Organ chip culture plate

Abstract

The utility model relates to an organ chip culture plate which comprises a culture plate body, a plurality of groups of independent cell culture areas with the same structure are arranged on the culture plate body, and each cell culture area comprises an upper-layer cell culture chamber, a lower-layer cell culture chamber and a porous membrane which are positioned in a central area, a porous membrane is connected between the upper-layer cell culture chamber and the lower-layer cell culture chamber, the upper-layer cell culture chamber and the lower-layer cell culture chamber are both communicated with the porous membrane, each of the upper-layer cell culture chamber and the lower-layer cell culture chamber is provided with a group of fluid inlets and outlets, and the cell culture area further comprises four liquid storage cups, the four liquid storage cups are arranged on the peripheries of the cell culture chambers respectively, two liquid storage cups are communicated with the upper-layer cell culture chamber through the corresponding inlets and outlets, and the other two liquid storage cups are communicated with the lower-layer cell culture chamber through the corresponding inlets and outlets. According to the utility model, various organ interfaces can be constructed with high throughput, and the efficiency is improved.

Description

Technical Field

[0001] This invention belongs to the field of biomedical engineering, and in particular relates to an organ-on-a-chip culture plate. Background Technology

[0002] With the development of cell biology and organoid technology, three-dimensional cell culture technology is gradually replacing traditional two-dimensional cell culture technology. Currently, many cell types possess strong self-assembly capabilities, such as pluripotent stem cells, tumor cells, and tissue cells. Three-dimensional cell spheres are three-dimensional aggregates formed by the self-assembly of various cells, more closely resembling the structural morphology of in vivo tissue cells and more conducive to the study of their functional mechanisms. Therefore, three-dimensional cell spheres can be used in numerous biological and biomedical research fields, such as developmental biology, pathology, pharmacology, and cancer treatment.

[0003] A search revealed the patent: High-throughput Suspension Culture Plate and High-throughput Multi-Organ Co-culture Chip (CN201920547410.6). The suspension culture plate has multiple protrusions on one side of the plate, each protrusion having a raised pattern on its end face. The culture chip includes a plate body with multiple culture wells and fluid manipulation channels formed on it. The fluid manipulation channels are configured to manipulate the fluid within the culture wells. The co-culture chip is constructed by suspending the multiple protrusions of the suspension culture plate corresponding to the multiple culture wells of the culture chip. The suspension culture plate is mounted on the culture chip. However, this structure has relatively low throughput, limits the number of organ interfaces that can be constructed, and is not compatible with existing cell culture plates, making it unfriendly to users.

[0004] In view of the above-mentioned shortcomings, the designer has actively researched and innovated in order to create a new type of organ-on-a-chip culture plate with greater industrial application value. Utility Model Content

[0005] To address the aforementioned technical problems, the purpose of this invention is to provide an organ-on-a-chip culture plate.

[0006] To achieve the above objectives, the present invention adopts the following technical solution:

[0007] An organ-on-a-chip culture plate includes a culture plate body with several sets of identical and independent cell culture regions. Each cell culture region includes an upper cell culture chamber, a lower cell culture chamber, and a porous membrane located in the central region. The upper and lower cell culture chambers are connected by the porous membrane, and both the upper and lower cell culture chambers are in communication with the porous membrane. Each upper and lower cell culture chamber has a set of fluid inlets and outlets. The cell culture region also includes four liquid reservoirs, which are arranged around the cell culture chambers. Two of the liquid reservoirs are connected to the upper cell culture chamber through their corresponding inlets and outlets, and the other two liquid reservoirs are connected to the lower cell culture chamber through their corresponding inlets and outlets.

[0008] Preferably, in the organ-on-a-chip culture plate, the upper cell culture chamber and the lower cell culture chamber have the same structure, which are square or rhomboid, with a side length of 0.5 to 5 cm and a height of 0.1 to 2 mm.

[0009] Preferably, in the organ-on-a-chip culture plate, the porous membrane has a pore size of 0.2-10 μm, and the material of the porous membrane includes, but is not limited to, PC, PET or PDMS.

