Vascular perfusion culture device and culture method

Abstract

The present invention provides a vascular perfusion culture device and a culture method. The present invention belongs to the field of medical devices, including a culture box, a culture dish, a peristaltic pump, a monitoring component, an infusion tube group, a first infusion tube and an infusion device. The culture dish is placed in the culture box, one end of the first infusion tube is connected to one end of the culture dish, the other end of the first infusion tube passes through the side wall of the culture box and is connected to the infusion device, one end of the infusion tube group is connected to the infusion device, and the other end of the infusion tube group passes through the peristaltic pump and the wall of the culture box in turn and is connected to the other end of the culture dish. The monitoring component is arranged on the infusion tube group. The purpose is to solve the problem that it is difficult to maintain a sterile culture environment for the culture medium in the prior art and it is impossible to simulate the environment in the body. The technical effect achieved is: to achieve precise control of the flow rate and pressure of the culture medium, simulate the environment in the human body, and ensure that the culture medium is cultured in a sterile environment.

Description

Technical Field

[0001] The present invention relates to the technical field of medical devices, in particular to a vascular perfusion culture device and a vascular perfusion culture method. Background Art

[0002] Coronary artery bypass grafting is an important surgical method for the treatment of critical coronary heart disease. The great saphenous vein is the most commonly used vascular material in surgery. However, vascular stenosis and occlusion are common problems after surgery. How to establish an in vitro perfusion model that simulates the body in order to study the mechanism of vascular stenosis is an important issue that needs to be solved. Today's culture mostly involves cutting the blood vessels into rings and placing them directly in a culture dish, which cannot allow the blood vessels to withstand the corresponding arterial pressure. In order to allow the blood vessels to withstand the corresponding arterial pressure, some people have proposed the use of a separate special culture dish, so that the blood vessels are placed in a special culture dish, but the existing special culture dishes are still difficult to maintain a sterile culture environment and cannot simulate the environment in the body. Summary of the invention

[0003] The first aspect of the present invention provides a vascular perfusion culture device to solve the defects in the prior art that it is difficult to maintain a sterile culture environment for blood vessel culture and cannot simulate the in vivo environment, and to achieve precise control of the flow and pressure of the culture medium used for culturing blood vessels, simulate the in vivo environment of the human body, and ensure that the blood vessels are cultured in a sterile environment.

[0004] The present invention provides a vascular perfusion culture device, comprising a culture box, a culture dish, a peristaltic pump, a monitoring component, an infusion tube group, a first infusion tube and an infusion device, the culture dish is placed in the culture box, one end of the first infusion tube is connected to one end of the culture dish, the other end of the first infusion tube passes through the side wall of the culture box and is connected to the infusion device, one end of the infusion tube group is connected to the infusion device, the other end of the infusion tube group passes through the peristaltic pump and the wall of the culture box in sequence and is connected to the other end of the culture dish, and the monitoring component is arranged on the infusion tube group.

[0005] According to the vascular perfusion culture device of the present invention, a peristaltic pump is used to provide a power source for the flow of the culture medium, and the blood pressure and blood flow rate in the human body are simulated to control the pressure on the culture medium and the flow rate of the culture medium, thereby achieving precise control of the flow rate and pressure of the culture medium and simulating the internal environment of the human body. The setting of the incubator ensures that the culture medium is cultured in a sterile environment, thereby providing strong support for the study of culture vessel restenosis.

[0006] In addition, the vascular perfusion culture device according to the present invention may also have the following additional technical features: In some embodiments of the present invention, the monitoring component includes a flow sensor, and the flow sensor is mounted on the infusion tube set.

[0007] By adopting the above-mentioned embodiment, the flow sensor can monitor the flow of the culture medium in the infusion tube group in real time, so that the peristaltic pump can adjust the flow and flow rate of the culture medium in real time according to the flow of the culture medium monitored by the flow sensor, thereby realizing the precise adjustment of the flow of the culture medium according to the actual situation of the human body.

