Isolated organ stable pressure perfusion module, perfusion system and perfusion method

Abstract

Provided are an isolated organ steady pressure perfusion module, perfusion system and perfusion method, the isolated organ steady pressure perfusion module comprising: a steady pressure blood bin comprising a perfusion chamber and an overflow chamber; the pouring cavity and the overflow cavity are in overflow communication through the overflow hole; the blood inlet connector, the blood outlet connector, the exhaust and fluid infusion connector and the overflow connector are communicated with the pressure stabilizing blood bin internally and externally, the blood inlet connector and the blood outlet connector are both communicated with the perfusion cavity, and the exhaust and fluid infusion connector and the overflow connector are both communicated with the overflow cavity; the pressure stabilizing blood bin is connected to the lifting frame in a height-adjustable manner. Therefore, when the perfusion module is connected with an external power module, unstable pressure of liquid at the input end can be eliminated, and stable pressure flow suitable for physiological needs of organs can be output. And the device adapts to various blood pumps and is wide in universality.

Description

Technical Field

[0001] The present application relates to the field of medical devices, and in particular to an isolated organ steady pressure perfusion module, a perfusion system and a perfusion method. Background Art

[0002] Organ transplantation is the ultimate treatment for many terminal diseases. However, the shortage of donated organs has led to an increasing number of patients losing their lives while waiting. Organ shortage has become a major obstacle to the development of this life-saving technology. Although in the long run, increasing the organ donation rate and developing xenotransplantation are potential solutions, there is an urgent need to improve organ preservation technology so that marginal donors that were previously considered unsuitable for transplantation can be more effectively evaluated and repaired in vitro to improve their utilization rate. Under the traditional static cold preservation (SCS) method, the in vitro preservation time of donor organs usually does not exceed 12 hours, and the metabolic activity of the organs is inhibited, which cannot meet the needs of in vitro evaluation and repair of marginal donors. Normothermic mechanical perfusion (NMP) is a new organ preservation method that mimics the in vivo environment. Compared with static cold preservation, normothermic mechanical perfusion (NMP) can continuously provide oxygenation and nutrition to ex vivo organs, maintain organ metabolism and function, significantly prolong the preservation time of organs, and has the ability to evaluate donor organs in real time in vitro to screen out high-quality organs for transplantation. This technology also has the potential to improve the function of donor organs through in vitro treatment.

[0003] The key to normothermic mechanical perfusion (NMP) technology is to simulate the in vivo physiological environment in vitro. Among them, maintaining appropriate blood pressure in the blood vessels of the organ to be transplanted is particularly critical. Taking the liver as an example, constant high portal vein pressure may damage the liver and increase the risk of dysfunction after transplantation. At the same time, the mechanical stress caused by the blood flow rate that meets the physiological value is indispensable for maintaining the normal function of vascular endothelial cells. In the liver, the hepatic artery and portal vein have different blood flow requirements. The hepatic artery requires a mean arterial pressure of about 75mmHg and a pulsating blood flow of 0.25L / min to 0.6L / min; the portal vein requires a blood pressure of about 5mmHg to 10mmHg and a stable non-pulsating blood flow of about 1L / min. However, due to the limitations of factors such as blood pump performance and system cost, it is difficult for existing technologies to accurately achieve the above indicators.

[0004] In view of the stable blood flow required by the portal vein, the Chinese invention patent with the announcement number "CN113396898A" discloses "organ perfusion device and perfusion method without interruption of blood flow". The perfusion device performs room temperature perfusion of the ex vivo organ throughout the transplantation process, including a first container, a second container, a first flow path, a second flow path, a third flow path and a fourth flow path, wherein the organ in the donor acquisition stage, the second container, the third flow path and the fourth flow path form a second cycle for perfusing the organ in the donor acquisition stage, and after the organ is removed from the body, it can switch to the first cycle formed by the second container, the first flow path, the second flow path and the ex vivo organ in the first container to perfuse the organ in the post-ex vivo storage stage, and the third pump can provide power for the second cycle. The perfusion device and perfusion method can maintain the uninterrupted blood flow of the ex vivo organ throughout the transplantation process through mechanical perfusion, can recycle the blood of the organ, can effectively avoid the interruption of the blood supply of the organ throughout the transplantation process, and improve the prognosis of the organ transplantation. This is a technical solution that uses an independent blood pump to supply blood to the portal vein.

[0005] The Chinese invention patent with the announcement number "CN109688811B" discloses "a perfusion circuit assembly and a liver chamber assembly for ex vivo liver perfusion". The perfusion circuit assembly for ex vivo liver perfusion comprises at least one pump, which provides perfusion fluid to the hepatic artery and the portal vein through a first branch line and a second branch line, respectively; and also comprises a liver chamber assembly, which is configured to be connected to a liver outlet line of the vena cava and at least one reservoir. The second branch line also comprises at least one valve. The perfusion circuit assembly also comprises a gas exchanger. Sensors and control systems may also be provided. The liver chamber assembly comprises a liver support structure and a device for mechanically manipulating, in particular compressing, at least a portion of the perfused liver ex vivo. This is a technical solution for simultaneously supplying blood to the hepatic artery and the portal vein through proportional shunting using a pulsatile blood pump.

[0006] The Chinese utility model patent with the announcement number "CN212035659U" discloses "a rat liver normal temperature mechanical perfusion machine". The perfusion machine includes an intravenous cannula, a peristaltic pump, an oxygenator, a reservoir, a temperature controller and a liver trough connected in sequence through the intravenous cannula, a bile collector for collecting bile in the liver, and a computer data terminal for machine monitoring and control. A dialysis device is connected between the liver trough and the reservoir through a hose. The dialysis device is used to recover and filter the liquid in the liver trough and re-discharge it into the reservoir for circulation. The perfusion process becomes automated and digitized, and the data in the perfusion process is convenient to collect and monitor in real time; it realizes normal temperature mechanical perfusion, non-water bath heating, and the system is simple and easy to carry. This is a solution for gravity perfusion using a reservoir combined with two flow controllers and sensors at the inlet and outlet.

[0007] However, these methods have certain limitations, such as large fluctuations in blood pressure, high system cost, high complexity in operation and control, and low reliability. Among them, large fluctuations in blood pressure are not suitable for the physiological needs of organs and are a more urgent problem to be solved. Summary of the invention

[0008] This application is made in view of the above-mentioned state of the prior art, and the present application aims to solve or alleviate at least one of the above-mentioned problems.

[0009] In a first aspect, the present application aims to provide an isolated organ steady pressure perfusion module.

[0010] The technical solution adopted by the present application to solve its technical problems is: an ex vivo organ steady pressure perfusion module, including: a pressure-stabilizing blood bin, including a perfusion chamber and an overflow chamber, the perfusion chamber and the overflow chamber are connected by overflow through an overflow hole; a blood inlet interface, a bleeding interface, an exhaust and fluid-replenishing interface, and an overflow interface that are connected to the pressure-stabilizing blood bin internally and externally, the blood inlet interface and the bleeding interface are both connected to the perfusion chamber, the exhaust and fluid-replenishing interface and the overflow interface are both connected to the overflow chamber; and a lifting frame, the pressure-stabilizing blood bin is height-adjustably connected to the lifting frame.

