CN109362710B

CN109362710B - Liver perfusion device

Info

Publication number: CN109362710B
Application number: CN201811432911.6A
Authority: CN
Inventors: 梁铭炬; 霍枫; 周伟津; 谭晓宇; 魏晓磊; 汪邵平; 许晓珊; 盛恒炜; 吴懿苗; 郑于剑; 任晓龙; 林超; 张春虹; 曾时金; 何锡然; 刘华敏; 张琳; 邝伟键; 何霖; 关烨锋
Original assignee: Guangdong Ding Watson Medical Equipment Co Ltd
Current assignee: Guangdong Ding Watson Medical Equipment Co Ltd
Priority date: 2018-11-28
Filing date: 2018-11-28
Publication date: 2020-03-10
Anticipated expiration: 2038-11-28
Also published as: CN109362710A

Abstract

The invention discloses a liver perfusion device, which comprises a host machine, an air-oxygen mixer component and a monitoring component, wherein a consumable component is clamped on a workbench of the host machine, and when different livers need to be perfused, only the consumable component needs to be replaced, so that the liver perfusion device is convenient; moreover, a temperature adjusting component connected with a consumable component pipeline is arranged in the main machine, so that the temperature of circulating water entering the first lung membrane oxygenator and the second lung membrane oxygenator for heat exchange can be adjusted through the temperature adjusting component, and liver perfusion can be performed under different temperature conditions according to actual needs; in addition, the host has different liver perfusion modes, a user can set the hepatic artery and portal vein perfusion methods according to actual needs, the oxygenation degree of the perfusion solution is adjusted according to the air-oxygen mixer, and different medicines are injected by the micro-injection pump, so that the effects of long-term preservation, improvement, repair and the like of the liver are realized.

Description

Liver perfusion device

Technical Field

The invention relates to the technical field of organ transplantation equipment, in particular to a liver perfusion device.

Background

Liver transplantation is the only effective means for treating end-stage liver diseases due to various causes, but transplant waiting list and pre-transplant fatality rate continue to be high due to organ shortage, and the number of livers suitable for transplantation is still limited by cold preservation, ischemia-reperfusion injury, and the like, in spite of recent increase in the number of donors.

The limbic donor liver is more susceptible to ischemia-reperfusion injury, resulting in a higher incidence of primary reactive Power (PNF). Static Cold Storage (SCS) is suitable for high quality organs, while viability of the peripheral donor organ is a limiting factor. Thus, the need for high-risk donor organs has led to interest in new technologies that are desirable for improving preservation quality, assessing organ viability, and even repairing pre-harvest organ damage prior to transplantation. The liver perfusion technology can not only improve the clinical effect of the edge liver supply at present, but also enlarge the donor pool. A large body of experimental evidence shows that preservation at temperatures and oxygenation close to physiological conditions can avoid ischemia-reperfusion injury.

The perfusion (MP) is a novel organ preservation and transportation mode, the self blood vessel is connected to an organ perfusion system after the organ is obtained, and the system continuously perfusates isolated organs with perfusion liquid in the organ preservation and transportation stage, and simultaneously supplies oxygen, nutrient substances and the like to the isolated organs. Compared with traditional Static Cold Storage (SCS), MP can better preserve isolated organs, even standard external organs. Future perfusion may be applied to organ resuscitation in other ways, even to optimize organs as a vehicle for drug delivery. The drug is delivered by NMP for delipidation of the steatosis liver, immunomodulation to induce immune tolerance, gene therapy, etc. Meanwhile, the mesenchymal stem cells can also be targeted and delivered by NMP in a suitable way for transplantation and the like.

Liver perfusion can be classified into low temperature (4-6 ℃), sub-low temperature (10-13 ℃), sub-normal temperature mechanical attention (20-25 ℃), and normal temperature perfusion (37 ℃) according to different maintenance temperatures, but in the field of liver transplantation, main parameters such as liver perfusion mode, perfusion flow rate, pressure, oxygenation degree, temperature and the like are not uniformly recognized at present.

Disclosure of Invention

In order to overcome the defects of the prior art, the invention provides a liver perfusion device which can be suitable for perfusion under different temperature conditions and can adjust perfusion pressure and perfusion flow according to actual needs.

In order to solve the technical problems, the technical scheme adopted by the invention specifically comprises the following contents:

liver perfusion device, including host computer and empty oxygen blender subassembly, the inside of host computer be provided with be used for to power supply unit, temperature regulation subassembly, monitoring subassembly of liver perfusion device power supply and with monitoring subassembly communication connection's control module, the liver perfusion mechanical device still includes the joint and is in consumptive material subassembly on the host computer workstation, the temperature regulation subassembly with empty oxygen blender subassembly all is through the tube coupling consumptive material subassembly, wherein:

the consumable component comprises a bionic liver storage component for storing a liver, a hepatic artery intubation tube inserted into a hepatic artery, a first pulmonary membrane oxygenator connected with the hepatic artery intubation tube, a portal vein intubation tube inserted into a hepatic portal vein, a second pulmonary membrane oxygenator connected with the portal vein intubation tube, a first centrifugal blood pump, a second centrifugal blood pump and a bile collecting component connected with the liver, wherein the first centrifugal blood pump is used for driving perfusate stored in the bionic liver storage component to enter the first pulmonary membrane oxygenator for oxygenation and then is perfused into the liver through the hepatic artery intubation tube; the second centrifugal blood pump is used for driving perfusate stored in the bionic liver storage device assembly to enter the second lung membrane oxygenator for oxygenation and then is perfused into the liver through the portal vein cannula; the bile collecting component is used for collecting bile generated in the liver perfusion process; the outlet end of the air-oxygen mixer assembly is connected with the air inlet of the first lung membrane oxygenator and the air inlet of the second lung membrane oxygenator through a pipeline;

the temperature adjusting assembly comprises a water tank arranged in the main machine, a temperature adjuster used for adjusting the water temperature of the water tank and an electronic water pump, and the electronic water pump is used for driving circulating water in the water tank to enter the first lung membrane oxygenator and the second lung membrane oxygenator through pipelines to respectively exchange heat with perfusion liquid entering the first lung membrane oxygenator the second lung membrane oxygenator.

Further, the consumable assembly also includes a first thrombus filter coupled between the first pulmonary membrane oxygenator and the hepatic arterial cannula, and a second thrombus filter coupled between the second pulmonary membrane oxygenator and the portal venous cannula.

Still further, the consumable assembly further comprises a first thrombus filter holder for securing the first thrombus filter, and a second thrombus filter holder for securing the second thrombus filter.

Still further, the liver perfusion apparatus further comprises a micro-syringe pump communicatively coupled to the control module, the micro-syringe pump being coupled to the first thrombus filter and the second thrombus filter via tubing.

Further, the bile collection assembly comprises a bile collector and a bile cannula connected with the bile collector pipeline.

Still further, the monitoring component comprises a bile titration sensor arranged at the liquid outlet end of the bile intubation, and the bile titration sensor is in communication connection with the control module.

Still further, the monitoring assembly includes a hepatic artery pressure sensor connected to the line connecting the first thrombus filter and the hepatic artery cannula, and a portal vein pressure sensor connected to the line connecting the second thrombus filter and the portal vein cannula, and both the hepatic artery pressure sensor and the portal vein pressure sensor are communicatively connected to the control module.

Furthermore, the monitoring assembly comprises a first flow sensor arranged at the liquid outlet end of the first centrifugal blood pump and a second flow sensor arranged at the liquid outlet end of the second centrifugal blood pump, and the first flow sensor and the second flow sensor are both in communication connection with the control module.

Furthermore, the monitoring assembly comprises a first temperature probe arranged at the liquid outlet end of the first centrifugal blood pump and a second temperature probe arranged at the liquid outlet end of the second centrifugal blood pump, and the first temperature probe and the second temperature probe are both in communication connection with the control module.

Further, bionical liver storage subassembly includes the box body and connects the lid at box body top, bottom in the box body is provided with the apotheca that is used for storing the perfusate, the periphery of apotheca is provided with the chamber of icing of character cut in bas-relief, the upper portion of apotheca is provided with the liver and hangs the piece, the lateral wall of apotheca is provided with two liquid outlets, and two the liquid outlet respectively the pipe connection first centrifugal blood pump with the second centrifugal blood pump.

Still further, the liver suspension member includes a bracket attached to a top of the storage chamber and a T-shaped membrane fixedly attached to the bracket for suspending the liver.

Furthermore, a support bracket is arranged in the storage chamber and is arranged below the support in parallel.

