Background
In medical equipment such as hemodialysis, washing, and purification, blood of a patient flows out of the body and returns to the body through an extracorporeal circulation path constituted by a hemodialysis apparatus line. In the circulation system, 3 parts of a blood circuit, a liquid circuit and a monitoring system are mainly included. The dialyzate enters a dialyzer and undergoes the processes of dispersion, convection, ultrafiltration and the like on the blood of a patient through a dialysis membrane, and redundant harmful substances and water in the body of the patient are removed.
In the process of blood purification, if the filter breaks membranes, blood can permeate to the waste liquid end through the filter membrane, so that blood leakage is caused, and the life safety of a patient is threatened. Therefore, any blood purification system requires a blood leakage monitoring device to monitor the blood leakage in the waste fluid in real time for ensuring the safety of the patient during treatment.
The traditional blood leakage monitoring method is realized by adopting an optical principle, namely, a light emitting diode emits a beam of light which passes through a waste liquid container, a light sensitive sensing circuit arranged at the other end of the waste liquid container converts a transmission light signal into an electric signal, and the blood leakage phenomenon is judged by comparing the magnitude of the electric signal. Due to different colors of ultrafiltrate, the photosensitive sensing circuit receives different light intensity signals of different patients, which easily causes false alarm of blood leakage.
The invention patent "a blood leakage monitoring system for blood purification (CN 201210257765.4)" proposes to use a color sensor instead of a photosensor as a transmitted light receiving element. The disadvantage of using a photosensitive receiving diode for receiving transmitted light information is alleviated in a certain procedure, but the influence of uncertain factors such as the existence of air bubbles in waste liquid cannot be completely eliminated, and the blood in the waste liquid can be detected by a sensor only when the blood reaches a certain amount under the influence of the sensitivity response range of the sensor.
Disclosure of Invention
The invention provides a device and a method for realizing blood leakage monitoring by using surface acoustic waves in a blood purification system, which are used for overcoming the defects in the prior art.
The invention is realized by the following technical scheme:
a device for realizing blood leakage monitoring by using surface acoustic waves in a blood purification system comprises a waste liquid sample introduction hose, a Murphy's dropper, a right drainage tube, a first silica gel hose, a first microfluidic channel inlet and outlet, a left drainage tube, a waste liquid bag, a microfluidic platform, a first microfluidic channel, a first interdigital transducer, a second microfluidic channel inlet and outlet, a second silica gel hose, a third microfluidic channel, a first injection pump, a third interdigital transducer, a third microfluidic channel inlet and outlet, a third silica gel hose, a second injection pump, a fourth interdigital transducer, a driving detection circuit and a microcontroller, wherein the waste liquid sample introduction hose is connected with the Murphy's dropper is simultaneously connected with the right drainage tube and the left drainage tube, the other end of the right drainage tube is connected with one end of the first silica gel hose, the other end of the first silica gel hose is connected with the first microfluidic channel inlet and outlet, the other end of the left drainage tube is connected with a waste liquid bag, the Murphy's dropper is vertically arranged higher than the microfluidic platform, a three-fork opening is arranged at the inlet of a third microfluidic channel, the third microfluidic channel is respectively connected with a first microfluidic channel and a second microfluidic channel through the three-fork opening, a first interdigital transducer and a second interdigital transducer are arranged at two sides of the outlet of the first microfluidic channel before the three-fork opening, a third interdigital transducer and a fourth interdigital transducer are arranged at two sides of the outlet of the third microfluidic channel before the outlet of the third microfluidic channel, the first microfluidic channel and the third microfluidic channel are fixedly arranged on the microfluidic platform, the outlet of the second microfluidic channel and the outlet of the third microfluidic channel corresponding to the third microfluidic channel are respectively connected with a first injection pump and a second injection pump through a second silica gel hose and a third silica gel hose, the first interdigital transducer, the second interdigital transducer, the third interdigital transducer and the fourth interdigital transducer are connected with a driving detection circuit, and the driving detection circuit is connected with the microcontroller.