[0011] As a further improvement of the present application, it also includes a drain plate, which is arranged at the junction of the perfusion chamber and the overflow chamber, and the drain plate is arranged obliquely relative to the vertical direction. The drain plate has an overflow hole connecting the perfusion chamber and the overflow chamber, the perfusion chamber is arranged at the oblique lower side of the drain plate, and the overflow chamber is arranged at the oblique upper side of the drain plate.

[0012] As a further improvement of the present application, the shell of the pressure-stabilizing blood chamber includes an annular middle layer and end covers mirrored on both sides of the annular middle layer, the blood inlet interface, the bleeding interface, the exhaust and fluid replenishment interface, and the overflow interface are all located in the annular middle layer, and the two ends of the drainage plate are connected to the inner wall of the annular middle layer.

[0013] As another improvement of the present application, the axis of the overflow interface is parallel to the upper surface of the drainage plate; the blood inlet interface is lower than the height of the overflow hole, and the axes of the bleeding interface and the exhaust and fluid replenishment interface extend in the vertical direction. The bleeding interface is connected to the lowest point in the vertical direction of the perfusion chamber, and the exhaust and fluid replenishment interface is connected to the highest point in the vertical direction of the overflow chamber.

[0014] As another improvement of the present application, the exhaust and rehydration interface is equipped with a multi-way valve, and the multi-way valve is also connected to a one-way exhaust valve, the outside atmosphere, and the rehydration bottle respectively. The multi-way valve selectively switches between connecting the exhaust and rehydration interface with the exhaust valve, directly connecting the exhaust and rehydration interface with the outside atmosphere, and connecting the exhaust and rehydration interface with the rehydration bottle. Both axial ends of the annular intermediate layer are sealed and covered with a flexible material film, and the facing surfaces of the two end covers are provided with a card groove, and a sealing strip is installed in the card groove. The axial end edge of the annular intermediate layer and the side edge of the guide plate are squeezed and contacted with the sealing strip through the flexible material film; the infusion cavity and the overflow cavity are formed between the two parallel flexible material films, and a cavity is also formed between the flexible material film and the adjacent end cover.

[0015] As a further improvement of the present application, the lifting frame is provided with a scale, and the pressure-stabilizing blood chamber is connected to the lifting frame by magnetic attraction, or the pressure-stabilizing blood chamber is connected to the lifting frame in a height-adjustable manner through an electric drive device.

[0016] As another improvement of the present application, the overflow hole itself is horizontal in direction, and the overflow hole is located above the centroid of the pressure-stabilizing blood chamber; the overflow hole includes an upper square hole and a lower square hole separated from each other, and the bottom surfaces of the inner walls of the upper square hole and the lower square hole themselves are parallel to the horizontal plane.

[0017] As a further improvement of the present application, the angle formed between the upper surface of the guide plate and the horizontal plane ranges from 30° to 70°.

[0018] As a further improvement of the present application, the end cover is connected to the lifting frame via a connecting arm, and the connecting arm is provided with a weight sensor for monitoring the total weight of the pressure-stabilizing blood chamber.

[0019] As a further improvement of the present application, the material of the annular intermediate layer and the end cap is polymethyl methacrylate, and the material of the flexible material film is polydimethylsiloxane.

[0020] In a second aspect, an isolated organ steady pressure perfusion system is provided, which includes an isolated organ steady pressure perfusion module of the present application, wherein the blood inlet interface of the pressure-stabilizing blood bin is connected to a blood distribution module, the overflow interface of the pressure-stabilizing blood bin is connected to a blood storage module, and the bleeding interface of the pressure-stabilizing blood bin can be connected to the perfused organ; the blood storage module and the blood distribution module are connected via a power module, and the blood storage module, the power module, the blood distribution module, the pressure-stabilizing blood bin, and the perfused organ sequentially form a one-way circulation connection.

[0021] As a further improvement of the present application, the blood distribution module is connected to the perfused organ through an oxygenation module, the pressure-stabilizing blood tank is connected to the vein of the perfused organ, and the oxygenation module is connected to the artery of the perfused organ.

[0022] In a third aspect, a method for steady pressure perfusion of an isolated organ is provided, which uses an isolated organ steady pressure perfusion system of the present application, and the method for steady pressure perfusion of an isolated organ comprises the following steps:

[0023] Step S1: in the pre-charging state, the power module is started, and liquid including blood and / or perfusion liquid enters the perfusion chamber from the blood inlet interface under the drive of the power module, and the liquid level of the perfusion chamber gradually rises, while there is no liquid in the overflow chamber, and the overflow interface is in a closed state;

[0024] Step S2: in the overflow starting state, the liquid level of the perfusion chamber rises and passes over the overflow hole, the liquid flows smoothly into the overflow chamber with the help of a guide plate arranged obliquely relative to the vertical direction, and the overflow interface is in a closed state;

[0025] Step S3: in the low-point working state, the amount of the liquid in the overflow chamber is just enough to immerse the overflow interface, the pressure-stabilizing blood chamber begins to provide the perfused organ with stable liquid, and the overflow interface is in a closed state;

[0026] Step S4: in the high-point working state, the liquid in the overflow chamber flows into the blood storage module through the overflow interface, and the liquid level in the overflow chamber begins to drop.

[0027] As an improvement of the present application, after step S4, the method further includes:

[0028] Step S5: when the liquid level in the overflow chamber drops to just enough to submerge the overflow interface, closing the overflow interface to stop the liquid from flowing out of the overflow chamber;

[0029] Step S6: Circular working state. After completing step S5, return to step S3 and circulate the operation between step S3 and step S5 until the perfusion process is completed.

[0030] As a further improvement of the present application, the weight of the pressure-stabilizing blood chamber is measured by a weight sensor, and the discharge of liquid from the overflow chamber through the overflow interface is started or stopped based on the weight data.

[0031] The beneficial effects of the isolated organ steady pressure perfusion module of the present application are: it adopts a unique dual-chamber design. The dual-chamber design allows the liquid containing unstable pressure to enter the perfusion chamber from the blood inlet interface first. The liquid in the perfusion chamber can overflow to the overflow chamber through the overflow hole, maintaining the stability of the liquid level in the perfusion chamber, isolating the fluctuating pressure in the perfusion chamber, and providing a stable perfusion pressure. The pressure-stabilizing blood tank is height-adjustably connected to the lifting frame 16, so that the perfusion pressure can be adjusted. The perfusion chamber directly infuses the required organ through the bleeding interface. Secondly, the overflow interface plays the role of discharging the liquid, and the exhaust and rehydration interface plays an auxiliary role in discharging gas or temporarily replenishing liquid. On the whole, the isolated organ steady pressure perfusion module of the present application can resolve the unstable pressure of the liquid at the input end, and then output a steady pressure flow suitable for the physiological needs of the organ.

[0032] In a preferred design, an obliquely arranged drainage plate with overflow holes is used to ensure that only when the liquid level is higher than the overflow hole on the upper side of the drainage plate, the overflowed blood or perfusion liquid will flow smoothly from the perfusion chamber to the overflow chamber along the drainage plate. This design allows the overflowed liquid to fall gently along the inclined surface of the drainage plate, ensuring the gradual and smooth transfer of the liquid, effectively avoiding bubbles generated by the mutual impact between liquids during overflow, reducing mechanical and chemical damage to the blood, and effectively preventing the mixing of blood or perfusion liquid with gas during the overflow process. The oxidation reaction caused by a large amount of blood foam and oxygen in the existing overflow scheme is avoided. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] In order to more clearly illustrate the technical solution in the embodiment, the drawings of the embodiment will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without creative work.

