Cell 3D culture chip

Abstract

The utility model provides a cell 3D culture chip, which comprises a base and a plurality of groups of culture parts arranged in the base, the culture parts are filled with culture solution, each culture part comprises a culture cavity, at least one fluid cavity connected with the culture cavity and a culture channel communicated with the culture cavity and the fluid cavity, a sealing cover is arranged at the top of the culture cavity, and an opening communicated with the outside is formed in the top of the fluid cavity. According to the utility model, shear stress can be provided, so that an actual shear stress environment in the chip is closer to that of a human body, and the cell culture efficiency and culture quality are improved.

Description

TECHNICAL FIELD

[0001] The utility model relates to the field of biology technique, concretely relates to a cell 3D culture chip. BACKGROUND

[0002] Cell 3D culture and organoid culture technology has important implications in studying cell behavior and disease mechanism. Cell 3D culture and organoid culture often need to reproduce various physical, chemical and biological factors that cells face in the body in vitro as much as possible to create an environment closer to the physiological state, so as to more accurately study the behavior, morphology, structure and function of cells. Cells in the body will be affected by various physical factors, including pressure, tension and shear stress, so cell culture needs to simulate some more complex tissue or organ function.

[0003] The human body environment simulation process provides shear stress for cell culture, which can be realized by complex structure and fluid parameter control in the culture cavity to improve cell growth and gene expression, and the microenvironment created by the culture chip is closer to the microenvironment of cells in the human body than the traditional experimental environment, and is more easily to simulate the more complex microenvironment in the body.

[0004] The existing cell 3D culture chip has the problems of low cell culture efficiency and large gap between the shear stress provided by the microenvironment and the human body. UTILITY MODEL CONTENT

[0005] In view of the deficiencies of the prior art, the utility model provides a cell 3D culture chip, which can provide shear stress to make the chip more close to the actual shear stress environment of the human body, improve the culture efficiency and culture quality of cells.

[0006] The technical scheme of the utility model is as follows:

[0007] A cell 3D culture chip, comprising a base and a plurality of culture units arranged in the base, the culture unit is filled with culture solution, the culture unit comprises a culture cavity, at least one fluid cavity connected with the culture cavity and a culture channel connecting the culture cavity and the fluid cavity, the top of the culture cavity is provided with a sealing cover, and the top of the fluid cavity is provided with an opening communicating with the outside.

[0008] As a preferred embodiment, the base is provided with a stepped structure to divide the base into a culture area and a base area, and the culture unit is arranged in the culture area.

[0009] As a preferred embodiment, the base is provided with a chip cover covering the cell 3D culture chip.

[0010] As a preferred implementation, the gap between the chip cover and the culture area forms a gas cavity, and the bottom of the chip cover is provided with a vent hole for communicating the gas cavity with the outside.

[0011] As a preferred implementation, the sealing cover is integrally formed with the culture cavity.

[0012] As a preferred implementation, the sealing cover is detachably connected with the culture cavity.

[0013] As a preferred implementation, the culture passage is located in the base area, and the liquid level of the culture solution in the culture part is higher than the culture passage.

[0014] Compared with the prior art, the utility model has the following advantages:

[0015] The utility model provides a cell 3D culture chip, including base and a plurality of groups of culture parts of setting in the base, the culture part is filled with culture solution, the culture part includes a culture cavity, at least one fluid cavity of connecting culture cavity and the culture passage of communicating culture cavity and fluid cavity, the culture cavity top is provided with sealing cover, the fluid cavity top is provided with the opening of communicating outside, culture cavity top setting sealing cover, when the liquid level of culture solution in the culture part rises to the culture passage, culture cavity will constitute airtight environment, through change fluid cavity's gas pressure state can press down and raise fluid cavity's liquid level height, thereby change culture cavity's liquid level height, in this way simulate cell in human body environment in body fluid provides shear stress, make the shear stress environment in microenvironment more close to human actual shear stress environment, improve the culture efficiency and culture quality of cell. BRIEF DESCRIPTION OF DRAWINGS

[0016] In order to more clearly illustrate the technical scheme in the embodiment of the utility model or prior art, the following will briefly introduce the drawing needed to be used in the embodiment or prior art description, obviously, the drawing in the following description only some embodiments of the utility model, for ordinary skilled person in the art, under the premise of not paying the creative labor, still can obtain other drawings according to these drawings.

