CN104686502A - Safety protection enhanced organ low-temperature machine perfusion preservation device and method - Google Patents

Abstract

The invention discloses a safety protection-enhanced low-temperature machine perfusion preservation device and method for organs. The device includes an organ box for placing organs to be transplanted, a low-temperature constant temperature box, a perfusion power source, a perfusion circuit, a perfusion preparation circuit, a flushing circuit, and sensor components arranged on each pipeline circuit. The perfusion circuit is composed of a perfusion power source, a filter, a buffer, an air bubble trap, a first perfusion pipeline, a main channel pipeline of a Y-shaped pipeline and a second branch channel pipeline, organ arteriovenous blood vessels, and a second perfusion pipeline. The perfusion preparation circuit is composed of a perfusion power source, a filter, a buffer, an air bubble trap, a first perfusion pipeline, a main channel pipeline of a Y-shaped pipeline, and a first branch channel pipeline. The flushing circuit is a flushing pipe. The invention optimizes the design of the perfusion circuit, adds bubble traps and bubble detectors to the perfusion circuit, and eliminates the perfusion bubbles in real time through the selection of the perfusion circuit and the flushing circuit, thereby improving the safety of perfusion.

Description

Device and method for safety-enhanced low-temperature machine perfusion preservation of organs

technical field

The invention belongs to the field of biomedical instruments, and in particular relates to a low-temperature machine perfusion preservation device and method for enhanced in vitro safety protection of organs to be transplanted.

Background technique

Organ transplantation has become one of the effective measures to save the lives of patients with multiple organ failure. The emergence of organ cryopreservation technology provides a solution to solve the shortage of transplanted organ donors and maintain organ function in the process of ex vivo, which greatly improves the clinical application of organ transplantation technology.

Pure cryopreservation and mechanical continuous perfusion are the most important methods for in vitro preservation of isolated organs in the past three decades. The simple cold storage method is characterized by reducing the metabolic rate of organs by providing a low temperature environment of 0-4 °C and using a preservation solution with high osmotic pressure to prevent organ edema. However, this preservation method cannot provide continuous nutrients and oxygen supply for organs to be transplanted. Therefore, cryopreservation can only be extended to a limited extent but cannot completely prevent the loss of organ function. Continuous low-temperature machine perfusion preservation (CHP) is to pump the perfusate into the organ with low flow and low pressure, so as to maintain the temperature of the perfusate and the organ to be transplanted at a low state, so as to supply the basic nutrients required for organ metabolism at low temperature and maintain the normal temperature. The purpose of removing the relevant waste. Clinical research data from FDA, NHS and other institutions have proved that hypothermic perfusion of transplanted organs can effectively reduce complications such as delayed recovery of transplanted kidney function (DGF), and improve the success rate of organ transplantation. Hypothermic perfusion of transplanted organs has become the recommended standard for organ transplantation by authoritative organizations such as FDA and NHS.

However, the effective time limit for organ preservation using these methods is short, and it is difficult to preserve the isolated kidney for more than 24-30 hours in clinical practice. Among them, factors such as the safety protection of the perfusion device itself, the timely handling of possible failures, and the physiological simulation of the organ preservation environment may affect the effect of organ preservation and the effective time limit for preservation. Aiming at this, the present invention discloses a safety protection-enhanced low-temperature mechanical perfusion preservation device and method. The preservation device buffers the instantaneous high pressure of perfusion by optimizing the design of the perfusion circuit, real-time removal of perfusion air bubbles, reasonable placement of sensors in the perfusion circuit to monitor the activity of perfusion organs and perfusion parameters, and provides fault alarms and good human-computer interaction for intelligent adjustment of the perfusion process , so as to improve the safety and stability of perfusion, so as to prolong the effective storage time of organs as much as possible.

Contents of the invention

In order to make up for the deficiencies in the existing in vitro preservation technology of transplanted organs and improve the safety and stability of low-temperature mechanical perfusion, the present invention proposes a safety protection-enhanced low-temperature mechanical perfusion preservation device and method.

One object of the present invention is to provide a low-temperature machine perfusion preservation device with enhanced safety protection.

The low-temperature machine perfusion preservation device of the present invention mainly includes an organ box for placing organs to be transplanted, a low-temperature incubator, a perfusion power source, a perfusion circuit, a perfusion preparation circuit, a flushing circuit, and a sensor assembly, wherein the sensor assembly includes a temperature sensor, a liquid level Sensors, biochemical sensors, pressure sensors;

The organ box used to place the organ to be transplanted is placed in a low-temperature incubator so that the temperature of the organ box is maintained at a low temperature of 0-4°C; the top of the organ box is provided with a gas exchange port for filtering bacteria and exchanging gas. Maintain a stable perfusion air pressure; a contact temperature sensor is provided on the side of the organ box to measure the temperature of the perfusate in the organ box; a liquid level sensor is provided on the outer wall of the organ box to monitor the level of the perfusate;

The organ box is made of medical transparent material to facilitate the monitoring of the morphological changes of the organs in the box. At the same time, it should be small and compact so that the organ can easily and safely move among the equipment used for perfusion, storage, analysis, and transportation of the organ to be transplanted.

