Disposable continuous oxygenation mechanical perfusion circulation system for ex-vivo organs and working method

Abstract

Disclosed in the present invention are a disposable continuous oxygenation mechanical perfusion circulation system for ex-vivo organs and a working method. A circulation pipeline of the circulation system is provided with a deoxygenated return line and an oxygenated perfusion line; an output end of a low-temperature organ storage container is connected to the deoxygenated return line, and a pump tube and an oxygenator are arranged in the deoxygenated return line; an organ adapter sleeve assembly is detachably mounted on an organ tray assembly; the organ tray assembly is arranged in a cavity of the low-temperature organ storage container; and an output end of the oxygenator is connected to the oxygenated perfusion line, an automatic bubble separator mounted on the oxygenated perfusion line is connected to an input end of the organ adapter sleeve assembly, and a pressure sensor is mounted on the oxygenated perfusion line. The present invention has the following advantages: the ability to provide an automatic bubble removal function; having an oxygenation function in addition to a low-temperature mechanical perfusion function; being lightweight and being convenient for portable transport of a perfusion apparatus; and having higher safety and reliability.

Description

A disposable ex vivo organ continuous oxygenation mechanical perfusion circulation system and its working method

[0001] This disclosure claims priority to Chinese Patent Application No. 202411972161.7, filed with the Chinese Patent Office on December 30, 2024, entitled "A disposable ex vivo organ continuous oxygenation mechanical perfusion circulation system and working method", the entire contents of which are incorporated herein by reference. Technical Field

[0002] This invention relates to the field of medical devices for the repair and preservation of ex vivo organs, and in particular to a disposable ex vivo organ continuous oxygenation mechanical perfusion circulation system and its working method. Background Technology

[0003] As is well known, organ transplantation is the most effective treatment for end-stage organ failure, and voluntary organ donation after death is the main source of transplant organs. However, due to factors such as organ donors, organ allocation, and transportation, the quality of donor kidneys has declined due to prolonged ischemia time and the increasing number of high-risk donors, making them more susceptible to delayed graft function recovery and primary non-function of the transplanted kidney. Compared with traditional organ cryopreservation techniques, cryogenic mechanical perfusion, especially continuous oxygenation cryogenic mechanical perfusion, has significant advantages. Medical practice and scientific literature show that continuous oxygenation cryogenic mechanical perfusion can significantly reduce the incidence of delayed graft function recovery and primary non-function of the transplanted kidney, and can also promote early recovery of transplanted kidney function.

[0004] Extensive research has been conducted in the field of organ transplantation regarding organ preservation and transplantation. For example, US Patent 8927257B2 discloses an organ transport container system. In this patent, the organ container system forms a closed loop with the organ's artery via a transfer catheter, and further forms a closed circulation loop with the perfusion system. An external oxygen supply source oxygenates the perfusion fluid through an oxygenator, allowing for cryogenic mechanical perfusion of the organ to be repaired, thereby achieving organ preservation, transportation, and repair. However, it has several problems, specifically:

[0005] 1. Safety issues in organ repair caused by insufficient pressure monitoring: After the organ to be repaired is connected to the organ tray connector of the disposable circulatory system, it is usually necessary to manually pre-perfuse the organ to remove gas at the end of the circulatory system to prevent the possibility of embolism during subsequent organ perfusion. During manual pre-perfusion, if the perfusion pressure is not monitored, there is a risk of irreversible organ damage before organ perfusion repair due to excessive pressure, which may lead to kidney abandonment or poor recovery quality in the later stages of transplantation surgery.

[0006] 2. Safety issues in organ repair caused by the risk of air bubble embolism: When residual air bubbles appear during organ perfusion, it is necessary to manually remove the air bubbles or repeatedly enter the washing mode to prevent the air bubbles from causing organ embolism. Therefore, the timeliness and effectiveness of organ repair are greatly affected.

[0007] 3. Issues with the effectiveness of organ repair due to long operation time: Because organ loading requires manual pre-perfusion, the waiting time before officially entering the perfusion mode is long, which affects the timeliness of organ repair.

[0008] 4. Implementation cost of the technical solution: The centrifugal pump structure and the single-cycle system structure used in the solution provided by this patent are complex and costly.

[0009] Meanwhile, US Patent 7691622B2 relates to apparatus and methods for perfusing one or more organs, tissues, or the like to monitor, maintain, and / or restore organ viability. Its focus is on avoiding damage to the organ during perfusion while monitoring, maintaining, and / or restoring organ viability and preserving the organ for storage and / or transport. However, it still has many drawbacks:

[0010] 1. Safety risks to organ repair caused by air bubble embolism: In the initial stage of mechanical perfusion, a small number of air bubbles may remain at the end of the circulating fluid circuit and cannot be automatically discharged. These air bubbles need to be removed manually to prevent them from causing organ embolism during the perfusion stage. This operation affects the waiting time for normal perfusion. In addition, because the air bubble outlet at the end is on the side, residual air bubbles at the tip of the transfer tube cannot be completely removed even by manual handling due to buoyancy. Therefore, the timeliness and effectiveness of organ repair are affected.

[0011] Because the circulating fluid circuit is an airtight closed system, perfusion needs to be paused periodically during the perfusion process to purge the gas collected in the air bubble trap. Furthermore, the system needs to repeatedly confirm that there are no air bubbles in the circulating fluid circuit before resuming the perfusion mode, which affects the timeliness of organ repair.

[0012] When the circulation system encounters a large number of continuous air bubbles due to leakage or other abnormal conditions, the air bubble separator cannot expel the air bubbles in time and they overflow from the perfusion fluid path. During subsequent perfusion, the air bubbles will flow into the organ and cause organ embolism during perfusion.

[0013] 2. Safety risks to organ repair caused by sudden high perfusion pressure: The circulating fluid circuit is an airtight circulating system, and the cleaning fluid circuit is not equipped with pressure monitoring. When the cleaning fluid circuit is abnormally blocked, the system cannot detect high perfusion pressure, which poses a risk of organ damage, and there is no corresponding protection against this fatal risk.