[0008] In some embodiments of the present invention, the flow sensor includes a micro piezoelectric ultrasonic sensor chip and a sensor housing. The sensor housing is sleeved on the infusion tube set, and the micro piezoelectric ultrasonic sensor chip is arranged in the sensor housing.

[0009] By adopting the above embodiment, the two miniature piezoelectric ultrasonic sensor chips are arranged in cooperation to measure the time difference of ultrasonic wave propagation downstream and upstream to directly calculate the fluid velocity, which is suitable for low flow rate conditions and can detect tiny time changes, thereby achieving accurate measurement.

[0010] In some embodiments of the present invention, a miniature piezoelectric ultrasonic sensor chip includes an insulating sheet, a piezoelectric layer, a top electrode layer and a bottom electrode layer. The piezoelectric layer is arranged between the top electrode layer and the bottom electrode layer, the bottom electrode layer is arranged between the piezoelectric layer and the insulating sheet, and the top electrode layer is arranged opposite to the side wall of the infusion tube group.

[0011] In some embodiments of the present invention, the micro piezoelectric ultrasonic sensor chip further includes a buffer layer and an insulating layer, the buffer layer is arranged between the insulating sheet and the piezoelectric layer, and the insulating layer is arranged on the insulating sheet.

[0012] By adopting the above embodiment, provision of the insulating layer realizes electrical isolation and insulation.

[0013] In some embodiments of the present invention, the monitoring component further includes a pressure sensor, and the pressure sensor is connected in parallel to the infusion tube group or the first infusion tube.

[0014] By adopting the above embodiment, the provision of the pressure sensor 9 realizes real-time monitoring of the culture medium pressure.

[0015] In some embodiments of the present invention, the infusion device includes a pressurized bag and a liquid bag, the pressurized bag is mounted on the liquid bag, and the end of the first infusion tube away from the culture dish is connected to the liquid bag and the end of the infusion tube group away from the culture dish is connected to the liquid bag.

[0016] By adopting the above embodiment, the pressurized bag applies pressure to the liquid bag to achieve rapid and reliable injection of the culture medium into the culture dish.

[0017] In some embodiments of the present invention, the infusion tube group includes a second infusion tube, a Luer connector and a third infusion tube, one end of the second infusion tube passes through the side wall of the incubator and is connected to the culture dish, the other end of the second infusion tube is connected to one end of the third infusion tube through the Luer connector, and the other end of the third infusion tube passes through the peristaltic pump and is connected to the infusion device.

[0018] By adopting the above embodiment, the provision of the Luer connector enables the alcohol to be injected into the second infusion tube and the third infusion tube through the Luer connector when the device is not in use, thereby ensuring the sterile culture of the device.

[0019] In some embodiments of the present invention, a controller is further included, and the peristaltic pump, the pressure sensor and the flow sensor are all electrically connected to the controller.

[0020] The second aspect of the present invention provides a vascular perfusion culture method, which uses all the technical features of the first aspect of the present invention, and in addition, further comprises the following steps: Step S100: starting the incubator, and using a pressurized bag to inject the culture medium in the liquid bag into the culture dish in the incubator through the first infusion tube; Step S200: starting the peristaltic pump to allow the culture medium to form a dynamic flow in the culture dish, the first infusion tube, the second infusion tube, the third infusion tube and the liquid bag; Step S300: using a pressure sensor and a flow sensor to monitor the culture medium flow and culture medium pressure in real time and feed back to the controller; Step S400: adjusting the peristaltic pump according to the culture medium flow rate and the culture medium pressure to simulate human blood pressure to provide pressure to the culture medium; Step S500: Cultivation is completed.

[0021] In summary, the present application includes the following beneficial technical effects: a peristaltic pump is used to provide a power source for the flow of the culture medium, and the blood pressure and blood flow rate in the human body are simulated to control the pressure on the culture medium and the flow rate of the culture medium, thereby achieving precise control of the flow rate and pressure of the culture medium, simulating the internal environment of the human body, and ensuring that the culture medium is cultured in a sterile environment through the setting of an incubator, which provides strong support for the study of vascular restenosis in the culture medium. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Various other advantages and benefits will become apparent to those of ordinary skill in the art by reading the detailed description of the preferred embodiments below. The accompanying drawings are only for the purpose of illustrating the preferred embodiments and are not to be considered as limiting the present invention. Moreover, the same reference numerals are used throughout the accompanying drawings to represent the same components. In the accompanying drawings: Figure 1 A first view of a perspective view of a vascular perfusion culture device according to some embodiments of the present invention is schematically shown.