The perfusion circuit consists of a perfusion power source, a filter, a buffer, an air bubble trap, a first perfusion pipeline, a main channel pipeline of a Y-shaped pipeline, a second branch channel pipeline of a Y-shaped pipeline, an organ arteriovenous blood vessel, a second Consists of two perfusion pipelines, in which the air bubble trap has a three-channel structure; the perfusion liquid inlet of the organ box is connected to one end of the perfusion power source through the first perfusion pipeline, and the other end of the perfusion power source is connected to the liquid inlet of the filter through the first perfusion pipeline , the first liquid outlet of the filter communicates with the buffer, where the buffer is used to moderate the instantaneous high pressure perfusion of the perfusion power source, and the second liquid outlet of the filter communicates with the first channel interface of the bubble trap through the first perfusion pipeline; The second channel interface of the trap is connected to the main channel pipeline of the Y-shaped pipeline, the second branch channel pipeline of the Y-shaped pipeline is connected with the artery of the organ to be transplanted, the vein of the organ to be transplanted is connected with one end of the second perfusion pipeline, and the second perfusion pipeline The other end extends below the perfusate level of the organ box to form a perfusion circuit;

The perfusion preparation circuit is composed of a perfusion power source, a filter, a buffer, an air bubble trap, the first perfusion pipeline, the main channel pipeline of the Y-shaped pipeline, and the first branch channel pipeline of the Y-shaped pipeline; the perfusion preparation circuit and The perfusion circuit shares channels and functional components between the inlet of the first perfusion pipeline and the main channel pipeline of the Y-shaped pipeline, and the outlet of the perfusion preparation circuit extends into the perfusate of the organ box through the first branch channel pipeline of the Y-shaped pipeline Below the liquid surface, a preparatory perfusion circuit is formed;

The flushing circuit is a flushing pipeline, one end of the flushing pipeline extends into the bubble trap through the third channel interface of the bubble trap, and the other end extends into the perfusate below the liquid surface of the organ box;

In the perfusion circuit, the perfusion preparation circuit, and the flushing circuit, the first branch passage line of the first perfusion pipeline, the flushing pipeline, and the Y-shaped pipeline that extends into the organ box is not directly connected to the blood vessels of the organ to be transplanted. Reduce the impact of perfusion air bubbles on organs.

A pressure sensor is provided on the perfusion power source and the filter part of the first perfusion pipeline to monitor the perfusion pressure of the perfusion power source; a dosing/sampling is provided on the filter and the bubble trap part of the first perfusion pipeline The mouth is convenient for biological immune modification and analysis of organ physiological parameters during the perfusion process;

A first valve is set on the main channel of the Y-shaped pipeline to control the opening and closing of the circuit; a second valve is set on the first branch channel of the Y-shaped pipeline to control the opening and closing of the preparatory perfusion circuit ; A biochemical sensor and a pressure sensor are provided on the second branch channel pipeline of the Y-shaped pipeline, which are respectively used to monitor the organ activity and the perfusion pressure of the organ;

A biochemical sensor is provided in the second perfusion pipeline for monitoring organ activity after perfusion.

The third channel interface of the bubble trap is connected to one end of the flushing pipeline, and the other end of the flushing pipeline extends below the perfusate liquid level of the organ box to form a flushing circuit; a third valve is provided on the flushing pipeline to control the opening of the flushing and close;

Bubble detectors are installed at the first channel interface and the second channel interface of the bubble trap to detect whether there are bubbles in the circuit before the perfusion starts, and whether there are bubbles generated during the perfusion process.

In the bubble trap, the lengths of the pipelines extending from the first channel interface and the second channel interface respectively into the bubble trap are the same, and longer than the length of the pipeline extending into the bubble trap from the third channel interface, so as to facilitate capturing the bubbles in the perfusate.

The filter membrane in the filter must be placed above the liquid level of the buffer, so that the buffer can accommodate harmful substances filtered out by the filter.

By comparing and analyzing the pressures of the two pressure sensors respectively located on the pipelines of the first perfusion channel and the second branch channel of the Y-shaped pipeline, it is possible to monitor whether pipeline blockage occurs in the system.

Through the cooperative work of the two biochemical sensors respectively located on the second branch channel pipeline of the Y-shaped pipeline and the second perfusion pipeline, the organ activity before, during and after perfusion can be monitored.

A non-contact temperature sensor and a liquid level sensor are installed on the outside of the bubble trap to monitor the temperature and liquid level of the perfusate inside.

The working process, perfusion parameter control and data analysis of the whole device can be monitored by a central control module. Once a fault occurs, a real-time alarm will be issued, and the human-computer interaction module will provide user operation and information display. The central control module is connected with the human-computer interaction module, data storage and analysis module, and sensor acquisition module through I/O, connected with the perfusion module through the drive unit, connected with the power management module through the serial port, and connected with the 3G communication module through the network interface connect. The power management module is responsible for the switch control of the system power supply, the acquisition and display of battery power, the control of battery charge and discharge, the alarm of insufficient power, and the reset and restart of the power supply. The human-computer interaction module provides user operation and information display, and the fault alarm during the perfusion process can be displayed and alarmed by the human-computer interaction module. The 3G communication module realizes the remote monitoring, positioning and analysis of organ perfusion parameters, biochemical parameters, GPS and other information to be saved during transportation. The data storage and analysis module is used to store various data of the system, including sensor component acquisition parameters and peripheral output display device display Time, voice, image, video and other information, and analyze the above data, give the analysis results of organ diastolic pressure, systolic pressure, perfusion flow, organ swelling degree, oxygen concentration change, etc., and comprehensively evaluate organ activity.

Another object of the present invention is an organ preservation and monitoring method based on the above-mentioned device, the method comprising the following steps:

Step (1). Place the organ to be transferred in the organ box, connect the artery of the organ to be transferred to the second branch channel of the Y-shaped pipeline, and connect the vein of the organ to be transferred to the second perfusion pipeline;

Step (2). After the system is turned on, first perform a self-check on power-on to check whether the consumables such as pipes in the system are installed in place and whether the functional components such as sensors and perfusion power sources can work normally. After confirmation, initialize and start the sensor components and human-machine Interaction module; start the data storage and analysis module through the central control module to evaluate the organ activity, comprehensively compare the organ activity data and the perfusion parameters set by the human-computer interaction module, generate optimized perfusion parameter settings, and start low-temperature perfusion according to the optimized settings; During the process, the system operation is detected by the central control module, and the perfusion execution is adjusted or the operator is reminded based on the detection results; the perfusion parameters and organ parameters during the perfusion process can be saved in real time, and can also be monitored remotely through the 3G communication module.