According to the device for monitoring blood leakage by using the surface acoustic waves in the blood purification system, the microfluidic platform is divided into the microchannel layer, the piezoelectric layer and the temperature control layer, the temperature sensor thermocouple is clamped between the piezoelectric layer and the temperature control layer, and the temperature sensor thermocouple is positioned below the first interdigital transducer.
The device for monitoring blood leakage in the blood purification system by using the surface acoustic wave is characterized in that the piezoelectric layer is lithium niobate (LiNbO 3).
The device for monitoring blood leakage in the blood purification system by using the surface acoustic wave is characterized in that the temperature control layer is a semiconductor refrigeration sheet.
According to the device for realizing blood leakage monitoring by using the surface acoustic wave in the blood purification system, the microcontroller controls the constant current source to drive the temperature control layer, the thermocouple is connected with the temperature measurement circuit, and the temperature measurement circuit is connected with the microcontroller.
The device for monitoring blood leakage in the blood purification system by using the surface acoustic waves is characterized in that the first microfluidic channel and the third microfluidic channel are snakelike.
The device for monitoring blood leakage in the blood purification system by using the surface acoustic wave is characterized in that the second microfluidic channel is linear.
The device for realizing blood leakage monitoring by using the surface acoustic wave in the blood purification system is characterized in that the directions of the surface acoustic waves generated by the first interdigital transducer, the second interdigital transducer, the third interdigital transducer and the fourth interdigital transducer are perpendicular to or form a certain angle with the flowing direction of the liquid in the microfluidic channel.
The device for realizing blood leakage monitoring by using the surface acoustic wave in the blood purification system adopts a symmetrical circuit, the first interdigital transducer, the second interdigital transducer, the first phase shifter and the first amplifier form a first oscillating circuit, and the third interdigital transducer, the fourth interdigital transducer, the second phase shifter and the second amplifier form a second oscillating circuit.
A method for monitoring blood leakage using surface acoustic waves in a blood purification system as described above, comprising the steps of:
a. according to the following steps: 1, proportioning an ellagic acid reagent and 0.025mol/L calcium chloride solution in proportion, pre-warming in a water bath at 37 ℃, and filling the proportioned solution into a first injection syringe of an injection pump;
b. starting a power supply of the device, and heating the microfluidic platform to maintain the temperature at 37 ℃;
c. and starting the second injection pump on the premise that the blood purification system works. The second injection pump works in a ' pull ' mode, so that the waste liquid flows into the right drainage tube, the first micro-fluidic channel and the third micro-fluidic channel from the Murphy's dropper and finally flows into the second injection pump; the second injection pump mainly has the function of preventing the pressure generated by the blood purification system from being insufficient to enable the waste liquid to enter the right drainage tube through the Murphy's dropper; the volume of the injection tube used by the second injection pump is determined according to the waste liquid amount generated by one-time blood purification;
d. the first injection pump starts to inject a reagent prepared by mixing ellagic acid and 0.025mol/L calcium chloride solution into the second microfluidic channel, the injection speed is adjustable, the default flow rate is 3uL/s, and the waste liquid flows into the third microfluidic channel after flowing through the first microfluidic channel and the reagent of the second microfluidic channel and mixing;
the oscillation frequency of a first oscillation circuit formed by the first interdigital transducer and the second interdigital transducer changes along with the change of the content of the solution in the first microfluidic channel, and the oscillation frequency of a second oscillation circuit formed by the third interdigital transducer and the fourth interdigital transducer is influenced by a reagent of the second microfluidic channel besides the content of the solution in the first microfluidic channel;
when the waste liquid does not contain blood, the solution content of the first microfluidic channel and the second microfluidic channel is stable, the oscillation frequencies of the first oscillation circuit and the second oscillation circuit are basically stable, and the fluctuation in the period is counteracted by frequency mixing, so that the frequency signal after frequency mixing and filtering tends to be stable;
when the waste liquid contains blood, the solution flowing into the third microfluidic channel changes the oscillation frequency of the second oscillation circuit due to the interaction between the blood and the reagent flowing into the second microfluidic channel, so that the frequency signal after the frequency mixing and filtering is changed, and the blood content in the waste liquid is in a proportional relation with the frequency signal measured by the microcontroller;
e. and judging whether the frequency of the signal after the frequency mixing filtration exceeds a limit value or not by measuring the frequency of the signal after the frequency mixing filtration and according to the proportional relation between the blood content in the waste liquid and the frequency signal, and if the frequency exceeds the limit value, sending an alarm signal.
