CN104705288B - Subnormal temperature transplant organ vitro intelligent supports System and method for - Google Patents

Subnormal temperature transplant organ vitro intelligent supports System and method for Download PDF

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CN104705288B
CN104705288B CN201510085534.3A CN201510085534A CN104705288B CN 104705288 B CN104705288 B CN 104705288B CN 201510085534 A CN201510085534 A CN 201510085534A CN 104705288 B CN104705288 B CN 104705288B
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organ
perfusion
parameter
temperature
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CN104705288A (en
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王玲
徐铭恩
李欢
张平
赖雪聪
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Hangzhou Dianzi University
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Hangzhou Dianzi University
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Abstract

The open a kind of subnormal temperature transplant organ vitro intelligent of the present invention supports System and method for.This system mainly includes the storage of sensor acquisition module, perfusion/oxygenation module, safety protection module, human-computer interaction module, data and analyzes module, mixed-media network modules mixed-media, power management module, central control module, by building fully simulated pulsating wave perfusion, temperature controls and oxygenate supplies united body physiological environmental simulation, multiple sensors is coordinated to monitor every life index, it is achieved organ is multi-functional, multi-parameter intelligent preserves.The method is the feature design according to transplant organ storage in vitro, analysis, perfusion/oxygenate Intelligence Feedback regulation and control, fault alarm and security protection, network data including organ real-time physiological parameter are shared and long-range monitoring etc., it is possible to realize preserving the most for a long time.Present system has fully simulated pulsating wave perfusion and dynamic simulation feedback control technology, and perfusion pressure is closer to human body, and parameter regulation and control are more accurate, wider.

Description

Subnormal temperature transplant organ vitro intelligent supports System and method for
Technical field
The invention belongs to biomedical instrument field, be specifically related to a kind of for treating that transplant organ external subnormal temperature intelligence fills The System and method for that note preserves.
Background technology
Organ will be disengaged from the vivo environment of human or animal in vitro situation, if being not seeking to provide suitable existence into it Environment, then organ will gradually exhaustion necrosis.Organ transplant has become gives treatment to effectively arranging of multiple organ failure patient vitals One of execute.Along with scientific research and the raising of medical level, kind and the accommodation of organ transplant constantly expand, organ transplant simultaneously Demand also sharply increase.Adding up according to the Ministry of Public Health, China there are about 1,500,000 people every year needs organ transplant, but only has 10,000 people every year Transfer operation can be accepted.Limiting the main cause that organ transplant is extensively carried out, one is the shortage of organ donor quantity, and two is organ Utilization rate low.The wasting reason of organ resource is a lot, lacks effective organ external support technology, cannot simply have Effect judges that organ viability is one of wasting major reason.
The appearance of organ external support technology, for solving the organ merit during transplant organ donor lacks and maintains in vitro It is provided that solution, substantially increases the clinical practice of organ transplantation technique.But, transplant organ under current technical conditions Preservation effective time limit shorter, the Dispersing Monkey Kidney Cell in Tissue Culture holding time is difficult to the effective preservation more than 24-30h, liver and heart clinically Time is shorter, and it is huge to preserve system complex, and transport and allotment on a large scale to transplant organ propose the biggest challenge.The lowest Temperature machinery perfusion (Continuous Hypothermic Perfusion, CHP) can be used to improve the ischemic of cold storage Damage, but owing to the perfusion liquid temperature of CHP needs to maintain about 4 DEG C, low temperature inevitably causes transplant organ to damage. Normal temperature (37 DEG C) machine perfusion shows good effect in animal organ's transplanting, and simply normal temperature machine perfusion needs complexity Heat perfusion unit and oxygenate system, its extensive application clinically of the volumetric constraint that equipment is huge, and the regular of 37 DEG C Temperature condition preserves the most optimum for organ or must still wait to discuss.Reduce filling temperature to subnormal temperature scope (20 DEG C~30 DEG C) the oxygen demand of temperature control requirement and perfusion can be substantially reduced thus simplify equipment, have simulated organ physiology bar concurrently simultaneously The advantage of part.
Present invention is directed at this, it is proposed that the System and method for that under a kind of subnormal temperature, organ vitro intelligent perfusion preserves, structure Build fully simulated pulsating wave perfusion, temperature controls and oxygenate supplies united body physiological environmental simulation, coordinates multiple sensors prison Survey every life index, it is achieved organ is multi-functional, multi-parameter intelligent preserves, and improves the integrated of system based on modularized design Degree is to facilitate vehicle-mounted transport.The present invention provides a kind of system and method by the subnormal temperature intelligence of human controllable external to transplant organ Perfusion can be changed and carry out simulated organ body physiological environment, maintain organ viability, extend the holding time, realize organ perfusion process simultaneously The noninvasive real-time monitoring of multi-parameter, assesses automatically according to organ viability or prompting improves preservation process.The present invention can reduce and waits to transplant The ischemic hypoxia infringement of organ, it is to avoid tradition store method, on organ structure and the impact of function, can solve to wait to transplant simultaneously Organ transportation is difficult, utilization rate is the highest and a difficult problem for bio-modification difficulty under isolated organ refrigerated condition.
