Intelligent tear film bionic generator

Abstract

The present application relates to a kind of intelligent tear film biomimetic generator, including generator body, the generator body includes upper body and lower body, the upper body is provided with upper chamber, lower body is provided with lower chamber, the membrane structure is sealingly arranged between the lower chamber and upper chamber, the lower chamber is provided with the culture solution flow circulation system for adjusting the pressure in lower chamber, so that the corneal shape of tissue engineering cornea is formed and is raised upwards, the upper chamber is provided with the drop intelligent dispersion system simulating tear film rupture.The present application is used by the combination of drop intelligent dispersion system and culture solution flow circulation system, for the first time realizes the simulation of tear film generation this physiological process, to realize the physiological environment of overall simulation corneal surface, it provides the possibility for the proliferation cultivation cornea related cell, and by data control analysis and summary, for improving the quality of tissue engineering cornea provides reliable guarantee.The present application can also be used for the research of tear film related physiology and pathophysiology mechanism.

Description

Technical Field

[0001] The present invention belongs to the field of cell culture apparatus, and in particular relates to an intelligent tear film bionic generator. Background Art

[0002] The eyeball is an organ with intraocular pressure, which is crucial for embryonic development and homeostasis. Furthermore, the intraocular environment is a fluid environment, and hydrostatic pressure also promotes the growth of cells such as the corneal endothelium. Currently, there is no culture device that can simultaneously simulate both intraocular and hydrostatic pressures in vitro. This makes it impossible to simultaneously provide mechanical pressure similar to that of intraocular pressure to corneal stromal and endothelial cells, maintain their properties, promote extracellular matrix production, and improve the transparency and biomechanical parameters of tissue-engineered corneas. More importantly, existing technologies lack detailed simulation and analysis of the mechanisms and physiological changes associated with tear film formation, making it impossible to quantify the impact of this inevitable state on corneal quality. This hinders in-depth research into the corneal physiological environment and, consequently, further improvements in the quality of artificial corneas.

[0003] In response to the above technical problems, it is necessary to improve the existing bioreactor so that it can simulate the physiological phenomenon of tear film rupture, truly simulate the physiological environment of corneal epithelial cells, stromal cells and endothelial cells, and provide a quantitative basis for improving the quality of tissue-engineered corneas. Summary of the Invention

[0004] In view of this, the purpose of the present invention is to provide an intelligent tear film bionic generator with the function of intelligently controlling the simulation of tear film rupture and comprehensively simulating the corneal physiological environment, thereby solving the problem that the existing technology cannot provide the tear film generation function.

[0005] The purpose of the present invention is achieved through the following technical solutions:

[0006] The intelligent tear film bionic generator includes a reactor body, which includes an upper body and a lower body. The upper body is provided with an upper chamber, and the lower body is provided with a lower chamber. An amniotic membrane is sealed between the lower chamber and the upper chamber. A culture fluid flow circulation system is provided in the lower chamber for adjusting the internal pressure of the lower chamber so that the amniotic membrane bulges upward to form a corneal shape. A drop intelligent diffusion system that simulates tear film rupture is provided above the upper chamber.

[0007] Furthermore, the intelligent droplet diffusion system includes a driving mechanism, a droplet tank, a droplet head, a droplet forming mechanism and a control system. The driving mechanism includes a left-right movable push rod fixed in the upper chamber and a forward-backward movable push rod fixed on the telescopic rod of the left-right movable push rod. The droplet tank is fixed on the telescopic rod of the forward-backward movable push rod. The droplet head is fixed below the tear liquid tank. The droplet forming mechanism includes a liquid separation rod and a liquid separation driver. The circumferential surface of the liquid separation rod at the same height is provided with a plurality of concave grooves for accommodating drops. The liquid separation driver includes a servo rotary motor. The servo rotary motor is fixed on the drip tank, the driving wheel is fixed on the main shaft of the servo rotary motor, and the driven wheel is fixed on the other end of the liquid separation rod located in the concave groove, meshing with the driving wheel for transmission, driving the liquid separation rod to rotate. The control system includes a high-definition scanner and a processing chip. The high-definition scanner is used to image the amniotic membrane morphology and transmit the data to the processing chip. The processing chip filters out the highest position area according to the data, determines the spatial position coordinates of the area, and then moves the center of the drip head to the coordinate position.

[0008] Furthermore, the culture fluid circulation system includes a culture fluid storage tank and a culture fluid inflow passage and a culture fluid outflow passage connected to the culture fluid storage tank, and the culture fluid outflow passage is provided with a micro-pressure regulator.