[0023] Figure 2 A second view of a perspective view of a vascular perfusion culture device according to some embodiments of the present invention is schematically shown.

[0024] Figure 3A first perspective view schematically illustrates a vascular perfusion culture device according to some embodiments of the present invention, without a culture box and a support.

[0025] Figure 4 A second perspective view schematically illustrates a vascular perfusion culture device according to some embodiments of the present invention without a culture box and a support.

[0026] Figure 5 A third view schematically illustrates a perspective view of a vascular perfusion culture device according to some embodiments of the present invention.

[0027] Figure 6 Schematic diagram of a vascular perfusion culture device according to some embodiments of the present invention Figure 5 A partial enlarged view of .

[0028] Figure 7 The working principle diagram of the vascular perfusion culture device according to some embodiments of the present invention is schematically shown.

[0029] Figure 8 The control principle diagram of the peristaltic pump and the throttle valve of the vascular perfusion culture device according to some embodiments of the present invention is schematically shown.

[0030] Fig. 9 The control principle of the peristaltic pump of the vascular perfusion culture device according to some embodiments of the present invention is schematically shown.

[0031] Fig.10 The structure diagram of the flow sensor of the vascular perfusion culture device according to some embodiments of the present invention is schematically shown.

[0032] Fig.11 Schematically showing a cross-sectional view of a micro piezoelectric ultrasonic sensor chip of a vascular perfusion culture device according to some embodiments of the present invention.

[0033] Reference numerals: 1. Incubator, 11. Partition, 12. Door, 13. Sealing ring, 2. Culture dish, 3. Controller, 4. Peristaltic pump, 41. Throttle valve, 5. Bracket, 6. Infusion device, 61. Pressurized bag, 62. Liquid bag, 63. Air bag, 7. Infusion tube set, 71. Luer connector, 72. First infusion tube, 73. Second infusion tube, 74. Third infusion tube, 8. Flow sensor, 81. Sensor housing, 82. Micro piezoelectric ultrasonic sensor chip, 821. Insulating sheet, 822. Insulating layer, 823. Buffer layer, 824. Piezoelectric layer, 825. Top electrode layer, 826. Bottom electrode layer, 9. Pressure sensor, 10. Monitoring component. DETAILED DESCRIPTION

[0034] The exemplary embodiments of the present disclosure will be described in more detail below with reference to the accompanying drawings. Although the exemplary embodiments of the present disclosure are shown in the accompanying drawings, it should be understood that the present disclosure can be implemented in various forms and should not be limited by the embodiments described herein. On the contrary, these embodiments are provided in order to enable a more thorough understanding of the present disclosure and to fully convey the scope of the present disclosure to those skilled in the art.

[0035] It should be understood that the terms used herein are only for the purpose of describing specific example embodiments and are not intended to be limiting. Unless the context clearly indicates otherwise, the singular forms "one", "an" and "" as used herein may also be meant to include plural forms. The terms "include", "comprise", "contain", and "have" are inclusive and therefore specify the presence of stated features, steps, operations, elements and / or parts, but do not exclude the presence or addition of one or more other features, steps, operations, elements, parts, and / or combinations thereof. The method steps, processes, and operations described herein are not interpreted as necessarily requiring them to be performed in the specific order described or illustrated, unless the execution order is clearly indicated. It should also be understood that additional or alternative steps may be used.

[0036] Although the terms first, second, third, etc. can be used in the text to describe multiple elements, components, regions, layers and / or sections, these elements, components, regions, layers and / or sections should not be limited by these terms. These terms can only be used to distinguish an element, component, region, layer or section from another region, layer or section. Unless the context clearly indicates, terms such as "first", "second" and other numerical terms do not imply order or sequence when used in the text. Therefore, the first element, component, region, layer or section discussed below can be referred to as the second element, component, region, layer or section without departing from the teaching of the example embodiments.