Summary of the invention
In order to make up the deficiency in existing transplant organ storage in vitro technology, improve transplant organ external support technology, this Invention provides the System and method for that under a kind of subnormal temperature, transplant organ vitro intelligent perfusion preserves.
It is an object of the present invention to provide a kind of subnormal temperature transplant organ vitro intelligent and support system.This system passes through structure Build fully simulated pulsating wave perfusion, temperature controls and oxygenate supplies united body physiological environmental simulation, coordinates multiple sensors prison Survey every life index, it is achieved organ is multi-functional, multi-parameter intelligent preserves, thus maintains organ viability as far as possible, extends and protects Deposit the time.
The technical scheme that the present invention provides is specific as follows:
Under a kind of subnormal temperature, transplant organ vitro intelligent supports system, mainly includes sensor acquisition module, perfusion/oxygenate The storage of module, safety protection module, human-computer interaction module, data and analysis module, mixed-media network modules mixed-media, power management module, central authorities Control module;
Described sensor acquisition module at least includes that temperature sensor, pressure sensor, liquid level sensor, oxygen concentration pass Sensor, for detecting the parameters relevant to perfusion such as the temperature of perfusate, pressure, liquid level, oxygen concentration, simultaneously need to have for examining Survey the biochemical sensor of transplant organ activity, video acquisition sensor;The biochemical parameter that described biochemical sensor gathers for Different Organs functional characteristic, can be gas concentration lwevel (pCO2), lactic dehydrogenase in oxygen concentration in blood (pO2), blood (LDH),Microglobulin, creatinine, glucose, base excess (BE), ionization calcium level or other physiological parameter.
Described perfusion/oxygenation module at least include organ box, perfusate, heat exchanger, oxygenator, filter, passage, Perfusion power source, the main responsible flushing of transplant organ, perfusion, oxygen supply and subnormal temperature thermostatic control.Described organ box should be able to Allow organ easily and safely for perfusion, store, analyze, transport the appearance of movement between this equipment treating transplant organ Device;Described perfusate should be able to provide necessary nutrition and protection for transplant organ;Described heat exchanger should be able to be organ box There is provided subnormal temperature thermostatic control with perfusate, with the heat exchange unit of semiconductor refrigerating heater composition and can be passed by temperature Sensor feedback regulation reaches the constant control of design temperature;Described oxygenator can be the built-in of hollow microporous fibers film composition Formula small oxygen clutch;Described filter can filter the harmful substances such as the microthrombus in perfusate;Described passage is perfusion Liquid flows in system provides pipeline to connect;Described perfusion power source at least should include motor, peristaltic pump, magnetic valve, in order to Controlled perfusion power and channel selecting are provided.
Described safety protection module includes startup self-detection module, consumptive material state confirmation module, alarm module;Described opens Check when machine selftest module is used for starting shooting whether each functional unit of system can normally work;Described consumptive material state confirmation module is led to Crossing system switching switching, system the most normally starts and determines whether various consumptive material has been mounted to position;Described alarm module Including temperature over-range warning, pressure limit warning, liquid level and flow overload alarm, bubble warning, sensor fault and actuator Part fault alarm;
Described human-computer interaction module is responsible for setting the perfusion/oxygenate parameter of organ to be saved and the choosing of perfusion mode Select, can be set by keyboard or touch-screen etc.;This module is responsible for the perfusion ginseng of real-time monitoring and display system output simultaneously Number information, can pass through the output display units such as charactron, liquid crystal display, dot matrix screen and realize;
Described data storage is used for each item data of the system that stores with analyzing module, joins including sensor acquisition module collection The information such as time that several and peripheral output display unit shows, voice, image, video, and above-mentioned data are analyzed, give Going out organ diastolic pressure, shrink the analysis results such as pressure, perfusion flow, organ swelling degree, oxygen concentration change, comprehensive assessment organ is lived Property;
Described mixed-media network modules mixed-media is for realizing the information such as transportation organ perfusion to be saved parameter, biochemical parameter, GPS Remotely monitor, position and analyze;
Described power management module be used for the switch control rule to system power supply, acquisition and the display of battery electric quantity, The control of battery charging and discharging, electricity deficiency are reported to the police and power reset such as restarts at the operation, as needed ability after power-off for some The hardware recovered, can restart power supply and can recover by central control module request power management module after breaking down;
Described central control module is mainly used in accepting perfusion parameter that the detection of sensor acquisition module obtains and man-machine The perfusion parameter that interactive module sets, realizes entirety after carrying out data analysis and process and controls logic.
Described central control module leads to analysis module, sensor acquisition module with human-computer interaction module, data storage Cross I/O to connect, be connected by driver element with perfusion/oxygenation module, safety protection module, pass through serial ports with power management module Connect, be connected by network interface with network communication module.
It is a further object to provide the organ intelligence method for filling being applied to said system.The method is basis The feature design of transplant organ storage in vitro, including the analysis of organ real-time physiological parameter, perfusion/oxygenate Intelligence Feedback regulation and control, Fault alarm is shared and long-range monitoring etc. with security protection, network data, it is possible to realize preserving the most for a long time.