[0014] 3. Complex structure leads to cost inefficiency: The leakage monitoring structure used in the organ container uses an independent water tank cavity, which is complex and uneconomical.

[0015] 4. Lack of organ oxygen-carrying and repair function: The perfusion circulation system provided by this invention does not support oxygenation perfusion function. Summary of the Invention

[0016] This invention aims to solve the above-mentioned technical problems and provides a disposable ex vivo organ continuous oxygenation mechanical perfusion circulation system that can automatically separate air bubbles and provide continuous oxygenation. It meets the requirements of lightweight and miniaturization while facilitating the turnover and transportation of transport equipment in multiple scenarios.

[0017] The present invention also provides a method for operating a disposable ex vivo organ continuous oxygenation mechanical perfusion circulation system, with an automatic air venting process and uninterrupted continuous mechanical perfusion.

[0018] To solve the above-mentioned technical problems, the present invention provides a disposable ex vivo organ continuous oxygenation mechanical perfusion circulation system, wherein the circulation pipeline of the circulation system has an oxygen delivery pipeline and an oxygen-carrying perfusion pipeline;

[0019] The circulation system includes an organ cryopreservation container, an oxygenator, an automatic bubble separator, an organ transfer sleeve assembly, an organ tray assembly, a pressure sensor, and a pump tube.

[0020] The output end of the organ cryogenic storage container is connected to the oxygen delivery pipeline to be carried, and the pump pipe and oxygenator are installed in the oxygen delivery pipeline to be carried.

[0021] The organ transfer cannula assembly is detachably mounted on the organ tray assembly;

[0022] The organ tray assembly is disposed within the cavity of the organ cryogenic storage container;

[0023] The output end of the oxygenator is connected to the oxygen-carrying perfusion line, the automatic bubble separator installed in the oxygen-carrying perfusion line is connected to the input end of the organ transfer cannula assembly, and the pressure sensor is installed in the oxygen-carrying perfusion line.

[0024] The present invention provides a disposable ex vivo organ continuous oxygenation mechanical perfusion circulation system, wherein the organ transfer sleeve assembly includes a base and a flip cover;

[0025] The base is provided with a through hole, and a flexible gasket is provided at the through hole;

[0026] The flip cover is mounted on the base, and one side of the flip cover and one side of the base are rotatably connected. The flip cover is provided with a water-resistant and breathable membrane installation port, and a water-resistant and breathable membrane is provided at the water-resistant and breathable membrane installation port. The flip cover is provided with a pipe leading to the inside of the flip cover. The bottom of the inner side of the flip cover has a clamping end face. After the flip cover and the base are closed, the clamping end face and the flexible gasket clamp the renal artery for perfusion.

[0027] The present invention provides a disposable ex vivo organ continuous oxygenation mechanical perfusion circulation system, wherein the organ transfer sleeve assembly further includes a support, the support having a support body with a transverse mounting groove on the support body, a top groove on the top of the support body, and a closed bottom support and flip cover installed at the transverse mounting groove.

[0028] The present invention provides a disposable ex vivo organ continuous oxygenation mechanical perfusion circulation system, wherein the automatic bubble separator comprises: a shell, a first water-resistant and air-permeable membrane, an inlet pipe, and an outlet pipe;

[0029] The shell consists of a bottom shell and a cover. The interior of the shell is a sealed cavity. The cover is provided with a gas escape port, and a first water-resistant and breathable membrane is provided at the gas escape port.

[0030] A liquid inlet pipe, which is arranged on the housing;

[0031] A drain pipe is arranged on the housing.

[0032] This invention provides a disposable ex vivo organ continuous oxygenation mechanical perfusion system. The organ cryogenic storage container has a stepped rear wall with a liquid level inlet groove. The extension height of the liquid level inlet groove within the organ cryogenic storage container is lower than the perfusion solution level. A limiting groove for the perfusion solution inlet pipe is reserved on the side wall of the organ cryogenic storage container. Combined with information from the bubble sensor and the 3-axis accelerometer in the equipment control system, commands are issued to stop the perfusion system in the event of a dual warning.

[0033] The present invention provides a disposable ex vivo organ continuous oxygenation mechanical perfusion circulation system, wherein the organ cryogenic storage container is provided with a suspended island structure.

[0034] The present invention also provides a method for operating a disposable ex vivo organ continuous oxygenation mechanical perfusion circulation system, which includes an exhaust mode and a perfusion mode, wherein the exhaust mode and the perfusion mode are performed in the disposable ex vivo organ continuous oxygenation mechanical perfusion circulation system mentioned above.

[0035] The present invention also provides a method for operating a disposable ex vivo organ continuous oxygenation mechanical perfusion circulation system, wherein the exhaust mode method is as follows:

[0036] (1) When perfusion is started, the ultrasonic bubble sensor in the bubble monitoring hose area detects that the circulation pipeline is air. The first clamp valve and the second clamp valve are energized. The gas at the front end of the automatic bubble separator will be separated from the water-resistant and breathable membrane at the top of the automatic bubble separator. The gas at the rear end of the automatic bubble separator passes through the bubble monitoring hose, the organ perfusion main tube, and the cleaning drain tube in sequence to avoid the organ to be perfused and repaired.

[0037] (2) During the perfusion process, since the ultrasonic bubble sensor in the bubble monitoring hose area detects that the circulation pipeline is filled with air, the first clamp valve and the second clamp valve are both energized. The gas at the front end of the automatic bubble separator will be separated from the water-resistant and breathable membrane at the top of the automatic bubble separator. The gas at the rear end of the automatic bubble separator passes through the bubble monitoring hose, the organ perfusion main tube, and the cleaning drain tube in sequence to prevent bubbles from flowing into the organ to be perfused and repaired, causing embolism.

