodiment of the present application;

[0023] Figure 2 A schematic diagram of the modules of the perfusion repair system provided in an embodiment of the present application.

[0024] The reference numerals are as follows:

[0025] 100. Infusion repair system;

[0026] 10. Organ room;

[0027] 20. perfusion liquid circulation device; 21. perfusion pipeline; 22. peristaltic pump; 23. oxygenation module; 231. oxygenator; 232. gas supply unit; 24. detoxification module; 25. buffer box;

[0028] 30. Drug delivery module;

[0029] 40. Monitoring module;

[0030] 50. Detection module; 51. Flow detection unit; 52. Pressure detection unit;

[0031] 60. Control module;

[0032] 70. Temperature control module; 71. Temperature control container; 72. Heat exchange unit;

[0033] 80. Stimulation module;

[0034] G. Isolated organs. DETAILED DESCRIPTION

[0035] In the description of the present application, it should be understood that if terms such as "center", "longitudinal", "lateral", "length", "width", "thickness", "up", "down", "front", "back", "left", "right", "vertical", "horizontal", "top", "bottom", "inside", "outside", "clockwise", "counterclockwise", "axial", "radial", "circumferential" and the like appear to indicate the orientation or position relationship, unless otherwise specified, they are understood to be based on the orientation or position relationship shown in the drawings, which is only for the convenience of describing the present application and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore cannot be understood as limiting the present application.

[0036] In addition, if there is a feature defined as "first" or "second", it is only used for descriptive purposes and cannot be understood as indicating or implying relative importance or implicitly indicating the number of technical features indicated. Features defined as "first" or "second" may explicitly or implicitly include at least one of the defined features. If there is a description of "plurality", the general meaning is to include at least two, such as two, three, etc., unless otherwise clearly and specifically defined.

[0037] In this application, unless otherwise clearly specified and limited, the terms such as "installed", "connected", "connected", "fixed" and so on should be understood in a broad sense. For example, it can be a fixed connection, a detachable connection, or an integrated connection; it can be a mechanical connection or an electrical connection, it can be a direct connection, or it can be an indirect connection through an intermediate medium, it can be the internal connection of two elements or the interaction relationship between two elements. For those skilled in the art, the specific meanings of the above terms in this application can be understood according to the specific circumstances.

[0038] In the description of this specification, if the terms "one embodiment", "some embodiments", "example", "specific example", or "some examples" appear, it means that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present application. In this specification, the schematic representations of the above terms do not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described may be combined in any one or more embodiments or examples in a suitable manner. In addition, those skilled in the art may combine and combine the different embodiments or examples described in this specification and the features of the different embodiments or examples, unless they are contradictory.

[0039] It should be noted that the "physiological parameters" in the embodiments of the present application mainly refer to data such as the concentration of nutrients, electrolytes, pH, metabolic waste content, oxygen or carbon dioxide concentration in the perfusion fluid; the "perfusion parameters" in the embodiments of the present application mainly refer to data such as the flow rate and pressure of the perfusion fluid in the perfusion fluid circulation loop.

[0040] It should be noted that the "ex vivo organ G" in the embodiments of the present application can be provided by small animals.

[0041] It should be noted that the perfusion repair system 100 for the isolated organ G provided in the embodiment of the present application is particularly suitable for mechanical perfusion of an isolated liver organ. When the perfusion repair system 100 is applied to the isolated liver organ, the isolated liver organ is fixedly placed in the organ chamber 10, and the pipeline outlet of the perfusion liquid circulation device 20 is directly connected to the portal vein of the isolated liver organ to input the perfusion liquid into the isolated liver organ. The isolated liver organ discharges the perfusion liquid into the cavity of the organ chamber 10 through the vena cava, and the perfusion liquid further flows back to the perfusion liquid circulation device 20 through the organ chamber 10 to achieve continuous circulation perfusion.