[0034] Figure 1 It is a front view of an embodiment of an isolated organ steady pressure perfusion module of the present application;

[0035] Figure 2 This application Figure 1 AA section view;

[0036] Figure 3 It is a right view of an embodiment of the isolated organ steady pressure perfusion module of the present application;

[0037] Figure 4 This application Figure 3 BB cross-sectional view;

[0038] Figure 5 is an exploded view of an embodiment of an isolated organ steady pressure perfusion module of the present application;

[0039] Figure 6 It is a three-dimensional diagram of an embodiment of the annular intermediate layer and the guide plate of the present application;

[0040] Figure 7 It is a three-dimensional diagram of an embodiment of the annular intermediate layer and the guide plate of the present application;

[0041] Figure 8 is a three-dimensional diagram of an embodiment of the end cap of the present application;

[0042] Fig. 9 (a) is a schematic diagram of a first use state of the isolated organ steady pressure perfusion module of the present application;

[0043] Fig. 9 (b) is a schematic diagram of a second use state of the isolated organ steady pressure perfusion module of the present application;

[0044] Fig. 9 (c) is a schematic diagram of a third use state of the isolated organ steady pressure perfusion module of the present application;

[0045] Fig. 9 (d) is a schematic diagram of a fourth use state of the isolated organ steady pressure perfusion module of the present application;

[0046] Fig.10 It is a flow chart of an embodiment of an isolated organ steady pressure perfusion module of the present application;

[0047] Fig.11 is a pressure curve diagram of an embodiment of the liquid at the outlet of the power module of the present application;

[0048] Fig.12 is a pressure curve diagram of an embodiment of the liquid received by the perfused organ of the present application;

[0049] Fig.13 It is a curve diagram showing the relationship between the inclination angle of the drainage plate, the opening frequency of the overflow interface, and the contact speed between the liquid and the liquid surface of the overflow chamber in one embodiment of the isolated organ steady pressure perfusion module of the present application;

[0050] Fig.14 This application Fig.13 A partial enlarged image of the content in the dotted box.

[0051] Description of Reference Numerals

[0052] 1-lug; 2-bolt hole; 3-blood inlet interface; 4-perfusion chamber; 5-annular middle layer; 6-bleeding interface; 7-connecting arm; 8-exhaust and rehydration interface; 9-end cover; 10-overflow chamber; 11-sealing strip; 12-drainage plate; 13-overflow interface; 14-pipeline; 15-tube clamp valve; 16-lifting frame; 17-flexible material membrane; 18-arc-shaped convex edge; 19-upper square hole; 20-lower square hole; 21-straight groove; 22-circular groove; 23-flange stop; 24-straight convex rib; 25-circular convex rib; 26-horizontal extension platform; 27-power module; 28-blood distribution module; 29-oxygenation module; 30-perfused organ; 31-blood storage module. DETAILED DESCRIPTION

[0053] The isolated organ steady pressure perfusion module, the isolated organ steady pressure perfusion system, and the isolated organ steady pressure perfusion method of the present application are further described in detail below in conjunction with specific embodiments.

[0054] See also Figures 1 to 8 The embodiment of the present application provides an isolated organ steady pressure perfusion module, which includes a lifting frame 16, and the lifting frame 16 is electrically driven. The perfusion module includes a pressure-stabilizing blood bin and a clamp valve 15, and the lifting frame 16 is assembled with the pressure-stabilizing blood bin through a connecting arm 7 with an integrated weight sensor. The overall shape of the pressure-stabilizing blood bin is a round pancake, that is, the inner wall of the pressure-stabilizing blood bin includes a concave surface. At the same time, the pressure-stabilizing blood bin is a double-chamber structure consisting of a perfusion chamber 4 and an overflow chamber 10. The perfusion chamber 4 and the overflow chamber 10 are separated from each other by an inclined (here, it means inclined relative to the vertical direction) drainage plate 12, so that the perfusion chamber 4 is arranged on the oblique lower side of the drainage plate 12, and the overflow chamber 10 is arranged on the oblique upper side of the drainage plate 12. The upper half of the drainage plate 12 is provided with a through overflow hole, and the fluid can flow from one chamber to another only when the liquid level of a chamber exceeds the lower edge of the overflow hole.

[0055] The beneficial effects of adopting the above technical solution are: the design of the round pancake-shaped pressure-stabilizing blood chamber and the double chamber consisting of the perfusion chamber 4 and the overflow chamber 10 are all designed to reduce the sudden change in shear rate when the blood flows inside. The design of the drainage plate 12 with overflow holes ensures that only when the liquid level is higher than the overflow hole on the upper side of the drainage plate 12, the overflowed blood or perfusion liquid will flow smoothly from the perfusion chamber 4 to the overflow chamber 10 along the drainage plate 12. This design method ensures the gradual and smooth transfer of liquid, effectively avoids bubbles generated by the mutual impact between liquids during overflow, and reduces the mechanical and chemical damage to the blood.

[0056] Combination Figure 2 and Figure 4As shown, the pressure-stabilizing blood chamber includes an annular middle layer 5, left and right end covers 9 and a flexible material membrane 17. Both ends of the drainage plate 12 are connected to the inner wall of the annular middle layer 5. The perfusion chamber 4 is connected to a blood inlet interface 3 and a bleeding interface 6, and the heights of these two interfaces are lower than the lower edge of the overflow hole on the drainage plate 12. The overflow chamber 10 is connected to an exhaust and liquid replenishment interface 8 and an overflow interface 13, and the exhaust and liquid replenishment interface 8 is located at the highest point of the overflow chamber 10. The exhaust and liquid replenishment interface 8 will only be opened when there is a need for exhaust during the pre-filling stage of the normal temperature mechanical perfusion technology (NMP), or when a large amount of liquid needs to be quickly replenished in the pressure-stabilizing blood chamber under special circumstances. In addition, the overflow interface 13 is at the lowest point of the overflow chamber 10, and as shown Figure 1 As shown, the overflow interface 13 is connected to a pipeline 14 at its downstream, and a pipe clamp valve 15 that can be opened and closed is installed on the pipeline 14.

[0057] The beneficial effect of adopting the above technical solution is that it can ensure that both the blood inlet interface 3 and the bleeding interface 6 are located below the liquid level of the perfusion chamber 4 under normal working conditions, and ensure that the pressure-stabilizing blood chamber is not connected to the atmosphere under normal working conditions, thereby preventing the blood or perfusion fluid in the pressure-stabilizing blood chamber from being contaminated by pollutants in the air.

[0058] In addition, the tube clamp valve 15 is opened and closed according to the real-time weight sensor data, which ensures that the liquid level in the overflow chamber 10 is lower than the threshold value, and at the same time ensures that the overflow interface 13 is always immersed in liquid to prevent air from entering the system, thereby avoiding the mixing of blood or perfusion fluid and air in the pipeline, thereby maintaining the relative closure of the entire pressure-stabilized blood chamber and the integrity of the blood.

[0059] In another embodiment, if Figure 4 As shown, the axis of the overflow interface 13 is parallel to the upper surface of the drainage plate 12. The blood inlet interface 3 needs to be lower than the height of the overflow hole. The axes of the bleeding interface 6 and the exhaust and liquid replenishment interface 8 extend in the vertical direction, and the axes of the bleeding interface 6 and the exhaust and liquid replenishment interface 8 can overlap on the same spatial plumb line. The bleeding interface 6 is connected to the lowest point in the vertical direction of the perfusion chamber 4, and the exhaust and liquid replenishment interface 8 is connected to the highest point in the vertical direction of the overflow chamber 10.