After the method specifically system boot, first start the start in power management module and safety protection module certainly Inspection module, consumptive material state confirmation module, see whether system can normally work, to be confirmed after carry out initializing and start sensor and adopt Collection module and human-computer interaction module;Stored and analyze module evaluation organ viability, Integrated comparative organ viability's data by data Perfusion/oxygenate the parameter set with human-computer interaction module, produces the perfusion/oxygenate parameter optimized and arranges, open according to optimal design-aside Organ aerobic perfusion under beginning subnormal temperature;Accessing safety protection module detection by central control module during perfusion is System runs, and the information be given according to safety protection module adjusts perfusion/oxygenation module and performs or remind operator;Perfusing course can Stored and analyze module by data and preserve perfusion parameter and organ parameter in real time, it is possible to remotely supervised by mixed-media network modules mixed-media Control.
In said method, key technology mainly includes that the analysis of organ real-time physiological parameter, perfusion/oxygenate Intelligence Feedback are adjusted Control, fault alarm are shared and remotely monitoring with security protection, network data, specific as follows:
Organ real-time physiological Parameter analysis: according to pressure sensor, TEMP in perfusing course sensor acquisition module The parameter that device, oxygen concentration sensor collect, is stored and analyzes by data storage with analyzing module through central control module Set up perfusion temperature, pressure, flow, oxygen concentration relation table;Several pressure sensors according to sensor acquisition module gather Pressure parameter, stores and analyzes organ vascular patency degree, simultaneously by data storage with analyzing module through central control module Judge blood vessel blockage position;The parameter collected according to liquid level sensor in sensor acquisition module, leads to through central control module Cross data storage and analysis module stores and analyzes and determines whether to add desired substance, and whole dress by liquid feeding/sample tap Put whether transportation rollover or pipe leakage occurs;The biochemical ginseng gathered according to sensor acquisition module mesophytization sensor Number, stores and analyzes organ changes of function by data storage with analyzing module through central control module;Data storage and analysis Module synthesis analyzes above-mentioned data message, monitors perfusing course organ through central control module in real time by central control module Activity change;
Perfusion/oxygenate Intelligence Feedback regulation and control: according to above-mentioned transplant organ real-time physiological Parameter analysis, and relatively man-machine friendship The transplant organ perfusion mode of mutual module setting and perfusion/oxygenate parameter, optimize perfusion mode and parameter according to comparative result, in Centre control module controls to drive perfusion/oxygenation module to perform perfusion, heat exchange and oxygen supply;The wherein feedback regulation master of perfusion parameter Passage control to be included, temperature adjusting, pressure controlling, oxygen concentration regulation and control, flow detection and control, the protection etc. of bubble;
For passage control, rely primarily on the valve placed on system pipeline and open to the selection realizing multiple passage and close Close;
For temperature adjusting, semiconductor refrigerating heater can be used to carry out regulator control system temperature with under satisfied different perfusion mode Temperature control needs;Owing to the present invention is to organ storage in vitro in subnormal temperature scope (20 DEG C~30 DEG C), utilizes and partly lead Body refrigeration heater realizes the temperature regulation of scope little to perfusate, it is sufficient to reach effectively to control to make whole system be in constant temperature Under state, and semiconductor refrigerating heater does not has moving component, it is to avoid can be consumed because of what frequent opening and closing refrigeration unit caused Become estranged mechanical damage;
For the pressure controlling in filling process, using the mode of simulative heartbeat Rhythm Curve, simulated organ is won in vivo Dynamic pressure curve can use closed loop feedback to regulate system, as utilized pressure sensor as feed back input, peristaltic pump conduct Targeting controls the realization of goal closed-loop control to pressure, uses pid algorithm using time shaft as parameter Solid rocket engine amplitude;
Regulate and control for the oxygen concentration in perfusate, utilize oxygenator to provide required oxygen in perfusate;
For flow detection and the control of perfusing course, can be according to peristaltic pump number of revolutions per minute and each perfusion Amount carrys out calculated flow rate, it is achieved the automatic detection to perfusion flow;
Protect for the bubble in perfusing course, gas bubble detection and multiple-way duct system can be used to realize bubble Remove.The front end that the present invention enters organ at perfusate arranges gas bubble detection and two-way pipe-line system, if perfusion during bubble-free Liquid is directly entered organ, and otherwise pipeline is switched to rinse path eliminating bubble.
Fault alarm and security protection: system by analyte sensors module gather information, power management module information and Other work state information of system obtains fault and the potential safety hazard that system exists, and on the output device of human-computer interaction module Display alarm content in real time.For the fault can got rid of by machine self, system has automatic fault and gets rid of function.For The fault that can not automatically get rid of, machine will be taked the safety precautions such as shutdown, and pass through human-computer interaction module and security protection Module notifies user, asks manual intervention.Such as after temperature, pressure, flow overload alarm and bubble are reported to the police, system can stop Operating, need to manually boot.