[0037] For ease of description, spatial relative terms may be used in the text to describe the relationship of one element or feature relative to another element or feature as shown in the figure, such as "inside", "outside", "inner side", "outer side", "below", "below", "above", "above", etc. Such spatial relative terms are intended to include different orientations of the device in use or operation in addition to the orientation depicted in the figure. For example, if the device in the figure is flipped, the element described as "below other elements or features" or "below other elements or features" will then be oriented as "above other elements or features" or "above other elements or features". Therefore, the example term "below..." can include both upper and lower orientations. The device can be additionally oriented and rotated 90 degrees or in other directions and the spatial relative descriptors used in the text are interpreted accordingly.

[0038] like Figures 1 to 11 As shown, according to an embodiment of the first aspect of the present invention, a vascular perfusion culture device is proposed, including a culture box 1, a culture dish 2, a peristaltic pump 4, a monitoring component 10, an infusion tube group 7, a first infusion tube 72 and an infusion device 6, the culture dish 2 is placed in the culture box 1, one end of the first infusion tube 72 is connected to one end of the culture dish 2, the other end of the first infusion tube 72 passes through the side wall of the culture box 1 and is connected to the infusion device 6, one end of the infusion tube group 7 is connected to the infusion device 6, the other end of the infusion tube group 7 passes through the peristaltic pump 4 and the wall of the culture box 1 in sequence and is connected to the other end of the culture dish 2, and the monitoring component 10 is arranged on the infusion tube group 7.

[0039] In the above embodiment, it should be noted that a plurality of partitions 11 are arranged at intervals in the incubator 1, a door 12 is rotatably connected to the side of the incubator 1, two through holes are arranged on the side wall of the incubator 1, a sealing ring 13 is arranged in each through hole, and the sealing ring 13 is a rubber ring. The infusion tube group 7 and the first infusion tube 72 are respectively connected to the culture dish 2 through a through hole, one of the sealing rings 13 is sleeved on the infusion tube group 7 and has an interference fit with the infusion tube group 7, and the other sealing ring 13 is sleeved on the first infusion tube 72 and has an interference fit with the first infusion tube 72, and the infusion tube group 7 and the corresponding sealing ring 13 are secondary sealed by a sealing film; the first infusion tube 72 and the corresponding sealing ring 13 are secondary sealed by a sealing film; and the blood vessels to be cultured are placed in the culture dish 2.

[0040] It also includes a bracket 5 , and an infusion device 6 is suspended at the upper end of the bracket 5 . The height of the bracket 5 is higher than the height of the incubator 1 .

[0041] Incubator 1 is a carbon dioxide incubator.

[0042] A throttle valve 41 is provided on the infusion tube set 7 and is located at the outlet of the peristaltic pump 4 to achieve precise control of the pressure and flow of the culture medium.

[0043] The technical effect achieved by the above embodiment is: the device provides a power source for the flow of the culture medium used for culturing blood vessels through the peristaltic pump 4, simulates the blood pressure and blood flow rate in the human body to control the pressure on the culture medium and the flow rate of the culture medium, and realizes precise control of the flow rate and pressure of the culture medium, simulates the internal environment of the human body, and ensures that the culture medium is cultured in a sterile environment through the setting of the incubator 1, providing strong support for the study of culture vessel restenosis.

[0044] Optional, such as Figures 1 to 4 and Figure 7 , Fig.10 and Figure 1 As shown, the monitoring component 10 includes a flow sensor 8 , and the flow sensor 8 is sleeved on the infusion tube set 7 .

[0045] In the above optional embodiment, it should be noted that the infusion tube set 7 and the first infusion tube 72 are both made of transparent soft tubes.

[0046] The beneficial effects of the above optional embodiments are: the flow rate of the culture medium in the infusion tube group 7 can be monitored in real time through the flow sensor 8, so that the peristaltic pump 4 can adjust the flow rate and flow rate of the culture medium in real time according to the flow rate of the culture medium monitored by the flow sensor 8, thereby realizing the precise adjustment of the flow rate of the culture medium according to the actual situation of the human body.