The key technologies in the above method mainly include safety protection and fault alarm, perfusion intelligent feedback control, network data sharing and remote monitoring, as follows:

Safety protection and fault alarm need to consider the situation of pipeline blockage, accumulated bubbles in perfusate, temperature exceeding limit and liquid level exceeding limit:

Aiming at the blockage of the pipeline, it is proposed to use the drastic change of the pressure difference between the two ends of the perfusion pipeline before and after the blockage to detect the blockage of the pipeline, and accurately determine the blockage position, which is achieved by setting pressure sensors after the perfusion power source and before the organ arterial entrance. When the pipeline is blocked, the system will automatically alarm and send out a pulsed positive pressure wave at the head end. The wavelet transform extracts the pressure mutation information, and obtains the time difference between the positive pressure wave passing through the pressure sensor before the venous entrance of the organ twice. Finally, the position of the pipeline blockage can be determined by integrating the propagation speed of the positive pressure wave.

For the protection of air bubbles during the perfusion process, air bubble detectors and multi-channel piping systems can be used to remove air bubbles. In the present invention, a bubble detector and a two-way pipeline (ie, Y-shaped pipeline and flushing pipeline) system are arranged at the front end of the perfusate entering the organ. If there is no bubble, the perfusate directly enters the organ; otherwise, the pipeline is switched to the flushing circuit or the preparatory perfusion circuit to eliminate air bubbles. .

For the monitoring of temperature and liquid level during the perfusion process, install temperature sensors and liquid level sensors on the outside of the organ box and the bubble trap respectively to monitor the storage temperature of transplanted organs and the temperature and liquid level of the perfusate in real time. When the temperature detected by the temperature sensor exceeds Set the range (0-4°C), the system will alarm, and automatically take safety measures to shut down. At the same time, the human-computer interaction module will notify the user to request manual intervention. Similarly, the liquid level sensor detects that the liquid level exceeds the limit, such as severe vibration during transportation. If the box rolls over and causes perfusate leakage, it will also shut down and alarm to request manual intervention.

For other failures that cannot be automatically eliminated, such as low battery power, the machine will also take safety protection measures such as shutdown, and notify the user through the human-computer interaction module and safety protection module to request manual intervention.

Perfusion intelligent feedback control: According to the organ activity parameters collected by the biochemical sensor, combined with the perfusion parameters collected by other sensors, and compared with the perfusion mode and parameters set by the human-computer interaction module, the perfusion parameters are optimized according to the perfusion experience data stored in the system. Results The central control module controls and drives the perfusion power source to perform perfusion or flushing; the feedback regulation of perfusion parameters mainly includes perfusion channel control, pressure regulation, and flow detection and control;

For perfusion channel control, the valves placed on the perfusion pipeline are mainly used to realize the opening and closing of multiple perfusion channels;

For the pressure regulation during the perfusion process, the method of simulating the heartbeat rhythm curve is adopted. The pressure curve of the pulsation of the simulated organ in the body can adopt a closed-loop feedback adjustment system, such as using a pressure sensor as a feedback input and a peristaltic pump as a targeted control target to achieve pressure control. The closed-loop control adopts the PID algorithm to advance the control curve amplitude with the time axis as a parameter;

For the flow detection and control of the perfusion process, the perfusion flow can be calculated according to the number of rotations of the perfusion power source (such as a peristaltic pump) per minute and the volume of perfusate extruded by each rotation, thereby realizing automatic detection of the perfusion flow.

Network data sharing and remote monitoring: Various types of data and information during organ perfusion, preservation, and transportation can be grouped and recorded, and provided to doctors, scientists, or other institutions for research through 3G network modules, and realize the physiological function of organs to be transplanted. Remote monitoring of parameters, GPS location and other information.

Compared with background technology, the beneficial effect that the present invention has is:

(1) Improve the safety and stability of perfusion

The device optimizes the design of the perfusion circuit, and the perfusate inlet is not directly connected to the blood vessel inlet of the transplanted organ; a buffer is installed after the perfusion power source and filter to collect harmful substances generated during the perfusion and perfusion process and buffer the instantaneous high pressure of the perfusion; in the perfusion circuit Add bubble traps and bubble detectors, and eliminate perfusion bubbles in real time through the selection of perfusion circuits and flushing circuits. A series of measures can improve the safety of perfusion. Sensors are reasonably placed in the perfusion circuit to monitor the activity of perfused organs and perfusion parameters, and provide fault information. An alarm and a good human-computer interaction module can be used for intelligent adjustment of the perfusion process, which can improve the stability of the perfusion. The improvement of perfusion safety and stability is of great significance for prolonging the effective storage time of organs as much as possible.

(2) The perfusion storage device adopts full simulation pulsation wave perfusion and dynamic simulation feedback control technology, and the perfusion pressure and perfusion waveform can be closer to the human body.

(3) Reserving the dosing/sampling port can facilitate the perfusion process for biological immune modification and analysis of organ physiological parameters, and can also be used for drug treatment according to organ activity.