[0042] As mentioned above, the general concept of the embodiment of the present application is to provide a perfusion repair system 100 for an ex vivo organ G, which is convenient for systematically conducting research on organ pathology / physiology, drug development, hemodynamics, immune stress, etc. by simulating the physiological environment of the organ through the organ chamber 10 and the perfusion fluid circulation device 20 through structural optimization design of the perfusion repair system 100, so as to facilitate long-term ex vivo preservation and repair, and further designs a drug delivery module 30 capable of supplying drugs, a monitoring module 40 capable of real-time monitoring and analysis of the physiological parameters of the perfusion fluid in the ex vivo organ G, a detection module 50 for detecting the perfusion parameters in the perfusion fluid circulation loop, and a control module 60 for controlling the working parameters of the perfusion fluid circulation device 20, thereby providing strong support for research on organ pathology / physiology, drug development, hemodynamics, immune stress, etc.

[0043] Based on the above general concept, reference Figure 1 and Figure 2As shown, the embodiment of the present application provides a perfusion repair system 100 for an isolated organ G, comprising: an organ chamber 10, for accommodating an isolated organ G and a perfusion solution; a perfusion solution circulation device 20, wherein the liquid inlet of the perfusion solution circulation device 20 is connected to the liquid outlet of the organ chamber 10, and the liquid outlet of the perfusion solution circulation device 20 is used to communicate with the blood vessels of the isolated organ G in the organ chamber 10 to form a perfusion solution circulation loop; a drug administration module 30, connected to the perfusion solution circulation device 20, for supplying drugs to the perfusion solution circulation loop; a monitoring module 40, for analyzing the physiological parameters of the perfusion solution in the isolated organ G; a detection module 50, connected to the perfusion solution circulation device 20, for detecting the perfusion parameters in the perfusion solution circulation loop; and a control module 60, connected to the perfusion solution circulation device 20 and the detection module 50, for adjusting the working parameters of the perfusion solution circulation device 20 according to the perfusion parameters detected by the detection module 50.

[0044] It should be understood that in the perfusion repair system 100 provided in this embodiment, after the ex vivo organ G is fixed in the organ chamber 10, it only needs to be in contact and connected with the liquid outlet of the perfusion liquid circulation device 20 through a pipeline to receive the perfusion liquid delivered by the perfusion liquid circulation device 20. When the perfusion liquid returns to the perfusion liquid circulation device 20, it enters the cavity of the organ chamber 10 after being discharged through the ex vivo organ G, and returns to the perfusion liquid circulation device 20 through the liquid inlet of the perfusion liquid circulation device 20 connected to the cavity. Therefore, the perfusion process of the ex vivo organ G is significantly optimized, and the convenience and efficiency of the operation are greatly improved.

[0045] The perfusion liquid circulation device 20 is mainly composed of functional components that provide perfusion power, oxygen source, etc. and multiple perfusion pipelines 21. The perfusion pipelines 21 are connected between these functional components, and at least one perfusion pipeline 21 is connected to the outlet of the organ chamber 10 as the outlet of the perfusion liquid circulation device 20, and at least one perfusion pipeline 21 is connected to the blood vessel of the isolated organ G as the inlet of the perfusion liquid circulation device 20, thereby forming a perfusion liquid circulation loop, so that the perfusion liquid can circulate in the perfusion liquid circulation loop; the drug administration module 30 is connected to the perfusion liquid circulation loop through a three-way valve, so that the drug can be accurately added to the perfusion liquid and transported to the isolated organ G together with the perfusion liquid, thereby allowing the operator to flexibly adjust the type, concentration and drug administration time of the drug according to the treatment or research needs, and by switching the three-way valve, the drug can be quickly and safely added without affecting the normal circulation of the perfusion liquid, so as to facilitate drug research and the repair of the isolated organ G.

[0046] The monitoring module 40 is connected to the perfusion fluid circulation loop through a three-way valve to contact the perfusion fluid and analyze the physiological parameters of the perfusion fluid in the isolated organ G in real time to reflect the state of the isolated organ G. The monitoring module 40 can easily obtain the perfusion fluid sample flowing through the isolated organ G through the connection with the three-way valve, perform real-time analysis, and feed back the results to the control module 60 or present them visually to the operator, so as to facilitate research on organ pathology / physiology, drug development, immune stress, etc.