[0047] Optional, such as Fig.10 As shown, the flow sensor 8 includes a micro piezoelectric ultrasonic sensor chip 82 and a sensor housing 81 . The sensor housing 81 is sleeved on the infusion tube set 7 , and the micro piezoelectric ultrasonic sensor chip 82 is disposed in the sensor housing 81 .

[0048] In the above optional embodiment, it should be noted that two micro piezoelectric ultrasonic sensor chips 82 are spaced apart in the sensor housing 81, and the two micro piezoelectric ultrasonic sensor chips 82 are relatively arranged on both sides of the infusion tube group 7 and the distance between one micro piezoelectric ultrasonic sensor chip 82 and the incubator 1 is greater than the distance between the other micro piezoelectric ultrasonic sensor chip 82 and the incubator 1.

[0049] The beneficial effect of the above optional embodiment is: the fluid velocity is directly calculated by measuring the time difference between the downstream and upstream propagation of ultrasonic waves through the coordinated setting of two miniature piezoelectric ultrasonic sensor chips 82, which is suitable for low flow rate conditions and can detect tiny time changes, thereby achieving accurate measurement.

[0050] Optional, such as Fig.11As shown, the micro piezoelectric ultrasonic sensor chip 82 includes an insulating sheet 821, a piezoelectric layer 824, a top electrode layer 825 and a bottom electrode layer 826, the piezoelectric layer 824 is arranged between the top electrode layer 825 and the bottom electrode layer 826, the bottom electrode layer 826 is arranged between the piezoelectric layer 824 and the insulating sheet 821, and the top electrode layer 825 is arranged opposite to the side wall of the infusion tube group 7.

[0051] The micro piezoelectric ultrasonic sensor chip 82 further includes a buffer layer 823 and an insulating layer 822 . The buffer layer 823 is disposed between the insulating sheet 821 and the piezoelectric layer 824 . The insulating layer 822 is disposed on the insulating sheet 821 .

[0052] The beneficial effect of the above optional embodiment is that electrical isolation and insulation are achieved through the provision of the insulating layer 822 .

[0053] Optional, such as Figures 1 to 4 and Figure 7 As shown, the monitoring component 10 also includes a pressure sensor 9 , which is connected in parallel to the infusion tube group 7 or the first infusion tube 72 .

[0054] In the above optional embodiment, it should be noted that the pressure sensor 9 is connected in parallel with the infusion tube 7 or the first infusion tube 72 via a hose.

[0055] The beneficial effect of the above optional embodiment is that real-time monitoring of the culture medium pressure is achieved through the provision of the pressure sensor 9.

[0056] Optional, such as Figures 1 to 4 As shown, the infusion device 6 includes a pressurized bag 61 and a liquid bag 62. The pressurized bag 61 is sleeved on the liquid bag 62. The end of the first infusion tube 72 away from the culture dish 2 is connected to the liquid bag 62, and the end of the infusion tube group 7 away from the culture dish 2 is connected to the liquid bag 62.

[0057] In the above optional embodiment, it should be noted that the infusion device 6 also includes an air bag 63, and the air bag 63 is connected to the pressurized bag 61 through a hose.

[0058] The beneficial effect of the above optional embodiment is that the culture medium can be quickly and reliably injected into the culture dish 2 by applying pressure to the liquid bag 62 through the pressurized bag 61 .

[0059] Optional, such as Figures 1 to 4 As shown, the infusion tube group 7 includes a second infusion tube 73, a Luer connector 71 and a third infusion tube 74. One end of the second infusion tube 73 passes through the side wall of the incubator 1 and is connected to the culture dish 2. The other end of the second infusion tube 73 is connected to one end of the third infusion tube 74 through the Luer connector 71. The other end of the third infusion tube 74 passes through the peristaltic pump 4 and is connected to the infusion device 6.