Network data is shared with remotely monitoring: in organ perfusion, preservation, transportation, various types of data and information can To be grouped record, and it is supplied to doctor, scientist or other mechanisms for research by network, it is achieved treat that transplant organ is raw The long-range monitoring of the reason information such as parameter, GPS location.
Compared with background technology, the invention have the advantages that:
1, the present invention is directed to the system scheme that intelligent subnormal temperature machine perfusion proposes, can truer simulated organ Physiological environment, and minimize biological oxygenate/filter and the design of semiconductor heat crosspoint, both met subnormal temperature machine perfusion pair Temperature and the demand of oxygen supply, can improve again level of integrated system, the most portable preferably uses;
2, present system has fully simulated pulsating wave perfusion and dynamic simulation feedback control technology, perfusion pressure closer to Human body, parameter regulation and control are more accurate, wider;Filling temperature can keep constant temperature with subnormal temperature scope (20 DEG C~30 DEG C), permissible Take into account organ immunity bio-modification operation needs;
3, mixed-media network modules mixed-media realizes transportation and treats remotely monitoring and the analysis of the information such as transplant organ biochemical parameter, GPS.
Accompanying drawing explanation
Fig. 1 is present system principle schematic;
Fig. 2 is perfusion/oxygenation module and the sensor acquisition module device schematic diagram of the embodiment of the present invention;
Wherein 1. organ, 2. organ box, 2-1 gas exchanges mouth, 3. pump, 4. filter, 5. oxygenator, 6. bubble trap, 6-1. first passage interface, 6-2. second channel interface, 6-3. third channel interface, 7. the first perfusion pipeline, 8. flushing pipe, 9. the second perfusion pipeline, 10.Y type branch road pipe, 10-1. the first branched bottom pipeline, 10-2. the second branched bottom pipeline, 10- 3. main channel pipeline, 11. buffers, 12. liquid level sensors, 13. non-contact temperature sensors, 14-1. the first valve, 14- 2. the second valve, 14-3. the 3rd valve, 15. biochemical sensors, 16. pressure sensors, 17. oxygen concentration sensors, 18. dosings/ Sample tap, 19. semiconductor refrigerating heaters, 20. contact type temperature sensors, 21. gas bubble detections.
Detailed description of the invention
Below in conjunction with the accompanying drawings the present invention is further analyzed.
Fig. 1 provides subnormal temperature transplant organ vitro intelligent and supports system principle schematic diagram.
After system boot, first start the startup self-detection module in power management module and safety protection module, consumptive material State confirmation module, sees whether system can normally work, to be confirmed after carry out initializing and start sensor acquisition module and people Machine interactive module, stores and analyzes module synthesis evaluation organ viability by data, Integrated comparative organ viability's data and man-machine The perfusion that interactive module sets/oxygenate parameter produces the perfusion/oxygenate parameter optimized and arranges, and starts subnormal temperature according to optimal design-aside Lower organ aerobic perfusion, and access safety protection module detecting system fortune by central control module during perfusion OK, the information be given according to safety protection module adjusts perfusion/oxygenation module and performs or remind operator.Perfusing course can pass through Data storage and analysis module preserve perfusion parameter and organ parameter in real time, it is possible to remotely monitored by mixed-media network modules mixed-media.
Fig. 2 provides perfusion/oxygenation module and sensor acquisition module in subnormal temperature transplant organ vitro intelligent support system A kind of embodiment device schematic diagram;
As in figure 2 it is shown, organ 1 is placed in an organ box 2 during preserving, the bottom of organ box 2 is equipped with semiconductor system Cold heater 19 is to realize the subnormal temperature thermostatic control during whole preservation, and the top of organ box 2 is provided with gas exchanges mouth 2-1 To play filter bacteria, exchanging gas, the effect of maintenance organ box stable gas pressure, organ box side is provided with contact temperature and passes Sensor 20 is with the temperature of perfusate in measurement organ box 2, and organ outer box wall is equipped with liquid level sensor 12.
Organ box 2 is connected by the first perfusion pipeline 7 with perfusion/oxygenate device, and wherein perfusion/oxygenate device is near device Official's box 2 end starts to be composed in series by the first perfusion pipeline 7 by pump 3, filter 4, oxygenator 5, and had on filter 4 successively Liquid outlet, this liquid outlet connects with buffer 11, thus plays the effect of mild perfusion pressure;
Close pump 3 one end of the first described perfusion pipeline 7 stretches to organ box 2 inner bottom part, requires this pipeline not simultaneously Contacting with the organ to be transferred 1 being placed in organ box 2, close oxygenator 5 one end of the first perfusion pipeline 7 is passed through bubble trap The first passage interface 6-1 of 6 stretches into bubble trap 6;
The second channel interface 6-2 of described bubble trap 6 stretches in organ box 2 by Y type branch road pipe 10, wherein Y type The main channel pipeline 10-3 of branch road pipe 10 stretches into bubble trap 6, the first branch by the second channel interface 24_2 of bubble trap 6 Passage tube 10-1 stretches in organ box 2 below perfusate liquid level, and the artery of the second branched bottom pipeline 10-2 and organ 1 is even Logical;The third channel interface 6-3 of bubble trap 6 stretches in organ box 2 by flushing pipe 8, constitutes flush loop;Second perfusion One end of pipeline 9 connects with the vein of organ 1, and the other end stretches in organ box 2 below perfusate liquid level.