Further, a sealing cover is connected to the top of the ice adding chamber.

Further, the bottom of the storage chamber is inclined, and the two liquid outlets are arranged on the side wall forming an acute angle with the bottom.

Furthermore, the support bracket comprises a first support frame, a second support frame and a third support frame which are sequentially arranged from bottom to top, the second support frame is a silica gel film with holes, and the first support frame and the third support frame are used for fixing the second support frame.

Further, the temperature regulator comprises a PI patch heating film arranged on the outer wall of the water tank and a compressor unit arranged inside the main machine.

Further, the monitoring assembly comprises a temperature sensor and a liquid level sensor which are arranged in the water tank, and the temperature sensor and the liquid level sensor are both in communication connection with the control module.

Further, the air-oxygen mixer assembly comprises an oxygen gas storage bottle, a carbon dioxide gas storage bottle and a gas mixer, the oxygen gas storage bottle is connected with the first gas inlet of the gas mixer through a pipeline, the carbon dioxide gas storage bottle is connected with the second gas inlet of the gas mixer through a pipeline, and the gas outlet of the gas mixer is respectively connected with the first lung membrane oxygenator and the second lung membrane oxygenator through a pipeline.

Still further, the monitoring assembly comprises a first gas flow controller arranged on a pipeline connecting the oxygen gas storage cylinder and the first gas inlet, and a second gas flow controller arranged on a pipeline connecting the carbon dioxide gas storage cylinder and the second gas inlet.

Preferably, the monitoring assembly further comprises a blood gas analyzer in communicative connection with the control module.

Preferably, the consumable assembly further comprises a first lung membrane oxygenator support for securing the first lung membrane oxygenator and a second lung membrane oxygenator support for securing the second lung membrane oxygenator.

Preferably, the power supply unit includes an alternating current power supply and a storage battery.

Preferably, an operation display screen is arranged on the host and electrically connected with the control module.

Further, the first centrifugal blood pump comprises a first driving motor connected with the control module in a communication manner and a first pump head connected with the first driving motor, the first driving motor is used for driving the first pump head to rotate, and the control module controls the rotating speed of the first driving motor by using a PID algorithm; the second centrifugal blood pump comprises a second driving motor and a second pump head, the second driving motor is in communication connection with the control module, the second pump head is connected with the second driving motor, the second driving motor is used for driving the second pump head to rotate, and the control module controls the rotating speed of the second driving motor through a PID algorithm.

Preferably, the centrifugal blood pump further comprises two hand-cranking pump assemblies, and the two hand-cranking pump assemblies are respectively used for driving the first centrifugal blood pump and the second centrifugal blood pump to work.

More preferably, the hand pump assembly comprises a base, a housing mounted on an upper portion of the base, and a handle attached to the housing.

More preferably, a network module is further arranged in the host, the control module is connected with a remote monitoring system through the network module, and the remote monitoring system is used for remotely monitoring the liver perfusion device.

More preferably, the remote monitoring system comprises a message server in communication connection with the control module, a database server for storing data, a big data analysis server for big data processing of data in the database server, a Web server and a remote monitoring terminal in communication connection with the Web server; and the message server is in communication connection with the Web server and the database server, and the database server is in communication connection with the Web server and the big data analysis server.

Compared with the prior art, the invention has the beneficial effects that:

1. the temperature adjusting component connected with the pipeline of the consumable component is arranged in the main machine of the liver perfusion device, so that the temperature of circulating water entering the first lung membrane oxygenator and the second lung membrane oxygenator and exchanging heat with perfusion liquid entering the first lung membrane oxygenator and the second lung membrane oxygenator can be adjusted through the temperature adjusting component, and further, the liver perfusion can be performed under different temperature conditions according to actual needs.

2. The liver perfusion device disclosed by the invention also comprises a monitoring component and a control module in communication connection with the monitoring component, wherein the monitoring component can monitor data such as water temperature, perfusion liquid flow and pressure in the liver perfusion process in real time and transmit the monitoring data to the control module in real time, so that an operator can conveniently adjust liver perfusion parameters in time according to the monitoring condition to relieve damage in the liver perfusion process.

3. The liver perfusion device disclosed by the invention is provided with the operation display screen on the host machine, and not only can display the monitoring data of the monitoring assembly and the processing result of the control module, so that an operator can know the liver perfusion condition in time, but also can conveniently adjust the parameters of the perfusion liquid and the like according to the actual condition, and the liver physiological function can be repaired conveniently.

4. The host of the liver perfusion device disclosed by the invention is also internally provided with a network module, and the control module is in communication connection with the remote monitoring system through the network module, so that the host can transmit various parameters in the liver perfusion process to the remote monitoring system, a liver transplantation expert can conveniently analyze the liver perfusion according to the data, the optimal condition of the liver perfusion can be found out, and meanwhile, the remote monitoring of the liver perfusion device can be realized through the remote monitoring system.

5. The liver perfusion device disclosed by the invention further comprises two hand-operated pump assemblies, and the two hand-operated pump assemblies are respectively used for driving the first centrifugal blood pump and the second centrifugal blood pump to work, so that the liver perfusion device can be ensured to normally operate under the conditions of power failure, power equipment failure and the like.

The foregoing description is only an overview of the technical solutions of the present invention, and in order to make the technical means of the present invention more clearly understood, the present invention may be implemented in accordance with the content of the description, and in order to make the above and other objects, features, and advantages of the present invention more clearly understood, the following preferred embodiments are described in detail with reference to the accompanying drawings.

Drawings

FIG. 1 is a schematic diagram of a liver perfusion apparatus according to the present invention;

FIG. 2 is a schematic mechanical diagram of the mainframe of FIG. 1;

FIG. 3 is a schematic view of the consumable assembly of FIG. 1;

FIG. 4 is a bottom view of FIG. 3;

FIG. 5 is a schematic structural diagram of the bionic liver storage device assembly shown in FIG. 3;

FIG. 6 is a schematic view of the liver when placed in the storage chamber;

FIG. 7 is a schematic structural view of the air oxygen mixer assembly of FIG. 1;

FIG. 8 is a schematic view of the bladder juice collection assembly of FIG. 3;

FIG. 9 is a schematic view of the first pump assembly of FIG. 1;

FIG. 10 is a diagram of a display interface of the hepatic artery pressure sensor and the portal vein pressure sensor after zeroing, as displayed by the operation display screen;

FIG. 11 is a pre-filled page displayed by the operator display screen;

FIG. 12 is a perfusion parameter setting page displayed by the operator display screen;

FIG. 13 illustrates a hepatic artery perfusion mode setting page displayed on the display screen;

FIG. 14 is a portal perfusion mode setting page displayed by the operator display screen;

FIG. 15 is a perfusion monitoring interface displayed by the operator display screen;

FIG. 16 is a schematic diagram of a remote monitoring system;

FIG. 17 is a remote monitoring interface displayed by the terminal;

FIG. 18 is a device list interface displayed by the terminal;

FIG. 19 is a liver ID input interface displayed by the terminal;

FIG. 20 is a hepatic artery perfusion status monitoring page displayed at the terminal;

FIG. 21 is a portal perfusion status monitoring page displayed by the terminal;

FIG. 22 is a graph showing the trend of the mean pressure of the hepatic artery during normal temperature perfusion in the liver perfusion device;

FIG. 23 is a diagram showing the trend of systolic pressure of hepatic artery during normal temperature perfusion in the liver perfusion device;

FIG. 24 is a diagram illustrating the trend of diastolic pressure change of hepatic artery during normal temperature perfusion in the liver perfusion device;

FIG. 25 is a graph showing the trend of the arterial pulse rate of the liver during perfusion at normal temperature;

FIG. 26 is a diagram illustrating the trend of hepatic artery flow during normal temperature perfusion of the liver perfusion device;

FIG. 27 is a graph showing the trend of portal vein pressure during perfusion at normal temperature in a liver perfusion device;

FIG. 28 is a graph showing the trend of portal vein flow during normal perfusion in a liver perfusion device;

FIG. 29 is a graph showing the perfusion temperature variation trend of the liver perfusion device during normal temperature perfusion;

FIG. 30 is a graph showing the trend of the oxygen partial pressure and the carbon dioxide partial pressure during normal temperature perfusion of the liver perfusion device;

FIG. 31 is a graph showing the trend of pH change in a liver perfusion device during perfusion at normal temperature;

FIG. 32 is a graph showing the trend of the blood glucose and lactic acid levels during normal perfusion in a liver perfusion device;

FIG. 33 is a graph showing the trend of glutamate pyruvate transaminase content during normal temperature perfusion in a liver perfusion device;