[0038] The present invention also provides a method for operating a disposable ex vivo organ continuous oxygenation mechanical perfusion circulation system, wherein the perfusion mode method is as follows:

[0039] (1) The perfusion mode is carried out in the single-use ex vivo organ continuous oxygenation mechanical perfusion circulation system mentioned above. The tiny bubbles flowing out of the oxygenator flow into the liquid inlet pipe of the automatic bubble separator and are separated from the second water-resistant and air-permeable membrane at the top outlet under the action of buoyancy.

[0040] (2) The perfusion fluid without air bubbles flows into the organ to be repaired in sequence through the air bubble monitoring hose, the organ perfusion main tube, the organ perfusion tube, and the organ transfer sleeve assembly. Then the perfusion fluid in the organ cryogenic storage container flows from the oxygenator through the pump for circulation.

[0041] It should be noted that the disposable circulation system provided by this invention is applied to cryogenic oxygen-carrying mechanical perfusion equipment. When this cryogenic oxygen-carrying mechanical perfusion equipment is used in the field of organ transplantation, it can greatly improve the reliability and safety of organ transplantation.

[0042] The present invention has the following beneficial effects:

[0043] (1) The present invention uses an automatic bubble separation device, combined with the developed organ transfer sleeve assembly, which can realize the automatic bubble removal function of the entire perfusion process. There is no need for manual intervention, interruption or termination of the perfusion process due to the influence of bubbles in the liquid path, and the reliability and efficiency of organ perfusion repair are high.

[0044] (2) The micro hollow fiber membrane oxygenator involved in this invention adopts the fiber tube end potting and sealing process, has a compact overall size, and the interface layout of the oxygenator makes the flow of the one-time filling circulation liquid more simplified and reasonable, the volume of the overall filling system can be effectively miniaturized and lightened, and can smooth the peak and valley values ​​of the filling pressure, so as to realize the portable transportation of the oxygen-carrying mechanical filling equipment.

[0045] (3) The oxygenator of the present invention adopts micro hollow fiber membrane oxygenator technology, which enables oxygen and perfusion fluid to be fully oxygenated, and enables the circulating fluid circuit to carry oxygen to the organ for oxygen perfusion; on the basis of low temperature mechanical perfusion, it has the function of oxygenation of perfusion fluid. Attached Figure Description

[0046] Figure 1 is a perspective view of a disposable ex vivo organ continuous oxygenation mechanical perfusion circulation system according to an embodiment of the present invention.

[0047] Figure 2 is a perspective view of a disposable ex vivo organ continuous oxygenation mechanical perfusion circulation system in another direction according to an embodiment of the present invention.

[0048] Figure 3 is an exploded view of a disposable ex vivo organ continuous oxygenation mechanical perfusion circulation system according to an embodiment of the present invention.

[0049] Figure 4 is a schematic diagram of a single-use ex vivo organ continuous oxygenation mechanical perfusion circulation system according to an embodiment of the present invention.

[0050] Figure 5 is a perspective view of the organ transfer cannula assembly in an embodiment of the present invention, showing the kidney K.

[0051] Figure 6 is an exploded view of the organ transfer cannula assembly in an embodiment of the present invention.

[0052] Figure 7 is a cross-sectional view of the organ transfer cannula assembly in an embodiment of the present invention.

[0053] Figure 8 is an unfolded view of the organ transfer cannula assembly in an embodiment of the present invention, with some structures omitted in the figure.

[0054] Figure 9 is a diagram of the base structure in an embodiment of the present invention.

[0055] Figure 10 is a diagram of the flip cover structure in an embodiment of the present invention.

[0056] Figure 11 is a structural diagram of the support structure in an embodiment of the present invention.

[0057] Figure 12 is a diagram of the tray structure in an embodiment of the present invention.

[0058] Figure 13 shows an example of the engagement state of the sliding slot and sliding buckle at arrow S in Figure 12 in an embodiment of the present invention.

[0059] Figure 14 is a perspective view of the automatic bubble separator in an embodiment of the present invention.

[0060] Figure 15 is an exploded view of the automatic bubble separator in an embodiment of the present invention.

[0061] Figure 16 is a cross-sectional view of the automatic bubble separator in an embodiment of the present invention.

[0062] Figure 17 is a cross-sectional view of the organ cryopreservation container in an embodiment of the present invention.

[0063] Figure 18 is a schematic diagram of the internal structure of the organ cryopreservation container in an embodiment of the present invention.

[0064] Figure 19 is a perspective view of the container compartment of the organ cryogenic storage container in an embodiment of the present invention.

[0065] Figure 20 is a two-dimensional view of the container compartment of the organ cryopreservation container in an embodiment of the present invention.

[0066] Figure 21 is a perspective view of the container compartment of the organ cryopreservation container in an embodiment of the present invention.

[0067] Figure 22 is a perspective view of the micro hollow fiber membrane oxygenator in an embodiment of the present invention.

[0068] Figure 23 is a cross-sectional view of the micro hollow fiber membrane oxygenator in an embodiment of the present invention.

[0069] Figure 24 is a flowchart of the perfusion control of disposable consumables in a disposable ex vivo organ continuous oxygenation mechanical perfusion circulation system. Detailed Implementation

[0070] To make the technical means, creative features, objectives and effects of this invention easier to understand, the invention will be further described below with reference to specific embodiments.

[0071] An embodiment of the present invention provides a disposable ex vivo organ continuous oxygenation mechanical perfusion circulation system (hereinafter referred to as "the system"). As shown in Figures 1 to 4, the system includes an organ cryogenic storage container 1, an oxygenator (e.g., a miniature hollow fiber membrane oxygenator 2), an automatic bubble separator 3, an organ transfer sleeve assembly 4, an organ tray assembly 5, a pressure sensor 6, and a pump tube. In this embodiment, the pump 7 is a roller pump, and the pump tube is separable from the pump body. The pump tube of the roller pump belongs to the disposable ex vivo organ continuous oxygenation mechanical perfusion circulation system (also referred to as "disposable circulation system").