In bubble trap 6, stretch into the pipe of bubble trap 6 respectively from first passage interface 6-1 and second channel interface 6-2 Road length is identical, and is longer than the duct length stretching into bubble trap 6 from third channel interface 6-3, to facilitate in capture perfusate Bubble.
Described organ box 2, perfusion/oxygenate device, bubble trap 6, Y type branch road pipe the 10, second perfusion pipeline 9 composition fills Flow back to road, perfusate in this loop to organ perfusion.
Liquid feeding/sampling is left on section of tubing between bubble trap 6 and the oxygenator 5 of the first described perfusion pipeline 7 Mouth 18, in liquid feeding during to facilitate perfusate liquid level too low, or extraction loop, liquid is analyzed, and is simultaneously provided with oxygen concentration sensing Device 17, is used for detecting perfusion and starts oxygen concentration in front perfusate;Between pump 3 and the filter 4 of the first described perfusion pipeline 7 Section of tubing is provided with pressure sensor 16, in order to monitor the injection pressure of pump 3;
The main channel pipeline 10-3 of Y type branch road pipe 10 installs the first valve 14-1, in order to control perfusion unlatching and Close;First branched bottom pipeline 10-1 of Y type branch road pipe 10 installs the 3rd valve 14-3, in order to control perfusion run-up mode Open and close;Flush loop flushing pipe 8 is installed the second valve 14-2, in order to control the open and close rinsed.
The pipeline connected with first passage interface 6-1, the second channel interface 6-2 of bubble trap 6 seals in gas respectively Bubble detector 13, is used for detecting perfusion and starts whether to exist in front loop bubble, and whether perfusing course produces bubble.
At organ arterial inlet, on the second branched bottom pipeline 10-2 of Y type branch road pipe 10, biochemical sensor is installed 15, pressure sensor 16, enter into organ viability and the pressure of perfusate before perfusion in order to detect;In organ vein exit Oxygen concentration sensor 17, biochemical sensor 15, respectively organ oxygen content, device after detection perfusion is sealed in respectively on two perfusion pipelines 9 Official's activity;
Bubble trap 6 outer wall, equipped with liquid level sensor 12 and non-contact temperature sensor 13, is respectively used to detect bubble The liquid level of liquid storage and temperature in trap 6.
The present invention proposes four kinds of perfusion mode, respectively rinse mode, run-up mode, Constant pressure perfusion pattern, pulsation and fills Stream mode, its object is to guarantee the safety and stability of organ perfusion.Rinse mode and run-up mode are used for getting rid of whole perfusate Bubble in road, Constant pressure perfusion pattern and the mode of operation that pulsation perfusion mode is the normal perfusion of organ.
1. rinse mode
Perfusion system schematic diagram as shown in Figure 2, in this mode, the first valve 14-1 closes, and the second valve 14-2 opens, Oxygenator 5 cuts out and stops providing oxygen.Pump 3 operates, and is discharged by flushing pipe 8 by liquid, thus get rid of through pump 3, filter 4, Oxygenator 5, bubble trap 6, oxygen concentration sensor 17, dosing/sample tap 18, gas bubble detection 21, biochemical sensor 15, flushing Bubble in pipeline 8.The removal of bubbles in this perfusion loop is treated by the way of observation or employing gas bubble detection detect automatically Rinse mode can be stopped afterwards.
2. run-up mode
Perfusion system schematic diagram as shown in Figure 2, in this mode, the first valve 14-1 opens, and the second valve 14-2 closes, 3rd valve 14-3 opens, and oxygenator 5 cuts out does not provides oxygen.Pump 3 operates, and is arranged by the first branched bottom pipeline 10-1 by liquid Go out, thus get rid of through pump 3, filter 4, oxygenator 5, bubble trap 6, oxygen concentration sensor 17, dosing/sample tap 18, bubble Bubble in detector 21, Y type branch road pipe the 10, first branched bottom pipeline 10-1.By observing or using gas bubble detection certainly The mode of dynamic detection detects in perfusion loop whether there is bubble, can stop run-up mode after treating removal of bubbles.
3. Constant pressure perfusion pattern
Perfusion system schematic diagram as shown in Figure 2, in this mode, the arteries of organ and the second of Y type branch road pipe 10 Branched bottom pipeline 10-2 connects, and the first valve 14-1 opens, and the second valve 14-2 closes, and the 3rd valve 14-3 closes, oxygenate Device 5 is opened provides oxygen.Pump 3 continuously runs, and perfusate is through pump 3, filter 4, oxygenator 5, bubble trap 6, oxygen concentration sensing Device 17, dosing/sample tap 18, gas bubble detection 21, Y type branch road pipe 10, pipeline 10-3, biochemical sensitive 15, pressure sensor 16, Second branched bottom pipeline 10-2 enters organ.Connect the second perfusion channel 9 through organ vein blood vessel and perfusate is discharged to organ Perfusion loop is formed in box.In this mode, by the pressure sensing on the second branched bottom pipeline 10-2 of Y type branch road pipe 10 Device 15 obtains current injection pressure in real time, thus carries out feedback regulation, controls perfusion pressure and is under constant-mode.