[0047] The detection module 50 can be set in the perfusion pipeline 21 on the perfusion fluid circulation loop to detect the perfusion parameters in the perfusion fluid circulation loop in real time; the control module 60 is respectively communicated with the functional components in the perfusion fluid circulation device 20 and the detection module 50, so as to adjust the working parameters of the perfusion fluid circulation device 20 according to the perfusion parameters detected by the detection module 50, so as to quickly analyze the current perfusion state according to the perfusion parameters fed back by the detection module 50 in real time, and adjust the working parameters of the perfusion fluid circulation device 20 automatically or according to preset rules to ensure that the perfusion process is always in the optimal state. Therefore, the close cooperation between the detection module 50 and the control module 60 not only improves the automation degree and response speed of the perfusion repair system 100, but also ensures the stability and reliability of the perfusion process, and provides more accurate and effective support for the perfusion repair of the isolated organ G.

[0048] refer to Figure 1 and Figure 2 As shown, in some embodiments, the perfusion liquid circulation device 20 includes a perfusion pipeline 21 and a peristaltic pump 22 arranged on the perfusion pipeline 21; the detection module 50 includes a flow detection unit 51 and a pressure detection unit 52, the flow detection unit 51 and the pressure detection unit 52 are arranged on the perfusion pipeline 21 between the peristaltic pump 22 and the organ chamber 10, the flow detection unit 51 is used to detect the flow of the perfusion liquid in the perfusion liquid circulation loop, and the pressure detection unit 52 is used to detect the pressure of the perfusion liquid in the perfusion liquid circulation loop; the control module 60 is connected to the flow detection unit 51 and the pressure detection unit 52, and is used to adjust the rotation speed of the peristaltic pump 22 according to the flow of the perfusion liquid detected by the flow detection unit 51 and the pressure of the perfusion liquid detected by the pressure detection unit 52.

[0049] The perfusion liquid circulation device 20 in the embodiment of the present application includes a perfusion pipeline 21 and a peristaltic pump 22 arranged on the perfusion pipeline 21. The perfusion pipeline 21 can provide a circulation channel for the perfusion liquid; the peristaltic pump 22 is arranged on the perfusion pipeline 21 as a power source and is connected to the control module 60 for communication and is controlled by the control module 60 to output different powers according to the adjustment instructions given by the control module 60, so as to provide the perfusion liquid in the perfusion liquid circulation loop with perfusion power; the flow detection unit 51 and the pressure detection unit 52 are arranged between the peristaltic pump 22 and the organ On the perfusion pipeline 21 between the chambers 10, the flow detection unit 51 can be provided with a flow sensor, and the pressure detection unit 52 can be provided with a pressure sensor, so as to respectively detect the flow perfusion parameters and pressure perfusion parameters of the perfusion fluid in the perfusion fluid circulation loop, and feed back the detected flow perfusion parameters and pressure perfusion parameters to the control module 60. The control module 60 sends an adjustment instruction to the peristaltic pump 22 according to the received flow perfusion parameters and pressure perfusion parameters to adjust the rotation speed of the peristaltic pump 22, so as to achieve the expected perfusion flow and pressure targets.

[0050] In order to achieve constant pressure or constant flow perfusion, in some embodiments, the control module 60 is configured to increase or decrease the speed of the peristaltic pump 22 based on a preset flow threshold, when the flow of the perfusion fluid detected by the flow detection unit 51 does not match the preset flow threshold, so as to maintain constant flow perfusion of the perfusion fluid; and / or the control module 60 is configured to increase or decrease the speed of the peristaltic pump 22 based on a preset pressure threshold, when the pressure of the perfusion fluid detected by the pressure detection unit 52 does not match the preset pressure threshold, so as to maintain constant pressure perfusion of the perfusion fluid.