Description of drawings

Fig. 1 is a schematic diagram of the principle of the perfusion device of the present invention;

Fig. 2 is a schematic diagram of the control principle of the perfusion device system of the present invention;

3 is a schematic diagram of the driving waveform and the perfusion pressure waveform of the perfusion power source in the flushing mode, the constant pressure perfusion mode, and the pulsating perfusion mode;

1. Organ, 2. Organ Box, 2-1 Gas Exchange Port, 3. Perfusion Power Source, 4. Filter, 5. Bubble Trap, 5-1. First Channel Interface, 5-2. Second Channel Interface , 5-3. Third channel interface, 6. First perfusion pipeline, 7. Flushing pipeline, 8. Second perfusion pipeline, 9. Y-shaped pipeline, 9-1. First branch channel pipeline, 9-2. Second branch channel pipeline, 9-3. Main channel pipeline, 10. Buffer, 11. Liquid level sensor, 12. Bubble detector, 13-1. First valve, 13-2. Second valve, 13 -3. The third valve, 14. Biochemical sensor, 15. Pressure sensor, 16. Dosing/sampling port, 17. Low temperature thermostat, 18. Contact temperature sensor, 19. Non-contact temperature sensor.

Detailed ways

The present invention is further analyzed below in conjunction with accompanying drawing.

Fig. 1 shows the schematic diagram of the principle of the perfusion device of the present invention.

As shown in Figure 1, the low-temperature machine perfusion preservation device of the present invention mainly includes an organ box (2) for placing organs to be transplanted, a low-temperature constant temperature box (17), a perfusion power source (3), a perfusion circuit, a perfusion preparation circuit, Flushing circuit, sensor components, where the sensor components include temperature sensors, liquid level sensors, biochemical sensors, pressure sensors;

The organ box (2) for placing the organ to be transplanted is placed in a low-temperature incubator (17), so that the temperature of the organ box (2) is maintained in a low temperature environment of 0-4°C; the top of the organ box (2) 11 is open There is a gas exchange port (2-1), which is used to filter bacteria, exchange gas, and maintain a stable perfusion pressure; the side of the organ box (2) is provided with a contact temperature sensor (18), which is used to measure the perfusion in the organ box (2) The temperature of the liquid; the outer wall of the organ box (2) is provided with a liquid level sensor (11) for monitoring the liquid level of the perfusate;

The organ box (2) is made of medical transparent materials to facilitate the monitoring of changes in the shape of the organs in the box. At the same time, it should be small and compact so that the organs can be easily and safely placed between the equipment for perfusion, storage, analysis, and transportation of the organ to be transplanted. to move between.

The perfusion circuit is composed of a perfusion power source (3), a filter (4), a buffer (10), an air bubble trap (5), the first perfusion pipeline (6), and the main channel pipeline of the Y-shaped pipeline (9) 9-3. The second branch channel pipeline 9-2 of the Y-shaped pipeline (9), organ blood vessels, and the second perfusion pipeline (8); the perfusion liquid inlet of the organ box (2) passes through the first perfusion pipeline (6) Connected to one end of the perfusion power source (3), the other end of the perfusion power source (3) communicates with the liquid inlet of the filter (4) through the first perfusion pipeline (6), and the first liquid outlet of the filter (4) is connected to the The buffer (10) is connected, where the buffer (10) is used to moderate the instantaneous high pressure of the perfusion power source (3), and the second liquid outlet of the filter (4) passes through the first perfusion pipeline (6) and the air bubble trap ( 5) The first channel interface (5-1) is connected; the second channel interface (5-2) of the bubble trap (5) is connected to the main channel pipeline (9-3) of the Y-shaped pipeline (9), and the Y-shaped pipeline The second branch channel pipeline (9-2) of (9) communicates with the artery of the organ to be transplanted, the vein of the organ to be transplanted communicates with one end of the second perfusion pipeline (8), and the other end of the second perfusion pipeline (8) extends into A perfusion circuit is formed below the perfusate liquid surface of the organ box (2);

The perfusion preparation circuit is composed of a perfusion power source (3), a filter (4), a buffer (10), an air bubble trap (5), the first perfusion pipeline (6), and the main channel pipeline of the Y-shaped pipeline (9) (9-3), the first branch channel pipeline (9-1) of the Y-shaped pipeline (9); the perfusion preparation circuit and the perfusion circuit are connected between the entrance of the first perfusion pipeline (6) and the Y-shaped pipeline (9) The main channel pipeline (9-3) shares channels and functional components, while the outlet of the perfusion preparation circuit extends into the organ box (2) through the first branch channel pipeline (9-1) of the Y-shaped pipeline (9). Below the surface of the perfusate, a preparatory perfusion circuit is formed;

In the perfusion circuit, perfusion preparation circuit, and flushing circuit, the first branch channel pipeline (9-1) of the first perfusion pipeline (6), flushing pipeline (7), and Y-shaped pipeline (9) extends into the organ box (2 ) are not directly connected to the blood vessels of the organ to be transplanted (1) to minimize the impact of perfusion air bubbles on the organ.

A pressure sensor (15) is provided on the perfusion power source (3) and the filter (4) part of the first perfusion pipeline (6) to monitor the perfusion pressure of the perfusion power source (3); (6) There are dosing/sampling ports (16) on the filter (4) and bubble trap (5) part of the pipeline, which is convenient for biological immune modification and organ physiological parameter analysis during the perfusion process;

A first valve (13-1) is provided on the main channel pipeline (9-3) of the Y-shaped pipeline (9) to control the opening and closing of the perfusion circuit; the first branch channel pipeline of the Y-shaped pipeline (9) There is a second valve (13-2) on the road (9-1), which is used to control the opening and closing of the perfusion preparation circuit; There are biochemical sensors (14) and pressure sensors (15), respectively used to monitor organ activity and organ perfusion pressure;

A biochemical sensor (14) is provided in the second perfusion pipeline (8) for monitoring organ activity.