[0060] In the above optional embodiment, it should be noted that the first infusion tube 72 and the third infusion tube 74 are both connected to the liquid bag 62 through the Luer connector 71.

[0061] The beneficial effect of the above optional embodiment is: through the setting of the Luer connector 71, alcohol can be injected into the second infusion tube 73 and the third infusion tube 74 through the Luer connector 71 when the device is not in use, thereby ensuring the sterile culture of the device.

[0062] Optional, such as Figures 1 to 4 As shown, the controller 3 is also included, and the peristaltic pump 4, the pressure sensor 9 and the flow sensor 8 are all electrically connected to the controller 3.

[0063] In the above optional embodiment, it should be noted that the throttle valve 41 and the incubator 1 are also electrically connected to the controller 3 .

[0064] According to an embodiment of the second aspect of the present invention, a vascular perfusion culture method is provided, which uses all the technical features of the embodiment of the first aspect of the present invention, and in addition, further comprises the following steps: Step S100: starting the incubator 1, and using the pressurized bag 61 to inject the culture medium in the liquid bag 62 into the culture dish 2 in the incubator 1 through the first infusion tube 72; Step S200: starting the peristaltic pump 4 so that the culture medium forms a dynamic flow in the culture dish 2, the first infusion tube 72, the second infusion tube 73, the third infusion tube 74 and the liquid bag 62; Step S300: using the pressure sensor 9 and the flow sensor 8 to monitor the culture medium flow and culture medium pressure in real time and feed back to the controller 3; Step S400: adjusting the peristaltic pump 4 according to the culture medium flow rate and the culture medium pressure to simulate human blood pressure to provide pressure to the culture medium; Step S500: Cultivation is completed.

[0065] In the above optional embodiment, it should be noted that, in step S300, the method for manufacturing the flow sensor 8 is to install the micro piezoelectric ultrasonic sensor chip 82 on two opposite sides of the sensor housing 1 respectively; the method for manufacturing the micro piezoelectric ultrasonic sensor chip 82 includes the following steps: First, select SOI insulating sheet 821 as the substrate. The thickness of the top silicon layer of the SOI insulating sheet is 5 microns. Clean the surface of the SOI insulating sheet 821 to ensure that there is no dust, oil or other impurities on the surface of the SOI insulating sheet 821, so as to provide a clean environment for the subsequent deposition of thin films.

[0066] Second, a 100-nanometer-thick SiO2 insulating layer 822 is grown on the SOI insulating sheet 821 by thermal oxidation technology to achieve electrical isolation.

[0067] Third, by using magnetron sputtering technology, a Pt / Ti composite layer with a thickness of 100 nanometers is sputtered on the SiO2 insulating layer 822 as the bottom electrode layer 826, wherein the Ti layer serves as an adhesion layer between the SiO2 insulating layer 822 and the Pt layer.

[0068] Fourth, in order to better control the growth direction of the PZT piezoelectric layer 824 thin film, a LNO material with a thickness of 20 nanometers is grown on the surface of the bottom electrode layer 826 as a buffer layer 823 .

[0069] Fifth, a PZT piezoelectric layer 824 with a thickness of 1 micron is sputtered using magnetron sputtering technology.

[0070] Sixth, wet etching is used to expose the bottom electrode pad area by etching the PZT piezoelectric layer 824.

[0071] Seventh, the SOI insulating film 821 substrate is mechanically thinned to 350 microns by chemical mechanical polishing technology.

[0072] Eighth, a 250-nanometer Au / Cr top electrode layer 825 is magnetron sputtered on the PZT piezoelectric layer 824 , and then the top electrode layer 825 is photolithographically patterned.

[0073] Ninth, the silicon substrate is completely etched through DRIE deep silicon etching technology. The SiO2 insulating layer 822 in the middle of the SOI insulating sheet 821 is a self-stop layer. Finally, the resin is removed to form a PMUTs, i.e., a micro piezoelectric ultrasonic sensor chip 82 vibration cavity.