The invention has the advantages that: the invention eliminates the influence of uncertain factors such as air bubbles, environmental factors and the like, and avoids the phenomenon of blood leakage and false alarm. Through the regulation and control of the reagent injected into the second microfluidic channel and the high sensitivity of the surface acoustic wave, the blood leakage detection sensitivity can be adjusted at will, and different response requirements in actual use are met.
Detailed Description
In order to make the objects, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are some, but not all, embodiments of the present invention. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
A device for realizing blood leakage monitoring by using surface acoustic waves in a blood purification system comprises a waste liquid sample introduction hose 1, a Murphy's dropper 2, a right drainage tube 3, a first silica gel hose 4, a first microfluidic channel inlet and outlet 5, a left drainage tube 6, a waste liquid bag 7, a microfluidic platform 8, a first microfluidic channel 9, a firstinterdigital transducer 10, a secondinterdigital transducer 11, a secondmicrofluidic channel 12, a second microfluidic channel inlet andoutlet 13, a secondsilica gel hose 14, a third microfluidic channel 15, afirst injection pump 16, a thirdinterdigital transducer 17, a third microfluidic channel inlet andoutlet 18, a thirdsilica gel hose 19, asecond injection pump 20, a fourthinterdigital transducer 21, adriving detection circuit 22 and amicrocontroller 23, wherein the waste liquid sample introduction hose 1 is connected with the Murphy's dropper 2, the Murphy's dropper 2 is simultaneously connected with the right drainage tube 3 and the left drainage tube 6, the other end of the right drainage tube 3 is connected with one end of a first silica gel hose 4, the other end of the first silica gel hose 4 is connected with a first microfluidic channel inlet and outlet 5, the other end of the left drainage tube 6 is connected with a waste liquid bag 7, the Murphy's dropper 2 is vertically arranged higher than the microfluidic platform 8, a three-fork opening is arranged at the inlet of a third microfluidic channel 15, the third microfluidic channel 15 is respectively connected with a first microfluidic channel 9 and a secondmicrofluidic channel 12 through the three-fork opening, a firstinterdigital transducer 10 and a secondinterdigital transducer 11 are arranged at two sides of the outlet of the first microfluidic channel 9 in front of the three-fork opening, a thirdinterdigital transducer 17 and a fourthinterdigital transducer 21 are arranged at two sides of the outlet of the third microfluidic channel 15 in front of the outlet of the thirdmicrofluidic channel 18, the first microfluidic channel 9 and the third microfluidic channel 15 are both fixedly arranged on the microfluidic platform 8, and a secondinterdigital transducer 13, a third interdigital transducer and a thirdinterdigital transducer 13, The third microfluidic channel inlet andoutlet 18 is respectively connected with thefirst injection pump 16 and thesecond injection pump 20 through the secondsilica gel hose 14 and the thirdsilica gel hose 19, the firstinterdigital transducer 10, the secondinterdigital transducer 11, the thirdinterdigital transducer 17 and the fourthinterdigital transducer 21 are connected with thedriving detection circuit 22, and thedriving detection circuit 22 is connected with themicrocontroller 23. The invention eliminates the influence of uncertain factors such as air bubbles, environmental factors and the like, and avoids the phenomenon of blood leakage and false alarm. Through the regulation and control of the reagent injected into the second microfluidic channel and the high sensitivity of the surface acoustic wave, the blood leakage detection sensitivity can be adjusted at will, and different response requirements in actual use are met.
Specifically, as shown in the figure, the microfluidic platform 8 according to the present embodiment is divided into amicrochannel layer 30, apiezoelectric layer 31 and atemperature control layer 32, wherein atemperature sensor thermocouple 33 is sandwiched between thepiezoelectric layer 31 and thetemperature control layer 32, and thetemperature sensor thermocouple 33 is located below the firstinterdigital transducer 10.