[0010] Preferably, in the organ-on-a-chip culture plate, the liquid storage cup is a cylindrical liquid storage cup with a notch.

[0011] Preferably, in the organ-on-a-chip culture plate, the overall structure of the culture plate body and the reservoir cup is adapted to a 48-well and / or 96-well plate.

[0012] Preferably, in the organ-on-a-chip culture plate, the culture plate body is formed by injection molding of a polymer material, the material of which includes, but is not limited to, PS, PC or PMMA, and the upper cell culture chamber, the lower cell culture chamber and the porous membrane are assembled by adhesive bonding, thermoforming or laser welding.

[0013] Preferably, in the organ-on-a-chip culture plate, both the upper and lower cell culture chambers are square structures with a side length of 1 cm and a height of 0.5 mm. The porous membrane has a pore size of 8 μm and is made of PET.

[0014] Preferably, in the organ-on-a-chip culture plate, both the upper and lower cell culture chambers are square structures with a side length of 2cm and a height of 1mm. The porous membrane has a pore size of 10μm and is made of PDMS.

[0015] Preferably, in the organ-on-a-chip culture plate, both the upper and lower cell culture chambers are rhomboid in shape, with a side length of 1 cm and a height of 1 mm. The porous membrane has a pore size of 4 μm and is made of PC.

[0016] Preferably, the organ-on-a-chip culture plate has 12 or 24 independent cell culture regions within the culture plate itself.

[0017] By means of the above solution, this utility model has at least the following advantages:

[0018] This invention enables high-throughput construction of various organ interfaces at low cost, with simple operation and significantly improved efficiency. Furthermore, the culture plate structure is compatible with existing cell culture plates, making it compatible with most current detection equipment and user-friendly.

[0019] The above description is only an overview of the technical solution of this utility model. In order to better understand the technical means of this utility model and to implement it in accordance with the contents of the specification, the preferred embodiments of this utility model are described in detail below with reference to the accompanying drawings. Attached Figure Description

[0020] To more clearly illustrate the technical solutions of the embodiments of this utility model, the drawings used in the embodiments will be briefly introduced below. It should be understood that the following drawings only show some embodiments of this utility model and should not be regarded as a limitation on the scope. For those skilled in the art, other related drawings can be obtained based on these drawings without creative effort.

[0021] Figure 1 This is a schematic diagram of the structure of this utility model;

[0022] Figure 2 This is a schematic diagram of the cell culture region of this utility model;

[0023] Figure 3 This is a schematic diagram of the upper cell culture chamber and its entrance / exit. Detailed Implementation

[0024] To make the objectives, technical solutions, and advantages of the embodiments of this application clearer, the technical solutions of the embodiments of this application will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of this application, and not all embodiments. The components of the embodiments of this application described and shown in the accompanying drawings can generally be arranged and designed in various different configurations.

[0025] Therefore, the following detailed description of the embodiments of this application provided in the accompanying drawings is not intended to limit the scope of the claimed application, but merely to illustrate selected embodiments of the application. All other embodiments obtained by those skilled in the art based on the embodiments of this application without inventive effort are within the scope of protection of this application.

[0026] Example

[0027] like Figure 1 , Figure 2 and Figure 3 As shown, an organ-on-a-chip culture plate includes a culture plate body 10. The culture plate body 10 has several sets of identical and independent cell culture regions 100. Each cell culture region 100 includes an upper cell culture chamber 101, a lower cell culture chamber 102, and a porous membrane 103 located in the central region. The upper cell culture chamber 101 and the lower cell culture chamber 102 are connected by the porous membrane 103. Both the upper cell culture chamber 101 and the lower cell culture chamber 102 are connected to... The porous membrane 103 is interconnected. Both the upper cell culture chamber 101 and the lower cell culture chamber 102 are provided with a set of fluid inlets and outlets 104. The cell culture area 100 also includes four liquid storage cups 105, which are arranged around the cell culture chamber. Two of the liquid storage cups 105 are connected to the upper cell culture chamber 101 through their corresponding inlets and outlets 104, and the other two liquid storage cups 105 are connected to the lower cell culture chamber 102 through their corresponding inlets and outlets 104.

