Perfusate concentration control device for organ low-temperature preservation

Abstract

The invention relates to the technical field of medical instruments, and discloses a perfusate concentration control device for low-temperature preservation of organs. The device comprises a main controller, a diluent storage tank, a high-concentration liquid storage tank, a peristaltic pump, an injection pump, an electromagnetic valve group, a flow detection unit, an oxygenator, a temperature sensor, a heating and cooling module, a pressure sensor, a bubble sensor, an oxyhemoglobin saturation sensor and an organ bin. The double peristaltic pumps operate orthogonally at the 180-degree phase difference, and flow pulsation is eliminated; the continuous and precise conveying of high-concentration solute is realized by adopting a double-injection-pump alternative liquid supplementing and outputting mode; and the rotating speed of each pump is adjusted through a closed-loop feedback algorithm, so that stepless, continuous and accurate output of any target concentration from zero to the concentration of the stock solution is realized. The osmotic pressure concentration can be adjusted according to the needs of organ preservation, oxygenation, temperature control, pressure monitoring and multi-parameter safety detection functions are integrated, the stability of the physiological parameters of perfusate can be maintained, and the organ preservation damage is reduced.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of medical devices, in particular to a perfusion solution concentration control device for organ cryopreservation. BACKGROUND

[0002] Organ cryopreservation mechanical perfusion technology, as an important progress to replace traditional static cold preservation, continuously pumps low-temperature preservation solution into an isolated organ to simulate a physiological perfusion environment, providing oxygen and nutrients for the organ while removing metabolic waste, significantly extending the organ preservation time and improving post-transplant function. During organ preservation, the osmotic pressure of the preservation solution is a crucial physiological parameter, and its stability is directly related to the activity and function of cells - too high a concentration will cause cells to dehydrate and shrink, and too low a concentration will cause cells to swell and even rupture, which can lead to irreversible organ damage and seriously affect the success rate of transplantation.

[0003] Existing organ perfusion devices, such as the "organ perfusion device and organ perfusion system" disclosed in Chinese patent application CN110432260A, generally include basic components such as a liquid storage tank, a peristaltic pump, an oxygenator, a pressure sensor, and a temperature control system, which can achieve basic functions such as perfusion solution pumping, oxygenation, and temperature control. However, such devices still have obvious limitations: first, they cannot monitor and closed-loop feedback control the perfusion solution concentration in real time, and can only use pre-mixed preservation solution, which has limited concentration accuracy and cannot be dynamically adjusted according to the organ state; second, they lack precise flow coordination control mechanisms, and flow pulsation or interruption may occur during perfusion, affecting the organ perfusion effect; in addition, existing devices usually do not integrate multi-parameter safety monitoring and intelligent control functions, making it difficult to realize real-time assessment of organ metabolic state and implementation of individualized perfusion strategies.

[0004] Therefore, there is an urgent need for a dedicated device that can real-time, accurately, and closed-loop control the concentration of organ preservation solution to address the shortcomings of existing technology and meet the urgent need for improving organ transplantation quality in clinical practice. SUMMARY

[0005] To overcome the shortcomings of existing technology that can only provide fixed concentration perfusion solution, the present application provides a perfusion solution concentration control device that can achieve stepless, accurate, and continuous online adjustment of perfusion solution concentration and integrates multi-parameter monitoring functions to simulate the dynamic changes of osmotic pressure in a physiological environment and meet the individualized perfusion needs of different organs or the same organ at different preservation stages.

[0006] To solve the above technical problems, the present application adopts the following technical solutions: A perfusion solution concentration control device for organ cryopreservation, comprising: a main controller, a heating and cooling module, an oxygenator, a bubble sensor, a temperature sensor, a pressure sensor, an exhaust device, and a blood oxygen saturation sensor connected to the main controller, and an organ container; a dilution liquid storage tank for storing dilution liquid with a concentration of zero; a high-concentration liquid storage tank for storing high-concentration liquid with a set concentration; at least one peristaltic pump, the inlet of which is connected to the dilution liquid storage tank through a pipeline, and the outlet of which is connected to the inlet of the first flow sensor through a pipeline; two injection pumps, the pump ports of which are respectively connected to the high-concentration liquid storage tank through pipelines provided with electromagnetic valves, and are also respectively connected to the inlets of the second flow sensors through pipelines provided with electromagnetic valves; the electromagnetic valve groups are controlled by the main controller to make the two injection pumps alternately perform the operations of supplementing liquid and outputting; the first flow sensor and the second flow sensor, the outlets of which are in communication with the heating and cooling module, the oxygenator, the temperature sensor, the pressure sensor, the bubble sensor, the exhaust device, the organ container, and the blood oxygen saturation sensor; wherein the bubble sensor needs to be arranged before the exhaust device; the main controller is configured to execute a closed-loop control algorithm, receive the target concentration and the target flow value set by the user, and the detection values of each sensor, and adjust the peristaltic pump and the injection pump to realize the output of perfusion liquid with any target concentration between zero concentration and the set high-concentration liquid.

[0007] In one of the embodiments, a touch screen is further included; the touch screen is electrically connected to the main controller to provide an interface for the user to set perfusion process parameters and display running parameters; the perfusion process parameters include the target perfusion liquid concentration and the target perfusion flow.

[0008] In one of the embodiments, there are two peristaltic pumps, the inlets of which are connected to the dilution liquid storage tank through pipelines, and the outlets of which are connected to the inlets of the first flow sensors through pipelines.