[0017] Figure 1 It is the internal structure schematic view of a cell 3D culture chip of the utility model;

[0018] Figure 2 It is the structure schematic view of a cell 3D culture chip of the utility model;

[0019] Figure 3 It is Figure 2 It is the sectional structure schematic view of a cell 3D culture chip in the utility model;

[0020] Figure 4 Figure 2 is a cross-sectional view of a cell 3D culture chip according to an embodiment of the present application.

[0021] The drawings show:

[0022] 1 - base, 1A - culture area, 1B - base area, 2 - culture part, 3 - culture cavity, 31 - sealing cover, 4 - fluid cavity, 41 - opening, 5 - culture channel, 6 - chip cover, 61 - vent hole. DETAILED DESCRIPTION

[0023] The technical solutions in the embodiments of the present application will be clearly and completely described below with reference to the drawings in the embodiments of the present application. Obviously, the described embodiments are only part of the embodiments of the present application, rather than all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor fall within the scope of protection of the present application.

[0024] In the description of the present application, it should be noted that the orientations or positional relationships indicated by the terms "center", "upper", "lower", "left", "right", "vertical", "horizontal", "inner", "outer", etc. are based on the orientations or positional relationships shown in the drawings, and are only for the convenience of describing the present application and simplifying the description, and therefore cannot be understood as indicating or implying that the devices or elements referred to must have a particular orientation, be constructed and operated in a particular orientation, and therefore cannot be understood as limiting the present application. In addition, the terms "first", "second", "third", "fourth", etc. are only for the purpose of description, and cannot be understood as indicating or implying relative importance.

[0025] In the description of the present application, it should be noted that, unless otherwise explicitly specified and limited, the terms "mounting", "connection", "connection" should be understood broadly, for example, it can be fixedly connected, or it can be detachably connected, or integrally connected; it can be mechanically connected, or it can be electrically connected; it can be directly connected, or it can be indirectly connected through an intermediate medium, or it can be the communication between two elements. For those skilled in the art, the specific meaning of the above terms in the present application can be understood according to the specific circumstances.

[0026] Before describing the embodiments of the present application, it should be noted that cells are often exposed to fluid shear stress in the body, such as vascular endothelial cells in the blood being constantly subjected to the friction of blood flow. Therefore, by applying appropriate shear stress during cell culture, the physiological environment in the body can be simulated, so that the cells grow and differentiate under conditions closer to nature.

[0027] Specifically, appropriate shear stress can promote the growth and metabolism of cells. By stimulating cell surface receptors and signal transduction pathways, shear stress can activate intracellular metabolic pathways, improve cell energy supply and material metabolism levels, which helps cells maintain viability and proliferative capacity during culture, resulting in more cells for subsequent experiments or treatment. Therefore, it is particularly important to simulate the shear stress of fluid flow in the human body during cell culture. The following will describe how to simulate the shear stress in the human body through a cell 3D culture chip to achieve the purpose of promoting cell culture.

[0028] Referring to Figures 1 to 3 The utility model embodiment proposes a cell 3D culture chip, which can be applied to the fields of cell 3D culture, organoid culture, and tissue culture, etc. The cell 3D culture chip comprises a base 1 and a plurality of groups of culture units 2 arranged in the base. The culture units 2 are filled with culture solution. Each culture unit 2 comprises a culture cavity 3, at least one fluid cavity 4 connected to the culture cavity 3, and a culture channel 5 connecting the culture cavity 3 and the fluid cavity 4. The culture cavity 3 is provided with a sealing cover 31 at the top. The fluid cavity 4 is provided with an opening 41 at the top for communication with the outside.

