A multi-organ parallel perfusion system

Abstract

The utility model provides a kind of multi-organ parallel perfusion system, comprising: multiple organ warehouses, for accommodating organ tissue, the branch of multiple organ warehouses is connected in total circuit in parallel;Pulsation device, for providing liquid driving force for total circuit;Corresponding branch regulating valve of multiple organ warehouses is set, for adjusting the flow and pressure of the branch of multiple organ warehouses;Total flow detection device and total pressure detection device;Branch flow detection device and branch pressure detection device;And first control device, the flow value of total circuit and the liquid pressure value of total circuit are used as feedback to adjust the output of pulsation device, second control device, corresponding branch regulating valve is adjusted based on the branch flow data and branch liquid pressure data of branch, to maintain the flow and pressure of this branch at target value.

Description

Technical Field

[0001] This application relates to organ perfusion, and more specifically, to a system for achieving parallel perfusion of multiple organs. Background Technology

[0002] Organ perfusion is a technique that simulates the in vivo environment to provide oxygen, nutrients, and remove metabolic waste from organs outside the body. This technique can extend the storage time of organs before transplantation and avoid damage. Organ perfusion is currently applied in the fields of life sciences and medical device technology, and is suitable for biomedical research scenarios such as organ preservation, tissue engineering, and drug screening.

[0003] Most existing organ perfusion devices are designed for single organs, such as liver perfusion devices and kidney perfusion systems. Although these devices can maintain the metabolic state of a single organ relatively well, they have significant shortcomings in simulating multi-organ synergistic environments, complex physiological feedback, and drug delivery pathways.

[0004] Multi-organ perfusion (MOP) is a technique that connects multiple organs simultaneously to an artificial circulatory system, allowing them to be perfused and maintain their activity under simulated in vivo physiological conditions. This technique is widely used in organ preservation, pre-transplant assessment, in vitro pharmacodynamic studies, research on multi-organ interaction mechanisms, and regenerative medicine.

[0005] Currently, there is no mature system that can simultaneously simulate the perfusion states of multiple organs while taking into account the differentiated needs of each organ (such as pressure, flow rate, temperature, pH, etc.). Furthermore, most systems only maintain a constant perfusion state, lacking simulation of cardiac pulsation, making it difficult to realistically reconstruct the human hemodynamic environment. Existing multi-organ perfusion devices generally use a main pump to generate a fixed or semi-fixed pulsatile pressure waveform, and then adapt the perfusion needs of different organs through regulating valves in each branch. However, the physiological requirements for perfusion pressure and flow rate differ significantly among organs. Traditional master-slave control structures are prone to insufficient perfusion in some branches, or the system frequently entering an unstable state, and cannot dynamically balance the main output among multiple perfusion branches, limiting the overall responsiveness and accuracy of the system. Summary of the Invention

[0006] The purpose of this invention is to provide an intelligent pulsation control system that uses branch feedback to guide the dynamic adjustment of the main loop. This system can adjust the pulsation pressure waveform of the main circulation according to the real-time needs of multiple organ perfusion branches, thereby achieving cross-branch pressure coordination, personalized perfusion maintenance, and optimal system energy efficiency control. This results in a compact, parameter-adjustable intelligent pulsation control multi-organ perfusion device.

[0007] A multi-organ parallel perfusion system according to an embodiment of this application includes: multiple organ compartments for containing organ tissues, wherein branches containing the multiple organ compartments are connected in parallel in a main circuit; a pulsating device for providing fluid driving force to the main circuit; branch regulating valves corresponding to the multiple organ compartments for regulating the flow rate and pressure of the branches containing the multiple organ compartments; a total flow detection device for detecting the flow rate value of the main circuit; a total pressure detection device for detecting the fluid pressure value of the main circuit; a branch flow detection device for detecting the branch flow rate data of each branch containing the multiple organ compartments; and a branch pressure detection device for detecting the branch fluid pressure data of each branch containing the multiple organ compartments; a first control device for adjusting the output of the pulsating device based on the flow rate value and the fluid pressure value of the main circuit as feedback; and a second control device for adjusting the corresponding branch regulating valve based on the branch flow rate data and the branch fluid pressure data to maintain the flow rate and pressure of the branch at target values.

[0008] Preferably, the multi-organ parallel perfusion system further includes a temperature control module for adjusting the temperature within each of the multiple organ compartments.

[0009] Preferably, in a multi-organ parallel perfusion system, the pulsation device includes a centrifugal pump that uses PID control to simulate the periodic pressure changes of the heart.

[0010] Preferably, in a multi-organ parallel perfusion system, the pulsation device includes a volumetric pump that simulates the periodic pressure changes of the heart through PID control.

[0011] Preferably, in a multi-organ parallel perfusion system, the branch regulating valve is an electrically controlled miniature valve.