[0009] In one of the embodiments, the peristaltic pumps all adopt a six-roller structure, and the two peristaltic pumps are operated orthogonally with a phase difference of 180 degrees.

[0010] In one of the embodiments, the main controller controls the electromagnetic valve group to switch the liquid path state when the liquid in the injection pump reaches a minimum capacity threshold.

[0011] In one of the embodiments, the heating and cooling module is any one of a semiconductor refrigeration sheet, a compressor refrigeration unit, or a split-type cold and heat circulation module.

[0012] In one of the embodiments, the main controller adopts a 32-bit ARM architecture microprocessor.

[0013] In one embodiment, it further includes: The biochemical sensor module, installed in the reflux tubing of the organ compartment, monitors the glucose concentration, lactate concentration, and pH value in the perfusion fluid in real time. The main controller analyzes the data: if the glucose concentration decreases or the lactate concentration increases, it indicates that the organ is metabolically active or the perfusion is insufficient; if the pH value decreases, it indicates that the organ is acidosis and the composition of the perfusion fluid needs to be adjusted. A multi-channel diversion valve, installed on the outlet pipeline of the oxygenator, divides the perfusion fluid into multiple channels. Each channel is equipped with an independent flow sensor, pressure sensor, and bubble sensor, enabling independent perfusion control of multiple organs. Waste liquid collection tank is used to collect return injection liquid that does not require circulation. The waste liquid collection tank is equipped with a liquid level sensor. When the liquid level reaches 80%, the touch screen prompts the operator to empty the tank to prevent waste liquid from overflowing.

[0014] In one embodiment, the main controller is configured to execute a closed-loop control algorithm, receive user-defined target concentration and target flow rate values, as well as detection values ​​from various sensors, and adjust the peristaltic pump and injection pump to achieve the output of perfusion fluid with any target concentration from zero to a set high concentration, specifically including: The main controller determines the target concentration based on the set parameters. and the initial concentration value of high concentration solution Real-time calculation of the required target flow rate of diluent and high concentration liquid target flow rate The calculation formula is: The main controller independently receives feedback signals from the first and second flow sensors. Through two independent PID controllers, it adjusts the total speed of the two peristaltic pumps and the injection speed of the currently operating syringe pump, respectively, to make the actual flow rates of the diluent and the high-concentration solution approximate the target flow rates of the diluent and the high-concentration solution, thereby synthesizing a solution with the target concentration. The infusion fluid; by changing and It can achieve from zero to Output of perfusion fluid at any target concentration between [specific values].

[0015] Compared with the prior art, the beneficial technical effects of the present invention are: This invention achieves stepless, continuous, and online adjustable perfusion fluid concentration: It breaks through the limitations of premixing or fixed ratio modes in the prior art, and can dynamically and seamlessly adjust the perfusion fluid to any target concentration according to the actual state of the organ and the needs of different preservation stages during the organ preservation process, providing the optimal preservation environment for the organ. This is a major advancement in the field.

[0016] High stability and high continuity of precise conveying are realized: pulsation of large flow dilution liquid conveying is eliminated by orthogonal operation of double peristaltic pumps, and interruption problem of small flow high concentration liquid conveying is solved by alternate work of double injection pumps, the pulsation problem of large-scale dilution liquid conveying and the intermittent problem of small-dose high-concentration liquid conveying are solved, which provides key technical support for stepless concentration adjustment.

[0017] Real full-process closed-loop precise control is realized: based on real-time feedback of double flow sensors, dilution liquid and high concentration liquid are independently controlled in closed loop, which ensures the accuracy and stability of mixed concentration, and effectively maintains the dynamic balance of osmotic pressure inside and outside the organ.

[0018] Multi-parameter safety monitoring and intelligent control function are integrated: the system integrates pressure, temperature, bubble, blood oxygen saturation and other multi-parameter monitoring and linkage protection, which greatly improves the safety and reliability of the system, and provides data support for organ vitality evaluation.

[0019] The man-machine interface is good and the operation is simple: integrated design, parameter centralized setting and display, convenient for clinical use and promotion.

[0020] The present application realizes precise, stable and continuous control of organ preservation solution concentration through ingenious hardware design and intelligent control algorithm, effectively overcomes the shortcomings of the prior art, and has important significance for improving the success rate of organ transplantation. BRIEF DESCRIPTION OF DRAWINGS

[0021] Figure 1 The figure is a schematic diagram of the overall structure of the device in the embodiment of the present application. Figure 2 The figure is a control logic flow chart of the device in the embodiment of the present application. Figure 3 The figure is a double peristaltic pump orthogonal operation output curve diagram in the embodiment of the present application. Figure 4 The figure is a schematic diagram of the accuracy and stability of the perfusion solution concentration control in the embodiment of the present application. Figure 5 The figure is a comparison diagram of stepless concentration output mode and traditional pretreatment mixing mode in the embodiment of the present application. DETAILED DESCRIPTION

[0022] A preferred embodiment of the present application will be described in detail below with reference to the accompanying drawings.