[0029] Specifically, each group of culture units 2 comprises at least one culture cavity 3 as a cell culture space and at least one fluid cavity 4 connected to the culture cavity 3 and the outside environment. The culture cavity 3 and the fluid cavity 4 are connected through the culture channel 5. The culture solution can be added to the culture unit 2 through the opening 41 at the top of the fluid cavity 4. The culture solution flowing into the fluid cavity 4 enters the culture cavity 3 along the culture channel 5. The composition of the culture solution can be adjusted according to the actual needs of cell culture. Multiple groups of culture units 2 can realize the simultaneous culture of multiple groups of cells, especially when different culture solution control group experiments are set.

[0030] Further, the sealing cover 31 is arranged at the top of the culture cavity 3. When the liquid level of the culture solution in the culture part 2 rises to cover the culture channel 5, the culture cavity 3 will form a closed environment. The liquid level in the fluid cavity 4 can be lowered and raised by changing the air pressure state in the fluid cavity 4, so as to change the liquid level in the culture cavity 3. In this way, the shear stress provided by the body fluid in the human body environment is simulated. When the air pressure in the fluid cavity 4 is changed, a carbon dioxide incubator can be used to cooperate to realize air pressure control, and at the same time, the PH value of the culture medium for cell culture can be maintained relatively stable. Specifically, the culture medium used for cell culture generally contains a buffer system such as sodium bicarbonate. When carbon dioxide is dissolved in the culture medium, it will react with water to generate carbonic acid, which will dissociate into hydrogen ions and bicarbonate ions. During the metabolic process of cells, some acidic substances such as lactic acid will be produced, so that the pH value of the culture medium tends to decrease. The bicarbonate ions dissociated from the carbonic acid generated by the reaction of carbon dioxide and water can neutralize the acidic substances produced by cell metabolism, thereby offsetting the decrease in pH value to a certain extent and maintaining the relative stability of the pH value of the culture medium.

[0031] As a preferred embodiment, the base 1 is provided with a stepped structure to separate the base 1 into a culture area 1A and a base area 1B. The culture part 2 is arranged in the culture area 1A. The base 1 is provided with a chip cover 6 covering the cell 3D culture chip. The culture part 2 in the culture area 1A is protected by the chip cover 6 to avoid contamination of the culture part 2 caused by incorrect operation of the cell 3D culture chip. At the same time, the stepped structure design can facilitate the operator to take the cell 3D culture chip through the base area 1B. The chip cover 6 supported on the culture area 1A can also be taken along the edge of the base area 1B, reducing the operation difficulty of the operator.

[0032] As a preferred embodiment, the gap between the chip cover 6 and the culture area 1A forms a gas cavity. The bottom cover of the chip cover 6 is provided with a vent hole 61 for communicating the gas cavity with the outside. The cell 3D culture chip is generally placed in a culture box. The vent hole 61 can balance the air pressure in the culture box and the fluid cavity 4, and the liquid level in the culture cavity 3 can be affected by changing the air pressure in the culture box, so as to achieve the effect of simulating the shear stress in the human body. The vent hole 61 supports the gas flow between the culture box and the fluid cavity 4. Carbon dioxide and other gases can enter the culture solution through the fluid cavity to maintain the relative balance of the acid-base in the culture environment.

[0033] As a preferred embodiment, the sealing cover 31 and the culture cavity 3 are integrally formed, which can increase the stability and airtightness of the overall structure of the cell 3D culture chip, and ensure that the cell culture process in the culture cavity 3 is not affected by the outside world. Further, the material of the sealing cover can be soft silicone or other soft materials with elasticity, which can better seal the environment in the culture cavity 3.

[0034] As a preferred embodiment, the sealing cover 31 is detachably connected with the culture cavity 3, and the sealing cover 31 can also be mounted on the culture cavity 3 through detachable connection, so that an operator can conveniently observe and handle the culture cavity 3.

