Intelligent tear film bionic generator

Abstract

The invention relates to an intelligent tear film bionic generator which comprises a generator body, the generator body comprises an upper body and a lower body, the upper body is provided with an upper cavity, the lower body is provided with a lower cavity, and a film structure is arranged between the lower cavity and the upper cavity in a sealed mode. The lower cavity is internally provided with a culture solution flow circulating system which is used for adjusting the inner pressure of the lower cavity to enable the tissue engineering cornea to protrude upwards to form a cornea shape, and an intelligent dropping liquid dispersion system for simulating tear film rupture is arranged above the upper cavity. Through combined use of the dropping liquid intelligent dispersion system and the culture solution flow circulation system, simulation of a physiological process of tear film generation is realized for the first time, so that comprehensive simulation of a physiological environment of a cornea surface is realized, possibility is provided for proliferation and cultivation of cornea related cells, and through datamation control analysis and summarization, the cornea growth rate is improved. And reliable guarantee is provided for improving the quality of the tissue engineering cornea. The method can also be used for researching physiological and pathophysiological mechanisms related to the tear film.

Description

Technical Field

[0001] The 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 very important for the embryonic development and homeostasis of the eyeball. The eye is a liquid environment, and hydrostatic pressure also promotes cells such as the corneal endothelium. Currently, there is no culture equipment that can simulate both intraocular pressure and hydrostatic pressure in vitro, and it is impossible to provide mechanical pressure similar to intraocular pressure for corneal stromal cells and endothelial cells at the same time, maintain the characteristics of corneal stromal cells and endothelial cells, promote the production of extracellular matrix, and improve the transparency and biomechanical parameters of tissue-engineered corneas. More importantly, the existing technology does not simulate and analyze the mechanism and physiological changes of the tear film in detail, and cannot quantify the impact of this inevitable state on corneal quality, which restricts in-depth research on the corneal physiological environment, and also restricts the further improvement of the quality of artificial corneas.

[0003] In view of the above technical problems, it is necessary to improve the existing bioreactor so that it can simulate the physiological phenomenon of tear film rupture and truly simulate the physiological environment of corneal epithelial cells, stromal cells and endothelial cells, providing 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, which has the functions of intelligently controlling the simulation of tear film rupture and comprehensively simulating the corneal physiological environment, thereby solving the problem that the prior art cannot provide the tear film generation function.

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

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

[0007] Furthermore, the liquid drop intelligent diffusion system includes a driving mechanism, a liquid drop tank, a liquid drop head, a liquid drop forming mechanism and a control system, wherein the driving mechanism includes a left-right movable push rod fixed in the upper chamber and a forward-and-backward movable push rod fixed on a telescopic rod of the left-and-right movable push rod, the liquid drop tank is fixed on the telescopic rod of the forward-and-backward movable push rod, the liquid drop head is fixed below the tear liquid tank, the liquid drop forming mechanism includes a liquid separation rod and a liquid separation driver, the liquid separation rod is provided with a plurality of concave grooves for accommodating liquid drops on a circumferential surface at the same height, and the liquid separation driver includes a servo rotary motor The servo rotary motor is fixed on the drip box, 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, and 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 solution flow circulation system includes a culture solution storage box and a culture solution inflow passage and a culture solution outflow passage connected to the culture solution storage box, and the culture solution 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 can use the intelligent liquid drop diffusion system to disperse the liquid drops drop by drop onto the membrane structure below, and the liquid drops slowly diffuse on the upper surface of the amniotic membrane, thereby constructing a scene in which the tear film ruptures and the 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 liquid drops are dripped from the highest point and more evenly distributed on the entire amniotic membrane surface, thereby more realistically simulating the situation of tears diffusing 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 for studying the dynamic influence of intraocular pressure on the physiological environment of corneal endothelial cells and finding better parameterization.

[0015] In summary, the present invention realizes the simulation of the physiological phenomenon of tear film rupture for the first time through the combined use of the drop intelligent diffusion system and the culture fluid flow circulation system, thereby realizing 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, accelerating the quantification and progress of the research, which will certainly provide reliable guarantee for the quality of artificial corneas.