[0072] It is worth mentioning that the circulation pipeline of the disposable ex vivo organ continuous oxygenation mechanical perfusion circulation system provided by the present invention includes an oxygen delivery pipeline and an oxygen-carrying perfusion pipeline, both of which are sterile circulation pipelines. The output end of the organ cryogenic storage container 1 is connected to the oxygen delivery pipeline. Referring to Figure 4, the oxygen delivery pipeline includes a perfusion fluid inlet pipe T1 connected to the organ cryogenic storage container 1, a roller pump pipe T2 (located in the roller pump), and an oxygenation conduit T3 connected to the roller pump pipe T2. The pump body of the roller pump is set in the oxygen delivery pipeline to provide the delivery power of the circulation system. A miniature hollow fiber membrane oxygenator 2 is set in the oxygen delivery pipeline to facilitate the supply of oxygen to the circulation system. The output end of the miniature hollow fiber membrane oxygenator 2 is connected to the oxygen-carrying perfusion pipeline, which includes an oxygen input pipe T4 connected to the oxygen generation system 8, a bubble separation conduit T5 connected to the miniature hollow fiber membrane oxygenator 2, a bubble monitoring hose T6 connected to the automatic bubble separator 3, an organ perfusion main tube T7, an organ perfusion tube T8, and a cleaning drain tube T9. It should be noted that the end of the oxygen input pipe T4 is usually a quick connector. The organ perfusion main tube T7 is connected to the organ perfusion tube T8 and the cleaning drain tube T9 through a three-way connector P1. The organ perfusion tube T8 is equipped with a first clamp valve P2 (normally open), and the cleaning drain tube T9 is equipped with a second clamp valve P3 (normally closed). The bubble sensor P3 is installed on the bubble monitoring hose T6, and the pressure sensor 6 is installed on the organ perfusion main tube T7. The aseptic circulation tubing T mentioned above consists of the perfusion fluid inlet tube T1, roller pump tube T2, oxygenation catheter T3, oxygen input tube T4, bubble separation catheter T5, bubble monitoring hose T6, organ perfusion main tube T7, organ perfusion tube T8, and cleaning drain tube T9. Pressure sensor 6 is installed in the oxygen-carrying perfusion tubing to detect the pressure value of the circulation system, realizing the pressure limit risk protection of the circulation system, and providing technical guarantee for the safety of the organ to be repaired K and the effectiveness of transplantation.

[0073] Referring to Figure 3, the organ transfer cannula assembly 4, used to fix the organ to be repaired K (e.g., a kidney), is detachably installed on the organ tray assembly 5. In use, the organ to be repaired K is assembled with the organ transfer cannula assembly 4 to form a first semi-finished product. This first semi-finished product is then assembled into the tray groove of the organ tray assembly 5, and the artery length is adjusted to a suitable value to form a second semi-finished product. In this embodiment, the organ tray assembly 5 is arranged within the cavity of the organ cryogenic storage container 1; that is, the aforementioned second semi-finished product can be located within the cavity of the organ cryogenic storage container 1. The organ cryopreservation container 1 has a suspended island structure, such as a pressure sensor deck 60. The pressure sensor deck 60 houses the corresponding sensors, automatic bubble separator 3, and associated tubing. Pressure sensors 6 are distributed on the pressure sensor deck 60, and the automatic bubble separator 3 can be concealed at the bottom of the pressure sensor deck 60. The related tubing can also be distributed along the abdomen of the pressure sensor deck 60. The pressure sensor deck 60 is located at the edge of the organ cryopreservation container 1. If the related tubing has sufficient rigidity, it can be supported on the side of the organ cryopreservation container 1, forming a suspended structure. Of course, the requirements for suspension and installation can still be met by setting up corresponding connectors. In this embodiment, the pressure sensor deck 60 is used as a tubing deck. During operation, the tubing deck is fixed to the main control panel of the perfusion equipment via a rotatable T-shaped latch structure. Figure 3 shows the pressure sensor interface 61 and the oxygen interface T3a distributed at the free end of the oxygenation conduit T3.

[0074] In this embodiment, the automatic bubble separator 3 installed in the oxygen-carrying perfusion line is connected to the input end of the organ transfer cannula assembly 4. The two are used to separate bubbles in the circulatory system to ensure organ safety and to achieve safe fixation of the organ. Since the automatic bubble separator 3 and the organ transfer cannula assembly 4 are core components of the circulatory system, they will be described in detail below.

[0075] Referring to Figures 5-13, the organ transfer cannula assembly 4 includes a base 40, a flip cover 41, and a support. The base 40 has a through hole 400, at which a flexible gasket 401 is provided. The base 40 also has a flexible gasket mounting groove for installing the flexible gasket 401. The flexible gasket mounting groove improves both the stability of the flexible gasket 401 installation and its sealing effect. The flip cover 41 is mounted on the base 40, and one side of the flip cover 41 and one side of the base 40 are rotatably connected. The flip cover 41 has a water-resistant and breathable membrane mounting port 410, and a water-resistant and breathable membrane 411 is installed at the water-resistant and breathable membrane mounting port 410. The water-resistant and breathable membrane 411 can be fixed by ultrasonic welding or pressure-sensitive adhesive bonding. The flip cover 41 has a connecting pipe 412 leading into the interior of the flip cover 41. The bottom inner side of the flip cover 41 has a clamping end face 413. After the flip cover 41 and the base 40 are closed, the clamping end face 413 and the flexible washer 401 clamp the renal artery for perfusion. In this embodiment, the top of the flip cover 41 has a tubular portion for venting, and the opening at the top of the tubular portion is the water-resistant and breathable membrane mounting port 410, where the water-resistant and breathable membrane 411 is installed. Notably, to facilitate venting, the tubular portion is located directly above the through hole 400. The 411 water-resistant and breathable membrane can withstand pressures up to 150 mmHg, with an exhaust efficiency of no less than 893 ml / min / cm. 2 @7kpa. It should be noted that the above values ​​are for illustrative purposes only and are not limitations, and can be changed as needed in practice. The organ transfer cannula assembly 4 includes a stent with a stent body 42, a transverse mounting groove 420 on the stent body 42, a top groove 421 on the top of the stent body 42, and a closed base 40 and a flip cover 41 installed in the transverse mounting groove 421.