[0060] In another embodiment, theoretical calculations and experimental studies have shown that the angle between the upper surface of the drain plate 12 and the horizontal plane affects the following factors: the contact speed of the liquid with the liquid surface of the overflow chamber 10 when the liquid flows from the perfusion chamber 4 along the drain plate 12 into the overflow chamber 10, and the frequency of the overflow interface 13 discharging liquid from the overflow chamber 10.

[0061] For the convenience of comparison and explanation, the opening threshold of the tube clamp valve 15 at the overflow interface 13 is always set when the liquid level in the overflow chamber 10 is flush with the lower edge of the overflow hole on the drain plate 12, and the liquid is set to flow from the perfusion chamber 4 to the overflow chamber 10 at a constant flow rate. Under the above conditions, as the angle between the upper surface of the drain plate 12 and the horizontal plane gradually increases from 0°, the contact speed of the liquid with the liquid surface in the overflow chamber 10 after flowing down the drain plate 12 gradually increases, and the blood damage caused by the resulting liquid impact also gradually increases. At the same time, as the angle between the upper surface of the drain plate 12 and the horizontal plane gradually increases, when the opening threshold of the tube clamp valve 15 is reached, the volume of liquid in the overflow chamber 10 gradually increases. Therefore, when the aforementioned set conditions are met, the opening frequency of the tube clamp valve 15 at the overflow interface 13 gradually decreases, which helps to extend the service life of the tube clamp valve 15. Fig.13 As shown, the value corresponding to the angle of 45° between the upper surface of the drain plate 12 and the horizontal plane is taken as the reference value, and the increase or decrease ratio of the corresponding values ​​at other angles of different degrees is plotted. Among them, the horizontal axis is the angle between the drain plate 12 and the horizontal plane, and the vertical axis is the percentage relationship between the actual value and the reference value, and the vertical axis unit is a percentage sign. In addition, the solid line expresses the opening frequency of the overflow interface 13, and the dotted line expresses the contact speed between the liquid and the liquid surface of the overflow chamber 10. Fig.14 is right Fig.13 Further enlargement of the dotted box in the middle makes it easier to view the correspondence between the horizontal axis and the vertical axis more accurately.

[0062] After comprehensively considering the contact speed between the liquid and the liquid surface of the overflow chamber 10 and the opening frequency of the overflow interface 13, in order to minimize the blood damage caused by the liquid impact and reduce the opening frequency of the overflow interface 13 to extend the service life of the tube clamp valve 15, Fig.14 As shown, the preferred range of the angle between the upper surface of the guide plate 12 and the horizontal plane is 30° to 70°.

[0063] When the actual angle between the upper surface of the guide plate 12 and the horizontal plane is less than 30°, although the contact speed between the liquid and the liquid surface of the overflow chamber 10 is 17% or even more lower than that in the case of 45°, the overflow interface 13 needs to be opened and closed frequently. For example, when the angle is 10°, the opening frequency is about 360% of that in the case of 45°, which seriously increases the workload of the pipe clamp valve 15. Therefore, when the angle is less than 30°, the requirements cannot be met. On the contrary, when the angle is greater than 70°, as the angle increases, the opening frequency of the overflow interface 13 does not decrease significantly, but the contact speed will increase, resulting in enhanced liquid impact. Therefore, the interval with an angle greater than 70° is not the preferred range either.

[0064] The appropriate oblique angle of the drainage plate 12 can drain the blood smoothly. The oblique drainage plate 12 design can effectively prevent the mixing of blood or perfusion fluid with gas during the overflow process. It avoids the oxidation reaction caused by a large amount of blood foam and oxygen in the existing overflow solution, avoids damaging the blood quality, and ensures that the integrity of blood and perfusion fluid is protected.

[0065] like Figure 7 As shown, in another embodiment, the overflow hole itself is horizontal in direction, and the overflow hole is located above the centroid of the pressure-stabilizing blood chamber. The overflow hole includes an upper square hole 19 and a lower square hole 20. The height of the upper square hole 19 is higher than the height of the lower square hole 20. The cross-sectional contours of the upper square hole 19 and the lower square hole 20 are both rounded rectangles, and the opening area of ​​the lower square hole 20 is larger than the opening area of ​​the upper square hole 19. When the flow rate of blood or perfusion fluid entering the pressure-stabilizing blood chamber is less than or equal to the overflow capacity of the lower square hole 20, the liquid level will stabilize at the lower edge of the lower square hole 20. When the flow rate is large and exceeds the overflow capacity of the lower square hole 20, the liquid level will rise, the upper square hole 19 will begin to overflow, and the liquid level will eventually stabilize at the lower edge of the upper square hole 19. In addition, as Figure 7 As shown, due to the thickness of the drainage plate 12 itself, a horizontal extension platform 26 is naturally formed on the bottom surface of the inner wall of each of the upper square hole 19 and the lower square hole 20, and the horizontal extension platform 26 facilitates the smooth transition of blood.

[0066] The beneficial effect of adopting the above technical solution is that the double hole design is to achieve graded overflow. At the same time, the design of using two square holes instead of a large square hole is to avoid reducing the structural strength of the guide plate 12. Because the guide plate 12 is used to separate the perfusion chamber 4 and the overflow chamber 10, the left and right end caps 9 will press the guide plate 12 to achieve sealing, so the guide plate 12 must have sufficient structural strength to withstand pressure.

[0067] In another embodiment, a multi-way valve is first connected to the outside of the exhaust and rehydration interface 8. The multi-way valve is also connected to a one-way exhaust valve, the outside atmosphere, and the rehydration bottle. The multi-way valve can form three connection paths, namely, the connection path between the exhaust and rehydration interface 8 and the exhaust valve, the connection path between the exhaust and rehydration interface 8 and the outside atmosphere, and the connection path between the exhaust and rehydration interface 8 and the rehydration bottle. The multi-way valve can selectively switch between these three connection paths. The exhaust valve is also called a micro blood exhaust valve (also called a liquid filter valve). This micro blood exhaust valve is a one-way valve that only allows gas to pass in one direction and does not allow liquid to pass from any direction. Therefore, by using this valve, when a certain pressure difference is reached with the outside world, the gas in the pressure-stabilized blood chamber will be discharged into the atmosphere, while the outside air will not enter, and the blood or perfusion fluid in the pressure-stabilized blood chamber will not overflow to the outside world. When liquid needs to be supplemented, the multi-way valve on the outside of the exhaust and rehydration interface 8 is switched to a state connected to the rehydration bottle.

[0068] In another embodiment, if Figure 2 As shown, both sides of the pressure-stabilizing blood chamber are wrapped by a flexible material film 17, and the area of ​​the flexible material film 17 is much larger than the rigid opening area of ​​the axial end of the annular intermediate layer 5. When the pressure inside the pressure-stabilizing blood chamber changes, the flexible material film 17 may bulge outward or concave inward (since the flexible material film 17 is relatively not a rigid body, its shape may change dynamically during actual operation. In addition, for example Figure 5 The flexible material membrane 17 is hidden and not shown). The perfusion chamber 4 and the overflow chamber 10 are formed between the two parallel flexible material membranes 17, and a cavity is also formed between the flexible material membrane 17 and the adjacent end cap 9.