The third channel interface (5-3) of the bubble trap (5) is connected to one end of the flushing pipe (7), and the other end of the flushing pipe (7) extends below the perfusate level of the organ box (2), forming a flushing circuit ; There is a third valve (13-3) on the flushing pipeline (7), which is used to control the opening and closing of flushing;

The first channel interface (5-1) and the second channel interface (5-1) of the bubble trap (5) are equipped with air bubble detectors (12), which are used to detect whether there are bubbles in the circuit before the start of perfusion, and to detect whether the perfusion Whether the process produces bubbles.

In the bubble trap (5), the lengths of the pipes stretching into the bubble trap (5) from the first channel interface (5-1) and the second channel interface (5-2) respectively are the same, and longer than those from the third channel interface (5-5). -3) Length of tubing extending into the air bubble trap (5) to facilitate trapping air bubbles in the perfusate.

The filter membrane in the filter (4) must be placed above the liquid level of the buffer (10), so that the buffer (10) can accommodate harmful substances filtered out by the filter (4).

Through the pressure comparison analysis of the two pressure sensors (15) respectively located on the first perfusion channel (6) and the second branch channel pipeline (9-2) of the Y-shaped pipeline (9), it is possible to monitor whether there is a pipeline in the system clogged.

By cooperating with the two biochemical sensors (14) respectively located on the second branch channel pipeline (9-2) of the Y-shaped pipeline (9) and the second perfusion pipeline (8), it is possible to monitor before, during and after the perfusion. Organ viability after perfusion.

The outside of the bubble trap (5) is equipped with a non-contact temperature sensor (18) and a liquid level sensor (11), which are respectively used to monitor the temperature and liquid level of the perfusate inside.

The whole perfusion device has four perfusion modes to choose from, which are flushing mode, preparation mode, constant pressure perfusion mode and pulsating perfusion mode. Its purpose is to ensure the safety and stability of organ perfusion. The flushing mode and preparatory mode are used to eliminate air bubbles in the entire perfusion fluid path, and the constant pressure perfusion mode and pulsating perfusion mode are working modes for normal organ perfusion.

1. Flush mode

As shown in Fig. 1 , the schematic diagram of the perfusion device, in the flushing mode, the first valve (13-1) is closed and the third valve (13-3) is opened. The perfusion power source (3) operates, and the liquid is discharged from the flushing pipeline (7), thereby eliminating the perfusion power source (3), the pressure sensor (15) located on the first perfusion channel (6), the filter (4), The dosing/sampling port (16), the buffer (10), the bubble detector provided at the interface of the first channel of the bubble trap (5), the bubble trap (5), and the bubbles in the flushing pipeline (7). The flushing mode can be stopped after the air bubbles in the perfusion circuit are eliminated through observation or automatic detection by the bubble detector.

2. Ready mode

As shown in Fig. 1 , the schematic diagram of the perfusion device, in the preparatory mode, the first valve (13-1) is opened, the third valve (13-3) is closed, and the second valve (13-2) is opened. The perfusion power source (3) operates, and the perfusate is discharged from the first branch channel pipeline (9-1) of the Y-shaped pipeline (9). Thereby get rid of perfusion power source (3), be positioned at the pressure sensor (15) on the first perfusion channel, filter (4), dosing/sampling port (16), buffer (10), be respectively arranged on bubble trap (5 ) Two air bubble detectors at the first channel interface and the second channel interface, the air bubble trap (5), the first branch channel pipeline (9-1) of the Y-shaped pipeline (9), and the main channel pipeline (9-3 ) in the air bubbles. Detect whether there are air bubbles in the perfusion circuit by observation or automatic detection by the air bubble detector, and the flushing mode can be stopped after the air bubbles are eliminated.

3. constant pressure perfusion mode

As shown in Figure 1, the schematic diagram of the principle of the perfusion device, in the constant pressure perfusion mode, the arterial blood vessel of the organ is connected with the second branch channel pipeline (9-2) of the Y-shaped pipeline (9), and the first valve (13-1 ) is opened, the third valve (13-3) is closed, and the second valve (13-2) is closed. The perfusion power source (3) operates continuously, and the perfusate passes through the perfusion power source (3), the pressure sensor (15) located on the first perfusion channel, the filter (4), the dosing/sampling port (16), the buffer ( 10), two bubble detectors, the bubble trap (5), and the first branch channel pipeline (9-1 ) and the main access line (9-3) into the organ. In this mode, the current perfusion pressure is obtained in real time through the pressure sensor (15) on the second branch channel pipeline (9-2) of the Y-shaped pipeline (9), so as to perform feedback adjustment and control the perfusion pressure in a constant mode Down.

4. Pulse perfusion mode

As shown in Figure 1, the schematic diagram of the principle of the perfusion device, in the pulsating perfusion mode, the arterial blood vessels of the organ are connected to the second branch channel pipeline (9-2) of the Y-shaped pipeline (9), and the first valve (13-1) open, the third valve (13-3) is closed, and the second valve (13-2) is closed. The perfusion power source (3) operates in a pulsating manner, the perfusate enters the organ according to the perfusion circuit in the constant pressure perfusion mode shown in the above 3, and the pump operates in a periodic manner of acceleration-constant speed-deceleration-constant speed. The output perfusate produces a pulsation effect, thereby simulating the human heartbeat rhythm. The current perfusion pressure is obtained in real time through the pressure sensor (15) arranged on the second branch channel pipeline (9-2) of the Y-shaped pipeline (9), so as to perform feedback adjustment and control the pulsating pressure within a set range.