4. pulsation perfusion mode
Perfusion system schematic diagram as shown in Figure 2, in this mode, the arteries of organ and the second of Y type branch road pipe 10 Branched bottom pipeline 10-2 connects, and the first valve 14-1 opens, and the second valve 14-2 closes, and the 3rd valve 14-3 closes, oxygenate Device 5 is opened provides oxygen.Pump 3 operates in a pulsing mode, and liquid constant voltage as shown in above-mentioned 3 is crossed the perfusion path in stream mode and entered Organ, connects in perfusate is discharged to organ box by the second perfusion channel 9 through organ vein blood vessel and forms perfusion loop.Pump is to add Speed-constant speed-periodic mode of deceleration-constant speed operates, can by simulation human heartbeat's rhythm and pace of moving things in the way of arrange drive pump waveform, Frequency and amplitude so that the perfusion liquid of output produces pulsation effect, preferably simulate the pattern of supplying oxygen to body blood supply.By Y type Before on second branched bottom pipeline 10-2 of branch road pipe 10, pressure sensor 15 obtains in real time and enters organ, the current of perfusate fills Injection pressure power, thus carry out feedback regulation, control fluctuation pressure and be in setting range.
Oxygen concentration in perfusate is sampled by two oxygen concentration sensors 17, one of them oxygen concentration sensor 17 After oxygenator 5 to be placed on, oxygenator 5 is so conducive to provide the conservative control of oxygen.Here the preferred small-sized film of oxygenator Formula oxygenator, the two-part oxygenator that the hollow microporous fibers film of preferably molded-in formula is made.Another oxygen concentration sensor 17 connects Organ vein export on sample, by the collection of remaining oxygen amount it is recognised that organ eubolism is disappeared The amount of oxygen of consumption.
The oxygen content information obtained by the oxygen concentration sensor 17 after oxygenator 5 can control to adjust oxygenator 5 Provisions amount, reaches intended setting value.Gather the oxygen concentration sensor 17 in the second perfusion channel 9 that organ vein blood vessel connects The oxygen content information obtained, by data analysis such that it is able to learn the information such as organ oxygen demand.
Perfusate filter membrane in filter 4, can filter in liquid filling the harmful substances such as the fat granule of circulation, thrombus;Institute The filter membrane stated need to be placed on below the liquid level of buffer 11, and buffer can play storage harmful substance simultaneous buffering pump 3 and export The effect of pressure, the pressure making output is mild, transitional good.
Dosing/sample tap 18 may be used for adding medicine in perfusion loop, or take out liquid from perfusion loop, thus Organ can be treated or study.
Described bubble trap 6 is triple channel structure.In the case of normal perfusion, lead to through first passage interface 6-1 and second The pipeline of pipeline joint 6-2 connection forms perfusion path, is hindered by the second valve 14-2 through the perfusion path of third channel interface 6-3 Plug.When the bubble entered from the first perfusion pipeline 7 is through bubble trap, and bubble will be trapped in bubble trap on perfusate Layer.By rinse mode described above, the bubble of enrichment in bubble trap can be got rid of.
Under normal constant voltage or pulsation perfusion mode, certain interval of time is needed to run rinse mode.Purpose be in order to The micro bubble preventing from exceeding sensor accuracy of detection is accumulated for a long time, forms air pocket in bubble trap 6.Ordinary circumstance Under, gas bubble detection 21 detects in such a mode less than bubble, if the gas bubble detection 21 being positioned on the first perfusion pipeline 7 gathers To bubble, system switches to rinse mode by removal of bubbles.If the gas bubble detection 21 being positioned on Y type branch road pipe 10 collects Bubble, can open the 3rd valve 14-3 and get rid of bubble.
Contact type temperature sensor 20 can monitor organ place environment temperature, and non-contact temperature sensor 13 can be supervised Temperature in control perfusate.Here the measurement of perfusate temperature selects at bubble trap 6, can conveniently use contactless temperature Degree sensor, such as infrared temperature sensor.Semiconductor refrigerating heater 19 can maintain organ under a certain steady temperature, it is ensured that device The normal temperature requirement of official's perfusion.
The liquid level sensor 12 being positioned at organ box 2 side can measure the liquid level of perfusate in organ box thus measure liquid Volume, may be used for sense organ liquid environment, prevents fortuitous event from occurring, as caused perfusion liquid flow because of perfusion pipeline breaking Lose.The liquid level sensor 12 being positioned at bubble trap 12 can measure the liquid level of bubble trap thus measure liquid in bubble trap Volume, accumulates too much bubble in Anti-bubble trap.
Biochemical sensor 15 can facilitate user's biochemical reaction to monitor, and carries out monitoring and the analysis of organ parameter.