[0012] Preferably, the multiple organ compartments are integrally formed and have multiple independent organ-accommodating cavities.

[0013] This invention discloses a multi-organ synchronous perfusion device based on a parallel circulation system, suitable for simultaneous perfusion of multiple human organs or tissues. The device integrates a pulsation generator, independent branch regulators, and an intelligent control system to achieve independent flow, pressure, and temperature control for each organ. Compared to existing single-organ perfusion devices, this device can more realistically simulate the complex physiological states of the human body and can be widely used in organ preservation, drug screening, regenerative medicine research, and other scenarios. Attached Figure Description

[0014] To more clearly illustrate the embodiments of this application, the embodiments of this application will be described below in conjunction with the accompanying drawings. The drawings are merely illustrative, and the shapes, sizes, and positional relationships shown in the drawings are only examples and do not limit the scope of protection claimed by this application.

[0015] Figure 1 A schematic diagram of multi-organ perfusion is shown. Figure 2 The schematic diagram illustrates the overall structure of a multi-organ parallel perfusion device. Figure 3 This diagram illustrates the arterial circulation of a multi-organ parallel perfusion device according to an embodiment of the present invention. Figure 4 The diagram illustrates the venous circulation of a multi-organ parallel perfusion device according to an embodiment of the present invention. Detailed Implementation

[0016] The technical solution of this utility model will now be described with reference to the accompanying drawings. It should be understood that the described embodiments are only some implementations of this utility model, and not all embodiments. Based on the embodiments of this utility model, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this utility model. In the following description, the connection between devices can be a direct connection or a connection through other devices; the positional relationship and dimensions of the components are only illustrative and are not limited to the manner shown in the figures.

[0017] Figure 1 This is a schematic diagram of multi-organ perfusion. During multi-organ perfusion, the arterial circuit, driven by a perfusion pump, delivers oxygen- and nutrient-rich perfusion fluid (or blood) from the main circulatory system through various arterial branches to the arterial inlets of multiple organs. After the perfusion fluid completes material exchange within the organ tissues, it is recovered via the venous circuit, flowing from the venous outlets of each organ into venous conduits, and then back to the reservoir or oxygenation / heat exchange device in the main circulatory system, completing one perfusion cycle. Throughout the process, the arterial circuit provides positive driving force and pulsating pressure, while the venous circuit relies on gravity or negative pressure to assist in recovery. Together, they construct a closed, dynamic perfusion environment that simulates the human cardiovascular system. The organs placed in the organ perfusion chamber can be human or animal organs or tissues, natural or artificial organs or tissues, healthy or diseased organs or tissues, or in vivo or external human structures.

[0018] Figure 2 The schematic diagram illustrates the overall structure of a multi-organ parallel perfusion device. For example... Figure 2 As shown, the multi-organ parallel perfusion device includes: an organ compartment module 21 for placing organs, a heating module 22 for heating the organ compartment module 21, an arterial compartment 23 for arterial circuits, and a venous compartment 24 for venous circuits.

[0019] Figure 3 A schematic diagram of arterial circulation is shown to realize a multi-organ parallel perfusion device. Figure 4 A schematic diagram illustrating the venous circulation of a multi-organ parallel perfusion device is shown. Figure 3 As shown, the main body of the device can have three organ compartments 311-313 (expandable), for example, they can be used to place tissues such as the liver, kidney, and lung, respectively. Organ compartments 311-313 can also be used to place human organs or severed limbs, and the number is not limited to the three shown in the figure. The heating module 32 is used to ensure that the organs in the organ compartments are at a reasonable temperature, and is not limited to just heating; cooling can be performed under special requirements. Organ compartments 311-313 can be maintained at the same temperature or at different temperatures.

[0020] Multiple organ compartments can be molded into a single unit within a shell or module, which contains multiple independent but structurally continuous organ-accommodating cavities. These cavities are formed by a unified frame and are typically made of biocompatible, corrosion-resistant, and easy-to-clean materials (such as polycarbonate, medical-grade silicone, or stainless steel). Each organ compartment is equipped with an independent arteriovenous interface, sensor interface, and temperature-controlled contact surface.

[0021] Furthermore, multiple organ compartments can be molded separately, each a modular unit with complete perfusion capabilities, manufactured independently. These compartments are connected to the main circulation system via hoses, quick connectors, or external frames. Therefore, users can freely choose to connect one, two, or more organ compartments according to their needs, and the system supports gradual expansion or replacement of compartments. Additionally, different models or functions of compartments can be mixed and matched to meet specific requirements. This modular design allows for the disassembly and reconfiguration of each compartment, suitable for flexible configuration of different organs or diverse experimental conditions. Moreover, when an organ fails or needs replacement, it does not affect the operation of other compartments. In routine maintenance, each compartment can be disassembled, cleaned, and disinfected individually, making maintenance more convenient.