[0051] In the embodiment of the present application, one or more preset flow thresholds or pressure thresholds can be set according to the specific needs of the isolated organ G and the characteristics of the perfusion fluid circulation system. These thresholds represent the ideal flow / pressure range that the perfusion fluid should maintain during the circulation process. Taking flow feedback regulation as an example, the flow detection unit 51 monitors the flow of the perfusion fluid in the circulation loop in real time, and feeds back the detected flow perfusion parameter (such as the actual flow value) to the control module 60. The control module 60 compares the received flow perfusion parameter with the preset flow threshold. If the actual flow does not match the preset flow threshold (i.e., higher or lower than the threshold range), the control module 60 will automatically calculate and send an adjustment instruction to the peristaltic pump 22. The peristaltic pump 22 increases or decreases its speed according to the received adjustment instruction. The increase in speed will increase the flow of the perfusion fluid, while the decrease in speed will reduce the flow. Through this dynamic adjustment, the control module 60 can maintain constant flow perfusion of the perfusion fluid; the same is true for pressure feedback regulation, which will not be repeated here. Therefore, through real-time monitoring, feedback and dynamic adjustment, the stability and reliability of the perfusion fluid circulation system are ensured, providing strong support for the perfusion repair of the isolated organ G.

[0052] refer to Figure 2 As shown, in order to optimize the simulation of the organ physiological environment and promote the long-term in vitro preservation and repair of the isolated organ G, in some embodiments, the perfusion liquid circulation device 20 also includes an oxygenation module 23, a detoxification module 24 and a buffer box 25 arranged on the perfusion pipeline 21; the liquid inlet of the oxygenation module 23 is connected to the liquid outlet of the organ chamber 10, and the liquid outlet of the oxygenation module 23 is connected to the liquid inlet of the peristaltic pump 22, so as to oxygenate the perfusion liquid in the perfusion liquid circulation loop; the liquid inlet of the detoxification module 24 is connected to the liquid outlet of the peristaltic pump 22, so as to remove impurities contained in the perfusion liquid in the perfusion liquid circulation loop; the liquid inlet of the buffer box 25 is connected to the liquid outlet of the detoxification module 24, so as to eliminate bubbles contained in the perfusion liquid in the perfusion liquid circulation loop; the drug delivery module 30 is arranged on the perfusion pipeline 21 between the buffer box 25 and the detoxification module 24.

[0053] In the embodiment of the present application, the oxygenation module 23 is arranged on the perfusion pipeline 21, and its liquid inlet is connected to the liquid outlet of the organ chamber 10, and the liquid outlet is connected to the liquid inlet of the peristaltic pump 22. The main function of the oxygenation module 23 is to oxygenate the perfusion liquid flowing out of the organ chamber 10 and transport the oxygenated perfusion liquid to the peristaltic pump 22. The oxygenation module 23 can increase the dissolved oxygen content in the perfusion liquid to meet the oxygen demand of the isolated organ G. The liquid inlet of the detoxification module 24 is connected to the liquid outlet of the peristaltic pump 22, and is responsible for removing impurities contained in the perfusion liquid in the perfusion liquid circulation loop. These impurities mainly come from the drugs supplied by the drug administration module 30 and the metabolites produced by the isolated organ G itself.

[0054] The liquid inlet of the buffer box 25 is connected to the liquid outlet of the detoxification module 24. The liquid outlet of the buffer box 25 is used to communicate with the blood vessels of the isolated organ G in the organ chamber 10. The flow detection unit 51 and the pressure detection unit 52 are arranged on the perfusion pipeline 21 between the buffer box 25 and the organ chamber 10, and the monitoring module 40 is connected between the buffer box 25 and the pressure detection unit 52 through a three-way valve. The drug delivery module 30 is arranged on the perfusion pipeline 21 between the buffer box 25 and the detoxification module 24. The buffer box 25 can eliminate bubbles formed in the perfusion fluid during the drug delivery process of the drug delivery module 30 and the oxygenation process of the oxygenation module 23. When the perfusion fluid flows through the buffer box 25, the bubbles will be trapped in the box and gradually dissipated, thereby ensuring the continuity and stability of the perfusion fluid and avoiding subsequent damage to the isolated organ G.