[0009] Furthermore, the micro-pressure regulator includes a lifting push rod arranged on the side of the reactor body, the lifting push rod is provided with a pipeline fixing groove for fixing the culture fluid outflow passage, and the telescopic rod of the lifting push rod is provided with scale lines and text marks for displaying the height position of the pipeline fixing groove.

[0010] Furthermore, the culture fluid flow circulation system also includes a pressure sensor, which is used to detect the pressure of the lower chamber and is electrically connected to the processing chip.

[0011] Furthermore, the reactor body is made of transparent material.

[0012] Furthermore, the upper body is provided with a boss, the lower body is provided with a groove matching the boss, and a sealing gasket is provided between the boss and the groove.

[0013] The beneficial effects of the present invention are:

[0014] The present invention uses an intelligent drop diffusion system to disperse drops of liquid drop by drop onto the membrane structure below. The drops slowly diffuse on the upper surface of the amniotic membrane, thereby creating a scene where the tear film ruptures and tears soak the corneal surface. The system can be intelligently controlled and can intelligently identify the highest point of the amniotic membrane, so that the drops can be dripped from the highest point and distributed more evenly to the entire amniotic membrane surface, thereby more realistically simulating the situation of tears diffusing on the corneal surface. Furthermore, the present invention also constructs a micro-pressure adjustable culture chamber through a culture fluid flow circulation system, so that the intraocular pressure can be adjusted, thereby simulating different intraocular pressure levels, which provides the possibility of studying the dynamic impact of intraocular pressure on the physiological environment of corneal endothelial cells and finding better parameterization.

[0015] In summary, the present invention, through the combined use of the intelligent drop diffusion system and the culture fluid flow circulation system, has for the first time achieved the simulation of the physiological phenomenon of tear film rupture, thereby achieving a comprehensive simulation of the physiological environment of the cornea, providing the possibility for a comprehensive analysis of the proliferation and cultivation of corneal-related cells, and through digital control analysis and summary, it has accelerated the quantification and progress of the research, which will surely provide reliable guarantees for the quality of artificial corneas.

[0016] Other advantages, objects, and features of the present invention will be described in part in the following description and, in part, will be apparent to those skilled in the art upon examination of the following description or may be learned from practice of the present invention. The objects and other advantages of the present invention may be realized and obtained through the following description. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] In order to make the purpose, technical solutions and advantages of the present invention more clear, the present invention will be further described in detail below with reference to the accompanying drawings, in which:

[0018] Figure 1 It is the front view of the present invention;

[0019] Figure 2 is a cross-sectional view of the present invention;

[0020] Figure 3 for Figure 2 Cross-sectional view along AA direction;

[0021] Figure 4 is a cross-sectional view of a droplet forming mechanism;

[0022] Figure 5 It is the main view of the dispensing rod;

[0023] Figure 6 is a control diagram of the present invention;

[0024] Figure 7 Schematic diagram of the control system.

[0025] Description of reference numerals:

[0026] 1-upper body; 2-lower body; 3-upper chamber; 4-lower chamber; 5-amniotic membrane; 6-culture fluid flow circulation system; 7-drip intelligent diffusion system; 8-drip tank; 9-drip head; 10-control system; 11-left and right moving push rod; 12-forward and backward moving push rod; 13-dispensing rod; 14-concave groove; 15-servo rotary motor; 16-driving wheel; 17-driven wheel; 18-high-definition scanner; 19-processing chip; 20-display; 21-culture fluid inflow passage; 22-culture fluid outflow passage; 23-lifting push rod; 24-pipeline fixing groove; 25-boss; 26-groove; 27-loading and unloading port; 28-sealing cover; 29-sealing gasket; 30-pressure sensor. DETAILED DESCRIPTION

[0027] The preferred embodiments of the present invention will be described in detail below with reference to the accompanying drawings. It should be understood that the preferred embodiments are only for illustrating the present invention and are not intended to limit the scope of protection of the present invention.

[0028] like Figure 1-7 As shown, the intelligent tear film bionic generator includes a reactor body, which includes an upper body 1 and a lower body 2. The upper body is provided with an upper chamber 3, and the lower body is provided with a lower chamber 4. An amniotic membrane 5 is sealed between the lower chamber and the upper chamber, so that the upper and lower chambers are completely independent. A culture fluid flow circulation system 6 is provided in the lower chamber for adjusting the internal pressure of the lower chamber so that the amniotic membrane bulges upward to form a corneal shape, which can make the lower surface of the amniotic membrane withstand internal pressure and simulate the physiological state of the inner surface of the cornea. A drop intelligent diffusion system 7 simulating the rupture of the tear film is provided above the upper chamber, which can make the upper surface of the amniotic membrane diffuse on the surface of the cornea after the tear film ruptures, so that the amniotic membrane has a real physiological environment with internal and external pressure, providing a real physical environment for cell culture and providing a basis for parameterized research on artificial corneas.