Specifically, as shown in the figure, thepiezoelectric layer 31 in this embodiment is lithium niobate (LiNbO 3).
Further, as shown in the figure, thetemperature control layer 32 in this embodiment is a semiconductor cooling plate.
Further, as shown in the figure, themicrocontroller 23 according to the embodiment controls the constantcurrent source 51 to drive thetemperature control layer 32, thethermocouple 33 is connected to thetemperature measurement circuit 50, and thetemperature measurement circuit 50 is connected to themicrocontroller 23. The temperature of the microfluidic platform 8 is read by thetemperature measuring circuit 50.
Furthermore, as shown in the figure, the first microfluidic channel 9 and the third microfluidic channel 15 in this embodiment have a serpentine shape.
Further, as shown in the drawings, the secondmicrofluidic channel 12 of the present embodiment is linear.
Furthermore, as shown in the figure, the directions of the surface acoustic waves generated by the firstinterdigital transducer 10, the secondinterdigital transducer 11, the thirdinterdigital transducer 17 and the fourthinterdigital transducer 21 in the embodiment are perpendicular to or at an angle with respect to the liquid flowing direction of the microfluidic channel.
Further, as shown in the drawing, thedriving detection circuit 22 according to the present embodiment employs a symmetrical circuit, in which the firstinterdigital transducer 10, the secondinterdigital transducer 11, thefirst phase shifter 40, and the first amplifier 41 constitute afirst oscillation circuit 46, and the thirdinterdigital transducer 17, the fourthinterdigital transducer 21, thesecond phase shifter 42, and the second amplifier 43 constitute asecond oscillation circuit 47. Thefirst oscillator circuit 46 and thesecond oscillator circuit 47 are mixed by the multiplier 44, and the high frequency signal is filtered by the Low Pass Filter (LPF) 45, and the output low frequency signal is obtained by themicrocontroller 23 through frequency measurement.
As shown in fig. 1, the blood leakage monitoring device of the blood purification system of the present invention includes: the device comprises a waste liquid sampling hose 1, a Murphy's dropper 2, a right drainage tube 3, a first silica gel hose 4, a first micro-fluidic channel inlet and outlet 5, a left drainage tube 6, a waste liquid bag 7, a micro-fluidic platform 8, a first micro-fluidic channel 9, a firstinterdigital transducer 10, a secondinterdigital transducer 11, a secondmicro-fluidic channel 12, a second micro-fluidic channel inlet andoutlet 13, a secondsilica gel hose 14, a third micro-fluidic channel 15, afirst injection pump 16, a thirdinterdigital transducer 17, a third micro-fluidic channel inlet andoutlet 18, a thirdsilica gel hose 19, asecond injection pump 20, a fourthinterdigital transducer 21, adriving detection circuit 22 and amicrocontroller 23.
The waste liquid sampling hose 1 is connected with the Murphy's dropper 2, and the Murphy's dropper 2 is simultaneously connected with the right drainage tube 3 and the left drainage tube 6. The waste liquid flowing into the Murphy's dropper 2 from the waste liquid sampling hose 1 respectively flows into the right drainage tube 3 and the left drainage tube 6. The waste liquid flowing into the left drainage tube 6 is introduced into the waste liquid bag 7. The waste flowing into the right drainage tube 3 enters a first microfluidic channel inlet and outlet 5 where the microfluidic platform 8 is located through a first silica gel hose 4. The Murphy's dropper 2 is placed vertically and above the microfluidic platform 8.
As shown in fig. 2, the microfluidic platform 8 is divided into three layers:microchannel layer 30,piezoelectric layer 31, andtemperature control layer 32. Thepiezoelectric layer 31 is lithium niobate (LiNbO 3), but is not limited to lithium niobate. Thetemperature control layer 32 is a semiconductor refrigerating sheet. Atemperature sensor thermocouple 33 is sandwiched below the firstinterdigital transducer 10 between thepiezoelectric layer 31 and thetemperature control layer 32.