The working process, perfusion parameter control and data analysis of the whole device can be monitored by a central control module. Once a fault occurs, it will give a real-time alarm, and the human-computer interaction module will provide user operation and information display. The central control module is connected with the human-computer interaction module, data storage and analysis module, and sensor acquisition module through I/O, connected with the perfusion module through the drive unit, connected with the power management module through the serial port, and connected with the 3G communication module through the network interface connect. The power management module is responsible for the switch control of the system power supply, the acquisition and display of battery power, the control of battery charge and discharge, the alarm of insufficient power, and the reset and restart of the power supply. The human-computer interaction module provides user operation and information display, and the fault alarm during the perfusion process can be displayed and alarmed by the human-computer interaction module. The 3G communication module realizes the remote monitoring, positioning and analysis of organ perfusion parameters, biochemical parameters, GPS and other information to be saved during transportation. The data storage and analysis module is used to store various data of the system, including sensor component acquisition parameters and peripheral output display device display Time, voice, image, video and other information, and analyze the above data, give the analysis results of organ diastolic pressure, systolic pressure, perfusion flow, organ swelling degree, oxygen concentration change, etc., and comprehensively evaluate organ activity.

The organ preservation and monitoring method based on the above device, the method includes the following steps:

Step (1). Place the organ to be transferred (1) in the organ box (2), and connect the vein of the organ to be transferred (1) to the second branch channel line (9-2) of the Y-shaped pipeline (9) , the artery of the organ to be transferred (1) is connected with the second perfusion pipeline (8);

Step (2). As shown in Figure 2, after the system is turned on, it first conducts a self-inspection to check whether the consumables such as pipelines in the system are installed in place and whether functional components such as sensors and perfusion power sources (3) can work normally. After confirmation Initialize and start the sensor components and the human-computer interaction module; start the data storage and analysis module to evaluate the organ activity through the central control module, comprehensively compare the organ activity data and the perfusion parameters set by the human-computer interaction module, and generate optimized perfusion parameter settings. Optimize the settings to start low-temperature perfusion; during the perfusion process, use the central control module to detect the system operation, adjust the perfusion execution or remind the operator based on the detection results; the perfusion parameters and organ parameters during the perfusion process can be saved in real time, or through the 3G communication module for remote monitoring.

Fig. 3 shows schematic diagrams of driving waveforms and perfusion pressure waveforms of the perfusion power source (3) (such as a pump) in flushing mode, constant pressure perfusion mode, and pulsating perfusion mode.

Aiming at the blockage of the pipeline, it is proposed to use the drastic change of the pressure difference between the two ends of the perfusion pipeline before and after the blockage to detect the blockage of the pipeline, and accurately determine the blockage position. By setting two pressures after the perfusion power source (3) and before the organ vein entrance sensor (15) to achieve. When the pipeline is blocked, the system will automatically alarm and send out a pulsed positive pressure wave at the head end. The wavelet transform extracts the pressure mutation information, and obtains the time difference between the positive pressure wave passing through the pressure sensor (15) before the vein inlet of the organ twice, and finally the location of the pipeline blockage can be determined by integrating the propagation speed of the positive pressure wave.

Aiming at monitoring the temperature and liquid level during the perfusion process, a temperature sensor and a liquid level sensor (11) are installed on the outside of the organ box (2) and the bubble trap (5) respectively to monitor the storage temperature of the transplanted organ and the temperature and liquid level of the perfusate in real time. When the temperature detected by the temperature sensor exceeds the set range (0~4°C), the system will alarm and automatically take safety measures to stop the machine. At the same time, the human-computer interaction module will notify the user to request manual intervention. If the liquid level exceeds the limit, if the organ box (2) is overturned due to violent vibration during transportation, causing perfusate leakage, it will also shut down and alarm to request manual intervention.

For other failures that cannot be automatically eliminated, such as low battery power, the machine will also take safety protection measures such as shutdown, and notify the user through the human-computer interaction module and safety protection module to request manual intervention.

The low-temperature perfusion device proposed by the present invention improves the safety of perfusion and ensures the stability of perfusion by optimizing the perfusion circuit and rationally arranging the position of the sensor. In the present invention, the inlet of the perfusate is not directly connected to the blood vessels of the transplanted organ, and multiple valve structures are used to provide non-contact control for the switching of the fluid circuit, and buffer chambers and bubble traps (5) are added in the perfusion circuit to alleviate the transient perfusion High pressure, remove air bubbles in time, so as to improve the safety of perfusion; alarm in time if there is a fault, and can arrange fault handling methods according to the fault level and type. The invention can prolong the effective time limit of organ preservation, and can perform biological immune modification, organ physiological parameter analysis and organ treatment in the perfusion process.

The above embodiments do not limit the present invention, and the present invention is not limited to the above embodiments, as long as the requirements of the present invention are met, they all belong to the protection scope of the present invention.

Claims (10)

1. organ hypothermia machine perfusion save set, it is characterized in that comprising for place treat transplant organ organ box, cryostat, perfusion power source, perfusion loop, perfusion preparation loop, flush loop, the sensor cluster be located on each pipeline loop, wherein sensor cluster comprises temperature sensor, liquid level sensor, biochemical sensor, pressure sensor;

Described perfusion loop is made up of the main channel pipeline in perfusion power source, filter, buffer, bubble trap and the first perfusion pipeline, Y-piece road, the second branched bottom pipeline in Y-piece road, organ artery and vein vascular, the second perfusion pipeline, and wherein bubble trap is triple channel structure; The perfusion liquid inlet of organ box is connected with one end of perfusion power source by the first perfusion pipeline, the other end of perfusion power source is communicated with by the liquid-inlet of the first perfusion pipe-and-filter, the first liquid outlet of filter is communicated with buffer, buffer is for relaxing the instantaneous high pressure of perfusion power source perfusion herein, and the second liquid of filter exports the first passage orifice by the first perfusion pipeline and bubble trap; The second channel interface of bubble trap connects the main channel pipeline in Y-piece road, the second branched bottom pipeline in Y-piece road with treat that transplant organ artery is communicated with, treat that transplant organ vein is communicated with one end of the second perfusion pipeline, the other end of the second perfusion pipeline stretches into below the perfusate liquid level of organ box, forms a perfusion loop;