[0069] The beneficial effects of adopting the above technical solution are: on the one hand, when the pressure-stabilizing blood chamber is connected to a power module 27 such as a blood pump (see Fig.10 ), the negative impact of the injection pressure of the blood pump on the blood disturbance in the perfusion chamber 4 is itself not significant; on the other hand, the flexible material membrane 17 will further buffer the disturbance caused by the blood pump injection through its own elastic deformation. If the pressure-stabilizing blood bin is compared to a double-sided drum, the area of ​​the drum surface on both sides (i.e., the flexible material membrane 17) can be much larger than the area of ​​the drum edge (i.e., the middle layer 5). Such an area limitation, on the one hand, ensures that a circle of the edge of the flexible material membrane 17 is sealed and assembled, thereby partially isolating the internal and external environments of the pressure-stabilizing blood bin. Second, the flexible material membrane 17 has enough area to ensure that it has a sufficient axial concave-convex shape, thereby ensuring that the volume change range of the cavity of the pressure-stabilizing blood bin is also large.

[0070] In another embodiment, the pressure-stabilizing blood chamber has two working modes: one is that the exhaust and rehydration interface 8 only allows internal gas to be discharged, and does not allow external gas to enter. In this mode, when the blood in the overflow chamber 10 becomes less, it is not that the gas cavity of the overflow chamber 10 becomes larger, but the flexible material membrane 17 is deformed, and the two flexible material membranes 17 are concave close to each other, which is equivalent to the total volume of the overflow chamber 10 becoming smaller. Second, when in certain cases, the exhaust and rehydration interface 8 is not connected to the micro blood exhaust valve, the exhaust and rehydration interface 8 is directly connected to the outside atmosphere. In this mode, external gas can freely enter and exit the pressure-stabilizing blood chamber. At this time, the outside air entering from the exhaust and rehydration interface 8 is used to fill and enlarge the cavity.

[0071] The beneficial effects of adopting the above technical solution are: first, it is ensured that the pressure-stabilized blood chamber does not exchange air with the external gas to avoid its contamination. Secondly, even if there is no one-way control of the micro blood exhaust valve, so that the blood and air come into contact, this contact will be limited to the gas-liquid interface, and the impact will be small. Because in fact, what really has a negative impact on the blood is the full mixing of blood and gas, for example, the whole process of a large number of small bubbles floating from the bottom of the blood or perfusion fluid to the upper part.

[0072] like Figure 1 As shown, in another embodiment, the clamp valve 15 can be electrically driven or manually driven. When electrically driven, the control system automatically controls the opening and closing of the clamp valve 15 according to the weight sensor signal; when manually driven, the user controls the opening and closing according to the weight sensor signal.

[0073] In another embodiment, the lifting frame 16 drives the pressure-stabilizing blood bin so that it has only one vertical lifting degree of freedom. The lifting frame 16 is provided with a scale, and the pressure-stabilizing blood bin is connected to the lifting frame 16 by magnetic attraction, or the pressure-stabilizing blood bin is connected to the lifting frame 16 in an adjustable height by an electric drive device. The pressure-stabilizing blood bin and the connecting arm 7 are connected by magnetic attraction, which is convenient and fast, and allows for rapid disassembly and reorganization when necessary, which is convenient for maintenance and cleaning. The connecting arm 7 is connected to an end cap 9 through a servo motor, and the axis of the servo motor coincides with the axis of the pressure-stabilizing blood bin. A servo motor is added to rotate the pressure-stabilizing blood bin around its own axis to adjust the angle of the drainage plate 12. This changes the flow rate from the perfusion chamber 4 to the overflow chamber 10, and makes very fine adjustments to the output pressure.

[0074] The isolated organ steady pressure perfusion module disclosed in this application adopts an assembled structure. Figure 2 , 4 As shown in FIG. 8 , the edge of the end cover 9 is provided with a circle of flange stoppers 23, and the flange stoppers 23 are provided with bolt holes 2 in an annular array. The bolts passing through the bolt holes 2 and the sealing strip 11 are used to achieve sealing. Figure 8 As shown, each end cap 9 has two arcuate convex edges 18, the adjacent portions of the two arcuate convex edges 18 form a linear groove 21, and the opposite portions of the two arcuate convex edges 18 form an annular groove 22. The linear groove 21 and the annular groove 22 are the grooves on the facing surfaces of the two end caps 9. Figure 6 As shown, the axial end of the annular intermediate layer 5 forms an annular convex rib 25 , and the two sides of the guide plate 12 form a linear convex rib 24 .

[0075] During the installation process, the annular convex rib 25 is tightly fitted with the annular groove 22 through the sealing strip 11, and the linear convex rib 24 is tightly fitted with the linear groove 21 through the sealing strip 11. Then, the lug 1 on the outer wall of the annular intermediate layer 5 is used to position and align the annular intermediate layer 5, the end cover 9 and the flexible material film 17; the axial end edge of the annular intermediate layer 5 and the side edge of the guide plate 12 are squeezed and contacted with the sealing strip 11 through the flexible material film 17. Finally, the bolts are inserted into the bolt holes 2 and the end cover 9 is pressed with nuts to achieve assembly of the overall structure.

[0076] In another embodiment, the annular middle layer 5 and the two side end caps 9 of the pressure-stabilizing blood chamber are made of polymethyl methacrylate (PMMA) material to ensure the transparency and mechanical strength of the structure. The flexible material membrane 17 used is polydimethylsiloxane (PDMS), which is suitable for medical devices that contact blood due to its excellent biocompatibility and elasticity.

[0077] The beneficial effects of adopting the above technical solution are: the flexible material membrane 17, due to its excellent flexibility and blood compatibility, can provide the necessary buffering effect when in contact with blood, reduce fluid impact, and protect cells from mechanical damage. The flexible material membrane 17 can also be quickly replaced after each use. The deformable characteristics of the flexible material membrane 17 further enhance the functionality of the pressure-stabilizing blood chamber, making it more stable and safe when dealing with dynamic pressure changes.

[0078] In addition, blood, artificial blood or any other perfusion fluid that meets the organ perfusion requirements can be used in the pressure-stabilized blood chamber. For example, animal autologous blood after leukocyte removal can be used, and the blood density is 1050kg / m 3 .

[0079] The present application also provides an isolated organ steady pressure perfusion system. Fig.10 The flowchart shown in the figure shows an optional connection mode between the isolated organ steady pressure perfusion module and other modules in the normothermic mechanical perfusion technology (NMP) system, wherein the dashed box represents the isolated organ steady pressure perfusion module. The isolated organ steady pressure perfusion system also includes a power module 27, a blood distribution module 28, an oxygenation module 29, and a blood storage module 31. A typical representative of the power module 27 is a blood pump, and a representative of the perfused organ 30 is a liver having a hepatic artery and a portal vein.

[0080] The pulsating blood flow output by the blood pump is divided proportionally through the blood distribution module 28. It flows into the hepatic artery and the portal vein branch respectively. Among them, the fluid of the hepatic artery branch provides the hepatic artery with oxygenated blood or perfusion fluid that conforms to the physiological pulsation law of the artery after passing through the oxygenation module 29, and the fluid of the portal vein branch flows into the perfusion chamber 4 through the blood inlet interface 3. The liquid level in the perfusion chamber 4 is always consistent with the lower edge of the overflow hole on the drainage plate 12. When the liquid level of the perfusion chamber 4 exceeds the lower edge of the overflow hole, the excess blood or perfusion fluid will flow smoothly into the overflow chamber 10 along the drainage plate 12. The overflow chamber 10 discharges excess liquid to the blood storage module 31 through the tube clamp valve 15, and the opening and closing of the tube clamp valve 15 can be controlled based on the signal of the weight sensor.