[0076] Referring to Figure 6, a latch 403 is provided on the other side of the base 40, and a latch 414 is provided on the other side of the flip cover 41. The latch 414 and the latch 403 cooperate to improve the stability of the base 40 and the flip cover 41 after they are closed, thereby improving the safety of the organ K to be repaired placed inside the organ cryopreservation device 1. A shaft portion 415 is provided on one side of the flip cover 41, and a hanging ear 402 is provided on one side of the base 40. The hanging ear 402 and the shaft portion 415 form a rotatable connection structure.

[0077] The organ tray assembly 5 has a first tray 50 and a second tray 51, which are rotatably connected. The aforementioned support and the first tray 50 are detachably connected, providing the possibility for medical staff to use the system conveniently. After the first tray 50 and the second tray 51 are closed, the interior is a receiving cavity (the top of the tray is an overflow port for liquid to flow out) for the organ to be repaired to be placed there.

[0078] In particular, the first tray body 50 has a tray head 52, a sliding slot 520 is provided at the tray head, and a sliding buckle 422 is provided on the bracket, with the sliding buckle 422 and the sliding slot 520 connected.

[0079] The tray can accommodate organs and provide them with protection (limiting and covering). The sliding buckle 422 can slide and adjust at the sliding slot 520 to select the appropriate position according to the length of the artery of different organs (after adjustment, the sliding buckle 422 is locked onto the sliding slot 520). Liquid in the tray can flow out from the overflow port at the top of the tray.

[0080] It should be noted that after the first disc 50 and the second disc 51 are closed, the method of maintaining stability can refer to existing technology, including but not limited to the following forms: the first method is to use ropes to wrap and tie the two discs (trays) to make them close stably; the second method is to set an inverted U-shaped clamp at the top of the tray to clamp and close the first disc 50 and the second disc 52 (tray); the third method is to place the tray between two opposing clamping walls in the receiving cavity of the organ, so that the tray is stuck between the two clamping walls to achieve stable closure. As in this embodiment, referring to Figure 17, after the first disc 50 and the second disc 51 are closed, they are placed in the gap between the front side wall 100b and the stepped rear side wall 100e of the organ cryogenic storage container 1, that is, in the second semi-finished product placement space M shown in Figure 18.

[0081] Organ connection sealing: The upper surface of the organ arterial wall and the clamping end face 413 of the flap 41 form a seal under pressure, and the lower surface forms a seal with the flexible sealing pad. The flexible sealing pad is an elastomer material (including but not limited to rubber material), so it can adapt to the organ arterial wall with different individual differences and will not damage the organ arterial wall.

[0082] Automatic air venting: Under initial perfusion conditions, there will be a small amount of air inside the transfer tube and at the end of the perfusion loop. Under the action of pump pressure, the liquid in the perfusion loop flows through the tube into the cavity formed by the transfer tube and the organ. Under the action of gravity, the perfusion liquid gradually fills the entire cavity from low to high. At the same time, under the action of buoyancy, the air at the end of the circulation tube and the end of the transfer tube gradually rises and flows through the water-resistant and breathable membrane 411 of the transfer tube until the air is completely expelled and the liquid fills the cavity of the transfer tube. This completes the automatic air venting function of the circulation tube and its end.

[0083] The perfusion organ is connected to the transfer tube (the arterial wall K-1 of organ K passes through the through hole of base 40). The pre-treated arterial wall of the organ is clamped between the flap 41 and the base 40 to form a closed cavity (the perfusion fluid flows in from the transfer tube and enters the closed cavity composed of base 40, flap 41 and organ). The perfusion fluid in the circulatory system can enter the closed cavity through the transfer tube of flap 41 under the pump pressure (arrow F in Figure 7 indicates the direction of perfusion fluid flow). The upper surface of the arterial wall forms a seal with the inner wall of flap 41, and the lower surface of the arterial wall forms a seal with the flexible sealing gasket. Thus, under the action of pump pressure, the perfusion fluid will further flow through the blood vessels into the blood vessels inside the organ (the perfusion fluid flows out from the organ vein), thereby realizing the connection between the external perfusion fluid loop and the organ.

[0084] The present invention provides a disposable ex vivo organ continuous oxygenation mechanical perfusion circulation system. The structure of the automatic bubble separator 3 is shown in Figures 14-16. It includes a shell 30, a first water-resistant and breathable membrane 31, an inlet pipe 32, and an outlet pipe 33. The shell 30 consists of a bottom shell 300 and a cover 301. The bottom shell 300 is generally cylindrical with an open top. The cover 301 is installed at the open top, forming a sealed cavity inside the shell 30 after installation. The cover 301 has a gas escape port 301a, and the first water-resistant and breathable membrane 31 (waterproof) is installed at the gas escape port 301a. The inlet pipe 32 is arranged on the shell 30. In this embodiment, it is installed vertically on the upper part of the shell 30 and close to the cover 301. The outlet pipe 33 is arranged on the shell 30. In this embodiment, the first water-resistant and breathable membrane 31 is installed below the gas escape port 301a (this installation method is only an example; the specific position can be changed to meet functional requirements). The first water-resistant and breathable membrane 31 can withstand a maximum pressure of 150 mmHg, with an exhaust efficiency of no less than 893 ml / min / cm. 2 @7kpa. It should be noted that the above values ​​are for illustrative purposes only and are not definitive; they can be changed as needed in practice.