[0074] In the process of processing the PMUTs micro piezoelectric ultrasonic sensor chip 82, the mask is mainly used as a carrier of graphic information. Through the exposure process, the graphic is transferred to the exposed product, thereby realizing the transfer of the graphic. The design and manufacture of the mask have an important impact on the performance of the PMUTs micro piezoelectric ultrasonic sensor chip 82. In the design process of the mask, it is necessary to comprehensively consider factors such as the performance requirements of the PMUTs micro piezoelectric ultrasonic sensor chip 82, the feasibility of the manufacturing process, and the cost, so as to ensure the quality and production efficiency of the processed PMUTs micro piezoelectric ultrasonic sensor chip 82. According to the designed PMUTs micro piezoelectric ultrasonic sensor chip 82 preparation process, the entire processing process requires three layouts, namely, the photomask Bottome, the photomask Tope, and the photomask Cavity.

[0075] The flow monitoring method of the flow sensor 8 is to use the time-of-flight method to perform ultrasonic flow detection of low-flow flexible small pipes, mainly because it has the advantages of simple measurement principle, high precision, strong anti-interference ability, good real-time performance, easy integration and cost-effectiveness. This method directly calculates the fluid velocity by measuring the time difference between the propagation of ultrasonic waves in the downstream and upstream. It is suitable for low flow rates and can detect small time changes, thereby achieving accurate measurement. In addition, the time-of-flight method has good adaptability to the flexibility and size changes of the pipeline and is easy to maintain, making it an ideal choice for flow detection in low-flow flexible small pipes. The measurement principle of the time-of-flight method: the propagation speed of ultrasonic waves in the fluid is affected by the flow velocity of the fluid, that is, its actual propagation speed is the vector sum of the original sound velocity of the ultrasonic wave in the fluid and the flow velocity of the fluid itself. Therefore, the ultrasonic propagation time will be different when downstream and upstream. By measuring the flight time difference of the ultrasonic wave under the two propagation modes, the fluid flow velocity and flow rate can be further obtained.

[0076] When using the flow sensor 8 to monitor the flow rate, one of the micro piezoelectric ultrasonic sensor chips 82 first emits a sound wave under an excitation voltage pulse, and the other micro piezoelectric ultrasonic sensor chip 82 receives the sound wave, and the transmission time of the ultrasonic wave propagating downstream is t+. Then, the ultrasonic wave receiving the sound wave is emitted by the micro piezoelectric ultrasonic sensor chip 82, and the micro piezoelectric ultrasonic sensor chip 82 that emits the sound wave receives it, and the transmission time of the ultrasonic wave propagating upstream is t_. The time difference between upstream and downstream is calculated as: in, is the inner diameter of the pipe, is the refraction angle of ultrasound from the steel pipe into the water, is the flow rate of the fluid in the pipe, is the speed of sound. The flow rate of the fluid in the pipe is very small compared to the speed of sound. can be ignored, and after simplification, the propagation time difference can be expressed as: After obtaining the ultrasonic propagation time difference under forward and reverse flow, the flow velocity of the fluid in the tube can be obtained by inverse solution of the time difference: The propagation speed of ultrasound in the fluid in the tube can be considered constant under certain temperature and pressure, so the flow rate of the fluid in the tube can be seen from the above formula: The ultrasonic propagation time difference between forward and reverse flow Proportional, as long as you get The flow rate of the fluid in the tube can be obtained.

[0077] The beneficial effect of the above embodiment is that accurate control of the flow rate and pressure of the culture medium is achieved.

[0078] The above is only a preferred specific embodiment of the present invention, but the protection scope of the present invention is not limited thereto. Any changes or substitutions that can be easily thought of by a person skilled in the art within the technical scope disclosed by the present invention should be included in the protection scope of the present invention. Therefore, the protection scope of the present invention shall be subject to the protection scope of the claims.