[0023] Embodiment one The perfusion solution concentration control device for organ cryopreservation in the application comprises a main controller 1, a touch screen 2, a diluent storage tank 3, a high-concentration liquid storage tank 4, two six-roller peristaltic pumps 5 (a first peristaltic pump 5-1 and a second peristaltic pump 5-2), two injection pumps 6 (a first injection pump 6-1 and a second injection pump 6-2), an electromagnetic valve group 7, a first flow sensor 8-1, a second flow sensor 8-2, an oxygenator 9, a temperature sensor 10, a heating and cooling module 11, a pressure sensor 12, a bubble sensor 13, an exhaust device 14, a blood oxygen saturation sensor 15 and an organ bin 16. The components are connected by special pipelines (not marked separately in the drawing) to realize fluid conduction, form a complete perfusion system.

[0024] The diluent delivery unit based on the six-roller peristaltic pump 5 and the high-concentration liquid delivery unit based on the injection pump 6 and the electromagnetic valve group 7 constitute a continuous dynamic proportioning system under the cooperative control of the main controller 1. The system can realize stepless, continuous and stable output of any target concentration without pre-mixing according to the set value in the full range between zero and the high-concentration liquid stock concentration, and completely overcomes the defects of fixed concentration and real-time unadjustable in the prior art.

[0025] The main controller 1 adopts a 32-bit ARM architecture microprocessor, preferably an STM32F407 series, for receiving sensor detection data, analyzing touch screen 2 setting instructions, running a closed-loop control algorithm containing PID adjustment logic, and generating corresponding control signals.

[0026] The touch screen 2 is electrically connected with the main controller 1, used for setting target concentration and target flow value, and displaying running parameters in real time, including real-time concentration, flow, temperature, pressure, blood oxygen saturation data and equipment working state. Figure 1 In the embodiment, the touch screen 2 and the main controller 1 are integrally displayed.

[0027] The diluent storage tank 3 and the high-concentration liquid storage tank 4 are respectively used for storing diluent and high-concentration perfusion stock solution.

[0028] The diluent delivery unit comprises two six-roller structure peristaltic pumps 5, the inlets of the two peristaltic pumps 5 are connected to the diluent storage tank 3 through pipelines, the drive motors of the two peristaltic pumps 5 adopt step motors with a step angle of 1.8°, and are electrically connected with the main controller 1 through a drive module. The phase control signals output by the main controller 1 drive the two peristaltic pumps 5 to run orthogonally with a phase difference of 180 degrees, the periodic flow pulsation when a single pump runs is eliminated through staggered peak extrusion pipelines, and the stable, continuous and pulsation-free delivery of the diluent is realized, providing a stable basic flow for stepless adjustment of the concentration.

[0029] The high-concentration liquid delivery unit comprises two injection pumps 6 and an electromagnetic valve group 7 matched with each injection pump 6. The pump port of the injection pump 6 is connected to the high-concentration liquid storage tank 4 through a pipeline provided with the electromagnetic valve group 7, and is connected to the mixed output pipeline through another pipeline provided with the electromagnetic valve group 7. The injection pump has only one pump port, which is the outlet and also the inlet. The electromagnetic valve group 7 is controlled by the main controller 1 to switch the liquid path state, so that the two injection pumps 6 alternately perform the liquid supplementing and outputting operation, ensuring the continuous and uninterrupted output of the high-concentration liquid. The drive module of the injection pump 6 and the coil of the electromagnetic valve group 7 are electrically connected with the main controller 1 to respectively receive the pump body action instruction and the electromagnetic valve on-off control signal sent by the main controller 1. The unit realizes the micro, precise and uninterrupted delivery of the high-concentration solute, and provides an accurate solute source for the stepless adjustment of the concentration. The mixed output pipeline refers to the pipeline through which the high-concentration liquid and the dilution liquid flow. In the embodiment, the mixed output pipeline refers to the pipeline between the heating and cooling module 11 and the organ bin 16.

[0030] The flow detection unit comprises a first flow sensor 8-1 and a second flow sensor 8-2. The first flow sensor 8-1 is arranged on the pipeline downstream of the two peristaltic pumps 5 and before the mixed output pipeline. The second flow sensor 8-2 is arranged on the pipeline downstream of the electromagnetic valve group 7 and before the mixed output pipeline. The signal output ends of the two flow sensors are connected with the main controller 1 through data lines to transmit the real-time flow detection values to the main controller 1, forming a flow closed-loop feedback.

[0031] The main controller 1 is configured to execute a closed-loop control algorithm. According to the set target concentration and the initial concentration value of the high-concentration liquid , the main controller 1 calculates the required dilution liquid target flow and the high-concentration liquid target flow in real time, and the calculation formula is: The main controller 1 independently receives the feedback signals of the first flow sensor 8-1 and the second flow sensor 8-2, and precisely adjusts the total speed of the two peristaltic pumps 5 and the bolus speed of the currently working injection pump 6 through two independent PID controllers, so that the actual flow of the dilution liquid and the actual flow of the high-concentration liquid quickly approach the corresponding target values, thereby accurately synthesizing the perfusion liquid with the target concentration . By dynamically changing the target set values of and , the stepless and continuous output of any concentration between 0 and can be realized.

[0032] The oxygenator 9 is arranged on the mixed output pipeline and is used for oxygenating the mixed perfusion liquid.

[0033] The temperature sensor 10 is arranged on the mixed output pipeline near the outlet of the oxygenator 9, and the signal output end thereof is connected with the main controller 1, for feeding back the real-time temperature of the perfusion liquid.

[0034] The heating and cooling module 11 is an active temperature control component, which can adopt a semiconductor refrigeration sheet, a compressor refrigeration unit or a split type cooling and heating cycle module, and the control end thereof is electrically connected with the main controller 1 to receive the PWM adjustment signal or the switch control signal output by the main controller 1, so as to realize accurate regulation and control of the temperature of the perfusion liquid, and the temperature control range covers the required interval of organ cryopreservation.