[0055] refer to Figure 2As shown, in some embodiments, the perfusion repair system 100 also includes a temperature control module 70 and a stimulation module 80; the temperature control module 70 includes a temperature control container 71 and a heat exchange unit 72, the temperature control container 71 is filled with a heat exchange medium, the heat exchange unit 72 is connected to the temperature control container 71, the organ chamber 10 is arranged in the temperature control container 71, and the temperature control module 70 is used to adjust the temperature of the organ chamber 10; the stimulation module 80 is connected to the organ chamber 10, and is used to apply physical or chemical stimulation to the ex vivo organ G.

[0056] In the embodiment of the present application, when the heat exchange medium is gas, the temperature control container 71 can adopt a closed design, and when the heat exchange medium is liquid, the temperature control container 71 can be a semi-closed bathtub. For example, when the heat exchange medium is water, the temperature control container 71 can be a semi-closed water bathtub. The heat exchange unit 72 is connected to the temperature control container 71, and the heat of the external heat source or cold source is transferred to the heat exchange medium through a circulating flow, so as to control the internal temperature of the temperature control container 71. The organ chamber 10 is arranged in the temperature control container 71, so it can be affected by the temperature adjustment of the temperature control module 70. When the temperature of the organ chamber 10 needs to be adjusted, the temperature control module 70 will start the heat exchange unit 72 according to the preset temperature parameters or external instructions. The heat exchange unit 72 extracts the heat exchange medium from the temperature control container 71 through a circulating pump, and after being heated or cooled by the external heat source or cold source, it is sent back to the temperature control container 71. In this way, the heat exchange medium can circulate between the temperature control container 71 and the heat exchange unit 72, continuously transferring heat, thereby achieving precise control of the internal temperature of the organ chamber 10, ensuring that the internal temperature of the organ chamber 10 always remains within the target range, and providing support for research in organ pathology / physiology, drug development, hemodynamics, immune stress, etc.

[0057] The stimulation module 80 is connected to the organ chamber 10 and is used to apply physical or chemical stimulation to the isolated organ G. These stimulations may include various forms such as electrical stimulation, mechanical stimulation, and chemical drug stimulation. By artificially applying physical or chemical stimulation in a quantifiable manner, the isolated organ G is damaged to simulate the actual damage that may occur to the isolated organ G, establish various types of organ damage models, and study the changes in organ physiological functions and treatment effects under various damage conditions. A stimulation generator and a control system can be designed inside the stimulation module 80. The stimulation generator is responsible for generating the required stimulation signals (such as electric pulses, mechanical vibrations, drug solutions, etc.), while the control system is responsible for adjusting the parameters of the stimulation signals (such as intensity, frequency, duration, etc.) according to preset programs or external instructions, and transmitting them to the isolated organ G in the organ chamber 10; through the design of the stimulation module 80, the isolated organ G can be directional regulated and intervened, which is convenient for the establishment of various types of organ damage models.

[0058] In the embodiment of the present application, the heat exchange medium filled in the temperature control container 71 is preferably liquid (such as water), and the organ chamber 10 is arranged in the temperature control container 71 and is fully covered by the liquid to facilitate accurate temperature regulation of the organ chamber 10.

[0059] In a specific embodiment, the drug administration module 30 is composed of a drug storage device, a metering pump, and a mixing chamber connected in sequence. The mixing chamber is connected to the perfusion fluid circulation loop through a three-way valve. The metering pump is communicatively connected to the control module 60 and is controlled by the control module 60 to pump the drug into the mixing chamber according to a preset flow rate or rate, thereby ensuring accurate metering and uniform mixing of the drug; the monitoring module 40 includes a sensor array composed of a variety of high-precision sensors (such as pH sensors, ion concentration sensors, dissolved oxygen sensors, etc.), a data acquisition unit, a data analysis and processing unit, and a communication interface. The sensor array is connected to the data acquisition unit through a dedicated signal line or wirelessly to ensure real-time and accurate transmission of monitoring data. The data acquisition unit transmits the processed data to the data processing and analysis module through an internal bus or a dedicated interface for further analysis and processing. The data processing and analysis module sends the analysis results to the parameters and analysis results through the communication interface to an external host computer with visualization function, so that the operator can intuitively understand the state of the perfusion fluid and the reaction of the isolated organ G. Thus, the drug administration module 30 can inject specific drugs into the perfusion fluid according to the parameters set by the control module 60, while the monitoring module 40 monitors and visualizes the physiological parameters of the perfusion fluid in real time to conduct pharmacology, toxicology and efficacy related research.