The invention allows for the pressure reduction acute variation utilizing perfusion line clogging rear and front end to detect the blocking of pipeline Situation, and accurately determine its blocking position, we arrange two pressure sensors and realize here.When line clogging, system Automatic alarm, sends a pulse barotropic wave at head end, and barotropic wave reflects, at pipeline when propagating run into tamper along pipeline Head end can obtain twice barotropic wave information, and utilizes wavelet transformation to extract pressure jump information, it is thus achieved that barotropic wave passes twice through pressure The time difference of force snesor, the spread speed of last comprehensive barotropic wave may determine that the position of pipeline blockage.
The present invention supplies united body physiological environment mould by building fully simulated pulsating wave perfusion, temperature control and oxygenate Intend, coordinate multiple sensors to monitor every life index, it is achieved organ is multi-functional, multi-parameter intelligent preserves, and based on module Change the integrated level of design raising system to facilitate vehicle-mounted transport.The transplant organ external support system that the present invention proposes can be automatic Complete the detection of organ physiological status, the corresponding ginseng being automatically adjusted in perfusion liquid according to the condition detected and the parameter being manually entered Number, carries out subnormal temperature constant-temperature perfusion.The organ perfusion store method that the present invention provides can reduce the hypoxic-ischemic treating transplant organ Property infringement, it is to avoid tradition store method on organ structure and the impact of function, can solve to treat transplant organ transport difficult, profit simultaneously By the highest difficult problem difficult with bio-modification under isolated organ refrigerated condition of rate.The present invention can promote organ transplant to be correlated with skill simultaneously The development of art is as provided research platform for organ Out-body form changes of function study on monitoring or anti-for immunity before organ transplant Former modifications etc. provide research platform.
Above-described embodiment is not the restriction for the present invention, and the present invention is not limited only to above-described embodiment, as long as meeting Application claims, belongs to protection scope of the present invention.

Claims (8)

1. subnormal temperature transplant organ vitro intelligent supports system, it is characterised in that mainly include sensor acquisition module, perfusion/oxygen Compound module, safety protection module, human-computer interaction module, data storage with analyze module, mixed-media network modules mixed-media, power management module, in Centre control module;Described central control module and human-computer interaction module, data storage and analysis module, sensor acquisition module Connected by I/O, be connected by driver element with perfusion/oxygenation module, safety protection module, with power management module by string Mouth connects, and is connected by network interface with network communication module;
Described sensor acquisition module at least includes that temperature sensor, pressure sensor, liquid level sensor, oxygen concentration sense Device, simultaneously need to have for detecting the biochemical sensor of transplant organ activity, video acquisition sensor;Described perfusion/oxygenate Module at least includes organ box, perfusate, heat exchanger, oxygenator, filter, passage, perfusion power source, is mainly responsible for transplanting The flushing of organ, perfusion, oxygen supply and subnormal temperature thermostatic control;Described organ box should be able to allow organ easily and safely with In perfusion, store, analyze, transport the container of movement between this equipment treating transplant organ;Described perfusate should be able to be for transplanting Organ provides necessary nutrition and protection;Described heat exchanger should be able to provide subnormal temperature constant temperature control for organ box and perfusate System;Described perfusion power source at least should include motor, peristaltic pump, magnetic valve, in order to provides controlled perfusion power and passage Select;
Described safety protection module includes startup self-detection module, consumptive material state confirmation module, alarm module;Described start is certainly Inspection module checks whether each functional unit of system can normally work when being used for starting shooting;Described consumptive material state confirmation module is by being System switch switching, system the most normally starts and determines whether various consumptive material has been mounted to position;Described alarm module includes Temperature over-range warning, pressure limit warning, liquid level and flow overload alarm, bubble warning, sensor fault and performer event Barrier is reported to the police;
Described human-computer interaction module is responsible for setting the perfusion/oxygenate parameter of organ to be saved and the selection of perfusion mode, with Time be responsible for real-time monitoring and display system output perfusion parameter information;
Described data storage is used for each item data of the system that stores with analyzing module, and is analyzed above-mentioned data, comprehensively comments Estimate organ viability;
Described mixed-media network modules mixed-media is for realizing the long-range prison of transportation organ perfusion to be saved parameter, biochemical parameter, GPS information Control, position and analyze;
Described power management module has been used for acquisition and display, the battery of the switch control rule to system power supply, battery electric quantity The control of discharge and recharge, electricity deficiency are reported to the police and power reset reboot operation;
Described central control module is mainly used in accepting perfusion parameter and the man-machine interaction that the detection of sensor acquisition module obtains The perfusion parameter that module sets, realizes entirety after carrying out data analysis and process and controls logic.
2. subnormal temperature transplant organ vitro intelligent as claimed in claim 1 supports system, it is characterised in that described perfusion/oxygen In compound module, heat exchanger uses semiconductor cooler and the heat exchange unit of heater composition;Described oxygenator is that hollow is micro- The built-in small oxygen clutch of hole tunica fibrosa composition.