[0035] The pressure sensor 12 is arranged on the mixed output pipeline near the inlet end of the organ bin 16, and the signal output end thereof is connected with the main controller 1, for detecting the perfusion pressure in real time, and when the pressure exceeds the safety threshold value set through the touch screen 2, the main controller 1 triggers the pressure protection logic to reduce the pump speed or suspend the delivery.

[0036] As an optional technical solution, the bubble sensor 13 is arranged on the pipeline after the oxygenator 9, and the signal output end thereof is connected with the main controller 1, and when it is detected that there is a bubble in the pipeline, an alarm signal is sent to the main controller 1, and the main controller 1 synchronously triggers the exhaust device 14 connected with the oxygenator 9 or the high point of the pipeline to act.

[0037] The blood oxygen saturation sensor 15 is arranged on the liquid outlet pipeline of the organ bin 16, the detection probe thereof is in direct contact with the organ preservation liquid in the liquid outlet pipeline, the signal output end thereof is connected with the main controller 1 through a data line, for detecting the oxygen content data carried by the preservation liquid after flowing through the organ in real time, and transmitting the real-time parameters related to the oxygen metabolism of the organ to the main controller 1, to provide data support for the evaluation of the activity of the organ.

[0038] The organ bin 16 is used for accommodating an isolated organ and forming a one-way perfusion passage, and the structure thereof comprises: a liquid inlet interface connected with the mixed output pipeline through a pipeline near the downstream of the pressure sensor 12, for receiving the mixed perfusion liquid after oxygenation and temperature control; a liquid outlet interface arranged at the bottom or low position of the side surface of the organ bin 16, for guiding the preservation liquid after flowing through the organ to flow out in a one-way manner through a liquid outlet pipeline; and a fixing structure adapted to different organs arranged in the organ bin 16, for ensuring the position of the organ to be stable during the perfusion process, and ensuring that the preservation liquid can uniformly contact the surface of the organ and the internal blood vessel network of the organ, so as to realize effective perfusion.

[0039] The main controller 1 is configured to execute a closed-loop control algorithm, receives a target concentration, a target flow value and detection values of each sensor, calculates a required ratio of the diluent and the high-concentration liquid according to the target concentration and the real-time flow, dynamically adjusts the pump speed in combination with a flow feedback value, and realizes stepless, accurate and continuous control of the perfusion liquid concentration. Meanwhile, the heating and cooling module 11 is adjusted according to a temperature feedback value, the delivery unit output power is controlled according to a pressure feedback value, and control instructions are generated to drive the diluent delivery unit and the high-concentration liquid delivery unit to work cooperatively.

[0040] The communication module is further included to support wired or wireless network connection and realize remote data transmission and monitoring.

[0041] The main controller 1 coordinates the components to realize the following functions: 1) initial pipeline pre-charging and exhaust to eliminate the risk of air bubbles; 2) verification of the hardware linkage performance through the pre-charging action; 3) accurate proportioning of the diluent and the high-concentration liquid; 4) cooperative delivery of the double pumps to avoid flow pulsation and flow interruption; 5) closed-loop regulation and control of the flow, temperature, pressure and blood oxygen saturation; and 6) real-time monitoring of the organ viability and abnormal protection. During the process execution, the components are synchronously linked to ensure stable perfusion parameters and safe organ perfusion. The high-concentration liquid is a concept proposed relative to the diluent, and the high-concentration liquid is a liquid with a set concentration of solute, which contains key substances required for maintaining the viability of the organ during the preservation period; in the diluent, the concentration of the solute is zero.

[0042] When the power supply of the starting device is turned on, the main controller 1 is automatically powered on to execute a component self-checking program, and the mechanical component state and the sensor state are detected in sequence; the mechanical component state includes the pump body jamming state of the six-roller peristaltic pump 5, the stepping motor running state of the syringe pump 6, the on-off response of the electromagnetic valve group 7, the exhaust valve opening and closing state of the exhaust device 14; the sensor state includes the signal output of the first flow sensor 8-1, the second flow sensor 8-2, the temperature sensor 10, the pressure sensor 12, the bubble sensor 13 and the blood oxygen saturation sensor 15; if any component fails, the main controller 1 triggers an alarm and displays the fault identification on the touch screen 2, the process is paused, the fault is eliminated, and then the self-checking is restarted; if the self-checking is passed, the touch screen 2 displays a "system ready" interface.

[0043] The operator inputs the perfusion process parameters through the touch screen 2, including the target perfusion liquid concentration, the target perfusion flow, the target perfusion temperature, the perfusion pressure threshold, the blood oxygen saturation early warning value, the initial concentration of the high-concentration liquid, the pre-charging flow and the pre-charging time length; the main controller 1 automatically calculates the proportioning ratio based on "target perfusion liquid concentration = (high-concentration liquid target flow x high-concentration liquid initial concentration) / (diluent target flow + high-concentration liquid target flow)" (for example, 9:1 when the target 2% and the high-concentration liquid 20% are 9:1), and displays the proportioning parameters and the pre-charging parameters on the touch screen 2; after the operator confirms that there is no error, the "start pre-charging" is clicked, and the main controller 1 sends the pre-charging instructions.