[0029] In particular, the droplet intelligent dispersion system of the embodiment includes a driving mechanism, a droplet tank 8, a droplet head 9, a droplet forming mechanism, and a control system 10. The driving mechanism includes a left-right moving push rod 11 fixed in the upper chamber and a front-back moving push rod 12 fixed on the telescopic rod of the left-right moving push rod. The droplet tank is fixed on the telescopic rod of the front-back moving push rod. The droplet head is fixed below the tear liquid tank. The space position of the droplet head is adjusted by moving the driving mechanism forward and backward and left and right. The droplet forming mechanism includes a distribution rod 13 and a distribution driver. The circumferential surface of the distribution rod at the same height is provided with a plurality of concave grooves 14 for accommodating droplets. The distribution driver includes a servo rotary motor 15, a driving wheel 16, and a driven wheel 17. The servo rotary motor is fixed on the droplet tank. The driving wheel is detachably fixed on the main shaft of the servo rotary motor. The driven wheel is detachably fixed at the other end of the distribution rod located in the concave groove and is in meshing transmission with the driving wheel to drive the distribution rod to rotate. When the droplet in the concave groove is downward, the droplet flows out of the concave groove under the action of gravity. The distribution rod is horizontally arranged in the droplet channel. The outflowing droplet enters the droplet channel and finally flows out of the amniotic membrane surface through the droplet channel. The control system includes a high-definition scanner 18, a processing chip 19, and a display 20. The processing chip is in electrical communication with the high-definition scanner, the left-right moving push rod, the front-back moving push rod, and the servo rotary motor for driving control.

[0030] The specific control process is as follows:

[0031] When the amniotic membrane is deformed under the pressure of the lower chamber culture solution and its shape is fixed, the high-definition scanner is started to perform full-surface scanning on the external shape of the amniotic membrane to form three-dimensional data. The data are transmitted to the processing chip. The processing chip selects the highest position according to the data and determines the spatial coordinates of the position. The spatial coordinates mainly consider the values in the front-back and horizontal directions. The moving values of the left-right moving push rod and the front-back moving push rod are calculated according to the values in the front-back and horizontal directions, and the center of the droplet head is adjusted to the position.

[0032] When it is necessary to simulate the tear film rupture to perform droplet operation, the rotation radian value of the distribution rod is determined according to the number of the concave grooves on the distribution rod. Then, the servo rotary motor is controlled to rotate the same radian value by pre-setting the program in the processing chip, so as to complete one droplet. Of course, the distribution rod can be rotated multiple times to realize multiple continuous droplet operations when necessary.

[0033] Since the process can be automatically completed by the design program, the intelligent control of the tear film rupture process is realized, the blank of the unachievable physiological phenomenon of the tear film rupture is filled, the construction quality of the tissue-engineered cornea is improved, and the analysis and induction are more scientific through the data of the control and results, so as to realize the data controllable tissue-engineered cornea construction process.

[0034] The number of concave grooves of the liquid distribution rod is not limited, and is usually 2-6, and in the embodiment, the number is 4. The 4 concave grooves are uniformly distributed, and the included angle between any adjacent concave grooves is 90 degrees.

[0035] The droplet in the embodiment can be various culture solutions, medicinal solutions, and the like.

[0036] In the embodiment, the culture solution flow circulation system comprises a culture solution storage tank, a culture solution inflow passage 21, and a culture solution outflow passage 22 which are arranged in communication with the culture solution storage tank. The culture solution outflow passage is provided with a micro-pressure regulator. The pressure of the culture solution in the lower chamber can be adjusted to a predetermined value.

[0037] In the embodiment, the micro-pressure regulator comprises a lifting push rod 23 arranged on the side of the reactor body. The lifting push rod is provided with a pipeline fixing groove 24 for fixing the culture solution outflow passage. The telescopic rod of the lifting push rod is provided with scale lines and text marks for displaying the height position of the pipeline fixing groove. The height of the pipeline fixing groove is adjusted by the lifting push rod, so as to adjust the outlet pressure, change the internal pressure of the culture solution, change the pressure acting on the amniotic membrane surface, and realize different static pressure levels.