Being placed in cryostat for placing the organ box treating transplant organ, making organ box temperature maintain in 0 ~ 4 DEG C of low temperature environment;

Described perfusion preparation loop is made up of the main channel pipeline in perfusion power source, filter, buffer, bubble trap and the first perfusion pipeline, Y-piece road, the first branched bottom pipeline in Y-piece road, and wherein bubble trap is triple channel structure; Perfusion preparation loop and perfusion loop the first perfusion pipeline entrance to Y-piece road main channel pipeline between common-use tunnel and functional unit, and the outlet in perfusion preparation loop is stretched into below the perfusate liquid level of organ box by the first branched bottom pipeline in Y-piece road, form a preparation perfusion loop;

Described flush loop is flushing pipe, and bubble trap is stretched into through the third channel interface of bubble trap in one end of flushing pipe, and the other end stretches into below the perfusate liquid level of organ box;

The course of work of whole device, perfusion parameter control and data analysis is monitored by central control module, once the Realtime Alerts that breaks down, provide user operation and information displaying by human-computer interaction module; Described central control module is stored with human-computer interaction module, data and is connected by I/O with analysis module, sensor acquisition module, be connected by driver element with perfusion module, be connected by serial ports with power management module, be connected by network interface with 3G communication module.

2. organ hypothermia machine perfusion save set as claimed in claim 1, is characterized in that described organ box top has gas exchanges mouth, and for filter bacteria, exchanging gas, maintains perfusion stable gas pressure; The side of organ box is provided with contact type temperature sensor, for measuring the temperature of perfusate in organ box; The outer wall of organ box is provided with liquid level sensor, for monitoring perfusate liquid level.

3. organ hypothermia machine perfusion save set as claimed in claim 1, it is characterized in that in perfusion loop, perfusion preparation loop, flush loop, the first branched bottom pipeline in the first perfusion pipeline, flushing pipe, Y-piece road stretch into pipeline in organ box all not directly with treat that the blood vessel of transplant organ is connected, to reduce perfusion bubble as far as possible, organ is affected.

4. organ hypothermia machine perfusion save set as claimed in claim 1, is characterized in that on the perfusion power source and filter part subtube of the first perfusion pipeline, being provided with pressure sensor, in order to monitor the injection pressure of perfusion power source; The filter and bubble trap section of tubing of the first perfusion pipeline have dosing/sample tap, facilitates perfusing course to do biological immune and modify and organ physiological parameter analysis;

The main channel pipeline in Y-piece road is provided with the first valve, controls the open and close in this loop; The first branched bottom pipeline in Y-piece road is provided with the second valve, for controlling the open and close preparing perfusion loop; The second branched bottom pipeline in Y-piece road is provided with biochemical sensor, pressure sensor, is respectively used to the injection pressure monitoring organ viability and organ;

Biochemical sensor is provided with, for monitoring organ viability after perfusion at the second perfusion pipeline;

Flushing pipe is provided with the 3rd valve, for controlling the opening and closing of rinsing;

First passage interface, the second channel interface of bubble trap are equipped with gas bubble detection, start whether there is bubble in front loop, and whether perfusing course produce bubble in order to detect perfusion;

The outside of described bubble trap is provided with non-contact temperature sensor, liquid level sensor, respectively in order to monitor temperature and the liquid level of its inner perfusate.

5. organ hypothermia machine perfusion save set as claimed in claim 1, it is characterized in that in bubble trap, identical with the duct length that second channel interface stretches into bubble trap from first passage interface respectively, and be longer than the duct length stretching into bubble trap from third channel interface, to facilitate the bubble of catching in perfusate.

6. organ hypothermia machine perfusion save set as claimed in claim 1, is characterized in that the filter membrane in described filter must be placed on the ullage of buffer, is convenient to the harmful substance that buffer collecting filter leaches.

7. the organ based on organ hypothermia machine perfusion save set as claimed in claim 1 is preserved and method for supervising, it is characterized in that the method specifically comprises the following steps:

Step (1). be placed in organ box by organ to be transferred, and be connected with Y-piece road second branched bottom pipeline by the artery of organ to be transferred, the vein of organ to be transferred is connected with the second perfusion pipeline;

Step (2). after system boot, first startup self-detection is carried out, whether the consumptive materials such as detection system interior conduit are in place and whether the functional unit such as sensor, perfusion power source can normally work, and carry out initialization and start sensor assembly and human-computer interaction module after to be confirmed; Start data by central control module to store and analysis module evaluation organ viability, the perfusion parameter of Integrated comparative organ viability data and human-computer interaction module setting, produces the perfusion parameter optimized and arranges, start hypothermic perfusion according to optimal design-aside; In the process of perfusion, carry out detection system by central control module run, perform based on testing result adjustment perfusion or remind operator; Perfusion parameter in perfusing course and organ parameter can be preserved in real time, also carry out remote monitoring by 3G communication module;

Mainly comprise security protection in said method and fault alarm, perfusion Intelligence Feedback regulate and control, network data share and remote monitoring.