FIG. 34 is a graph showing the trend of the glutamic-oxaloacetic transaminase content of the liver perfusion device during normal temperature perfusion;

FIG. 35 is a graph showing the trend of hepatic artery flow during low temperature perfusion in a liver perfusion device;

FIG. 36 is a graph showing the trend of mean pressure change of hepatic artery during low-temperature perfusion of the liver perfusion device;

FIG. 37 is a diagram showing the perfusion temperature variation trend of hepatic artery during low-temperature perfusion of the liver perfusion device;

FIG. 38 is a graph showing the trend of portal vein flow during cryoperfusion in a liver perfusion device;

FIG. 39 is a graph showing the trend of the mean portal vein pressure during low temperature perfusion in a liver perfusion device;

FIG. 40 is a graph showing the temperature variation of portal vein perfusion during low temperature perfusion of a liver perfusion device;

FIG. 41 is a graph showing the trend of pH change during low temperature perfusion of a liver perfusion device;

FIG. 42 is a graph showing the trend of blood glucose and lactate levels during low temperature perfusion in a liver perfusion device;

wherein the reference numerals in fig. 1-9 are:

1. a host; 2. an air-oxygen mixer assembly; 3. a consumable component; 4. a biomimetic liver reservoir assembly; 5. a first pulmonary membrane oxygenator; 6. a second pulmonary membrane oxygenator; 7. a first centrifugal blood pump; 8. a second centrifugal blood pump; 9. a handrail; 10. a water tank; 11. an electronic water pump; 12. a hepatic artery pressure sensor; 13. a portal vein pressure sensor; 14. a first flow sensor; 15. a second flow sensor; 16. a first thrombus filter; 17. a second thrombus filter; 18. a box body; 19. a cover body; 20. a storage chamber; 21. an ice adding chamber; 22. a liquid outlet; 23. a support; 24. a T-shaped membrane; 25. a support bracket; 26. a sealing cover; 27. a water injection port; 28. a water outlet of the circulating waterway; 29. operating the display screen; 30. an oxygen cylinder; 31. a carbon dioxide gas cylinder; 32. a gas mixer; 33. a first gas flow controller; 34. a second gas flow controller; 35. a blood gas analyzer; 36. a micro-syringe pump; 37. a first lung membrane oxygenator stent; 38. a second lung membrane oxygenator stent; 39. a storage battery; 40. a base; 41. a housing; 42. a handle is shaken; 43. a first thrombus filter stent; 44. a second thrombus filter stent; 45. a bile collector; 46. bile intubation; 47. a bile titration sensor; 48. pointer tachometers.

Detailed Description

To further illustrate the technical means and effects of the present invention adopted to achieve the predetermined objects, the following detailed description of the embodiments, structures, features and effects according to the present invention with reference to the accompanying drawings and preferred embodiments is as follows:

fig. 1 is a schematic structural diagram of a liver perfusion apparatus according to the present invention, which includes a main machine 1, an air-oxygen mixer assembly 2, and a monitoring assembly, wherein a power supply unit for supplying power to the liver perfusion apparatus, a temperature adjustment assembly, and a control module in communication connection with the monitoring assembly are disposed inside the main machine 1, the control module is configured to control the operation of the liver perfusion apparatus, the liver perfusion apparatus further includes a consumable assembly 3 clamped on a table of the main machine 1, and the temperature adjustment assembly and the air-oxygen mixer assembly 2 are both connected to the consumable assembly 3 through a pipeline.

Because 3 joints of consumptive material subassembly are in on the workstation of host computer 1, when needs fill different livers, only need to change consumptive material subassembly 3 can, it is comparatively convenient.

As shown in fig. 3 and 4, the consumable assembly 3 comprises a bionic liver storage assembly 4 for storing a liver, a hepatic artery cannula inserted into a hepatic artery, a first pulmonary membrane oxygenator 5 connected with the hepatic artery cannula, a portal vein cannula inserted into a hepatic portal vein, a second pulmonary membrane oxygenator 6 connected with the portal vein cannula, a first centrifugal blood pump 7, a second centrifugal blood pump 8 and a bile collecting assembly 9 connected with the liver, wherein the first centrifugal blood pump 7 is used for driving perfusate stored in the bionic liver storage assembly 4 to enter the first pulmonary membrane oxygenator 5 for oxygenation and then to be perfused into the liver through the hepatic artery cannula; the second centrifugal blood pump 8 is used for driving perfusate stored in the bionic liver storage assembly 4 to enter the second lung membrane oxygenator 6 for oxygenation and then perfusing the perfusate into the liver through the portal vein cannula; the bile collecting component 9 is used for collecting bile generated in the liver perfusion process; the outlet end of the air-oxygen mixer component 2 is connected with the air inlet of the first lung membrane oxygenator 5 and the air inlet of the second lung membrane oxygenator 6 through a pipeline.

As shown in fig. 2, the temperature adjusting assembly includes a water tank 10 disposed in the main body 1, a temperature adjuster for adjusting the temperature of the circulating water in the water tank 10, and an electronic water pump 11, wherein the electronic water pump 11 is used for driving the circulating water in the water tank 10 to enter the first lung membrane oxygenator 5 and the second lung membrane oxygenator 6 through a pipeline to exchange heat with the perfusate entering the first lung membrane oxygenator 5 and the second lung membrane oxygenator 6, respectively, so that when liver perfusion needs to be performed under different temperature conditions, it is only necessary to change the temperature of the circulating water entering the first lung membrane oxygenator 5 and the second lung membrane oxygenator 6 to exchange heat with the perfusate in the first lung membrane oxygenator 5 and the second lung membrane oxygenator 6 through the temperature adjuster, thereby enabling the liver perfusion apparatus to perform liver perfusion at a low temperature, Liver perfusion was performed at or above room temperature.

In order to prevent harmful substances such as thrombus and particles in perfusate from entering the liver, the consumable assembly 3 further comprises a first thrombus filter 16 connected between the first pulmonary membrane oxygenator 5 and the hepatic artery intubation tube, and a second thrombus filter 17 connected between the second pulmonary membrane oxygenator 6 and the portal vein intubation tube, when in specific connection, the liquid outlet end of the first pulmonary membrane oxygenator 5 is connected with the liquid inlet end of the first thrombus filter 16 through a pipeline, and the liquid outlet end of the first thrombus filter 16 is connected with the hepatic artery intubation tube through a pipeline; the liquid outlet end of the second pulmonary membrane oxygenator 6 is connected with the liquid inlet end of the second thrombus filter 17 through a pipeline, and the liquid outlet end of the second thrombus filter 17 is connected with the portal vein intubation through a pipeline.

In order to facilitate the fixing and mounting of the first and second thrombus filters 16, 17, the consumable assembly 3 further comprises a first thrombus filter holder 43 for fixing the first thrombus filter 16, and a second thrombus filter holder 44 for fixing the second thrombus filter 17.

Because the liver perfusion device is in the process of liver perfusion, PH, pO2, pCO2, HCT, NA +, CA +, K +, cl-, HCO3 and the like in the perfusate can change, in order to ensure that the perfusate can be closer to the physiological environment, the liver perfusion device also comprises a micro-injection pump 36 which is in communication connection with the control module, and the micro-injection pump 36 is connected with the first thrombus filter 16 and the second thrombus filter 17 through a pipeline, so that the liver perfusion device can add heparin, prostaglandin, nutrient substances, ionic drugs and the like into the perfusate through the micro-injection pump 36, and the perfusate is more in line with the physiological environment. In this embodiment, the micro-injection pump 36 is connected to the first thrombus filter 16 and the second thrombus filter 17 through a three-way valve, and when the connection is concrete, the liquid outlet end of the micro-injection pump 36 is connected to the liquid inlet end of the three-way valve through a pipeline, the first liquid outlet end of the three-way valve is connected to the liquid inlet end of the first thrombus filter 16 through a pipeline, and the second liquid outlet end of the three-way valve is connected to the liquid inlet end of the second thrombus filter 17 through a pipeline.

As shown in fig. 8, the bile collecting assembly includes a bile collector 45 and a bile cannula 46 connected to the bile collector 45, so that the bile generated during the liver perfusion process flows into the bile collector 45 through the bile cannula 46, as a further preferred embodiment, in order to be able to monitor the bile generation condition during the liver perfusion process in real time, the monitoring assembly includes a bile titration sensor 47 disposed at the liquid outlet end of the bile cannula 46, and the bile titration sensor 47 is communicatively connected to the control module, so that the control module can receive the monitoring data of the bile titration sensor 47 in real time and calculate the bile generation amount according to the monitoring data of the bile titration sensor 47.