[0085] To facilitate the installation of the cover 301 and ensure its stability after installation, one side of the bottom shell 300 has an opening with an installation step 300a. The cover 301 is positioned at the installation step 300a. The cover 301 is connected to the bottom shell 300 via a sealing ring 34; alternatively, the cover 301 and the bottom shell 300 can be ultrasonically welded; or, the cover 301 and the bottom shell 300 can be bonded together with an adhesive, including but not limited to UV adhesive, as described in existing technologies. It should be noted that the above connection methods of the cover 301 and the bottom shell 300 are merely examples and not limitations. Existing technologies can also be referenced, as long as the connection of the cover 301 and the bottom shell 300 results in a sealed chamber inside the shell 30.

[0086] In this embodiment, the cover 301 includes a cover body, which has a plurality of gas escape ports 301a arranged circumferentially, and a drain pipe 33 is provided in the middle of the cover body. The inlet pipe 32 is provided on the bottom shell 300 near the cover 301.

[0087] In this embodiment, the drain pipe 33 is L-shaped, and its inlet extends into the cavity near the bottom. It should be noted that the shape of the drain pipe 33 includes, but is not limited to, an L-shape, and can be referenced from existing technologies provided that the functionality is met.

[0088] It should be noted that when the first water-blocking and breathable membrane 31 is arranged below the gas escape port 301a, in order to prevent the external environment from contaminating the liquid path inside the cavity during use or transportation, the cover 301 is provided on the side away from the cavity (outer side).

[0089] The automatic bubble separator operates as follows: S1. Under the initial filling conditions, in the filling liquid circuit, under the action of external pump pressure, a gas-liquid mixture of 0~240ml / min (preferably 240ml / min) enters the device cavity from the inlet pipe. Under the pump pressure, the liquid begins to cover the inlet 33a of the drain pipe 33. At this time, since the fluid leakage pressure threshold of the exhaust hole of the first water-blocking and air-permeable membrane 31 is lower than that at the inlet 33a of the drain pipe, the air inside the cavity is discharged out of the cavity through the exhaust hole of the first water-blocking and air-permeable membrane 31 and the gas escape port 301a in sequence under the pump pressure (when a second water-blocking and air-permeable membrane 35 is provided, the air inside the cavity is discharged out of the cavity through the exhaust hole of the first water-blocking and air-permeable membrane 31, the gas escape port 301a and the exhaust hole of the second water-blocking and air-permeable membrane 35 in sequence under the pump pressure).

[0090] S2. When the liquid level rises to the first water-blocking and breathable membrane 31, the fluid leakage pressure threshold of the vent hole of the first water-blocking and breathable membrane 31 is much higher than that at the inlet 33a of the drain pipe under the action of the first water-blocking and breathable membrane 31. The liquid cannot be discharged from the vent hole of the first water-blocking and breathable membrane 31. Under the action of the pump pressure, the liquid flows out from the inlet 33a and the outlet 33b of the drain pipe in sequence.

[0091] During the filling process, when bubbles continuously appear in the liquid circuit, the liquid is separated from the gas by the bubble separation device according to the above process.

[0092] Referring to Figures 17-21, the organ cryopreservation container 1 can be placed in a cryopreservation container to preserve organs. The organ cryopreservation container 1 has a container compartment 100 with an open top, which has a container bottom 100a, a container front side wall 100b, a container left side wall 100c, a container right side wall 100d, and a stepped container rear side wall 100e. The two sides of the stepped container rear side wall 100e are connected to their respective side walls by irregularly shaped inclined surfaces 100f. The irregularly shaped inclined surfaces 100f and the container left side wall 100c generally form a columnar volume area Q with a triangular cross-section. Similarly, the irregularly shaped inclined surfaces 100f and the container right side wall 100d generally form a columnar volume area Q with a triangular cross-section. The rear side wall 100e of the organ cryopreservation container 1 and the container front side wall 100b form a second semi-finished product placement space M. The organ cryogenic storage container 1 has an inner lid 101 and an outer lid 102 installed on the top of its container compartment. The outer lid 102 is fixed to the edge of the container compartment by an outer lid buckle 102a. A liquid level inlet groove 100e-1 is provided on the stepped rear side wall 100e of the container, while the outer lid 102 is provided with an outer lid sealing gasket 103, the inner lid 101 is provided with an inner lid sealing gasket 104, and the outer lid 102 is provided with an outer lid water-resistant and breathable membrane 105. Corresponding pipeline inlets are provided on the stepped rear side wall of the container compartment. It is worth mentioning that the back of the organ cryogenic storage container 1 has a concave design that allows the micro hollow fiber membrane oxygenator to be concealed there, saving space.

[0093] Referring to Figures 22-23, the miniature hollow fiber membrane oxygenator (which belongs to the prior art) has an oxygen inlet 21, an oxygen outlet 22, and an oxygenator inlet 23 (injection fluid inlet). The end of the miniature hollow fiber membrane oxygenator 2 is provided with an oxygenator exhaust port 24. The miniature hollow fiber membrane oxygenator is provided with an oxygenator support 26. The oxygenator support 26 is provided with an oxygenator injection fluid permeation hole 29. The hollow fiber tube provided in the oxygenator support 26 is close to the oxygen inlet 21 and is the hollow fiber tube oxygen inlet 25a. The other end is connected to the L-shaped oxygenator inlet 23. The hollow fiber tube has a hollow fiber tube oxygenation zone 25b and a hollow fiber tube exhaust end 25c. Both ends of the hollow fiber tube are sealed by potting sealant 28.