8. preserve and method for supervising based on the organ of organ hypothermia machine perfusion save set as claimed in claim 6, it is characterized in that described security protection and fault alarm mainly comprise following monitoring: line clogging, perfusate add up bubble, temperature over-range and liquid level transfinites:

For line clogging, utilize the pressure reduction acute variation of perfusion line clogging rear and front end to carry out the stopping state of testing pipes, and accurately determine its blocking position, by arranging pressure sensor to realize respectively after perfusion power source He before organ arterial inlet; When line clogging, system automatic alarm, a pulse barotropic wave is sent at head end, barotropic wave reflects when pipeline is propagated and run into tamper, twice barotropic wave information can be obtained at pipeline head end, and utilize wavelet transformation to extract pressure jump information, obtain the time difference that barotropic wave passes twice through pressure sensor before organ venous inlet, last comprehensive malleation velocity of wave propagation can determine the position of pipeline blockage;

For the bubble protection in perfusing course, gas bubble detection and the removal of multiple-way duct system realization to bubble can be adopted; The front end entering organ at perfusate arranges gas bubble detection and two-way pipe-line system, if perfusate directly enters organ during bubble-free, otherwise pipeline is switched to flush loop or bubble is got rid of in preparation perfusion loop;

For the monitoring of the temperature in perfusing course and liquid level, mounting temperature sensor and liquid level sensor outside organ box and bubble trap respectively, the temperature of Real-Time Monitoring transplant organ storage temperature and perfusate, liquid level, the temperature detected when temperature sensor exceedes the scope of setting, system alarm, automatically the security measure of shutting down is taked, notify that user asks manual intervention by human-computer interaction module simultaneously, in like manner liquid level sensor detects that liquid level transfinites, and causes perfusate to leak also by stopping alarm request manual intervention;

For the fault that other can not be got rid of automatically, machine also will take the safety precautions such as shutdown, and notify user by human-computer interaction module and safety protection module, request manual intervention.

9. preserve and method for supervising based on the organ of organ hypothermia machine perfusion save set as claimed in claim 6, it is characterized in that described perfusion Intelligence Feedback regulation and control are the organ viability's parameters gathered according to biochemical sensor, in conjunction with the perfusion parameter that other sensors gather, and and human-computer interaction module setting perfusion mode and parameter compare, optimize perfusion parameter according to system storage perfusion empirical data, control to drive perfusion power source to perform perfusion or flushing according to optimum results central control module; Wherein the feedback regulation of perfusion parameter mainly comprises perfusion channel control, pressure controlling and flow detection and control;

Control for perfusion channel, the main valve that perfusion pipeline is placed that relies on is to realize the open and close of multiple perfusion channel;

For the pressure controlling in filling process, adopt the mode of simulative heartbeat Rhythm Curve, the pressure curve of simulated organ pollex in vivo can adopt closed loop feedback regulating system;

For flow detection and the control of perfusing course, and the perfusate volume squeezed out can be rotated at every turn and calculate perfusion flow according to perfusion power source number of revolutions per minute, thus the automatic detection of realization to perfusion flow.

10. preserve and method for supervising based on the organ of organ hypothermia machine perfusion save set as claimed in claim 1, it is characterized in that described whole perfusion device has four kinds of perfusion mode available, be respectively rinse mode, run-up mode, Constant pressure perfusion pattern, pulsation perfusion mode; Rinse mode and run-up mode are for getting rid of the bubble in whole perfusion fluid path, and Constant pressure perfusion pattern and pulsation perfusion mode are the mode of operation of the normal perfusion of organ;

1. rinse mode

Under rinse mode, the first valve closing, the 3rd valve opening; Perfusion power source operates, liquid is discharged by flushing pipe, thus gets rid of the bubble through perfusion power source, the pressure sensor be arranged in the first perfusion channel, filter, dosing/sample tap, buffer, the gas bubble detection being located at bubble trap first passage interface, bubble trap, flushing pipe; Rinse mode can be stopped treated the removal of bubbles in this perfusion loop by the mode observed or adopt gas bubble detection automatically to detect after;

2. run-up mode

Under run-up mode, the first valve opening, the 3rd valve closing, the second valve opening; Perfusion power source operates, and is discharged by perfusate by Y-piece road first branched bottom pipeline; Thus get rid of perfusion power source, the pressure sensor be arranged in the first perfusion channel, filter, dosing/sample tap, buffer, two gas bubble detections being located at bubble trap first passage interface and second channel interface respectively, bubble trap, the first branched bottom pipeline in Y-piece road and the bubble of main channel pipeline; Detect in perfusion loop whether there is bubble by the mode observed or adopt gas bubble detection automatically to detect, after treating removal of bubbles, can rinse mode be stopped;

3. Constant pressure perfusion pattern

Under Constant pressure perfusion pattern, the arteries of organ connects with the second branched bottom pipeline in Y-piece road, the first valve opening, the 3rd valve closing, the second valve closing; Perfusion power source operates continuously, and the first branched bottom pipeline of perfusate through perfusion power source, the pressure sensor be arranged in the first perfusion channel, filter, dosing/sample tap, buffer, two gas bubble detections being located at bubble trap first passage interface and second channel interface respectively, bubble trap, Y-piece road and main channel pipeline enter organ; In this mode, by being located at the current injection pressure of pressure sensor Real-time Obtaining on the second branched bottom pipeline in Y-piece road, thus carry out feedback regulation, under control perfusion pressure is in constant-mode;

4. pulsation perfusion mode

Under pulsation perfusion mode, the arteries of organ connects with the second branched bottom pipeline in Y-piece road, the first valve opening, the 3rd valve closing, the second valve closing; Perfusion power source operates in a pulsing mode, perfusate enters organ by the perfusion loop in Constant pressure perfusion pattern, pump operates in acceleration-constant speed-periodic mode of deceleration-constant speed, makes the perfusion liquid exported produce pulsation effect, thus can simulate human heartbeat's rhythm and pace of moving things; By being located at the current injection pressure of pressure sensor Real-time Obtaining on the second branched bottom pipeline in Y-piece road, thus carrying out feedback regulation, controlling fluctuation pressure and being in setting range.