In order to know the pressure conditions of the hepatic artery and the portal vein in the liver perfusion process in time, the monitoring assembly comprises a hepatic artery pressure sensor 12 connected to a pipeline connecting the first thrombus filter 16 and the hepatic artery cannula, and a portal vein pressure sensor 13 connected to a pipeline connecting the second thrombus filter 17 and the portal vein cannula, and the hepatic artery pressure sensor 12 and the portal vein pressure sensor 13 are both in communication connection with the control module.

In order to know the perfusate flow of hepatic artery and portal vein in the liver perfusion process in time, the monitoring assembly comprises a first flow sensor 14 and a second flow sensor 15, wherein the first flow sensor 14 is arranged at the liquid outlet end of the first centrifugal blood pump 7, the second flow sensor 15 is arranged at the liquid outlet end of the second centrifugal blood pump 8, the first flow sensor 14 and the second flow sensor 15 are in communication connection with each other, so that the control module can timely receive monitoring data of the first flow sensor 14 and the second flow sensor 15, during specific connection, the first flow sensor 14 is clamped on a pipeline at the liquid outlet end of the first centrifugal blood pump 7, and the second flow sensor 15 is clamped on a pipeline at the liquid outlet end of the second centrifugal blood pump 8.

In order to know the perfusate temperature of hepatic artery and portal vein in the liver perfusion process in time, the monitoring subassembly is including setting up first temperature probe and setting of the play liquid end of first centrifugal blood pump 7 are in the second temperature probe of the play liquid end of second centrifugal blood pump 8, first temperature probe with the equal communication connection of second temperature probe control module, thereby make control module can in time receive first temperature probe with the monitoring data of second temperature probe, during the concrete connection, first temperature probe inserts on the pipeline of the play liquid end of first centrifugal blood pump 7, second temperature probe inserts on the pipeline of the play liquid end of second centrifugal blood pump 8.

As shown in fig. 5 and 6, the bionic liver storage assembly 4 comprises a box body 18 and a cover body 19 connected to the top of the box body 18, so as to ensure that the bionic liver storage assembly 4 can maintain a sterile environment.

When the device is specifically arranged, a storage chamber 20 for storing perfusate is arranged at the bottom in the box body 18, a concave ice adding chamber 21 is arranged at the periphery of the storage chamber 20, a liver suspension part is arranged at the upper part of the storage chamber 20, two liquid outlets 22 are arranged on the side wall of the storage chamber 20, and the two liquid outlets 22 are respectively connected with the first centrifugal blood pump 7 and the second centrifugal blood pump 8 through pipelines, so that the perfusate stored in the storage chamber 20 respectively enters the first centrifugal blood pump 7 and the second centrifugal blood pump 8 through the two liquid outlets 22; furthermore, when the liver is cold perfused, the speed of cooling the liver can be increased by adding ice to the ice adding chamber 21.

In order to further increase the cooling rate of the liver during cold perfusion, as shown in fig. 5 and 6, a sealing cover 26 is connected to the top of the ice adding chamber 21, so that the dissolution rate of ice cubes can be slowed down by the sealing cover 26.

As a further preferred embodiment, the liver hanging member comprises a support 23 connected to the top of the storage chamber 20 and a T-shaped membrane 24 fixedly connected to the support 23, the T-shaped membrane 24 is used for hanging the liver, and in particular, in order to make the placement state of the liver closer to the placement state in the human body, the liver is hung on the T-shaped membrane 24 in a way of through-stitching, so that the perfusion environment of the liver is closer to the living environment in the human body.

In order to prevent the liver suspended on the T-shaped membrane 24 from falling, a support bracket 25 is provided in the storage chamber 20, and the support bracket 25 is disposed in parallel below the support 23, so that the support bracket 25 can provide a certain supporting force to the suspended liver.

In order to ensure that the perfusion fluid can flow out of the storage chamber 20 through the two liquid outlets 22, as shown in fig. 6, the bottom of the storage chamber 20 is inclined, and the two liquid outlets 22 are disposed on the side wall forming an acute angle with the bottom.

As a further preferred embodiment, the support bracket 25 includes a first support frame, a second support frame and a third support frame that are sequentially arranged from bottom to top, and the second support frame is a silicone membrane with holes, the first support frame and the third support frame are used for fixing the second support frame, and when the support bracket is specifically connected, the storage chamber 20 is provided with a fixing block for placing the support bracket 25 on four corners of the inner wall thereof, and the four fixing blocks are located on the same horizontal plane, so that the fixing block divides the storage chamber 20 into an upper part and a lower part, and the first support frame contacts with the fixing block. Moreover, since the second support frame is a silicone membrane with holes, the perfusate flowing out of the liver can enter the storage chamber 20 through the holes on the silicone membrane so as to perfuse the liver in the next cycle.

The temperature regulator includes a PI patch heating film disposed on an outer wall of the water tank 10 and a compressor unit disposed inside the main unit 1, and when specifically connected, as shown in fig. 2, the water tank 10 is provided with a water filling port 27 for adding circulating water to the water tank 10, a circulating water path water outlet 28 for connecting a water inlet of the electronic water pump 11, a circulating water path water inlet for connecting a water outlet of the first lung membrane oxygenator 5 and a water outlet of the second lung membrane oxygenator 6, and a water outlet for discharging the circulating water, in the present invention, in order to ensure that the liver perfusion device is in a sterile environment, the circulating water is sterile deionized water, and specifically, during operation:

(1) when liver perfusion needs to be carried out under the condition of temperature higher than room temperature, the control module controls the PI patch heating film to work, so that the water temperature in the water tank 10 is increased; then the electronic water pump 11 is operated, so that the sterile deionized water in the water tank 10 flows out through the circulating water path water outlet 28 and enters the electronic water pump 11, and then the sterile deionized water flowing out from the water outlet of the electronic water pump 11 enters the first lung membrane oxygenator 5 and the second lung membrane oxygenator 6 through the first circulating water inlet pipeline and the second circulating water inlet pipeline respectively to exchange heat with the perfusate entering the first lung membrane oxygenator 5 and the second lung membrane oxygenator 6, so that the temperature of the perfusate is higher than the room temperature.

(2) When liver perfusion needs to be performed at a temperature lower than room temperature, the control module controls the compressor unit to work, so that the water temperature in the water tank 10 is reduced; then the electronic water pump 11 is operated, so that the sterile deionized water in the water tank 10 flows out through the circulating water path water outlet 28 and enters the electronic water pump 11, and then the sterile deionized water flowing out from the water outlet of the electronic water pump 11 enters the first lung membrane oxygenator 5 and the second lung membrane oxygenator 6 through the first circulating water inlet pipeline and the second circulating water inlet pipeline respectively to exchange heat with the perfusate entering the first lung membrane oxygenator 5 and the second lung membrane oxygenator 6, so that the temperature of the perfusate is lower than the room temperature.

In order to monitor the water temperature in the water tank 10, the monitoring component comprises a temperature sensor arranged in the water tank 10, and the temperature sensor is in communication connection with the control module, so that the control module can timely receive monitoring data of the temperature sensor.

As a further preferred embodiment, a liquid level sensor is further arranged in the water tank 10, and the liquid level sensor is in communication connection with the control module, so that the control module can timely receive monitoring data of the liquid level sensor, an operator can conveniently know whether the water level in the water tank 10 meets the use requirement in time, and when the liquid level sensor monitors that the water level in the water tank 10 meets the use requirement, the control module controls the liver perfusion device to start to perfuse the liver.

As shown in fig. 7, the air-oxygen mixer assembly 2 comprises an oxygen cylinder 30, a carbon dioxide cylinder 31 and a gas mixer 32, wherein the oxygen cylinder 30 is connected with a first air inlet of the gas mixer 32 through a pipeline, the carbon dioxide cylinder 31 is connected with a second air inlet of the gas mixer 32 through a pipeline, an air outlet of the gas mixer 32 is respectively connected with the first lung membrane oxygenator 5 and the second lung membrane oxygenator 6 through a pipeline, so that the oxygen and the carbon dioxide are mixed in the gas mixer 32 and then enter the first lung membrane oxygenator 5 and the second lung membrane oxygenator 6 through the air outlet, and when the air mixer assembly is specifically arranged, the air outlet of the gas mixer 32 is connected with a first gas pipeline for connecting the first lung oxygenator 5 and a second gas pipeline for connecting the second lung membrane oxygenator 6, thereby the mixed gas of oxygen and carbon dioxide is transmitted to the perfusate of the first pulmonary membrane oxygenator 5 and the second pulmonary membrane oxygenator 6 through the first gas pipeline and the second gas pipeline, and the purpose of adjusting the oxygen content of the perfusate is achieved.