[0044] The main controller 1 sends a pre-charging mode instruction to the electromagnetic valve group 7, turns on the passage of the diluent reservoir 3→ the six-roller peristaltic pump 5→ the first flow sensor 8-1→ the mixed output pipeline→ the oxygenator 9→ the heating and cooling module 11→ the bubble sensor 13→ the exhaust device 14, and turns off the passage of the high-concentration liquid reservoir 4 and the syringe pump 6, opens the exhaust valve of the exhaust device 14 and closes the inlet stop valve of the organ chamber 16; then the first peristaltic pump 5-1 and the second peristaltic pump 5-2 are controlled to run synchronously at a pre-charging flow rate (such as 2 mL / min), and the diluent is extracted from the diluent reservoir 3 and transported along the passage to sequentially fill each section of the pipeline and the internal gap of the oxygenator 9, and the residual air in the pipeline is discharged to the gas collection chamber through the exhaust valve of the exhaust device 14, and the operator can observe the exhaust condition through the transparent gas collection chamber.

[0045] During the pre-charging process, the main controller 1 synchronously verifies the hardware linkage performance: the first flow sensor 8-1 collects the pre-charging flow rate, and if the actual flow rate deviates from the set value within the allowable range, it is determined that the linkage between the pump body and the flow sensor is normal, otherwise the “pre-charging flow rate abnormality” alarm is triggered; the main controller 1 sends a simulated bubble signal to the bubble sensor 13, and if the bubble sensor 13 feedbacks normally and the exhaust valve of the exhaust device 14 remains open for 100 ms, it is determined that the bubble detection-exhaust linkage is normal, otherwise the corresponding alarm is triggered; based on the pressureless state of the pipeline in the pre-charging stage, the main controller 1 reads the signal of the pressure sensor 12, and if it is within the range of 0±0.5 mmHg, it is automatically zeroed, otherwise the “pressure sensor zero position abnormality” is prompted; the heating and cooling module 11 is controlled to start heating at 20% of the rated power, and if the temperature rises by ≥0.5°C within 30 s, the heating is normal, and then the cooling is switched for 30 s, and if it drops by ≥0.5°C, the cooling is normal, otherwise the “heating and cooling module fault” alarm is triggered.

[0046] When the pre-charging time reaches the set value or no new bubbles are generated in the gas collection chamber, the operator clicks “end pre-charging”, the main controller 1 stops the six-roller peristaltic pump 5, closes the exhaust valve of the exhaust device 14 and opens the inlet stop valve of the organ chamber 16, and the touch screen 2 displays “pre-charging completed - hardware linkage normal”, the operator clicks “start perfusion”, and the process enters the formal perfusion stage; if a fault alarm is triggered during pre-charging, the fault needs to be eliminated and pre-charging needs to be restarted.

[0047] The main controller 1 sends a synchronous driving signal to the two six-roller peristaltic pumps 5, controls the two pumps to run with a 180° phase difference (when one pump reaches the peak value of liquid pushing, the other pump is at the valley value), extracts the base liquid from the diluent reservoir 3 to the mixed output pipeline, and the initial total pump speed is set according to the target flow rate of the diluent (such as 0.9 mL / min); when the diluent flows through the first flow sensor 8-1, the sensor collects the instantaneous flow data and feeds back to the main controller 1.

[0048] The main controller 1 compares the actual flow rate with the diluent target flow rate, and starts the PID algorithm to control the pump speed: when the actual flow rate is lower than the target value, the drive voltage is increased to increase the pump speed; when the actual flow rate is higher than the target value, the voltage is reduced to reduce the pump speed. During the adjustment, the two pumps always maintain a 180° phase difference to ensure that the flow rate fluctuation is within the allowed range (e.g. Figure 3 ); if the actual flow rate deviates from the target value for 500ms (e.g. pipeline blockage, liquid shortage in the storage tank), the main controller 1 suspends the six-roller peristaltic pump 5, displays "diluent flow abnormality" on the touch screen 2 and sounds an alarm, and simultaneously suspends the syringe pump 6. After troubleshooting, click "resume perfusion" to restart the process.

[0049] At the same time as the diluent delivery starts, the main controller 1 sends a first conduction instruction to the electromagnetic valve group 7 to open the path of the first syringe pump 6-1 and the high-concentration liquid storage tank 4, the mixed output pipeline, and to cut off the second syringe pump 6-2. The first syringe pump 6-1 is controlled to push the concentrated liquid to the mixed output pipeline at a high-concentration liquid target flow rate (e.g. 0.1 mL / min) to mix with the diluent; at the same time, the second syringe pump 6-2 is controlled to extract concentrated liquid from the high-concentration liquid storage tank 4 to the full scale of the syringe (e.g. 50 mL) and standby.

[0050] The output pipeline of the first syringe pump 6-1 is close to the second flow sensor 8-2 at the inlet of the mixed output pipeline, which collects flow data in real time and feeds back to the main controller 1. The main controller 1 adjusts the step motor speed of the first syringe pump 6-1 through the PID algorithm to ensure that the flow rate is stable at the target value, and cooperates with the diluent flow rate to match; the first syringe pump 6-1 is equipped with an infrared liquid level sensor, which sends a "low liquid level signal" to the main controller 1 when the remaining liquid volume drops to the minimum threshold (e.g. 5 mL for a 50 mL syringe).