[0081] The beneficial effect of adopting the above technical solution is that the above design ensures that the blood or perfusion fluid flowing out of the bleeding interface 6 of the pressure-stabilized blood chamber remains stable and pulsating. Specifically, the smoothness of the flow is ensured by the liquid level in the perfusion chamber 4 being always kept constant. There is a height difference between the liquid level in the perfusion chamber 4 and the portal vein plane of the perfused organ 30. This height difference can be adjusted by changing the height of the lifting frame 16, thereby accurately controlling the perfusion pressure.

[0082] The isolated organ steady pressure perfusion system of the present application uses the lifting frame 16 to adjust the relative height between the lifting frame 16 and the plane where the blood vessels of the perfused organ 30 are located, so as to accurately control the pressure provided to the perfused organ 30. The height adjustment accuracy of the lifting frame 16 is, for example, 1 mm. Combined with the density of blood and perfusion fluid, the module can achieve a pressure control accuracy of up to 0.08 mmHg. This accuracy exceeds the commonly used solution of setting a separate blood pump to supply blood to the portal vein, and can well meet the physiological needs of 5 mmHg to 8 mmHg of stable non-pulsating blood flow required by the portal vein of the liver. In addition, the design of the isolated organ steady pressure perfusion system of the present application allows the perfusion flow to be adaptively adjusted according to the current state of the perfused organ 30 while maintaining the perfusion pressure at the desired value, without relying on additional manual or program control to adjust the flow, which increases the convenience of operation and the response speed of the system. The so-called adaptive adjustment of the perfusion flow means that the perfusion system can control the pressure at the entrance of the portal vein to a constant value, and its output flow will be automatically adjusted according to the changes in the liver state. For example, when the blood vessels in the liver constrict, the flow resistance of the liver will increase (increased flow resistance means that the required flow rate will decrease under the same pressure). At this time, the perfusion system will naturally reduce the flow rate while maintaining a certain pressure at the portal vein inlet.

[0083] The isolated organ steady pressure perfusion system of the present application modularizes each functional area. This design enables the isolated organ steady pressure perfusion module of the present application to be flexibly configured with other modules in the normothermic mechanical perfusion technology (NMP) system according to actual use requirements. The versatility of the module lies in that it does not require the blood pump connected to it to output an accurate and non-fluctuating flow rate, which greatly reduces the requirements for the blood pump control system and increases the flexibility of use. Therefore, whether it is a roller pump, a peristaltic pump or a centrifugal pump, this module and this system are compatible with them, expanding its application possibilities in various normothermic mechanical perfusion technology (NMP) systems.

[0084] The present application also provides an isolated organ steady pressure perfusion method. The isolated organ steady pressure perfusion method may include the following steps:

[0085] Step S1: Pre-charging state.

[0086] At this stage, the system starts pre-charging. First, the downstream flow path of the bleeding interface 6 is closed with a Robert clamp, and the clamp valve 15 downstream of the overflow interface 13 is closed. After the blood pump is started, blood or perfusion fluid enters the perfusion chamber 4 from the blood inlet interface 3 under the drive of the blood pump. At this time, the liquid level of the perfusion chamber 4 gradually rises, there is no liquid in the overflow chamber 10, and the value of the weight sensor has not reached the upper threshold. This state is as shown in the attached figure. Fig. 9 In Fig. 9 As shown in (a).

[0087] Step S2: overflow starting state.

[0088] As the liquid level in the perfusion chamber 4 gradually rises to the lower edge of the overflow hole on the drainage plate 12, the liquid begins to flow smoothly into the overflow chamber 10 along the drainage plate 12. At this time, the Robert clamp of the bleeding interface 6 and the pipe clamp valve 15 downstream of the overflow interface 13 continue to remain closed, and the value of the weight sensor gradually increases but still does not reach the upper threshold. This state is shown in the attached figure. Fig. 9 In Fig. 9 as shown in (b).

[0089] Step S3: Low point working state.

[0090] In this state, the amount of liquid in the overflow chamber 10 is just enough to submerge the overflow interface 13, and the reading of the weight sensor continues to increase but has not yet reached the upper threshold. At this time, the Robert clamp of the bleeding interface 6 is opened, and the clamp valve 15 downstream of the overflow interface 13 remains closed. The pressure perfusion module now begins to provide stable blood or perfusion fluid to the perfused organ 30. This state is shown in the attached figure. Fig. 9 In Fig. 9 as shown in (c).

[0091] Step S4: high point working state.

[0092] When the liquid level in the overflow chamber 10 reaches the set upper threshold, the control system switches the clamp valve 15 downstream of the overflow interface 13 from the closed state to the open state according to the signal of the weight sensor, or the weight sensor prompts the operator to switch manually. At this time, the blood or perfusion fluid in the overflow chamber 10 flows into the blood storage module 31 through the overflow interface 13, and the liquid level begins to drop. During this process, the bleeding interface 6 is always kept open, and the pressure perfusion module always provides stable blood or perfusion fluid to the perfused organ 30 according to the pressure setting value. This state is as shown in the attached figure. Fig. 9 In Fig. 9 as shown in (d).

[0093] Step S5: The liquid level drops to the lower threshold state.

[0094] When the liquid level in the overflow chamber 10 drops to just enough to immerse the overflow interface 13, the control system switches the clamp valve 15 from the open state to the closed state according to the reading of the weight sensor, or the weight sensor prompts the operator to manually operate. This operation ensures that no air enters the system pipeline, thereby preventing blood or perfusion fluid from mixing with air in the system pipeline, thereby maintaining the closedness of the system. During the above steps S3 to S5, the downstream pipeline 14 connected to the overflow interface 13 is always full of liquid, the bleeding interface 6 is always kept open, and the pressure perfusion module always provides stable blood or perfusion fluid to the perfused organ 30 according to the pressure setting value.

[0095] Step S6: Cycle working state.

[0096] After completing the above operations, the system returns to step S3 and cycles through steps S3 to S5 until the filling process is complete. The operator closes the module after the filling process is complete, marking the end of the entire process. Fig. 9 In Fig. 9 (c) and Fig. 9 as shown in (d).

[0097] The isolated organ steady pressure perfusion module, isolated organ steady pressure perfusion system, and isolated organ steady pressure perfusion method of the present application are used. The inaccurate flow and non-steady liquid flow output by the blood pump can be converted into a steady pressure flow suitable for the physiological needs of the organ. At the same time, the isolated organ steady pressure perfusion system can adaptively adjust the flow according to the state of the perfused organ 30 without additional manual or program control, and accurately and continuously maintain the desired perfusion pressure. In addition, the isolated organ steady pressure perfusion module is suitable for the pulsatile blood pump to provide the stable blood flow required by the portal vein, and at the same time resolves the problem of large output flow and pressure fluctuations of the pulsatile blood pump. The frequent mixing of blood or perfusion fluid and gas during the overflow process is avoided, and the generation of blood foam and the oxidation of oxygen are effectively prevented, thereby reducing the damage to blood or perfusion fluid, and improving the bionics and reliability of the mechanical perfusion equipment. The overall cost is low, the reliability is high, it is compatible with a variety of blood pumps, and the output pressure can be accurately controlled.