As shown in fig. 1, in themicrochannel layer 30, the first microfluidic channel 9 and the third microfluidic channel 15 have a serpentine shape, but are not limited to a serpentine shape. The secondmicrofluidic channel 12 is linear, but not limited to linear. The diameter ranges of the first micro-fluidic channel 9 and the third micro-fluidic channel 15 are 1 mu m-3 mm. And a three-fork opening is arranged at the inlet of the third microfluidic channel 15 and is respectively connected with the first microfluidic channel 9 and the secondmicrofluidic channel 12. The firstinterdigital transducer 10 and the secondinterdigital transducer 11 are arranged on two sides of the outlet of the first microfluidic channel 9 before the three-fork opening. And a thirdinterdigital transducer 17 and a fourthinterdigital transducer 21 are arranged at two sides of the micro-channel before the inlet and theoutlet 18 of the third micro-fluidic channel.
Further, the steps described in this embodiment include:
a. according to the following steps: 1, proportioning an ellagic acid reagent and 0.025mol/L calcium chloride solution, pre-warming in a water bath at 37 ℃, and filling the proportioned solution into an injection syringe of afirst injection pump 16;
b. the power supply of the device is turned on, and the micro-fluidic platform 8 is heated to maintain the temperature at 37 ℃;
c. with the blood purification system in operation, thesecond syringe pump 20 is turned on. Thesecond injection pump 20 works in a ' pull ' mode, so that the waste liquid flows into the right drainage tube 3, the first micro-fluidic channel 9 and the third micro-fluidic channel 15 from the Murphy's dropper 2 and finally flows into thesecond injection pump 20; thesecond injection pump 20 mainly functions to prevent the pressure generated by the blood purification system from being insufficient to make the waste liquid enter the right drainage tube 3 through the Murphy's dropper 2; the volume of the syringe used by thesecond syringe pump 20 is determined by the amount of waste liquid generated by one blood purification;
d. thefirst injection pump 16 starts to inject a reagent prepared by mixing ellagic acid and 0.025mol/L calcium chloride solution into the secondmicrofluidic channel 12, the injection speed is adjustable, the default flow rate is 3uL/s, and the waste liquid flows into the third microfluidic channel 15 after flowing through the first microfluidic channel 9 and the reagent of the secondmicrofluidic channel 12 and mixing;
the oscillation frequency of afirst oscillation circuit 46 formed by the firstinterdigital transducer 10 and the secondinterdigital transducer 11 changes along with the change of the content of the solution in the first microfluidic channel 9, and the oscillation frequency of asecond oscillation circuit 47 formed by the thirdinterdigital transducer 17 and the fourthinterdigital transducer 21 is influenced by the reagent in the secondmicrofluidic channel 12 in addition to the influence of the content of the solution in the first microfluidic channel 9;
when the waste liquid does not contain blood, the solution content of the first microfluidic channel 9 and the secondmicrofluidic channel 12 is stable, the oscillation frequency of thefirst oscillation circuit 46 and the oscillation frequency of thesecond oscillation circuit 47 are basically stable, and the fluctuation in the period is counteracted by the mixing effect, so that the frequency signal after mixing and filtering tends to be stable;
when the waste liquid contains blood, the solution flowing into the third microfluidic channel 15 causes the oscillation frequency of thesecond oscillation circuit 47 to change due to the interaction between the blood and the reagent flowing into the secondmicrofluidic channel 12, so that the frequency signal after the frequency mixing and filtering changes, and the blood content in the waste liquid is in a proportional relation with the frequency signal measured by the microcontroller;
e. and judging whether the frequency of the signal after the frequency mixing filtration exceeds a limit value or not by measuring the frequency of the signal after the frequency mixing filtration and according to the proportional relation between the blood content in the waste liquid and the frequency signal, and if the frequency exceeds the limit value, sending an alarm signal.
Finally, it should be noted that: the above examples are only intended to illustrate the technical solution of the present invention, but not to limit it; although the present invention has been described in detail with reference to the foregoing embodiments, it will be understood by those of ordinary skill in the art that: the technical solutions described in the foregoing embodiments may still be modified, or some technical features may be equivalently replaced; and such modifications or substitutions do not depart from the spirit and scope of the corresponding technical solutions of the embodiments of the present invention.