[0022] In the circulatory structure of the perfusion process, each organ compartment is connected in parallel within the main circulatory system via independent arterial and venous branches. For example, refer to... Figure 3 Each organ compartment has one or two arterial interfaces for the infusion of oxygenated blood or blood containing nutrients. The main circuit includes a pulsation device and a total pressure control device (which can be located at various points in the main circuit as needed) to simulate and regulate the heart's systolic / diastolic rhythm. A heating device controls the perfusion fluid temperature, for example, at 36–37.5°C, to maintain organ viability. Electronic flow control valves and pressure sensors are installed on the branch circuits and connected to the control system. At the start of operation, the user sets the perfusion fluid temperature, frequency, and target flow range on the operating interface. After system startup, it collects real-time data on pressure, flow rate, and other parameters from each organ branch and automatically adjusts to ensure stable perfusion to each organ.

[0023] like Figure 3 As shown, blood and perfusion fluid are stored in corresponding containers 310 and 320, respectively, and containers 310 and 320 are switched back and forth via an arterial switching electronic valve 33. Figure 4 As shown, in the venous circulation loop, the venous switching electronic valve 41 is used to control the switching of the circulation loop, and the venous retrieval power source 42 is used to accelerate the venous retrieval speed. During organ perfusion, blood and perfusion fluid (such as crystalloid solutions containing nutrients, plasma substitutes, or artificial perfusion fluids) usually need to be used alternately or switched back and forth to meet the different physiological needs and experimental requirements of the organ at different stages. Perfusion fluid can be used to wash away residual blood or metabolic products from the organ, preventing blood clotting and microthrombus formation. In addition, the perfusion fluid has a stable composition and is free of cells, which is conducive to precise control and modeling of flow rate, pressure, pH, temperature, etc.; perfusion fluid is preferred during the training of control algorithms (such as pulsatile PID) or debugging phases. By switching back and forth through the arterial switching electronic valve 33, blood perfusion and perfusion fluid perfusion can be achieved in one set of circulation tubing.

[0024] like Figure 3 As shown, the pulsating device 34 provides the driving force and the pulsation. The pulsating device 34 simulates the pulsating function of the heart and can provide periodic pressure fluctuations. The pulsating device 34 is not limited to using a drive source such as a centrifugal pump or a positive displacement pump. For example, a centrifugal pump generates pressure by rotating an impeller to drive liquid flow. Alternatively, a positive displacement pump delivers liquid by changing the volume of the working chamber.

[0025] like Figure 3 As shown, the pulsation device 34 transfers liquid (blood or perfusion fluid) to the heat exchange oxygenation device 35, which is used for oxygenation or heat exchange of the blood or perfusion fluid. Subsequently, the total flow detection device 36 and the total pressure detection device 37 are used to detect the total loop flow rate value Q_total and the total loop pipeline liquid pressure value P_total, respectively, as feedback data to participate in the pulsation PID algorithm. In multi-organ perfusion systems, the pulsation PID algorithm is mainly used to simulate the periodic blood flow changes generated by heartbeats to achieve high-precision, high-response pulsation control. The PID controller set in the control system of the perfusion system consists of three components: P (proportional), the proportional response to the current error magnitude (difference between the set value and the actual value); I (integral), the historical cumulative error, which addresses steady-state error; and D (derivative), the error change trend, which improves response speed and reduces oscillation. In pulsation control, the goal is to make the flow and pressure waveforms output by the pump or fluid drive system as close as possible to the set ideal pulsation curve (e.g., a sine wave or sawtooth wave with a cardiac cycle of 1 second and a pressure of 80–120 mmHg).

[0026] During perfusion, when the branch is closed, the main circuit is within a reasonable pressure and flow range. When the branch is opened and perfusion begins, it diverts a portion of the main circuit's flow, requiring dynamic adjustment of the main circuit's flow and pressure. To achieve a more stable and independently controlled multi-organ perfusion system, the system also includes (only one branch is schematically shown in the diagram; other branches have similar structures): a branch regulating valve 38 (e.g., an electrically controlled micro-valve) to control the flow and pressure of the branch (the simulated arterial inlet of the organ), serving as control parameters in the pulsation PID algorithm; a branch flow detection device 39 to detect the branch flow, serving as feedback data in the pulsation PID algorithm; and a branch pressure detection device 57 to detect the branch pressure, serving as feedback data in the pulsation PID algorithm. Through an improved PID control design, while the main arterial circuit outputs pulsations, the mutual interference between branches is reduced, achieving: the flow rate Q of each branch... i Stable, pressure setpoint P for each branch i Maintain, while ensuring that the total flow rate Q_total and the total pressure P_total satisfy the cardiac simulation output curve.