The monitoring assembly comprises an oxygen gas storage bottle 30, a first gas flow controller 33 and a second gas flow controller 34, wherein the first gas flow controller 33 is arranged on a pipeline connected with the first gas inlet, the second gas flow controller 34 is arranged on a pipeline connected with the second gas inlet, therefore, when the oxygen content of the perfusate needs to be accurately adjusted, the control module controls the first gas flow controller 33 and the second gas flow controller 34 to change the content of the oxygen and the carbon dioxide which enter the gas mixer 32 and are mixed, and the purpose of accurately adjusting the oxygen content of the perfusate is achieved.

In order to facilitate the operator to know the blood gas indexes of the perfusate such as PH, pO2, pCO2, HCT, NA +, CA +, K +, cl-, HCO3 and the like in time, the monitoring assembly further comprises a blood gas analyzer 35 in communication connection with the control module, so that people can know the physiological parameters of the perfusate in time, and the operator can adjust the physiological conditions of the perfusate in time according to the monitoring result of the blood gas analyzer 35, so that the perfusate can accord with the physiological environment.

During specific work, the blood gas analyzer 35 analyzes ASAT/GOT, ALAT/GPT, GLU, LAC, PH, pO2, pCO2, HCT, NA +, CA +, K +, cl-, HCO3, bile production amount and the like in the liver perfusion process, and generates a repair trend distribution map in the liver perfusion process, so that the quality condition of the liver in the perfusion process can be known in real time.

In order to facilitate the fixation of the first lung membrane oxygenator 5 and the second lung membrane oxygenator 6, the consumable assembly 3 further comprises a first lung membrane oxygenator holder 37 for holding the first lung membrane oxygenator 5 and a second lung membrane oxygenator holder 38 for holding the second lung membrane oxygenator 6.

In the present invention, the power supply unit includes an ac power supply and a storage battery 39, and when the power supply unit is specifically configured, as shown in fig. 1, the storage battery 39 is connected to the bottom of the main unit 1.

In order to facilitate an operator to know parameters such as water temperature, blood gas index, blood pressure, flow and the like in the liver perfusion process in time, an operation display screen 29 is arranged on the host, the operation display screen 29 is electrically connected with the control module, on one hand, the operation display screen 29 can display relevant information monitored by the monitoring component, such as ASAT/GOT, ALAT/GPT, GLU, LAC, PH, pO2, pCO2, HCT, NA +, CA +, K +, cl-, HCO3, bile generation amount, hepatic artery average pressure, systolic pressure, diastolic pressure, hepatic artery rate, upper limit value and lower limit value of hepatic artery target pressure, actual flow and target flow of hepatic artery, rotating speed of the first centrifugal blood pump 7, upper limit value and lower limit value of portal vein target pressure, actual flow and target flow of portal vein, rotating speed of the second centrifugal blood pump 8, during the liver perfusion process, Perfusion temperature, perfusion timer, hepatic artery, portal vein bleb cues, etc.; on the other hand, through operation display screen 29 can also set for temperature, blood gas index, perfusion pressure, flow, blood pressure isoparametric in the liver perfusion process to with above-mentioned parameter information transmission extremely control module makes control module controls according to the information received liver perfusion device carries out the liver and pours into, and is comparatively convenient.

In the present invention, the operation flow for setting the parameters such as temperature, blood gas index, perfusion pressure, flow rate, blood pressure, etc. in the liver perfusion process by using the operation display screen 29 is as follows:

s1: the liver perfusion apparatus is started and the hepatic artery pressure sensor 12 and portal vein pressure sensor 13 are zeroed.

The method specifically comprises the following steps: after the liver perfusion device is started, respectively shifting the zero setting knobs on the hepatic artery pressure sensor 12 and the portal vein pressure sensor 13 to be connected with the atmospheric pressure according to the indication of the hepatic artery pressure sensor 12 and the portal vein pressure sensor 13, then respectively clicking the hepatic artery pressure sensor zero setting button and the portal vein pressure sensor zero setting button on the operation display screen 29, and then, carrying out zero setting on the hepatic artery pressure sensor 12 and the portal vein pressure sensor 13 until the pressure values of the hepatic artery pressure sensor and the portal vein pressure sensor displayed on the operation display screen 29 are both 0, which indicates that the zero setting is successful, as shown in fig. 10; then, click the "pre-prime" button on the operation display 29 to enter the pre-prime page, as shown in fig. 11.

S2: performing pre-irrigation.

The method specifically comprises the following steps: as shown in fig. 11, on the pre-perfusion page, the running speeds of the first centrifugal blood pump 7 and the second centrifugal blood pump 8 are set, so that the first centrifugal blood pump 7 and the second centrifugal blood pump 8 rotate at a low speed to exhaust air in the pipeline of the liver perfusion device, and when the liver perfusion device runs stably and no air bubbles exist in the pipeline, the 'end pre-perfusion button' on the display screen 29 is clicked to operate, so that the pre-perfusion is ended; at the same time, the operation display screen 29 enters a perfusion parameter setting page, as shown in fig. 12.

S3: and setting perfusion parameters of the liver perfusion device during liver perfusion.

The method specifically comprises the following steps: firstly, inputting liver codes and liver quality of liver perfusion on a perfusion parameter setting page, wherein the codes are used for facilitating management and monitoring of parameters in a perfusion process, the control module can calculate flow required by liver perfusion according to the input liver quality, and the flow can be displayed in a flow display frame entering the perfusion parameter setting page; then, the "next" button on the operation display screen 29 is clicked, and the hepatic artery perfusion mode setting page is entered, as shown in fig. 13.

S4: setting a hepatic artery perfusion mode.

The method specifically comprises the following steps: selecting constant pressure perfusion or beating perfusion according to requirements on a hepatic artery perfusion mode setting page, wherein: the pulse mode can be a perfusion mode which performs pulse rate self-adaptive adjustment by constant pulse upper pressure and pulse lower pressure; constant pressure perfusion is continuous perfusion under a set constant pressure; meanwhile, the perfusion mode setting page also needs to input the temperature during liver perfusion and the upper limit value and the lower limit value of the hepatic artery target pressure, and then click the "next" button on the operation display screen 29 to enter the portal perfusion mode setting page, as shown in fig. 14.

S5: the portal perfusion mode is set.

The method specifically comprises the following steps: selecting constant pressure perfusion or constant flow perfusion according to the requirement on a portal vein perfusion mode setting page, wherein: the constant pressure perfusion is continuous perfusion under a set constant pressure, and the constant flow perfusion is continuous perfusion under a set constant flow rate; meanwhile, the portal vein perfusion mode setting page also needs to input the temperature during liver perfusion and the upper limit value and the lower limit value of the portal vein target pressure, and then click the "next" button on the operation display screen 29 to enter a perfusion monitoring interface, as shown in fig. 15.

S6: liver perfusion monitoring is performed through a perfusion monitoring interface.

It should be noted that, in the present invention, the perfusion monitoring interface respectively displays perfusion information of the hepatic artery and the portal vein, as shown in fig. 15, the two columns on the left of the perfusion monitoring interface display actual parameter values of perfusion, which specifically include: mean hepatic artery pressure, systolic pressure, diastolic pressure, hepatic artery pulse rate; an upper limit and a lower limit of a hepatic artery target pressure; actual flow and target flow of hepatic artery; the rotation speed of the first centrifugal blood pump 7; an upper and lower threshold for portal vein target pressure; portal vein actual flow and target flow; the rotational speed of the second centrifugal blood pump 8; the perfusion temperature; a perfusion timer; and a hepatic artery and portal vein bubble prompt and bile production amount counter.

The graphic display area of the perfusion monitoring interface is used for displaying a real-time oscillogram when hepatic artery and portal vein are perfused, and the real-time oscillogram comprises the following steps from top to bottom: real-time oscillograms of hepatic artery pressure, real-time oscillograms of hepatic artery flow, real-time oscillograms of portal vein pressure and real-time oscillograms of portal vein flow.

The right side of the perfusion monitoring interface is provided with a setting button which sequentially comprises the following steps: the device comprises an alarm sound adjusting button for setting alarm volume, a pump speed adjusting button for setting the rotating speeds of a first centrifugal blood pump 7 and a second centrifugal blood pump 8, a temperature adjusting button for setting perfusion temperature, a screen capture button for carrying out screen capture, a screen locking button for locking an operation display screen 29, a start-stop button for controlling the start and stop of perfusion of the liver perfusion device, and it needs to be explained that the pump speed adjusting button can be clicked only when the liver perfusion device stops perfusion.