Claims

1. A vascular perfusion culture device, characterized in that: The invention comprises a culture box (1), a culture dish (2), a peristaltic pump (4), a monitoring component (10), an infusion tube group (7), a first infusion tube (72) and an infusion device (6), wherein the culture dish (2) is placed in the culture box (1), one end of the first infusion tube (72) is connected to one end of the culture dish (2), the other end of the first infusion tube (72) passes through the side wall of the culture box (1) and is connected to the infusion device (6), one end of the infusion tube group (7) is connected to the infusion device (6), the other end of the infusion tube group (7) passes through the peristaltic pump (4) and the wall of the culture box (1) in sequence and is connected to the other end of the culture dish (2), and the monitoring component (10) is arranged on the infusion tube group (7).

2. The vascular perfusion culture device according to claim 1, characterized in that: The monitoring component (10) comprises a flow sensor (8), and the flow sensor (8) is sleeved on the infusion tube set (7).

3. The vascular perfusion culture device according to claim 2, characterized in that: The flow sensor (8) comprises a micro piezoelectric ultrasonic sensor chip (82) and a sensor housing (81); the sensor housing (81) is sleeved on the infusion tube set (7); and the micro piezoelectric ultrasonic sensor chip (82) is arranged in the sensor housing (81).

4. The vascular perfusion culture device according to claim 3, characterized in that: The micro piezoelectric ultrasonic sensor chip (82) comprises an insulating sheet (821), a piezoelectric layer (824), a top electrode layer (825) and a bottom electrode layer (826); the piezoelectric layer (824) is arranged between the top electrode layer (825) and the bottom electrode layer (826); the bottom electrode layer (826) is arranged between the piezoelectric layer (824) and the insulating sheet (821); and the top electrode layer (825) is arranged opposite to a side wall of the infusion tube assembly (7).

5. The vascular perfusion culture device according to claim 4, characterized in that: The micro piezoelectric ultrasonic sensor chip (82) further comprises a buffer layer (823) and an insulating layer (822); the buffer layer (823) is arranged between the insulating sheet (821) and the piezoelectric layer (824); and the insulating layer (822) is arranged on the insulating sheet (821).

6. The vascular perfusion culture device according to any one of claims 2 to 5, characterized in that: The monitoring assembly (10) further comprises a pressure sensor (9), wherein the pressure sensor (9) is connected in parallel to the infusion tube set (7) or the first infusion tube (72).

7. The vascular perfusion culture device according to claim 1, characterized in that: The infusion device (6) comprises a pressurized bag (61) and a liquid bag (62), wherein the pressurized bag (61) is sleeved on the liquid bag (62), and an end of the first infusion tube (72) facing away from the culture dish (2) is connected to the liquid bag (62) and an end of the infusion tube set (7) facing away from the culture dish (2) is connected to the liquid bag (62).

8. The vascular perfusion culture device according to claim 1, characterized in that: The infusion tube set (7) comprises a second infusion tube (73), a Luer connector (71) and a third infusion tube (74); one end of the second infusion tube (73) passes through the side wall of the incubator (1) to be connected to the culture dish (2); the other end of the second infusion tube (73) is connected to one end of the third infusion tube (74) via the Luer connector (71); and the other end of the third infusion tube (74) passes through the peristaltic pump (4) to be connected to the infusion device (6).

9. The vascular perfusion culture device according to claim 6, characterized in that: It also includes a controller (3), and the peristaltic pump (4), the pressure sensor (9) and the flow sensor (8) are all electrically connected to the controller (3).

10. A vascular perfusion culture method, characterized in that: Using the vascular perfusion culture device according to any one of claims 1 to 9, in addition, it also includes the following steps: Step S100: starting the incubator (1), and using the pressurized bag (61) to inject the culture medium in the liquid bag (62) into the culture dish (2) in the incubator (1) through the first infusion tube (72); Step S200: starting the peristaltic pump (4) so ​​that the culture medium forms a dynamic flow in the culture dish (2), the first infusion tube (72), the second infusion tube (73), the third infusion tube (74) and the liquid bag (62); Step S300: using a pressure sensor (9) and a flow sensor (8) to monitor the culture medium flow and culture medium pressure in real time and feed back to the controller (3); Step S400: adjusting the peristaltic pump (4) according to the culture medium flow rate and culture medium pressure to simulate human blood pressure to provide pressure to the culture medium; Step S500: Cultivation is completed.

Images