[0028] In this invention, the upper cell culture chamber 101 and the lower cell culture chamber 102 have the same structure. They are square or rhomboid, with a side length of 0.5 to 5 cm and a height of 0.1 to 2 mm. The porous membrane 103 has a pore size of 0.2 to 10 μm. The porous membrane 103 is made of materials including but not limited to: PC (polycarbonate), PET (polyethylene terephthalate), or PDMS (polydimethylsiloxane).

[0029] The liquid storage cup 105 described in this utility model is a liquid storage cup with a notch and a cylindrical structure. The notch is for easy observation of the culture chamber structure.

[0030] The overall structure of the culture plate body 10 and the liquid storage cup 105 described in this invention is compatible with 48-well and / or 96-well plates, which can improve applicability and reduce costs.

[0031] The culture plate body 10 described in this utility model is formed by injection molding of polymer materials, including but not limited to: PS (polystyrene), PC or PMMA (polymethyl methacrylate). The upper cell culture chamber 101, the lower cell culture chamber 102 and the porous membrane 103 are assembled by adhesive bonding, hot pressing or laser welding.

[0032] In this invention, the culture plate body 10 has 12 or 24 independent culture areas, so it can be grouped according to the experimental design and grouped experiments can be completed in the same chip.

[0033] Example 1

[0034] Based on the above embodiments, in this utility model, both the upper cell culture chamber 101 and the lower cell culture chamber 102 are square structures with a side length of 1cm and a height of 0.5mm. The porous membrane has a pore size of 8μm and is made of PET.

[0035] Example 2

[0036] Based on the above embodiments, in this utility model, both the upper cell culture chamber 101 and the lower cell culture chamber 102 are square structures with a side length of 2cm and a height of 1mm. The porous membrane has a pore size of 10μm and is made of PDMS.

[0037] Example 3

[0038] Based on the above embodiments, in this utility model, both the upper cell culture chamber 101 and the lower cell culture chamber 102 are rhomboid structures with a side length of 1cm and a height of 1mm. The porous membrane has a pore size of 4μm and is made of PC.

[0039] Upper cell culture chamber 101 and lower cell culture chamber 102

[0040] The working principle of this utility model is as follows:

[0041] (1) Sterilization treatment of organ-on-a-chip culture plates;

[0042] (2) Use collagen solution to modify the upper and lower surfaces of the porous membrane in the organ-on-a-chip;

[0043] (3) First, inoculate the cells (vascular endothelial cells) in the lower cell culture chamber. After inoculation, invert the organ-on-a-chip culture plate to allow the vascular endothelial cells to adhere to the lower surface of the porous membrane.

[0044] (4) Inoculate the cells (Caco-2 intestinal epithelial cells) in the upper cell culture chamber and let them stand to allow the cells to adhere to the upper surface of the porous membrane.

[0045] (5) After the upper and lower layers of cells are seeded, the required culture medium is added to the reservoir cup and the organ-on-a-chip culture plate is placed on a horizontal shaker to construct the intestinal barrier.

[0046] It should be noted that similar labels and letters in the following figures indicate similar items. Therefore, once an item is defined in one figure, it does not need to be further defined and explained in subsequent figures.

[0047] In the description of this application, it should be noted that the terms "vertical," "horizontal," "inner," and "outer," etc., indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings, or the orientation or positional relationship commonly used when the product is in use. They are used only for the convenience of describing this application and for simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation. Therefore, they should not be construed as limitations on this application. Furthermore, the terms "first," "second," etc., are used only to distinguish descriptions and should not be construed as indicating or implying relative importance.

[0048] Furthermore, terms such as "horizontal" and "vertical" do not imply that components must be absolutely horizontal or vertical, but rather that they can be slightly tilted. For example, "horizontal" simply means that its direction is more horizontal than "vertical," and does not mean that the structure must be completely horizontal, but can be slightly tilted.