[0016] Other advantages, objectives and features of the present invention will be described in the following description to some extent, and to some extent, will be obvious to those skilled in the art based on the following examination and study, or can be guided by the practice of the present invention. The objectives and other advantages of the present invention can 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 a front view of the present invention;

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

[0020] Figure 3 for Figure 2 Section view along AA direction;

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

[0022] Figure 5 It is the front 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-front and back moving push rod; 13-liquid separation 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 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 invention, rather than for limiting the protection scope of the invention.

[0028] like Figure 1-7 As shown, the intelligent tear film bionic generator includes a reactor body, and the reactor body 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 bear the 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 in the physiological state of the corneal surface after the tear film ruptures, so that the tears on the upper surface of the amniotic membrane diffuse on the corneal surface, so that the amniotic membrane has a real physiological environment under the action of internal and external pressures, providing a real physical environment for cell culture and providing a basis for parameterized research on artificial corneas.

[0029] In particular, the liquid drop intelligent diffusion system of the present embodiment includes a driving mechanism, a liquid drop tank 8, a liquid drop head 9, a liquid drop forming mechanism and a control system 10, wherein the driving mechanism includes a left-right movable push rod 11 fixed in the upper chamber and a forward-backward movable push rod 12 fixed on the telescopic rod of the left-right movable push rod, the liquid drop tank is fixed on the telescopic rod of the forward-backward movable push rod, the liquid drop head is fixed under the tear tank, and the spatial position of the liquid drop head is adjusted by moving the driving mechanism forward and backward and left and right, the liquid drop forming mechanism includes a liquid separation rod 13 and a liquid separation driver, and the circumferential surface of the liquid separation rod at the same height is provided with a plurality of concave grooves 14 for accommodating liquid drops, and the liquid separation driver includes a servo rotary motor 15, a driving wheel 16 and driven wheel 17, the servo rotary motor is fixed on the drip box, the driving wheel is folded and fixed on the main shaft of the servo rotary motor, the driven wheel is folded and 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, when the liquid drops in the concave groove are downward, under the action of gravity, the liquid drops flow out of the concave groove, and the liquid separation rod is horizontally arranged in the drip channel, the outflowing liquid drops enter the drip channel, and finally flow out through the drip channel and fall on the surface of the amniotic membrane, the control system includes a high-definition scanner 18, a processing chip 19, and a display 20, the processing chip is electrically connected with the high-definition scanner, the left and right moving push rod, the front and back moving push rod and the servo rotary motor for drive control.

[0030] The specific control process is:

[0031] When the amniotic membrane is deformed under the pressure of the culture fluid in the lower cavity and its shape is fixed, the high-definition scanner is started to scan the entire surface of the external shape of the amniotic membrane to form three-dimensional data, and the data is transmitted to the processing chip. The processing chip selects the highest position based on the data and determines the spatial coordinates of the position. The spatial coordinates mainly consider the values ​​in the front and back and horizontal directions, and then calculates the movement values ​​of the left and right push rod and the front and back push rod based on the values ​​in the front and back and horizontal directions, and adjusts the center of the drip head to this position.

[0032] When it is necessary to simulate the tear film rupture and perform a dripping operation, the rotation arc value of the dispenser rod is determined according to the number of concave grooves on the dispenser rod, and then the servo rotation motor is controlled to rotate the same arc value through a preset program in the processing chip to complete a dripping operation. Of course, when necessary, it can be rotated multiple times to achieve multiple continuous dispersed dripping operations.

[0033] Since this process can be completed automatically using a design program, intelligent control of the tear film rupture process can be achieved, filling the gap that cannot be achieved by the physiological phenomenon of tear film rupture, improving the quality of tissue engineering corneal construction, and through the digitization of control and results, making analysis and induction more scientifically based, achieving data controllability of the tissue engineering corneal construction process.