[0027] In the improved PID control method design scheme, the control structure design includes master-slave hierarchical closed-loop control. In the first-level control, the total loop pulsation regulation (master PID) is used to output the set pulsation frequency / amplitude, and the total flow rate Q_total and total pressure P_total are used to feedback and regulate the output of the pulsating device (positive displacement pump, centrifugal pump); the PID controller calculates the pump speed or pulsation frequency. In the second-level control, each branch's regulating valve is controlled in a closed-loop manner (sub-controller PID), with each branch having an independent controller to regulate the opening of the electronic valve. The control objective is to maintain the flow rate Q in each branch. i and pressure P i At the target value.

[0028] In the improved PID control design scheme, a three-level control can also be included for individual branch closed-loop regulation. The prerequisite for three-level control is that the main circuit pressure must be ≥ the branch set pressure + ΔP_min; otherwise, a "main circuit pressure increase request" signal is issued. This is because the total circuit pressure must be slightly greater than the branch pressure for the branch to be regulated within the required range. For example, if the total circuit pressure is 100 for high pressure and 60 for low pressure, and a branch organ requires a pressure of around 120, the total circuit pressure cannot meet this requirement. Therefore, the total circuit pressure needs to be dynamically adjusted according to the branch's pressure requirement to satisfy it. In three-level control, the central controller analyzes the status of all branches. If any branch requires a higher peak pressure, the upper limit of the total circuit pulsation is adjusted, while the pulsation frequency remains unchanged. The main circuit controller sets the pulsation pressure as the envelope of the branch pressure demand, ensuring the adjustment space for each branch.

[0029] In actual perfusion, the kidneys may require a pulsatile pressure of 120–130 mmHg, while other organs only require 90 mmHg. In this case, the overall circuit pulsation must dynamically respond to the increased pressure demand from the kidneys. This intelligent pulsation control system, which uses branch feedback to guide dynamic adjustment of the main circuit, can adjust the pulsatory pressure waveform of the main circulation according to the real-time needs of multiple organ perfusion branches, thereby achieving cross-branch pressure coordination, personalized perfusion maintenance, and optimal system energy efficiency control. Furthermore, the intelligent control system, which periodically reports "pressure gap" or "risk of insufficient perfusion" status from branches, can automatically adjust perfusion parameters based on organ feedback.

[0030] Compared with the prior art, this utility model has the following advantages: it can connect and support the perfusion needs of multiple organs / tissues simultaneously, improving system efficiency; it is equipped with a pulsation simulation device to restore the real physiological state driven by the heart; it supports independent parameter adjustment and precisely controls the perfusion environment of each organ; the control system has a high degree of intelligence and is suitable for personalized parameter modeling and feedback optimization.

[0031] Although embodiments of the present invention have been specifically described, those skilled in the art will understand that various modifications, combinations, or substitutions may be made within the scope of the appended claims or their equivalents, based on design requirements and other factors.

Claims

1. A multi-organ parallel perfusion system, comprising: Multiple organ compartments are used to contain organ tissues, and the branches containing the multiple organ compartments are connected in parallel in the main circuit; A pulsating device is used to provide fluid driving force to the main circuit; The branch regulating valves, corresponding to the multiple organ compartments, are used to regulate the flow rate and pressure of the branches where the multiple organ compartments are located. Total flow detection device, used to detect the flow rate of the total loop; A total pressure detection device is used to detect the liquid pressure value of the total circuit; A branch flow detection device is used to detect the branch flow data of each branch in which the multiple organ compartments are located; as well as A branch pressure detection device is used to collect branch fluid pressure data for each branch in which the multiple organ compartments are located; as well as The first control device adjusts the output of the pulsating device by using the flow rate and liquid pressure values ​​of the total circuit as feedback. The second control device adjusts the corresponding branch regulating valve based on the branch flow rate data and the branch liquid pressure data to maintain the flow rate and pressure of the branch at the target value.

2. The multi-organ parallel perfusion system according to claim 1 further includes: The temperature control module is used to adjust the temperature in each of the multiple organ compartments.

3. The multi-organ parallel perfusion system according to claim 1 or 2, wherein: The pulsating device includes a centrifugal pump that uses PID control to simulate the periodic pressure changes of the heart.

4. The multi-organ parallel perfusion system according to claim 1 or 2, wherein: The pulsating device includes a volumetric pump that simulates the periodic pressure changes of the heart through PID control.

5. The multi-organ parallel perfusion system according to claim 1 or 2, wherein: The branch regulating valve is an electrically controlled miniature valve.

6. The multi-organ parallel perfusion system according to claim 1 or 2, wherein: The multiple organ compartments are integrally formed and have multiple independent organ-accommodating cavities.

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