The bottom of the perfusion monitoring interface is a page dicing button, from left to right, sequentially comprises a first switching button for switching the perfusion monitoring interface into a historical alarm recording interface, a second switching button for switching the perfusion monitoring interface into a historical perfusion data page, a third switching button for switching the perfusion monitoring interface into a perfusion parameter setting page, a fourth switching button for switching the display interface of the operation display screen 29 into the perfusion monitoring interface, and a fifth switching button for switching the perfusion monitoring interface into a blood gas analysis page, and what needs to be described is that: historical perfusion data and a perfusion trend curve chart under the liver ID can be checked through a historical perfusion data page; through the blood gas analysis page, the historical blood gas analysis data and the historical blood gas analysis curve can be inquired in the blood gas analysis historical database.

In other embodiments, the first centrifugal blood pump 7 comprises a first driving motor connected to the control module in communication with the control module and a first pump head connected to the first driving motor, the first driving motor is configured to drive the first pump head to rotate, and the control module controls the rotation speed of the first driving motor by using a PID algorithm; the second centrifugal blood pump 8 comprises a second driving motor in communication connection with the control module and a second pump head connected with the second driving motor, the second driving motor is used for driving the second pump head to rotate, and the control module controls the rotation speed of the second driving motor by using a PID algorithm, because the liver has two blood inlet vessels of a hepatic artery and a portal vein, and the blood supply modes of the hepatic artery and the portal vein are different, and in order to reduce the damage in the liver perfusion process, the physiological environments and the blood supply modes of the hepatic artery and the portal vein need to be closer to the in-vivo state in the liver perfusion process, therefore, in the invention, when the hepatic artery perfusion mode (namely constant pressure perfusion and pulsatile perfusion) and the portal vein perfusion mode (namely constant pressure perfusion and constant flow perfusion) need to be changed according to actual requirements, the control module only needs to adjust the rotation speeds of the first driving motor and the second driving motor, the method specifically comprises the following steps:

(1) when the perfusion mode of the hepatic artery is pulsatile perfusion, the control module performs actions of speed reduction and acceleration on the first driving motor in a cycle time period by utilizing a PID algorithm, so that the flow of perfusion liquid in a hepatic artery perfusion pipeline is fast and slow, the same mode as a cardiac blood supply mode is formed, and stable pulse rate, systolic pressure, diastolic pressure and pulse pressure difference are achieved.

(2) When the hepatic artery and/or the portal vein adopt constant-pressure perfusion, the control module utilizes a PID control algorithm to keep the rotating speed of the first driving motor and/or the second driving motor the same in different periods, so that the pressure of the hepatic artery perfusion pipeline and/or the portal vein perfusion pipeline is kept the same.

(3) When the portal vein adopts constant-current perfusion, the control module utilizes a PID control algorithm to keep the rotating speed of the second driving motor the same in different periods, so that the flow of the perfusion liquid in the portal vein perfusion pipeline is kept the same.

As a further preferred embodiment, the liver perfusion device further comprises two hand-pump assemblies, and the two hand-pump assemblies are respectively used for driving the first centrifugal blood pump 7 and the second centrifugal blood pump 8 to work, so as to ensure that the liver perfusion device works normally under the condition of power failure or abnormal power supply.

Specifically, as shown in fig. 9, the hand pump assembly includes a base 40, a housing 41 installed on the upper portion of the base 40, and a handle 42 connected to the housing 41, and since the handle 42 is symmetrically disposed on the left and right sides of the housing 41 with respect to the first centrifugal blood pump 7/the second centrifugal blood pump 8, and the output end of the handle 42 is connected to the input end of the first pump head/the second pump head, when two handles 42 of the hand pump assembly are shaken, the first pump head and the second pump head can be respectively driven to rotate, so as to achieve the purpose of driving the first centrifugal blood pump 7 and the second centrifugal blood pump 8 to work.

As a further preferred embodiment, in order to know the operating speed of the first pump head and the second pump head in time, each of the hand pump assemblies further comprises a pointer tachometer 48 for displaying the rotational speed of the handle 42, the pointer tachometer 48 being provided at the top of the housing 41. Moreover, in other embodiments, the hand pump assembly further includes an armrest 49, such that the armrest 49 ensures that the hand pump assembly remains stable during rocking of the handle 42.

In other embodiments, a network module is further disposed in the host 1, a network module is further disposed in the host, the control module is connected to a remote monitoring system through the network module, the remote monitoring system is configured to perform remote monitoring on the liver perfusion device, when the liver perfusion device is specifically connected, a first communication interface of the control module is in communication connection with the operation display screen 29, a second communication interface of the control module is in communication connection with the remote monitoring system through the network module, and the control module is in communication connection with the remote monitoring system, on one hand, the control module can receive a control instruction input through the operation display screen 29 in real time, so that the control module controls the liver perfusion device to operate according to the control instruction input through the operation display screen 29; on the other hand, the control module can also receive the instruction transmitted by the remote monitoring system, so that the control module controls the liver perfusion device to work according to the control instruction transmitted by the remote monitoring system, and further, the liver perfusion device is remotely controlled.

In the present invention, the remote monitoring system includes a message server in communication connection with the control module, a database server for storing data, a big data analysis server for processing big data of data in the database server, a Web server, and a remote monitoring terminal in communication connection with the Web server, specifically, in this embodiment, the network module is a WIFI module or a GPRS module or a 3G module or a 4G module, and the remote monitoring terminal includes a smart phone and a computer.

In specific connection, the message server is communicatively connected to the Web server and the database server, and the database server is communicatively connected to the Web server and the big data analysis server, as shown in fig. 16:

(1) the message server receives data transmitted by the control module, wherein the data comprises data information monitored by the monitoring component and a data processing result of the control module, such as ASAT/GOT, ALAT/GPT, GLU, LAC, PH, pO2, pCO2, HCT, NA +, CA +, K +, cl-, HCO3, bile generation amount, hepatic artery average pressure, systolic pressure, diastolic pressure, hepatic artery pulse rate, upper limit value and lower limit value of hepatic artery target pressure, actual hepatic artery flow and target flow, 7 rotating speed of a first centrifugal blood pump, upper limit value and lower limit value of portal vein target pressure, actual portal vein flow and target flow, 8 rotating speed of a second centrifugal blood pump, perfusion temperature, perfusion timer, hepatic artery, portal vein bubble prompt, bile generation counter meter and the like in a liver perfusion process; meanwhile, a liver perfusion control instruction is input through a computer or a mobile phone, the control instruction is transmitted to a Web server, and then the Web server transmits the control instruction to the message server.

(2) The message server transmits the received data to a database server for storage; meanwhile, the message server transmits the received data to the Web server, and the computer and the mobile phone can acquire the data received by the Web server so as to realize the remote monitoring of the liver perfusion device; in addition, the message server transmits the received control instruction to the control module, so that the remote control of the liver perfusion device is realized.

(3) The database server transmits the received data to the big data analysis server, the big data analysis server extracts useful information in the data by using a data analysis program to form perfusion trend curve graphs such as a hepatic artery pressure real-time waveform graph, a hepatic artery flow real-time waveform graph, a portal vein pressure real-time waveform graph, a portal vein flow real-time waveform graph perfusion curve graph and the like, the processing result is transmitted to the database server to be stored, then the perfusion trend curve graphs are transmitted to the message server, and finally the perfusion trend curve graphs are transmitted to the control module through the message server.

In the invention, the operation flow of inputting the perfusion control instruction and carrying out remote monitoring through the remote monitoring terminal is as follows:

s1: logging in the remote monitoring interface, specifically, inputting a user name and a password in the login interface, specifically as shown in fig. 17, and then clicking a "login" button to enter the device list interface.

S2: as shown in fig. 18, the ID of the liver perfusion apparatus to be remotely monitored is selected on the device monitoring list interface, a plurality of IDs can be simultaneously selected, and then the liver ID input interface can be accessed by clicking the selected ID.

S3: as shown in fig. 19, the ID of the liver to be perfused is input in the liver ID selection interface, and then the "ok" button is clicked, so that the hepatic artery perfusion state monitoring page and the portal vein perfusion state monitoring page can be accessed; as shown in fig. 20, on the hepatic artery perfusion state monitoring page, systolic pressure, diastolic pressure, average pressure, pulse rate, pumping speed of the first centrifugal blood pump 7, perfusion temperature, perfusion flow rate, historical perfusion pressure curve, historical flow rate curve, and the like of the hepatic artery can be realized; as shown in fig. 21, portal vein systolic pressure, diastolic pressure, average pressure, pulse rate, second centrifugal blood pump 8 pump speed, perfusion temperature, perfusion flow rate, historical perfusion pressure curve, historical flow rate curve, etc. may be implemented on the portal vein perfusion status monitoring page.