[0094] It is worth mentioning that the liquid level inlet groove 100e-1 of the organ cryopreservation container 1 is used as a limiting groove. The height of the liquid level inlet groove 100e-1 is slightly lower than the perfusion liquid surface (see Figure 20, the end of the liquid level inlet groove 100e extending downward from the rear side wall 100e of the stepped container is slightly lower than the perfusion liquid surface of the organ cryopreservation container 1). When the circulation system is tilted or leakage occurs, the liquid level inlet is higher than the liquid surface, which will cause the perfusion liquid to be unable to be pumped in, resulting in continuous bubbles. Combined with the information obtained by the 3-axis sensor, the system will obtain the equipment tilt or leakage failure, thereby realizing the early warning function. The specific analysis is as follows: The 3-axis sensor obtains the tilt angle information of the equipment or perfusion system through the sensor's posture. When the equipment tilts continuously under abnormal conditions, causing leakage in the circulation system, the height of the perfusion liquid conduit inlet at the limiting groove will be higher than the liquid surface, which will result in: (1) the perfusion liquid cannot be pumped into the circulation liquid path, and the perfusion pressure in the circulation liquid path cannot be maintained to keep it stable. After this information is sent back to the equipment control system, it will trigger a system warning. (2) Continuous bubbles are detected by the bubble sensor. This information is transmitted back to the equipment control system, triggering a system warning. Under the above dual warning conditions, the grouting system will stop operating.

[0095] The working method of the present invention is described in detail with reference to Figure 24:

[0096] 1. After the organ perfusion equipment is started and confirmed to be operating normally, as shown in Figure 7, the organ to be repaired is assembled with the transfer sleeve to form the first semi-finished product; further, as shown in Figure 12, the tray cover is opened, the first semi-finished product is assembled in the tray groove, and the artery is adjusted to a suitable length to form the second semi-finished product.

[0097] 2. The disposable oxygenation perfusion circulation system is assembled on the main control module of the oxygen-carrying cryogenic mechanical perfusion equipment, and the disposable organ container is placed in a cryogenic holding container pre-filled with cryogenic phase change material.

[0098] 3. Confirm that the disposable oxygenation perfusion circulation system is connected, start the venting mode, and continue until all the gas inside the circulation system is vented to complete the venting (cleaning) mode.

[0099] 4. Connect the second semi-finished product to the inlet of the disposable oxygenation perfusion circulation system, and further seal the inner and outer caps of the organ container. This completes the system configuration. Start the perfusion mode until the organ completes cryogenic mechanical perfusion repair.

[0100] Another embodiment of the present invention provides a method for operating a disposable ex vivo organ continuous oxygenation mechanical perfusion circulation system, which has an exhaust mode and a perfusion mode. The method of this embodiment operates in the disposable ex vivo organ continuous oxygenation mechanical perfusion circulation system mentioned above.

[0101] The method of exhaust mode of the working method of the disposable ex vivo organ continuous oxygenation mechanical perfusion circulation system is as follows: (1) When the perfusion is started, the ultrasonic bubble sensor in the bubble monitoring hose area detects that the circulation pipeline is air. The first clamp valve P2 and the second clamp valve P3 are in the energized state. The gas at the front end of the automatic bubble separator 3 will be separated from the first water-resistant and breathable membrane 31 at the top of the automatic bubble separator 3. The gas at the rear end of the automatic bubble separator 3 passes through the bubble monitoring hose T6, the organ perfusion main tube T7, and the cleaning drain tube T9 in sequence to avoid the organ to be perfused and repaired.

[0102] (2) During the perfusion process, since the ultrasonic bubble sensor in the bubble monitoring hose area detects that the circulation pipeline is air, the first clamp valve P2 and the second clamp valve P3 are both energized. The gas at the front end of the automatic bubble separator 3 will be separated from the first water-blocking and air-permeable membrane 31 at the top of the automatic bubble separator 3. The gas at the rear end of the automatic bubble separator 3 passes through the bubble monitoring hose T6, the organ perfusion main tube T7, and the cleaning drain tube T9 in sequence to prevent bubbles from flowing into the organ to be perfused and repaired, causing embolism.

[0103] The following describes the working method of a disposable ex vivo organ continuous oxygenation mechanical perfusion circulation system. The perfusion mode method is as follows: (1) After the disposable ex vivo organ continuous oxygenation mechanical perfusion circulation system is started, the tiny bubbles flowing out from the micro hollow fiber membrane oxygenator 2 flow into the liquid inlet pipe 32 of the automatic bubble separator 3 and are separated from the second water-resistant and breathable membrane 35 at the top outlet under the action of buoyancy.

[0104] (2) The bubble-free perfusion fluid flows into the organ to be repaired sequentially through the bubble monitoring hose T6, the organ perfusion main tube T7, the organ perfusion tube T8, and the organ transfer sleeve assembly 4. Then the perfusion fluid in the organ cryogenic storage container 1 flows through the pump to the micro hollow fiber membrane oxygenator 2 for circulation.

[0105] This invention defines the key technical parameters of infusion as follows: R 灌注阻力 =P 灌注压力 / V 灌注流量 V 灌注流量 =C 设定圈数 *K, which is: R 灌注阻力 =P 灌注压力 / (C) 设定圈数 *K), according to clinical statistics, normal human organs P 灌注压力With a typical value set at 30 mmHg, the output flow rate of the roller pump (i.e., pump 7) is within the range of 0~240 ml / min, and K is 4 ml / Cycle. From the above algorithmic relationship, it can be seen that perfusion resistance is directly proportional to perfusion pressure and inversely proportional to the set rotation speed. In the initial stage of organ perfusion, the vascular quality of the organ to be repaired is poor, typically R... 灌注阻力 The level is relatively high, and as the perfusion repair continues, R... 灌注阻力 To reduce the pressure, the main control module adjusts the roller pump speed to lower the strain P detected by the pressure sensor. 灌注压力 Maintain at the set value P 灌注压力 =30 mmHg typical value, until R 灌注阻力 It is trending towards a stable and repaired state.

[0106] Those skilled in the art will understand that the above embodiments are specific examples of implementing the present invention, and in practical applications, various changes in form and detail may be made without departing from the spirit and scope of the present invention.