[0098] Next, the pressure control principle and accuracy are described in detail. The perfused organ 30 takes the liver as an example. The liver has a portal vein and a hepatic artery. This mechanism relies on the lifting frame 16 to adjust the height of the pressure-stabilizing blood chamber, thereby changing the height difference between the liquid level in the perfusion chamber 4 and the plane where the blood vessels of the organ to be perfused are located, thereby accurately controlling the pressure at the blood vessels of the perfused organ 30. The height adjustment accuracy of the lifting frame 16 reaches 1 mm. Using this feature, this module can finely adjust the perfusion pressure to meet physiological needs.

[0099] Considering that the density of blood and perfusion fluid is roughly the same, the general value is 1050 kg / m 3 Under the assumption that the flow rate of the liquid flowing into the blood vessels of the perfused organ 30 remains constant for a short period of time, the accuracy of the perfusion pressure control can be calculated. The basic formula of liquid statics is applied: Δp = ρgΔh, where Δh is the change in liquid level, ρ is the density of the liquid, and g is the acceleration due to gravity (about 9.81 m / s 2 ), we can get the following formula:

[0100] Δp=1050kg / m 3 ×9.81m / s 2 ×0.001m=10.29Pa≈0.08mmHg

[0101] The above calculation results show that the module can achieve a pressure control accuracy of up to 0.08 mmHg, which exceeds the solution of using an independent blood pump to supply blood to the portal vein.

[0102] Under normal physiological conditions, the portal vein pressure range should be 5 mmHg to 10 mmHg. Taking into account the abnormal portal vein pressure that may occur in some pathological livers, the design of the isolated organ steady pressure perfusion module allows the pressure to be adjusted between 0 mmHg and 20 mmHg to meet different organ perfusion requirements. In order to achieve this pressure adjustment range, the height adjustment range that the lifting frame 16 must achieve is calculated. The pressure at the portal vein of the liver is determined by the height difference between the liquid level in the perfusion chamber 4 and the plane where the portal vein is located. In order to adjust the pressure from 0 mmHg to 20 mmHg, the static pressure formula h = p / ρg is applied, and the following formula can be obtained:

[0103]

[0104] Therefore, the lifting frame 16 needs to be able to rise or fall by at least 25.9 cm to achieve a corresponding change in the liquid level height difference within the range of 0 cm to 25.9 cm. This height range does not require high technical requirements for the lifting frame 16 and is feasible, ensuring the wide applicability and practicality of the module.

[0105] How to determine the state switching threshold of the pinch valve 15 is described in detail below.

[0106] First, after completing the connection with other modules of the normothermic mechanical perfusion technology (NMP) system and before pre-filling the isolated organ steady pressure perfusion module with liquid, the total weight M1 (in kilograms, kg) of the overall structure of the steady pressure blood chamber can be obtained through the connecting arm 7 with an integrated weight sensor, which includes the total weight of the annular intermediate layer 5, the end cover 9, the flexible material membrane 17, and the bolts and nuts used for assembly.

[0107] In the working state step S4, the liquid level in the overflow chamber 10 reaches the upper threshold, that is, d cm below the lower edge of the square hole on the drainage plate 12 (d becomes the upper limit margin, usually d = 2 cm to ensure accurate and timely switching of the clamp valve 15). At this time, the liquid level in the perfusion chamber 4 is flush with the lower edge of the square hole on the drainage plate 12. The total volume of the liquid in the pressure-stabilized blood chamber in this state is measured as V1 (in cubic meters, m 3 ). In the working state step S3, the amount of liquid in the overflow chamber 10 is just enough to immerse the overflow interface 13. At this time, the liquid level in the perfusion chamber 4 is still flush with the lower edge of the overflow hole on the drainage plate 12. The total volume of liquid in the pressure-stabilized blood chamber in this state is measured as V2 (in cubic meters, m 3 ). For different embodiments, the specific values ​​of M1, V1, and V2 are different.

[0108] Assume that the density of blood or perfusion fluid used in the normothermic mechanical perfusion (NMP) system is ρ.

[0109] Accordingly, the threshold value for the clamp valve 15 to switch to the open state is:

[0110] T open =M1+ρ×V1

[0111] When the weight sensor reading is higher than or equal to the opening weight T open When the duration exceeds 1 second, the clamp valve 15 will be automatically or manually switched to the open state from any previous state.

[0112] In contrast, the threshold value for the clamp valve 15 to switch to the closed state is:

[0113] T close =M1+ρ×V2

[0114] When the weight sensor reading is lower than or equal to the shut-off weight T close And when the duration exceeds 1 second, the pipe clamp valve 15 will be automatically or manually switched to the closed state from any previous state.

[0115] In one example, the shape of the pressure-stabilizing blood chamber is a round pancake, the total weight of the structure M1 is 0.58 kg, and the upper limit margin d is equal to 2 cm. The measurement shows: V1 = 0.0006 m 3 , V2=0.00038m 3 According to the above formula, we have: T open =1.21kg, T close =0.98kg. In the annular middle layer 5, the guide plate 12 is designed to be inclined at an angle of 45° to optimize the flow path of the liquid and reduce the impact between the liquids.

[0116] Press Attach Fig.10 The connection method shown connects this module with other modules in the normothermic mechanical perfusion technology (NMP) system, and the dotted box is the pressure perfusion module disclosed in the present invention. The power module uses a centrifugal pump to output pulsating blood flow that conforms to the law of arterial pressure changes. After being proportionally divided by the blood distribution module 28, the blood flows to the hepatic artery branch and the portal vein branch at the same time. After passing through the oxygenation module 29, the pulsating blood of the hepatic artery branch provides oxygenated blood to the hepatic artery of the perfused liver. The pulsating blood of the portal vein branch enters the perfusion chamber 4 through the blood inlet interface 3. When the liquid level of the perfusion chamber 4 exceeds the lower edge of the square hole on the drainage plate 12, the excess liquid will flow into the overflow chamber 10 and, under the control of the tube clamp valve 15, flow back to the blood storage module 31. The bleeding interface 6 of the perfusion chamber 4 is connected to the portal vein of the perfused liver to ensure that the perfusion pressure matches the physiological needs.

[0117] In one case, the pressure curve at the outlet of the power module 27 represented by the blood pump is shown in the attached figure. Fig.11 As shown in the figure, the blood pump pressure has obvious peaks and troughs, and the difference between the peaks and troughs is about 19 mmHg. After being processed by the isolated organ steady pressure perfusion module, the pressure curve output to the portal vein of the perfused liver is as shown in the attached figure. Fig.12 As shown, the absolute value of the pressure is stable at around 5.2 mmHg, and the pressure fluctuation is maintained below 0.5 mmHg. Fig.11 It is obviously much more stable, which is consistent with the normal pressure range of the portal vein under physiological conditions.

[0118] The above embodiments are only for illustrating the technical concept and features of the present application. The purpose is to enable people familiar with this technology to understand the content of the present application and implement it. It cannot be used to limit the protection scope of the present application. All equivalent changes or modifications made according to the spirit of the present application should be included in the protection scope of the present application.