[0035] As a preferred embodiment, the culture channel 5 is located in the base area 1B, and the liquid level of the culture solution in the culture part 2 is higher than the culture channel 5, so that the pressure in the culture cavity 3 and the fluid cavity 4 can be independently controlled, the air pressure in the fluid cavity 4 can be changed to adjust the liquid level height in the culture cavity 3, and the change process of the liquid level height difference can simulate the shear stress in the human body.

[0036] The working principle of the utility model is: the cell 3D culture chip is placed in a carbon dioxide incubator, the incubator changes the air pressure in the incubator through the carbon dioxide concentration, the fluid cavity 4 in the cell 3D culture chip is communicated with the environment of the incubator, the air pressure makes the culture solution in the fluid cavity 4 move with the liquid level difference, so that the culture solution in the culture cavity 3 also moves up and down with the change of the liquid level height, the movement frequency can be controlled according to the frequency required by the simulation of human pulse and cell culture, so that an environment simulating the shear stress in the human body can be formed in the culture cavity 3 of the cell 3D culture chip, the shear stress environment in the microenvironment is more close to the actual shear stress environment of the human body, and the culture efficiency and culture quality of cells are improved.

[0037] Embodiment 2

[0038] Referring to Figure 4 The difference between this embodiment 2 and embodiment 1 is that the bottom of the culture cavity 3 and the fluid cavity 4 is a hemispherical structure, wherein the design of the hemispherical surface helps to optimize the growth environment of cells in the 3D culture chip. On the one hand, the curved surface of the hemisphere can provide a more uniform cell attachment area, which is conducive to the uniform distribution and growth of cells. On the other hand, this design can also promote the flow and mixing of the culture medium in the chip, providing cells with more sufficient nutrients and oxygen, while removing metabolic waste, thereby maintaining a healthier cell growth environment.

[0039] Further, the hemispherical design can simulate the curved morphology of in vivo tissues or organs to some extent, providing cells with a growth space closer to the in vivo environment. This design helps to study the changes in cell behavior in complex microenvironments, as well as the interactions between cells and cells, cells and matrix. The hemispherical design can also improve the culture efficiency of the cell 3D culture chip. Since the curved surface of the hemisphere can increase the cell attachment area and promote the flow and mixing of the culture medium, the growth and differentiation process of the cells can be accelerated. At the same time, this design can also reduce the number of cells and the amount of culture medium required during the culture process, thereby reducing the culture cost.

[0040] The above merely describes the preferred embodiments of the present application and is not intended to limit the present application. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present application shall be included in the protection scope of the present application.

Claims

1. A cell 3D culture chip, characterized in that, The application relates to a 3D cell culture chip, which comprises a base (1) and a plurality of culture units (2) arranged in the base, the culture units (2) being filled with culture solution, the culture unit (2) comprising a culture cavity (3), at least one fluid cavity (4) connected with the culture cavity (3) and a culture channel (5) connecting the culture cavity (3) and the fluid cavity (4), and a sealing cover (31) arranged on the top of the culture cavity (3), and an opening (41) arranged on the top of the fluid cavity (4) and communicating with the outside.

2. The cell 3D culture chip according to claim 1, wherein, A stepped structure is arranged on the base (1) to divide the base (1) into a culture area (1A) and a base area (1B), and the culture unit (2) is arranged in the culture area (1A).

3. The cell 3D culture chip according to claim 2, wherein, A chip cover (6) is arranged on the base (1) to cover the 3D cell culture chip.

4. The cell 3D culture chip according to claim 3, wherein, A gap between the chip cover (6) and the culture area (1A) forms a gas cavity, and a vent hole (61) is arranged on the bottom of the chip cover (6) to connect the gas cavity with the outside.

5. The cell 3D culture chip according to claim 1, wherein The sealing cover (31) is integrally formed with the culture cavity (3).

6. The cell 3D culture chip according to claim 1, wherein The sealing cover (31) is detachably connected with the culture cavity (3).

7. The cell 3D culture chip according to claim 2, wherein The culture channel (5) is arranged in the base area (1B), and the liquid level of the culture solution in the culture unit (2) is higher than the culture channel (5).

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