[0051] The main controller 1 receives the signal and executes the switching within 10ms: the electromagnetic valve group 7 cuts off the first syringe pump 6-1 and the mixed output pipeline, and conducts the second syringe pump 6-2. The second syringe pump 6-2 immediately pushes the concentrated liquid at the target flow rate to achieve seamless connection; at the same time, the first syringe pump 6-1 switches to "liquid supplement mode" to extract concentrated liquid from the high-concentration liquid storage tank 4 to the full scale, standby for the next switching; during the switching period, the second flow sensor 8-2 continuously feeds back the flow rate, if there is a short-term fluctuation, the main controller 1 corrects the speed of the second syringe pump 6-2 within 200ms through the PID to make the flow rate return to the target value; if the flow rate deviates after switching, trigger the alarm and suspend the diluent delivery.

[0052] Based on the real-time data of the first flow sensor 8 and the second flow sensor 8-2, the main controller 1 calculates the actual concentration of the mixed perfusion liquid, and if it deviates from the target concentration by ±0.1% (e.g. target 2%, actual 1.85%), the diluent flow rate of the six-roller peristaltic pump 5 and the high-concentration liquid flow rate of the current working syringe pump 6 are adjusted simultaneously to calibrate the concentration to the target value.

[0053] The mixed perfusion solution flows into the oxygenator 9, the main controller 1 controls the external oxygen source to input oxygen into the oxygenator 9, oxygen transmission is realized through the hollow fiber membrane, and the oxygen partial pressure of the perfusion solution reaches the target value; the oxygenated perfusion solution flows into the temperature control pipeline of the heating and cooling module 11, the temperature sensor 10 (the probe is placed at the outlet) collects temperature data and feeds back, the main controller 1 compares the real-time temperature with the target temperature: when the temperature is higher than the target temperature +0.2℃, the refrigeration is started, when the temperature is lower than the target temperature-0.2℃, the heating is started, and the temperature control accuracy is ±0.2℃; if the temperature continuously deviates from the target value ±1℃ (such as module failure), the main controller 1 suspends the pump body and the oxygenator 9, opens the emergency cooling valve, triggers the “temperature abnormality” alarm, and restores the process after the fault is eliminated.

[0054] The temperature-controlled perfusion solution flows through the bubble sensor 13, the sensor monitors the bubbles through the photoelectric principle, if the diameter of the bubble is greater than 0.1mm, the main controller 1 immediately opens the exhaust valve of the exhaust device 14, and the perfusion solution containing the bubble is introduced into the gas collection chamber, and the exhaust valve of the exhaust device 14 is closed after the bubble sensor 13 has no bubble signal; the perfusion solution after exhaust flows through the pressure sensor 12, the sensor collects the perfusion pressure and feeds back, the main controller 1 compares the pressure threshold value: when the pressure is higher than the upper limit, the pump speed is reduced and the “overpressure warning” is displayed, and when the pressure is higher than the upper limit, the pump body is closed for emergency pressure relief; when the pressure is lower than the lower limit, the pump speed is increased, and if the pressure cannot be increased (such as pipeline leakage), the alarm is triggered and the process is suspended.

[0055] The pretreated perfusion solution enters the organ blood vessel system fixed by the silicone fixed support (simulating the anatomical position in vivo) through the arterial interface of the organ chamber 16, and completes arterial perfusion; the perfusion solution flows out from the venous end after flowing through the organ, is collected to the inclined liquid accumulation groove (inclined by 5°) at the bottom of the organ chamber 16, is guided back to the dilution liquid storage tank 3 to realize closed loop circulation if the backflow pump is configured, or is guided out to an external container for component analysis; the probe of the blood oxygen saturation sensor 15 is attached to the surface of the organ (such as the kidney cortex and the liver envelope), collects blood oxygen data and feeds back, and the main controller 1 analyzes: when the blood oxygen is greater than or equal to 80%, it is determined that the oxygen supply is normal, and the real-time display is displayed on the touch screen 2; when the blood oxygen is less than 80% and lasts for 10s, the “vitality warning” is triggered, prompting to check the oxygenator 9, flow or pressure parameters.

[0056] The main controller 1 stores the flow, temperature, pressure, blood oxygen saturation and the like at a frequency of 1Hz, displays them in the form of “number+curve” through the touch screen 2, and transmits them to an external monitoring system through the RS485 / Ethernet module (optional), supports remote monitoring, historical backtracking and report generation.

[0057] When perfusion reaches the preset time (such as 6h, 12h) or the operator clicks "stop perfusion", the main controller 1 sends a stop command: close the six-roller peristaltic pump 5, stop the perfusion liquid delivery of the injection pump 6, close the oxygen supply of the oxygenator 9, and close the heating and cooling module 11 to enter natural cooling; then the exhaust valve of the exhaust device 14 is kept open to exhaust the residual perfusion liquid in the pipeline, the touch screen 2 displays the "perfusion end" interface, and key data such as total perfusion time, average flow, average temperature, average pressure, and blood oxygen curve are displayed; the operator takes out the organ, cleans and disinfects the organ bin 16 and the pipeline, and then turns off the power of the device, and the process is completed.

[0058] Example Two As a preferred embodiment, example two is based on the structure in example one and adds "perfusate composition monitoring" and "multi-organ synchronous perfusion" functions, which are suitable for the in vitro preservation of organ clusters (such as liver-kidney combination), and the specific upgrades are as follows: (1) New components and functions Biochemical sensor module: installed in the organ bin backflow pipeline, it can detect the glucose concentration, lactic acid concentration and pH value of the perfusate in real time, and analyze the data through the main controller: if the glucose concentration decreases rapidly and the lactic acid concentration increases, it indicates that the organ is metabolically active or the perfusion is insufficient; if the pH value decreases, it indicates that the organ has acidosis, and the perfusate composition needs to be adjusted in time.