In addition, the start and stop of the first centrifugal blood pump 7 and the second centrifugal blood pump 8 can be controlled by the terminal; the perfusion temperatures of the hepatic artery and portal vein and the rotational speeds of the pump heads of the first centrifugal blood pump 7 and the second centrifugal blood pump 8 are set.

In the invention, the liver perfusion device is used for carrying out liver perfusion experiments, the liver perfusion experiments comprise a normal-temperature perfusion experiment and a low-temperature perfusion experiment, and the normal-temperature perfusion experiment and the low-temperature perfusion experiment are respectively described in detail below.

One, normal temperature perfusion experiment

1. Experimental procedure

(1) Selecting the liver of a common-grade three-way hybrid pig to carry out a perfusion experiment, fasting the three-way hybrid pig for 12 hours and forbidding water for 6 hours before the experiment is started, and then carrying out experimental animal anesthesia on the three-way hybrid pig according to a normal anesthesia procedure; the breathing machine is connected through an organ cannula to ensure that the three-way hybrid pig breathes in the operation; and simultaneously, monitoring the blood oxygen saturation of the animal in real time by using a monitoring instrument.

(2) Collecting blood: during the operation, the blood is released into the blood collecting bag through the abdominal artery cannula, and the leucocytes in the blood are filtered out, wherein the following items are required: before bleeding of the three-way hybrid pig, whole-body blood heparin bloom treatment is carried out on the three-way hybrid pig.

(3) Carrying out internal cold perfusion on the liver, and then obtaining the liver in an operation mode, wherein the perfusate for carrying out the internal cold perfusion on the liver is a shenbao with the temperature of 4 ℃, the perfusion volume of the hepatic artery and the portal vein is 1L, and the thoracic aorta section is ligated before the perfusion on the diaphragm to block the perfusate from flowing to the heart; after the cold perfusion in vivo is finished, the liver is rapidly obtained, and the hepatic artery is reserved to the main trunk of the abdominal aorta; after the liver was isolated, the portal vein of the liver was trimmed, the non-hepatic vascular branches were ligated, and all lymph nodes on the liver were removed.

(4) Setting perfusion parameters: the perfusion temperature is 37 ℃, the mean pressure of hepatic artery is 50mm, the pulsating pulse pressure difference is 20mmhg, the portal vein pressure difference is 8mm hg, and the hepatic artery perfusion mode is pulsating perfusion.

(5) In the experiment, the perfusate is prepared by mixing the priming solution and the leukocyte-removed blood according to the proportion of 1:3, and then 4666U heparin and 750mg cefuroxime sodium are added into each liter of the perfusate. The priming solution was prepared by mixing equal volumes of ringer's lactate, 20% mannitol, hydroxyethyl starch, and 1/6M sodium bicarbonate.

(6) The liver lavage is carried out, the lavage fluid is normal saline containing heparin, the content of the heparin is 12500U/L, and the lavage volume of the hepatic artery and the portal vein is 1L.

(7) Starting the liver perfusion device, and setting perfusion parameters, specifically: the hepatic artery perfusion pressure is 50mmHg, and the hepatic artery perfusion mode is pulsatile perfusion; the portal perfusion pressure is 8mmHg, and the portal perfusion mode is constant-flow perfusion.

(8) Start liver perfusion device carries out the liver and pours into, then extracts the perfusate every 1 hour, carries out the blood gas, electrolyte, temperature, blood sugar, metabolic waste, liver function and osmotic pressure to the perfusate of extraction and detects, records the flow and the pressure of learning of hepatic artery and portal vein simultaneously in real time, pours into and closes 7 hours after the liver perfusion device, between the laboratory glassware, the operation of liver perfusion device is stable.

2. Results of the experiment

During the experiment, the temperature, blood gas, flow and pressure of the liver are all in the physiological range, bile is continuously secreted, the blood sugar and the pH value are relatively stable, the content of glutamic-pyruvic transaminase is kept stable without rising, and fig. 22-34 are respectively a hepatic artery average pressure change trend graph, a hepatic artery systolic pressure change trend graph, a hepatic artery diastolic pressure change trend graph, a hepatic artery pulse rate change trend graph, a hepatic artery flow rate change trend graph, a portal vein pressure change trend graph, a portal vein flow rate change trend graph, a normal temperature perfusion temperature change trend graph, an oxygen partial pressure and carbon dioxide partial pressure change trend graph, a pH change trend graph, a blood sugar and lactic acid content change trend graph, a glutamic-pyruvic transaminase content change trend graph and a glutamic-oxaloacetic transaminase content change trend graph in the normal temperature perfusion experiment process.

3. Conclusion of the experiment

(1) As shown in FIGS. 22-25, the average hepatic artery pressure, systolic pressure, diastolic pressure, and pulsatile pulse rate during the experiment varied to a small extent, indicating that the liver perfusion apparatus can better control the pulsatile pressure entering the hepatic blood vessels to substantially stabilize at physiological levels.

(2) As shown in fig. 26, the flow of the hepatic artery was increasing over the period of time at the beginning of the experiment, then remained stable, and slightly fluctuated within the normal physiological level range, indicating that the hepatic artery microcirculation was continuously improving.

(3) As shown in FIG. 27, the average portal vein pressure during the experiment varied in a small amplitude, indicating that the liver perfusion apparatus can control the portal vein perfusion pressure well, so that the portal vein perfusion pressure can be stabilized at a physiological level during the perfusion process.

(4) As shown in fig. 28, portal venous flow increased over time during the start of the experiment, then remained steady and fluctuated slightly within normal physiological levels, indicating a continued improvement in portal microcirculation.

(4) As shown in fig. 29, the perfusion temperature was varied during the experiment in a small range, substantially maintained at about 37 ℃, and did not change significantly.

(5) As shown in fig. 30, the oxygen partial pressure and the carbon dioxide partial pressure of the perfusate varied during the experiment in a small range and fluctuated within the normal range.

(6) As shown in fig. 31, the pH of the perfusate varied only slightly during the experiment, indicating that pH balance could be maintained by adjusting the carbon dioxide ventilation, thereby demonstrating that the liver pH adjustment function was normal.

(7) As shown in FIG. 32, during the experiment, the content of blood sugar (abbreviated as Glu) remained relatively stable after a period of time, while the content of lactic acid (abbreviated as Lac) was continuously decreased, indicating that the sugar metabolism and the lactic acid metabolism of the liver were normal.

(8) As shown in FIG. 33, during the experiment, the content of glutamic pyruvic transaminase (ALT) was relatively stable, indicating that the liver cells were not necrosed after ischemia and reperfusion injury, and the function and morphology of the liver cells remained normal.

(9) As shown in FIG. 34, the level of aspartate Aminotransferase (AST) increased rapidly during the course of the experiment and was relatively stable after 5 hours from the start of the experiment, indicating that reperfusion injury of the liver was repaired.

In summary, when the liver perfusion device is used for normal-temperature perfusion for 7 hours, a large amount of secondary necrosis of liver cells does not exist, the liver anabolism function is normal, and the physiological state is maintained.

Second, Low temperature perfusion experiment

1. Procedure of experiment

The operation process of the low-temperature perfusion experiment is basically the same as that of the normal-temperature perfusion experiment, and the difference is only that: the perfusate temperature is 12-13 deg.C, hepatic artery pressure is 25mm hg, portal vein pressure is 3mm hg, hepatic artery perfusion mode is constant pressure perfusion, and the perfusate for in vivo cold perfusion is UW perfusate.

2. Results of the experiment

Fig. 35-42 are a hepatic artery flow rate trend graph, a hepatic artery mean pressure trend graph, a hepatic artery perfusion temperature trend graph, a portal vein flow rate trend graph, a portal vein mean pressure trend graph, a portal vein perfusion temperature trend graph, a pH trend graph, and a blood glucose and lactate content trend graph, respectively, during the low temperature perfusion experiment.

3. Conclusion of the experiment

(1) As shown in fig. 35 and 38, the hepatic artery flow and portal vein flow gradually increased during the experiment, indicating that as perfusion progressed, blood stasis inside the liver was gradually discharged and the vascular function of the liver improved at vinegar consumption.