Claims

A disposable ex vivo organ continuous oxygenation mechanical perfusion circulation system, characterized in that, The circulation system has a circulation pipeline for delivering oxygen and an oxygen injection pipeline. The circulatory system includes an organ cryopreservation container (1), an oxygenator (2), an automatic bubble separator (3), an organ transfer sleeve assembly (4), a pressure sensor (6), and a pump tube; The output end of the organ cryogenic storage container (1) is connected to the oxygen delivery pipeline to be carried, and the pump pipe and oxygenator (2) are installed in the oxygen delivery pipeline to be carried. The organ transfer sleeve assembly (4) is installed in the organ cryogenic storage container (1). The output end of the oxygenator (2) is connected to the oxygen-carrying perfusion pipeline, the automatic bubble separator (3) installed in the oxygen-carrying perfusion pipeline is connected to the input end of the organ transfer sleeve assembly (4), and the pressure sensor is installed in the oxygen-carrying perfusion pipeline. A disposable isolated organ continuous oxygenation mechanical perfusion circulation system according to claim 1, characterized in that, The circulation system also includes an organ tray assembly (5), which is arranged in the cavity of the organ cryogenic storage container (1), and the organ adapter sleeve assembly (4) is detachably installed on the organ tray assembly (5). A disposable isolated organ continuous oxygenation mechanical perfusion circulation system according to claim 1, characterized in that, The organ transfer cannula assembly (4) includes a base (40) and a flip cover (41), the flip cover (41) being disposed on the base (40), and one side of the flip cover (41) being rotatably connected to one side of the base (40). A disposable isolated organ continuous oxygenation mechanical perfusion circulation system according to claim 3, characterized in that, The base (40) is provided with a through hole (400), and a flexible washer (401) is provided at the through hole (400). The flip cover (41) is provided with a water-resistant and breathable membrane installation port (410), and a water-resistant and breathable membrane (411) is provided at the water-resistant and breathable membrane installation port (410). The flip cover (41) is provided with a pipe (412) leading to the inside of the flip cover. The flip cover (41) has a clamping end face (413) at the bottom of the inner side. After the flip cover (41) and the base (40) are closed, the clamping end face (413) and the flexible gasket (401) clamp the renal artery for perfusion. A disposable isolated organ continuous oxygenation mechanical perfusion circulation system according to claim 1, characterized in that, The organ transfer cannula assembly (4) also includes a stent, which has a stent body (42) with a transverse mounting groove (420) on the stent body (42) and a top slot (421) on the top of the stent body (42). The closed base (40) and the flip cover (41) are installed at the transverse mounting groove (420). A disposable isolated organ continuous oxygenation mechanical perfusion circulation system according to claim 1, characterized in that, The automatic bubble separator (3) includes: The housing (30) is composed of a bottom shell (300) and a cover (301). The housing (30) has a sealed cavity inside, and the cover (301) is provided with a gas escape port (301a). Liquid inlet pipe (32), which is arranged on the housing (30); A drain pipe (33) is arranged on the housing (30). A disposable isolated organ continuous oxygenation mechanical perfusion circulation system according to claim 6, characterized in that, A first water-resistant and breathable membrane (31) is provided at the gas escape port (301a). A disposable isolated organ continuous oxygenation mechanical perfusion circulation system according to claim 1, characterized in that, The organ cryogenic storage container (1) has a liquid level inlet groove on the rear side wall of the stepped container. The extension height of the liquid level inlet groove in the organ cryogenic storage container (1) is lower than the liquid level of the perfusion solution in the organ cryogenic storage container (1). A disposable isolated organ continuous oxygenation mechanical perfusion circulation system according to claim 1, characterized in that, The organ cryogenic storage container (1) is provided with a suspended island structure. A method for operating a disposable isolated organ continuous oxygenation mechanical perfusion circulation system, characterized in that, It includes venting mode and filling mode. The working method of a disposable isolated organ continuous oxygenation mechanical perfusion circulation system according to claim 10 is characterized in that, The method for the exhaust mode is as follows: (1) The exhaust mode is performed in the disposable ex vivo organ continuous oxygenation mechanical perfusion circulation system as described in any one of claims 1 to 9. When perfusion is started, the ultrasonic bubble sensor in the bubble monitoring hose area detects that the circulation pipeline is air. The first clamp valve (P2) and the second clamp valve (P3) are energized. The gas at the front end of the automatic bubble separator (3) will be separated from the first water-resistant and breathable membrane (31) at the top of the automatic bubble separator (3). The gas at the rear end of the automatic bubble separator (3) passes through the bubble monitoring hose (T6), the organ perfusion main tube (T7), and the cleaning drain tube (T9) in sequence to avoid the organ to be perfused and repaired. (2) During the perfusion process, since the ultrasonic bubble sensor in the bubble monitoring hose area detects that the circulation pipeline is air, the first clamp valve (P2) and the second clamp valve (P3) are both energized. The gas at the front end of the automatic bubble separator (3) will be separated from the first water-resistant and breathable membrane (31) at the top of the automatic bubble separator (3). The gas at the rear end of the automatic bubble separator (3) passes through the bubble monitoring hose (T6), the organ perfusion main tube (T7), and the cleaning drain tube (T9) in sequence to prevent bubbles from flowing into the organ to be perfused and repaired, causing embolism. The working method of a disposable isolated organ continuous oxygenation mechanical perfusion circulation system according to claim 10 is characterized in that, The method for the infusion mode is as follows: (1) The perfusion mode is carried out in the disposable ex vivo organ continuous oxygenation mechanical perfusion circulation system as described in any one of claims 1 to 9. The tiny bubbles flowing out of the oxygenator (2) flow into the liquid inlet pipe (32) of the automatic bubble separator (3) and are separated from the second water-resistant and breathable membrane (35) at the top outlet under the action of buoyancy. (2) The bubble-free perfusion fluid flows into the organ to be repaired sequentially through the bubble monitoring tubing (T6), the organ perfusion main tube (T7), the organ perfusion tube (T8), and the organ transfer sleeve assembly (4). Then the perfusion fluid in the organ cryogenic storage container (1) flows from the oxygenator (2) through the pump for circulation.

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