[0059] Multi-channel shunt valve: located in the oxygenator outlet pipeline, it can divide the perfusate into 2-4 paths (adjusted according to the number of organs), each path is equipped with independent flow sensor, pressure sensor and air bubble sensor, and independent perfusion control of multiple organs is realized.

[0060] Waste liquid collection tank: used to collect the backflow perfusion liquid that does not need to be circulated, a liquid level sensor is arranged in the tank, when the liquid level reaches 80%, the operator is prompted to pour through the touch screen to avoid waste liquid overflow.

[0061] (2) Changes in the working process after upgrading After mixing, the perfusate is oxygenated and temperature-controlled, then enters the multi-channel shunt valve, and the main controller adjusts the opening degree of each shunt valve according to the preset parameters to realize accurate distribution of different flow rates; After independent pressure and air bubble monitoring of each shunt perfusate, it enters the corresponding organ bin (multiple small organ bins can be set to replace the original single organ bin) respectively to perfuse different organs; The backflow perfusion liquid flows through the biochemical sensor module, and after composition detection, if it needs to be circulated, it is guided back to the diluent storage tank, and if it does not need to be circulated, it is guided into the waste liquid collection tank; The main controller can process multiple channel sensor data at the same time, and display the perfusion parameters of each organ in different areas on the touch screen to realize independent monitoring and regulation of multiple organ states.

[0062] To verify the stepless, accuracy and stability of the concentration control device in the present application, the following test is carried out: using the same device, the target concentrations are set to 0.98%, 1.33%, 1.72%, 2.16%, 2.62% and 3.06% in turn, and the measured concentration values are recorded after stable operation at each concentration point (this greatly saves the medicine, and only two cans of base liquid are consumed to complete the full gradient test).

[0063] Concentration gradient design basis: The present application selects six characteristic concentration points with clear physiological and physical significance for testing, to comprehensively verify the stepless regulation performance of the device in the full concentration range: 0.98%: simulates a near-physiological isotonic environment (close to the osmotic pressure of physiological saline 0.9%), to verify the accurate control ability of the device near the critical isotonic point. A small concentration deviation here can cause cell edema or shrinkage.

[0064] 1.33% and 1.72%: represent the typical working range of low-permeability preservation solution. The effective component concentration of many organ preservation solutions (such as some modified Collins solution) is in this range, which is used to induce moderate osmotic edema of cells to facilitate the introduction of protective substances.

[0065] 2.16%: as an intermediate reference point, located at the median value (~2%) of the entire test range, used to test the linearity and stability of the system in the central region.

[0066] 2.62% and 3.06%: represent the commonly used concentrations of high-permeability preservation solution. Such high-permeability environment is often used in static cold preservation or mechanical perfusion of liver, kidney and other organs, which effectively prevents cell edema by increasing osmotic pressure and provides high-energy substrates for organs. 3.06% is especially used to test the performance of the system near the high-concentration stock solution high-dilution limit.

[0067] This concentration gradient design spans multiple key physiological thresholds from near-physiological isotonicity to high permeability, aiming to verify the stepless, accurate and continuous control ability of the device under the most stringent conditions.

[0068] Test results: The results show that the average relative error of the system is only 1.54%, and the maximum relative error is not more than 3.03%, proving the accuracy of the concentration control; the average standard deviation of each concentration point is only 0.027%, showing excellent running stability.

[0069] As shown in Figure 4 , all measured values (hollow circles) are closely distributed near the target value (black solid circle), and the error bar (±1 standard deviation) range is very small. This proves that the device can accurately and stably maintain at any preset concentration point.

[0070] As Figure 5 shown, further reveals the core advantage of the application. The traditional premixing method can only provide limited, discrete concentration selection (block shown). And the application can generate from zero to the original liquid concentration between any value of perfusion fluid (solid line shown), to achieve truly stepless continuous output. The operator can adjust the concentration according to the needs of organ preservation, through the touch screen, arbitrary, continuous, the system can quickly respond and stabilize to the target value, which is not achieved by the prior art.

[0071] In summary, the application successfully realizes the stepless, accurate and continuous output of organ preservation solution concentration through the unique dual peristaltic pump-dual syringe pump cooperative control architecture and double closed-loop feedback algorithm, solves the concentration control problem that has long restricted the development of organ mechanical perfusion technology, and has important significance for improving the quality of transplanted organ preservation.

[0072] The terms used herein are merely used to describe specific embodiments and are not intended to limit the present application. The terms "include", "contain" and the like used herein indicate the presence of the described features, steps, operations and / or components, but do not exclude the presence or addition of one or more other features, steps, operations or components.

[0073] The technical features of the above embodiments can be combined in any way, and in order to make the description concise, not all possible combinations of the technical features in the above embodiments are described, but as long as the combination of the technical features does not exist contradictory, it should be considered as the scope of the present application.

[0074] It is obvious to those skilled in the art that the present application is not limited to the details of the above exemplary embodiments, and can be implemented in other specific forms without departing from the spirit or essential characteristics of the present application. Therefore, from any point of view, the embodiments should be regarded as exemplary and non-limiting, the scope of the present application is defined by the appended claims rather than the above description, therefore all changes falling within the meaning and scope of the equivalent elements of the claims are intended to be included in the present application, any reference signs in the claims should not be regarded as limiting the claims involved.