[0038] In the embodiment, the culture solution flow circulation system further comprises a pressure sensor 30 for detecting the pressure of the lower chamber and electrically connected with the processing chip. The processing chip determines the internal pressure data through the pressure sensor, and sends an adjusting instruction to the lifting push rod when the lifting push rod is electrically connected, so as to change the internal pressure.

[0039] In the embodiment, the reactor body is made of transparent materials such as glass and plastic. The internal components can be observed, and the shape of the amniotic membrane and the cell proliferation state can also be observed.

[0040] In the embodiment, the upper body is provided with a boss 25, the lower body is provided with a groove 26 matched with the boss, and a sealing gasket 29 is arranged between the boss and the groove. The upper and lower chambers are further sealed by the sealing gasket, so that the upper and lower surfaces of the amniotic membrane are completely isolated to form respective physiological environments.

[0041] In the embodiment, a loading and unloading port 27 is arranged above the upper chamber, and the driving mechanism can be installed and debugged. A sealing cover 28 is arranged above the loading and unloading port, and the upper chamber can be sealed by the sealing cover.

[0042] In the embodiment, a display is arranged outside the reactor body. The display can display the internal pressure, the scanner imaging, and the positions of the push rods in real time, and can also be operated and controlled through the display to replace the program control.

[0043] In this embodiment, the upper body and the lower body are connected and fixed by screws, so that the two can form a whole, and the fixing effect of the sealing gasket is increased, thereby enhancing the sealing level.

[0044] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not limiting. Although the present invention has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that the technical solutions of the present invention can be modified or replaced by equivalents without departing from the purpose and scope of the technical solutions, which should all be included in the scope of the claims of the present invention.

Claims

1. An intelligent tear film bionic generator, comprising a generator body, characterized in that: The generator body includes an upper body and a lower body, the upper body is provided with an upper chamber, the lower body is provided with a lower chamber, a membrane structure is sealed between the lower chamber and the upper chamber, the lower chamber is provided with a liquid flow circulation system for adjusting the internal pressure of the lower chamber so that the membrane structure bulges upward to form a liquid flow circulation system similar to the physiological state of the cornea, and a droplet intelligent diffusion system simulating tear film rupture is provided above the upper chamber. The droplet intelligent diffusion system includes a driving mechanism, a droplet tank, a droplet head, a droplet forming mechanism and a control system. The driving mechanism includes a left and right moving push rod fixed in the upper chamber and a forward and backward moving push rod fixed on the telescopic rod of the left and right moving push rod. The droplet tank is fixed on the telescopic rod of the forward and backward moving push rod, and the droplet head is fixed at the bottom of the tear tank. The drop forming mechanism includes a liquid separating rod and a liquid separating driver. The circumferential surface of the liquid separating rod at the same height is provided with a plurality of concave grooves for accommodating liquid drops. The liquid separating driver includes a servo rotating motor, a driving wheel and a driven wheel. The servo rotating motor is fixed on the liquid dropping box, the driving wheel is fixed on the main shaft of the servo rotating motor, and the driven wheel is fixed on the other end of the liquid separating rod located in the concave groove, meshing with the driving wheel for transmission, driving the liquid separating rod to rotate. The control system includes a high-definition scanner and a processing chip. The high-definition scanner is used to scan and image the amniotic membrane morphology and transmit the data to the processing chip. The processing chip filters out the highest position according to the data, determines the coordinate value of the position, and then moves the center of the drop head to the coordinate position.

2. The intelligent tear film bionic generator according to claim 1, characterized in that: The liquid flow circulation system comprises a culture solution storage tank and a culture solution inflow passage and a culture solution outflow passage which are connected to the culture solution storage tank. The culture solution outflow passage is provided with a micro-pressure regulator.

3. The intelligent tear film bionic generator according to claim 2, characterized in that: The micro-pressure regulator includes a lifting push rod arranged on the side of the generator body, the lifting push rod is provided with a pipeline fixing groove for fixing the culture fluid outflow passage, and the telescopic rod of the lifting push rod is provided with scale lines and text marks for displaying the height position of the pipeline fixing groove.

4. The intelligent tear film bionic generator according to claim 1, characterized in that: The liquid flow circulation system further includes a pressure sensor, which is used to detect the pressure of the lower chamber and is electrically connected to the processing chip.

5. The intelligent tear film bionic generator according to any one of claims 1 to 4, characterized in that: The generator body is made of transparent material.

6. The intelligent tear film bionic generator according to any one of claims 1 to 4, characterized in that: The upper body is provided with a boss, the lower body is provided with a groove matching the boss, and a sealing gasket is provided between the boss and the groove.

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