(2) As shown in fig. 36 and 39, the mean hepatic artery pressure and the mean portal vein pressure were relatively stable during the experiment, indicating that the liver perfusion apparatus can better control the perfusion pressure during the liver perfusion process.

(3) As shown in fig. 37 and fig. 40, the hepatic artery perfusion temperature and the portal vein perfusion temperature change in small amplitude and are stably maintained at about 12 ℃ during the experiment, which indicates that the hepatic perfusion device can better control the perfusion temperature during the perfusion process.

(4) As shown in fig. 41, the pH decreased slowly during the experiment, indicating that the liver had certain physiological metabolic functions during the low temperature perfusion.

(5) As shown in FIG. 42, the content of blood glucose (Glu) slightly fluctuates and the content of lactic acid (Lac) slowly increases during the experiment, indicating that the liver has a good micro-physiological metabolism during the low-temperature perfusion.

It should be noted that, in the description of the present invention, the terms "first", "second", "third", "fourth", and "fifth", etc. are used for descriptive purposes only and are not to be construed as indicating or implying relative importance.

The above embodiments are only preferred embodiments of the present invention, and the protection scope of the present invention is not limited thereby, and any insubstantial changes and substitutions made by those skilled in the art based on the present invention are within the protection scope of the present invention.

Claims

1. Liver perfusion device, including host computer, empty oxygen blender subassembly and monitoring subassembly, the inside of host computer be provided with be used for to the power supply unit of liver perfusion device power supply, temperature regulation subassembly and with monitoring subassembly communication connection's control module, control module is used for control liver perfusion device work, its characterized in that: still include the joint and be in consumptive material subassembly on the host computer workstation, the temperature regulation subassembly with air-oxygen mixer subassembly all passes through the pipe connection the consumptive material subassembly, wherein:

the temperature adjusting assembly comprises a water tank arranged in the main machine, a temperature adjuster used for adjusting the water temperature of the water tank and an electronic water pump, and the electronic water pump is used for driving circulating water in the water tank to enter the first lung membrane oxygenator and the second lung membrane oxygenator through pipelines to respectively exchange heat with perfusion liquid entering the first lung membrane oxygenator and the second lung membrane oxygenator;

the centrifugal blood pump device is characterized by further comprising two hand-operated pump assemblies, wherein the two hand-operated pump assemblies are respectively used for driving the first centrifugal blood pump and the second centrifugal blood pump to work;

the consumable assembly further comprises a first thrombus filter connected between the first pulmonary membrane oxygenator and the hepatic arterial cannula, and a second thrombus filter connected between the second pulmonary membrane oxygenator and the portal venous cannula; the liver perfusion device further comprises a micro-injection pump which is in communication connection with the control module, and the micro-injection pump is connected with the first thrombus filter and the second thrombus filter through a pipeline; the monitoring assembly further comprises a blood gas analyzer in communication with the control module.

2. A liver perfusion device according to claim 1, wherein: the consumable assembly also includes a first thrombus filter holder for securing the first thrombus filter, and a second thrombus filter holder for securing the second thrombus filter.

3. A liver perfusion device according to claim 1, wherein: the bile collecting assembly comprises a bile collector and a bile cannula connected with the bile collector pipeline.

4. A liver perfusion device according to claim 3, wherein: the monitoring assembly comprises a bile titration sensor arranged at the liquid outlet end of the bile intubation, and the bile titration sensor is in communication connection with the control module.

5. A liver perfusion device according to claim 1, wherein: the monitoring assembly comprises a hepatic artery pressure sensor connected to a pipeline connecting the first thrombus filter and the hepatic artery cannula, and a portal vein pressure sensor connected to a pipeline connecting the second thrombus filter and the portal vein cannula, and the hepatic artery pressure sensor and the portal vein pressure sensor are both in communication connection with the control module.

6. A liver perfusion device according to claim 1, wherein: the monitoring assembly comprises a first flow sensor arranged at the liquid outlet end of the first centrifugal blood pump and a second flow sensor arranged at the liquid outlet end of the second centrifugal blood pump, and the first flow sensor and the second flow sensor are both in communication connection with the control module.

7. A liver perfusion device according to claim 1, wherein: the monitoring assembly comprises a first temperature probe arranged at the liquid outlet end of the first centrifugal blood pump and a second temperature probe arranged at the liquid outlet end of the second centrifugal blood pump, and the first temperature probe and the second temperature probe are in communication connection with the control module.

8. A liver perfusion device according to claim 1, wherein: bionic liver storage component includes the box body and connects the lid at box body top, bottom in the box body is provided with the apotheca that is used for storing the perfusate, the periphery of apotheca is provided with the chamber of icing of character cut in bas-relief, the upper portion of apotheca is provided with the liver and hangs the piece, the lateral wall of apotheca is provided with two liquid outlets, and two the liquid outlet is the pipe connection respectively first centrifugal blood pump with the centrifugal blood pump of second.

9. A liver perfusion device according to claim 8, wherein: the liver hanging part comprises a bracket connected to the top of the storage chamber and a T-shaped membrane fixedly connected with the bracket, and the T-shaped membrane is used for hanging the liver; the storage chamber is internally provided with a support bracket which is arranged below the support in parallel.

10. A liver perfusion device according to claim 9, wherein: the top of the ice adding chamber is connected with a sealing cover.

11. A liver perfusion device according to claim 9, wherein: the bottom of the storage chamber is inclined, and the two liquid outlets are arranged on the side wall which forms an acute angle with the bottom.

12. A liver perfusion device according to claim 9, wherein: the support bracket comprises a first support frame, a second support frame and a third support frame which are sequentially arranged from bottom to top, the second support frame is a silica gel film with holes, and the first support frame and the third support frame are used for fixing the second support frame.

13. A liver perfusion device according to claim 1, wherein: the temperature regulator comprises a PI patch heating film arranged on the outer wall of the water tank and a compressor unit arranged inside the host.

14. A liver perfusion device according to claim 1, wherein: the monitoring assembly comprises a temperature sensor and a liquid level sensor which are arranged in the water tank, and the temperature sensor and the liquid level sensor are in communication connection with the control module.

15. A liver perfusion device according to claim 1, wherein: the air-oxygen mixer component comprises an oxygen gas storage bottle, a carbon dioxide gas storage bottle and a gas mixer, wherein the oxygen gas storage bottle is connected with a first gas inlet of the gas mixer through a pipeline, the carbon dioxide gas storage bottle is connected with a second gas inlet of the gas mixer through a pipeline, and a gas outlet of the gas mixer is respectively connected with the first lung membrane oxygenator and the second lung membrane oxygenator through pipelines; the monitoring assembly comprises a first gas flow controller arranged on a pipeline connected with the first gas inlet and a second gas flow controller arranged on a pipeline connected with the second gas inlet.

16. A liver perfusion device according to claim 1, wherein: the consumable assembly also includes a first lung membrane oxygenator support for securing the first lung membrane oxygenator and a second lung membrane oxygenator support for securing the second lung membrane oxygenator.

17. A liver perfusion device according to claim 1, wherein: the power supply unit includes an alternating current power supply and a storage battery.

18. A liver perfusion device according to claim 1, wherein: the host is provided with an operation display screen, and the operation display screen is electrically connected with the control module.

19. A liver perfusion device according to claim 1, wherein: the first centrifugal blood pump comprises a first driving motor connected with the control module in a communication mode and a first pump head connected with the first driving motor, the first driving motor is used for driving the first pump head to rotate, and the control module controls the rotating speed of the first driving motor by using a PID algorithm; the second centrifugal blood pump comprises a second driving motor and a second pump head, the second driving motor is in communication connection with the control module, the second pump head is connected with the second driving motor, the second driving motor is used for driving the second pump head to rotate, and the control module controls the rotating speed of the second driving motor through a PID algorithm.

20. A liver perfusion device according to claim 1, wherein: the hand pump subassembly includes the base, installs casing on base upper portion and connect in the crank on the casing.

21. A liver perfusion device as claimed in any one of claims 1 to 20, wherein: the device comprises a host, and is characterized in that a network module is further arranged in the host, the control module is connected with a remote monitoring system through the network module, and the remote monitoring system is used for remotely monitoring the liver perfusion device.

22. A liver perfusion device according to claim 21, wherein: the remote monitoring system comprises a message server in communication connection with the control module, a database server for storing data, a big data analysis server for processing big data in the database server, a Web server and a remote monitoring terminal in communication connection with the Web server; and the message server is in communication connection with the Web server and the database server, and the database server is in communication connection with the Web server and the big data analysis server.