Claims

1. An isolated organ steady pressure perfusion module, characterized in that: include: The pressure-stabilized blood chamber comprises a perfusion chamber (4) and an overflow chamber (10), wherein the perfusion chamber (4) and the overflow chamber (10) are connected to each other by overflow through an overflow hole; a blood inlet interface (3), a bleeding interface (6), an exhaust and fluid replenishment interface (8), and an overflow interface (13) that are connected to the inside and outside of the pressure-stabilizing blood chamber, wherein the blood inlet interface (3) and the bleeding interface (6) are both connected to the perfusion chamber (4), and the exhaust and fluid replenishment interface (8) and the overflow interface (13) are both connected to the overflow chamber (10); and A lifting frame (16), the pressure-stabilizing blood chamber being connected to the lifting frame (16) in a height-adjustable manner.

2. The isolated organ steady pressure perfusion module according to claim 1, characterized in that: The invention also comprises a drainage plate (12), wherein the drainage plate (12) is arranged at the junction of the perfusion chamber (4) and the overflow chamber (10), the drainage plate (12) is arranged obliquely relative to the vertical direction, and the drainage plate (12) has an overflow hole connecting the perfusion chamber (4) and the overflow chamber (10). The perfusion chamber (4) is arranged at the oblique lower side of the guide plate (12), and the overflow chamber (10) is arranged at the oblique upper side of the guide plate (12).

3. The isolated organ steady pressure perfusion module according to claim 2, characterized in that: The shell of the pressure-stabilizing blood chamber comprises an annular middle layer (5) and end covers (9) mirror-imaged on both sides of the annular middle layer (5); the blood inlet interface (3), the bleeding interface (6), the exhaust and fluid replenishment interface (8), and the overflow interface (13) are all located on the annular middle layer (5); and both ends of the drainage plate (12) are connected to the inner wall of the annular middle layer (5).

4. The isolated organ steady pressure perfusion module according to claim 2, characterized in that: The axis of the overflow interface (13) is parallel to the upper surface of the drainage plate (12); the blood inlet interface (3) is lower than the height of the overflow hole; the axes of the bleeding interface (6) and the exhaust and fluid replenishment interface (8) extend in the vertical direction; the bleeding interface (6) is connected to the lowest point in the vertical direction of the perfusion chamber (4); and the exhaust and fluid replenishment interface (8) is connected to the highest point in the vertical direction of the overflow chamber (10).

5. The isolated organ steady pressure perfusion module according to claim 3, characterized in that: The exhaust and liquid replenishment interface (8) is equipped with a multi-way valve, and the multi-way valve is also connected to a one-way exhaust valve, the outside atmosphere, and the liquid replenishment bottle respectively. The multi-way valve selectively switches between connecting the exhaust and liquid replenishment interface (8) with the exhaust valve, directly connecting the exhaust and liquid replenishment interface (8) with the outside atmosphere, and connecting the exhaust and liquid replenishment interface (8) with the liquid replenishment bottle; Both axial ends of the annular intermediate layer (5) are sealed and covered with a flexible material film (17); the facing surfaces of the two end covers (9) are provided with a card slot, and a sealing strip (11) is installed in the card slot; the axial end edge of the annular intermediate layer (5) and the side edge of the guide plate (12) are in extrusion contact with the sealing strip (11) through the flexible material film (17); The infusion chamber (4) and the overflow chamber (10) are formed between the two parallel flexible material films (17), and a cavity is also formed between the flexible material film (17) and the adjacent end cover (9).

6. The isolated organ steady pressure perfusion module according to claim 1, characterized in that: The lifting frame (16) has a scale, and the pressure-stabilizing blood chamber is connected to the lifting frame (16) by magnetic attraction, or The pressure-stabilized blood chamber is connected to the lifting frame (16) in a height-adjustable manner via an electric drive device.

7. The isolated organ steady pressure perfusion module according to claim 1, characterized in that: The overflow hole itself is horizontal in its penetration direction, and the overflow hole is located above the centroid of the pressure-stabilizing blood chamber; the overflow hole comprises an upper square hole (19) and a lower square hole (20) which are separated from each other, and the bottom surfaces of the inner walls of the upper square hole (19) and the lower square hole (20) are parallel to the horizontal plane.

8. The isolated organ steady pressure perfusion module according to claim 2, characterized in that: The angle formed between the upper surface of the guide plate (12) and the horizontal plane ranges from 30° to 70°.

9. The isolated organ steady pressure perfusion module according to claim 3, characterized in that: The end cover (9) is connected to the lifting frame (16) via a connecting arm (7), and the connecting arm (7) is provided with a weight sensor for monitoring the total weight of the pressure-stabilized blood chamber.

10. The isolated organ steady pressure perfusion module according to claim 5, characterized in that: The material of the annular intermediate layer (5) and the end cover (9) is polymethyl methacrylate, and the material of the flexible material film (17) is polydimethylsiloxane.

11. An isolated organ steady pressure perfusion system, characterized in that: It comprises an isolated organ steady pressure perfusion module according to any one of claims 1 to 10, characterized in that: the blood inlet interface of the steady pressure blood bin is connected to a blood distribution module (28), the overflow interface (13) of the steady pressure blood bin is connected to a blood storage module (31), and the bleeding interface (6) of the steady pressure blood bin can be connected to a perfused organ (30); The blood storage module (31) is connected to the blood distribution module (28) via a power module (27), and the blood storage module (31), the power module (27), the blood distribution module (28), the pressure-stabilizing blood chamber, and the perfused organ (30) are sequentially connected in a one-way circulation.

12. The isolated organ steady pressure perfusion system according to claim 11, characterized in that: The blood distribution module (28) and the perfused organ (30) are also connected via an oxygenation module (29); the pressure-stabilizing blood tank is connected to the vein of the perfused organ (30); and the oxygenation module (29) is connected to the artery of the perfused organ (30).

13. A method for stable pressure perfusion of an isolated organ, characterized in that: The isolated organ steady pressure perfusion system according to claim 11 or 12 is used, and the isolated organ steady pressure perfusion method comprises: Step S1: in a pre-charging state, the power module (27) is started, and liquid including blood and / or perfusion liquid enters the perfusion chamber (4) from the blood inlet interface (3) under the drive of the power module (27), the liquid level of the perfusion chamber (4) gradually rises, while there is no liquid in the overflow chamber (10), and the overflow interface (13) is in a closed state; Step S2: in the overflow starting state, the liquid level of the perfusion chamber (4) rises and passes over the overflow hole, the liquid flows smoothly into the overflow chamber (10) by means of a guide plate (12) arranged obliquely relative to the vertical direction, and the overflow interface (13) is in a closed state; Step S3: in a low-point working state, the amount of the liquid in the overflow chamber (10) is just enough to submerge the overflow interface (13), the pressure-stabilizing blood chamber begins to provide the perfused organ (30) with a stable amount of the liquid, and the overflow interface (13) is in a closed state; Step S4: In the high-point working state, the liquid in the overflow chamber (10) flows into the blood storage module (31) through the overflow interface (13), and the liquid level in the overflow chamber (10) begins to drop.

14. The isolated organ steady pressure perfusion method according to claim 13, characterized in that: After step S4, the method further includes: Step S5: when the liquid level in the overflow chamber (10) drops to a level just sufficient to submerge the overflow interface (13), closing the overflow interface (13) to stop the liquid from flowing out of the overflow chamber (10); Step S6: Circular working state. After completing step S5, return to step S3 and circulate the operation between step S3 and step S5 until the perfusion process is completed.

15. The isolated organ steady pressure perfusion method according to claim 14, characterized in that: The weight of the pressure-stabilized blood chamber is measured by a weight sensor, and based on the weight data, the discharge of liquid from the overflow chamber (10) via the overflow interface (13) is started or stopped.

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