[0060] In some embodiments, the organ chamber 10 is a closed cavity, and the closed organ chamber 10 can effectively isolate the interference of the external environment, thereby providing a stable, clean, and controllable living environment for the isolated organ G; the liquid outlet of the organ chamber 10 is arranged at the bottom of the organ chamber 10, which is conducive to reducing the generation of bubbles. If the liquid outlet is located at a higher position, the perfusion liquid may generate bubbles during the flow process due to flow rate changes, pipe bending, etc., and the design of the bottom liquid outlet is because the gravity that the perfusion liquid needs to overcome when flowing out of the organ chamber 10 is small, the flow rate is relatively stable, and it is not easy to generate bubbles, so this risk can be reduced. After the perfusion liquid passes through the organ chamber 10, it flows out from the bottom liquid outlet and enters subsequent oxygenation, detoxification, buffering and other treatments to complete the circulation process.

[0061] In some embodiments, the temperature control module 70 has a temperature adjustment range of 4°C-37°C; and / or the stimulation module 80 stimulates the isolated organ G by at least one of mechanical damage, drug injection, controlled hypoxia, or providing an oxygen-rich environment.

[0062] It can be understood that the perfusion repair system 100 of the embodiment of the present application has a relatively wide range of temperature regulation capabilities through the design of the temperature control module 70, and can realize mechanical perfusion at different temperatures such as room temperature mechanical perfusion, sub-low temperature mechanical perfusion, and low temperature mechanical perfusion. Among them, when approaching 4°C, the ex vivo organ G is in a low temperature environment. Low temperature can significantly reduce the metabolic needs of the organ and reduce ischemic damage. At low temperatures, since the perfusion fluid usually contains components that prevent cell damage, the perfusion repair system 100 of this embodiment can remove the original blood in the ex vivo organ G while reducing the immune response and maintaining the integrity of the organ structure; and 37°C is closer to the normal body temperature of the human body, so as to more realistically simulate the in vivo environment. At the same time, at this temperature, the perfusion repair system 100 can provide oxygen and nutrition to support the normal metabolism and function of the ex vivo organ G, which not only helps the repair and functional recovery of the organ, but also can evaluate the quality and functional status of the organ before transplantation. Therefore, the operator can adaptively control the ambient temperature of the ex vivo organ G according to different application scenarios of the perfusion repair system 100, so that the perfusion repair system 100 can better meet the needs of the ex vivo organ G for different temperature conditions.

[0063] The stimulation module 80 stimulates the isolated organ G in at least one of the following ways: mechanical injury, drug injection, controlled hypoxia, or provision of an oxygen-rich environment. Mechanical injury is to cause a certain degree of damage to the isolated organ G by physical means in order to study its self-repair ability and response mechanism; drug injection is to inject specific drugs into the isolated organ G, and observe the reaction and therapeutic effect of the isolated organ G to the drugs, so as to facilitate drug development and optimization of clinical treatment plans; controlled hypoxia is to simulate a hypoxic environment by adjusting the oxygen concentration in the organ chamber 10, and study the physiological changes and adaptability of the isolated organ G under hypoxic conditions; providing an oxygen-rich environment is the opposite of controlling hypoxia, and a high concentration of oxygen is provided to the organ chamber 10 to study the effect of an oxygen-rich environment on the isolated organ G.

[0064] refer to Figure 2 As shown, in some embodiments, the oxygenation module 23 includes an oxygenator 231 and a gas supply unit 232; the liquid inlet of the oxygenator 231 is connected to the liquid outlet of the organ chamber 10, and the liquid outlet of the oxygenator 231 is connected to the liquid inlet of the peristaltic pump 22; the gas supply unit 232 is connected to the oxygenator 231 for providing a gas source to the oxygenator 231.