[0034] The number of the concave grooves of the liquid dispensing rod is not limited, and can usually be 2-6. In this embodiment, there are 4 concave grooves, and the 4 concave grooves are evenly distributed, that is, the angle between any adjacent concave grooves is 90 degrees.

[0035] The dripping liquid in this embodiment can be various culture liquids, medical liquids, and other tear-like liquids.

[0036] In this embodiment, the culture fluid circulation system includes a culture fluid storage box and a culture fluid inflow passage 21 and a culture fluid outflow passage 22 connected to the culture fluid storage box, and the culture fluid outflow passage is provided with a micro-pressure regulator to adjust the culture fluid pressure in the lower chamber to reach a predetermined value.

[0037] In this embodiment, the micro-pressure regulator includes a lifting push rod 23 arranged on the side of the reactor body, and a pipeline fixing groove 24 for fixing the outflow passage of the culture solution is arranged on the lifting push rod, and a scale line and a text mark for indicating the height position of the pipeline fixing groove are arranged on the telescopic rod of the lifting push rod. The height of the pipeline fixing groove is adjusted by the lifting push rod, thereby adjusting the outlet pressure, so that the internal pressure of the culture solution is changed, and the pressure acting on the surface of the amniotic membrane changes, so as to achieve different static pressure levels.

[0038] In this embodiment, the culture fluid circulation system further includes a pressure sensor 30, which is used to detect the pressure of the lower chamber and is electrically connected to the processing chip. The processing chip determines the internal pressure data through the pressure sensor, and when electrically connected to the lifting push rod, it can issue an adjustment instruction to the lifting push rod, thereby changing the internal pressure.

[0039] In this embodiment, the reactor body is made of transparent materials such as glass and plastic, so that the internal actuators can be observed, and the morphology of the amniotic membrane and the cell proliferation state can also be observed.

[0040] In this 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 provided between the boss and the groove. The upper and lower chambers can be further sealed by the sealing gasket, so that the upper and lower surfaces of the amniotic membrane are completely isolated to form their own physiological environments.

[0041] In this embodiment, a loading and unloading port 27 is provided above the upper chamber, through which the drive mechanism can be installed and debugged, and a sealing cover 28 is provided above the loading and unloading port, through which the upper chamber can be sealed.

[0042] In this embodiment, a display is provided outside the reactor body, and the display can display the internal pressure, scanner imaging and the positions of each push rod in real time, and operation control can also be performed through the display instead of 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 solution of the present invention rather than to limit it. 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 solution of the present invention can be modified or replaced by equivalents without departing from the purpose and scope of the technical solution, which should 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 reactor 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 drop intelligent diffusion system simulating the rupture of tear film is provided above the upper chamber.

2. The intelligent tear film bionic generator according to claim 1, characterized in that: The liquid drop intelligent diffusion system includes a driving mechanism, a liquid drop box, a liquid drop head, a liquid drop forming mechanism and a control system. The driving mechanism includes a left-right movable push rod fixed in the upper chamber and a forward-and-backward movable push rod fixed on the telescopic rod of the left-and-right movable push rod. The liquid drop box is fixed on the telescopic rod of the forward-and-backward movable push rod. The liquid drop head is fixed below the tear liquid box. The liquid drop 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 liquid drops. The liquid separation driver includes a servo rotary motor, a driving wheel and a driven wheel. The servo rotary motor is fixed on the liquid drop box. The driving wheel is fixed on the main shaft of the servo rotary motor. The driven wheel is fixed on the other end of the liquid separation rod located in the concave groove, meshes with the driving wheel for transmission, and drives 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 scan and image the amniotic membrane morphology and transmit the data to the processing chip. The processing chip selects the highest position according to the data, determines the coordinate value of the position, and then moves the center of the liquid drop head to the coordinate position.

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

4. The intelligent tear film bionic generator according to claim 3, characterized in that: 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.

5. The intelligent tear film bionic generator according to claim 2, characterized in that: 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.

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

7. The intelligent tear film bionic generator according to any one of claims 1 to 5, 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.

Images