[0075] In addition, it should be understood that although the present application is described in the form of embodiments, each embodiment does not contain only one independent technical solution, and the description manner of the specification is only for the sake of clarity, those skilled in the art should consider the specification as a whole, and the technical solutions in each embodiment can be combined to form other embodiments that can be understood by those skilled in the art.

Claims

1. A device for controlling the concentration of perfusion fluid for organ cryopreservation, characterized in that, include: The main controller, a heating and cooling module connected to the main controller, an oxygenator, a bubble sensor, a temperature sensor, a pressure sensor, an exhaust device, a blood oxygen saturation sensor, and an organ compartment; A diluent storage tank is used to store diluents with a concentration of zero. High-concentration liquid storage tank, used to store high-concentration liquids of a set concentration; At least one peristaltic pump, the inlet of which is connected to a diluent storage tank via a pipeline, and the outlet of which is connected to the inlet of a first flow sensor via a pipeline; Two syringe pumps are connected to a high-concentration liquid storage tank via pipelines equipped with solenoid valves, and are also connected to the inlet of a second flow sensor via pipelines equipped with solenoid valves. The solenoid valve group is controlled by the main controller, so that the two syringe pumps alternately perform liquid replenishment and output operations. The outlets of the first and second flow sensors are connected to the heating and cooling module, oxygenator, temperature sensor, pressure sensor, bubble sensor, exhaust device, organ compartment, and blood oxygen saturation sensor; the bubble sensor needs to be installed before the exhaust device. The main controller is configured to execute a closed-loop control algorithm, receive the target concentration and target flow rate values ​​set by the user, as well as the detection values ​​of each sensor, and adjust the peristaltic pump and injection pump to achieve the output of perfusion fluid with any target concentration from zero concentration to a set high concentration.

2. The perfusion fluid concentration control device for organ cryopreservation according to claim 1, characterized in that, It also includes a touch screen; the touch screen is electrically connected to the main controller, providing users with an interface to set infusion process parameters and display operating parameters; the infusion process parameters include the target infusion fluid concentration and the target infusion flow rate.

3. The perfusion fluid concentration control device for organ cryopreservation according to claim 1, characterized in that, There are two peristaltic pumps. The inlets of the two peristaltic pumps are connected to the diluent storage tank through pipelines, and the outlets are connected to the inlet of the first flow sensor through pipelines.

4. A perfusion fluid concentration control device for organ cryopreservation according to claim 1 or 3, characterized in that, The peristaltic pumps all adopt a six-roller structure, and the two peristaltic pumps operate orthogonally with a 180-degree phase difference.

5. The perfusion fluid concentration control device for organ cryopreservation according to claim 1, characterized in that, The main controller controls the solenoid valve group to switch the liquid path state when the liquid in the injection pump reaches the minimum capacity threshold.

6. The perfusion fluid concentration control device for organ cryopreservation according to claim 1, characterized in that, The heating and cooling module can be any one of a semiconductor refrigeration chip, a compressor refrigeration unit, or a split-type hot and cold cycle module.

7. The perfusion fluid concentration control device for organ cryopreservation according to claim 1, characterized in that, The main controller uses a 32-bit ARM architecture microprocessor.

8. The perfusion fluid concentration control device for organ cryopreservation according to claim 1, characterized in that, Also includes: The biochemical sensor module, installed in the reflux tubing of the organ compartment, monitors the glucose concentration, lactate concentration, and pH value in the perfusion fluid in real time. The main controller analyzes the data: if the glucose concentration decreases or the lactate concentration increases, it indicates that the organ is metabolically active or the perfusion is insufficient; if the pH value decreases, it indicates that the organ is acidosis and the composition of the perfusion fluid needs to be adjusted. A multi-channel diversion valve, installed on the outlet pipeline of the oxygenator, divides the perfusion fluid into multiple channels. Each channel is equipped with an independent flow sensor, pressure sensor, and bubble sensor, enabling independent perfusion control of multiple organs. Waste liquid collection tank is used to collect return injection liquid that does not require circulation. The waste liquid collection tank is equipped with a liquid level sensor. When the liquid level reaches 80%, the touch screen prompts the operator to empty the tank to prevent waste liquid from overflowing.

9. The perfusion fluid concentration control device for organ cryopreservation according to claim 1, characterized in that, The main controller is configured to execute a closed-loop control algorithm, receive user-defined target concentration and target flow rate values, as well as detection values ​​from various sensors, and adjust the peristaltic pump and injection pump to achieve the output of perfusion fluid at any target concentration from zero to a set high concentration. Specifically, this includes: The main controller determines the target concentration based on the set parameters. and the initial concentration value of high concentration solution Real-time calculation of the required target flow rate of diluent and high concentration liquid target flow rate The calculation formula is: The main controller independently receives feedback signals from the first and second flow sensors. Through two independent PID controllers, it adjusts the total speed of the two peristaltic pumps and the injection speed of the currently operating syringe pump, respectively, to make the actual flow rates of the diluent and the high-concentration solution approximate the target flow rates of the diluent and the high-concentration solution, thereby synthesizing a solution with the target concentration. The infusion fluid; by changing and It can achieve from zero to Output of perfusion fluid at any target concentration between [specific values].

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