[0049] In the description of this application, it should also be noted that, unless otherwise expressly specified and limited, the terms "set up," "install," "connect," and "link" should be interpreted broadly. For example, they can refer to a fixed connection, a detachable connection, or an integral connection; they can refer to a mechanical connection or an electrical connection; they can refer to a direct connection or an indirect connection through an intermediate medium; and they can refer to the internal connection of two components. Those skilled in the art can understand the specific meaning of the above terms in this application based on the specific circumstances.

[0050] The above description is only a preferred embodiment of the present utility model and is not intended to limit the present utility model. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the technical principles of the present utility model, and these improvements and modifications should also be considered within the protection scope of the present utility model.

Claims

1. An organ-on-a-chip culture plate, comprising a culture plate body (10), characterized in that: The culture plate body (10) is provided with several sets of identical and independent cell culture regions (100). Each cell culture region (100) includes an upper cell culture chamber (101), a lower cell culture chamber (102), and a porous membrane (103) located in the central region. The upper cell culture chamber (101) and the lower cell culture chamber (102) are connected by a porous membrane (103). Both the upper cell culture chamber (101) and the lower cell culture chamber (102) are connected to the porous membrane (103). Both the upper cell culture chamber (101) and the lower cell culture chamber (102) are provided with a set of fluid inlets and outlets (104). The cell culture area (100) also includes four liquid storage cups (105). The four liquid storage cups (105) are arranged around the cell culture chamber. Two of the liquid storage cups (105) are connected to the upper cell culture chamber (101) through their corresponding inlets and outlets (104), and the other two liquid storage cups (105) are connected to the lower cell culture chamber (102) through their corresponding inlets and outlets (104).

2. The organ-on-a-chip culture plate according to claim 1, characterized in that: The upper cell culture chamber (101) and the lower cell culture chamber (102) have the same structure. They are square or rhomboid, with a side length of 0.5 to 5 cm and a height of 0.1 to 2 mm.

3. The organ-on-a-chip culture plate according to claim 1, characterized in that: The porous membrane (103) has a pore size of 0.2-10 μm, and the material of the porous membrane (103) includes, but is not limited to, PC, PET or PDMS.

4. The organ-on-a-chip culture plate according to claim 1, characterized in that: The liquid storage cup (105) is a liquid storage cup with a notch and a cylindrical structure.

5. An organ-on-a-chip culture plate according to claim 1, characterized in that: The overall structure of the culture plate body (10) and the liquid storage cup (105) is adapted to 48-well and / or 96-well plates.

6. An organ-on-a-chip culture plate according to claim 1, characterized in that: The culture plate body (10) is formed by injection molding of polymer materials, including but not limited to: PS, PC or PMMA. The upper cell culture chamber (101), the lower cell culture chamber (102) and the porous membrane (103) are assembled by adhesive bonding, hot pressing or laser welding.

7. An organ-on-a-chip culture plate according to claim 1, characterized in that: The culture plate body (10) has 12 or 24 independent cell culture areas.

8. An organ-on-a-chip culture plate according to any one of claims 1 to 7, characterized in that: Both the upper cell culture chamber (101) and the lower cell culture chamber (102) are square structures with a side length of 1cm and a height of 0.5mm. The porous membrane has a pore size of 8μm and is made of PET.

9. An organ-on-a-chip culture plate according to any one of claims 1 to 7, characterized in that: Both the upper cell culture chamber (101) and the lower cell culture chamber (102) are square structures with a side length of 2cm and a height of 1mm. The porous membrane has a pore size of 10μm and is made of PDMS.

10. An organ-on-a-chip culture plate according to any one of claims 1 to 7, characterized in that: Both the upper cell culture chamber (101) and the lower cell culture chamber (102) are rhomboid structures with a side length of 1 cm and a height of 1 mm. The porous membrane has a pore size of 4 μm and is made of PC.

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