[0065] In the embodiment of the present application, the gas supply unit 232 is responsible for providing a stable and pure gas source to the oxygenator 231. These gases come into contact with the perfusion fluid in the oxygenator 231, and oxygen is dissolved into the perfusion fluid through a physical or chemical process, thereby increasing the oxygen content of the perfusion fluid to maintain the cell activity and metabolic function of the isolated organ G.

[0066] In some embodiments, the gas source includes at least one of oxygen, carbon dioxide or hydrogen. The choice of the gas source can be determined based on the specific needs of the in vitro organ G experiment or repair.

[0067] In some embodiments, the perfusion repair system 100 is used to perform perfusion repair on an isolated liver. The liquid outlet of the perfusion liquid circulation device 20 can be connected to the portal vein of the isolated liver, so that the perfusion liquid flows out into the organ chamber 10 through the vena cava of the isolated liver, and circulates and perfuses through the liquid inlet of the perfusion liquid circulation device 20, so as to simplify the mechanical perfusion operation process of the isolated liver.

[0068] In a specific embodiment, when the ex vivo liver is perfused and repaired, the ex vivo liver is first placed in the organ chamber 10, and the required perfusion fluid is added to the organ chamber 10, and it is ensured that there is enough heat exchange medium in the temperature control container 71, and then the heat exchange unit 72 is operated. After the heat exchange medium reaches the set value, the peristaltic pump 22 is started. At this time, the perfusion fluid flows from the bottom of the organ chamber 10 through the oxygenator 231, the peristaltic pump 22, the detoxification module 24, the buffer box 25, the flow detection unit 51, and the pressure detection unit 52 and enters the portal vein of the ex vivo liver, and finally flows back to the organ chamber 10 through the vena cava for circulatory perfusion. In this process, the control module 60 automatically adjusts the speed of the peristaltic pump 22 according to the flow and pressure of the perfusion fluid detected by the flow detection unit 51 and the pressure detection unit 52 to achieve constant pressure or constant flow perfusion. When necessary, the gas supply unit 232 supplies gas to the oxygenator 231, and the perfusion fluid is oxygenated in the oxygenator 231 to achieve oxygen-carrying perfusion; when necessary, the drug administration module 30 injects specific drugs into the perfusion fluid according to the set parameters, and the monitoring module 40 monitors and displays the physiological parameters of the perfusion fluid in real time to facilitate pharmacological, toxicological and efficacy-related studies; when necessary, the stimulation module 80 performs external intervention measures such as mechanical injury, drug injection, hypoxia control or provision of an oxygen-rich environment on the isolated liver before or during perfusion, so as to facilitate the establishment of various types of liver injury models and study the changes in liver function and treatment effects under various injury conditions.

[0069] In summary, the perfusion repair system 100 provided in the present application has a high degree of integration and diversified functions. It can provide a physiological preservation and repair environment for the ex vivo organ G while taking into account various application needs such as organ pathology / physiology, drug development, hemodynamics, and immune stress.

[0070] Although the embodiments of the present application have been shown and described above, it can be understood that the above embodiments are exemplary and cannot be understood as limitations on the present application. Those skilled in the art can change, modify, replace and modify the above embodiments within the scope of the present application.

Claims

1. An isolated organ perfusion repair system, characterized in that: include: Organ chamber, used to contain isolated organs and perfusion fluid; a perfusion liquid circulation device, wherein the liquid inlet of the perfusion liquid circulation device is connected to the liquid outlet of the organ chamber, and the liquid outlet of the perfusion liquid circulation device is used to communicate with the blood vessels of the isolated organ in the organ chamber to form a perfusion liquid circulation loop; a drug delivery module connected to the perfusate circulation device and used for delivering drugs to the perfusate circulation loop; a monitoring module for analyzing physiological parameters of the perfusion fluid in the isolated organ; a detection module, connected to the perfusion liquid circulation device, and used for detecting perfusion parameters in the perfusion liquid circulation loop; as well as The control module is connected to the perfusion liquid circulation device and the detection module, and is used to adjust the working parameters of the perfusion liquid circulation device according to the perfusion parameters detected by the detection module.