3. subnormal temperature transplant organ vitro intelligent as claimed in claim 1 supports the organ intelligence method for filling of system, and it is special Levy after being system boot, first start the startup self-detection module in power management module and safety protection module, consumptive material shape State confirms module, sees whether system can normally work, to be confirmed after carry out initializing and start sensor acquisition module and man-machine Interactive module;Stored and analyze module evaluation organ viability, Integrated comparative organ viability's data and man-machine interaction mould by data Perfusion/oxygenate parameter that block sets, produces the perfusion/oxygenate parameter optimized and arranges, start device under subnormal temperature according to optimal design-aside Official's aerobic perfusion;During perfusion, access safety protection module detecting system by central control module run, according to The information that safety protection module is given adjusts perfusion/oxygenation module and performs or remind operator;Perfusing course can be deposited by data Storage and analysis module preserve perfusion parameter and organ parameter in real time, it is possible to remotely monitored by mixed-media network modules mixed-media.
4. the organ intelligence method for filling of system is supported as claimed in claim 3 based on subnormal temperature transplant organ vitro intelligent, It is characterized in that the method mainly includes following four aspects: the analysis of organ real-time physiological parameter, perfusion/oxygenate intelligence are instead Feedback regulation and control, fault alarm are shared and remotely monitoring with security protection, network data.
5. the organ intelligence method for filling of system is supported as claimed in claim 4 based on subnormal temperature transplant organ vitro intelligent, It is characterized in that described organ real-time physiological Parameter analysis is: according to pressure sensing in perfusing course sensor acquisition module The parameter that device, temperature sensor, oxygen concentration sensor collect, is stored by data storage with analyzing module and analyzes foundation Perfusion temperature, pressure, flow, oxygen concentration relation table;The pressure that several pressure sensors according to sensor acquisition module gather Parameter, stores and analyzes organ vascular patency degree by data storage with analyzing module, judge blood vessel blockage position simultaneously;Root The parameter collected according to liquid level sensor in sensor acquisition module, is stored and analyze by data storage determine with analysis module Whether add desired substance by liquid feeding/sample tap, and whether whole device rollover or pipe leakage occurs in transportation; The biochemical parameter gathered according to sensor acquisition module mesophytization sensor, is stored by data storage with analyzing module and analyzes Organ dysfunction changes;Data storage analyzes above-mentioned data message with analyzing module synthesis, is monitored in real time by central control module The activity change of perfusing course organ.
6. the organ intelligence method for filling of system is supported as claimed in claim 4 based on subnormal temperature transplant organ vitro intelligent, It is characterized in that described perfusion/oxygenate Intelligence Feedback regulation and control are: according to above-mentioned transplant organ real-time physiological Parameter analysis, and Compare transplant organ perfusion mode and perfusion/oxygenate parameter that human-computer interaction module sets, optimize perfusion mould according to comparative result Formula and parameter, central control module controls to drive perfusion/oxygenation module to perform perfusion, heat exchange and oxygen supply;Wherein perfusion parameter Feedback regulation mainly include passage control, temperature adjusting, pressure controlling, oxygen concentration regulation and control, flow detection and control, bubble Protection;
For passage control, rely primarily on the valve placed on system pipeline and open and close to the selection realizing multiple passage;
For temperature adjusting, semiconductor refrigerating heater can be used to carry out regulator control system temperature with the temperature under satisfied different perfusion mode Degree demand for control;
For the pressure controlling in filling process, use the mode of simulative heartbeat Rhythm Curve, simulated organ pollex in vivo Pressure curve can use closed loop feedback to regulate system;
Regulate and control for the oxygen concentration in perfusate, utilize oxygenator to provide required oxygen in perfusate;
For flow detection and the control of perfusing course, can come according to peristaltic pump number of revolutions per minute and each perfusion flow Calculated flow rate, it is achieved the automatic detection to perfusion flow;
Protect for the bubble in perfusing course, gas bubble detection and multiple-way duct system can be used to realize bubble is gone Remove;The front end entering organ at perfusate arranges gas bubble detection and two-way pipe-line system, if perfusate directly enters during bubble-free Entering organ, otherwise pipeline is switched to rinse path eliminating bubble.
7. the organ intelligence method for filling of system is supported as claimed in claim 4 based on subnormal temperature transplant organ vitro intelligent, It is characterized in that described fault alarm with security protection is: system gathers information, power management by analyte sensors module Module information and other work state information of system obtain fault and the potential safety hazard that system exists, and at human-computer interaction module Real-time display alarm content on output device;For the fault can got rid of by machine self, system has automatic fault row Except function;For the fault that can not automatically get rid of, machine will take stop safe safeguard measure, and by human-computer interaction module and Safety protection module notifies user, asks manual intervention.
8. the organ intelligence method for filling of system is supported as claimed in claim 4 based on subnormal temperature transplant organ vitro intelligent, It is characterized in that described network data is shared with remotely monitoring is: various types of numbers in organ perfusion, preservation, transportation Record can be grouped according to information, and be supplied to doctor, scientist or other mechanisms for research by network, it is achieved treat Transplant organ physiological parameter, the long-range monitoring of GPS position information.
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