2. The perfusion repair system according to claim 1, characterized in that: The perfusion liquid circulation device comprises a perfusion pipeline and a peristaltic pump arranged on the perfusion pipeline; The detection module includes a flow detection unit and a pressure detection unit, wherein the flow detection unit and the pressure detection unit are arranged on the perfusion pipeline between the peristaltic pump and the organ chamber, the flow detection unit is used to detect the flow of the perfusion solution in the perfusion solution circulation loop, and the pressure detection unit is used to detect the pressure of the perfusion solution in the perfusion solution circulation loop; The control module is connected to the flow detection unit and the pressure detection unit, and is used to adjust the rotation speed of the peristaltic pump according to the flow rate of the perfusion liquid detected by the flow detection unit and the pressure of the perfusion liquid detected by the pressure detection unit.

3. The perfusion repair system according to claim 2, characterized in that: The control module is configured to increase or decrease the rotation speed of the peristaltic pump based on a preset flow threshold value, so as to maintain constant flow perfusion of the perfusion liquid when the flow rate of the perfusion liquid detected by the flow detection unit does not match the preset flow threshold value; and / or The control module is configured to increase or decrease the rotation speed of the peristaltic pump based on a preset pressure threshold to maintain constant pressure perfusion of the perfusion fluid when the pressure of the perfusion fluid detected by the pressure detection unit does not match the preset pressure threshold.

4. The perfusion repair system according to claim 2, characterized in that: The perfusion liquid circulation device also includes an oxygenation module, a detoxification module and a buffer box arranged on the perfusion pipeline; The liquid inlet of the oxygenation module is in communication with the liquid outlet of the organ chamber, and the liquid outlet of the oxygenation module is in communication with the liquid inlet of the peristaltic pump, so as to oxygenate the perfusate in the perfusate circulation loop; The liquid inlet of the detoxification module is connected to the liquid outlet of the peristaltic pump to remove impurities contained in the perfusion liquid in the perfusion liquid circulation loop; The liquid inlet of the buffer box is connected to the liquid outlet of the detoxification module to eliminate bubbles contained in the perfusion liquid in the perfusion liquid circulation loop; The drug administration module is arranged on the perfusion pipeline between the buffer box and the detoxification module.

5. The perfusion repair system according to claim 1, characterized in that: The perfusion repair system also includes a temperature control module and a stimulation module; The temperature control module includes a temperature control container and a heat exchange unit, the temperature control container is filled with a heat exchange medium, the heat exchange unit is connected to the temperature control container, the organ chamber is arranged in the temperature control container, and the temperature control module is used to adjust the temperature of the organ chamber; The stimulation module is connected to the organ chamber and is used to apply physical or chemical stimulation to the isolated organ.

6. The perfusion repair system according to claim 5, characterized in that: The organ chamber is a closed cavity, and the liquid outlet of the organ chamber is arranged at the bottom of the organ chamber.

7. The perfusion repair system according to claim 5, characterized in that: The temperature control module has a temperature adjustment range of 4°C to 37°C; and / or The stimulation module stimulates the isolated organ in at least one of mechanical injury, drug injection, controlling hypoxia, or providing an oxygen-rich environment.

8. The perfusion repair system according to claim 4, characterized in that: The oxygenation module includes an oxygenator and a gas supply unit; The liquid inlet of the oxygenator is in communication with the liquid outlet of the organ chamber, and the liquid outlet of the oxygenator is in communication with the liquid inlet of the peristaltic pump; The gas supply unit is connected to the oxygenator and is used to provide a gas source to the oxygenator.

9. The perfusion repair system according to claim 8, characterized in that: The gas source includes at least one of oxygen, carbon dioxide or hydrogen.

10. The perfusion repair system according to any one of claims 1 to 9, characterized in that: The perfusion repair system is used to perform perfusion repair on an isolated liver. The liquid outlet of the perfusion liquid circulation device can be connected to the portal vein of the isolated liver, so that the perfusion liquid flows out into the organ chamber through the vena cava of the isolated liver and circulates and perfuses through the liquid inlet of the perfusion liquid circulation device.

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