Culture plate for organoid

Abstract

The utility model relates to the technical field of cell culture, and discloses a culture plate for an organoid, which comprises a plate body, a plurality of culture holes and a plurality of cells, the cover body is detachably arranged on the plate body and used for forming a closed space, and the culture holes are located in the closed space formed by the plate body and the cover body; wherein each culture hole is internally provided with a cell culture chamber, and a layer of sealing gasket for independently sealing each culture hole is arranged between the plate body and the cover body. According to the utility model, the culture plate can achieve effective sealing stability during transportation, so that the cell culture plate can be conveniently transported among different laboratories.

Description

Technical Field

[0001] The utility model belongs to the technical field related to cell culture, and particularly relates to a culture plate for organoids. Background Art

[0002] Cell culture plates are used to culture cells or bacteria. They are a common and important tool for culturing cells. They come in various shapes, specifications, and uses. The six-well plates commonly used on the market can achieve six different dynamic cultures of cells and organoids at one time, greatly shortening the cell usage and cycle in the early stage of process verification, and reducing R&D costs.

[0003] The six-well plate is a commonly used cell culture tool in the laboratory. It is designed to provide a suitable environment to support cell growth and reproduction in vitro. Cell culture, drug screening, toxicity testing, cell migration and invasion experiments can be achieved through the six-well plate. The bottom of the six-well plate can be flat, round or conical, depending on the cell type being cultured and the experimental requirements. For example, the flat bottom is suitable for cell culture that requires imaging or spectrophotometry, while the curved bottom is suitable for cells without contact inhibition, and the round bottom is suitable for suspension culture. This flexibility enables the six-well plate to meet the needs of a variety of cell culture and research. At the same time, culture chambers made of different membrane materials can be placed in the six-well plate to simulate the in vivo circulation environment and study the interaction between liquids.

[0004] It is difficult to directly cover the commercially available six-well cell culture plates with a cover plate to seal the entire plate, because all the wells of the six-well plate are located in the same cavity, making the culture plate prone to cell fluid leakage during transportation. Leakage will contaminate adjacent culture wells and cause cross-contamination of cell culture.

[0005] Therefore, the current culture plates are not suitable for directly loading cells and organoids for transfer and transportation. Generally, cells and organoids need to be transferred to culture bottles, or transferred to cryopreservation tubes after freezing and then transferred and transported. However, contamination is still easy to cause during the transfer process, and the process is relatively cumbersome, making the transfer more troublesome. Utility Model Content

[0006] In order to solve the deficiencies of the prior art, the present invention provides a culture plate which meets the sealing requirements of the cell culture plate through the design of a sandwich sealing gasket, while achieving the effect of mutual independence between culture wells and can be directly used for transfer and transportation.

[0007] The technical effects to be achieved by the present invention are achieved through the following aspects:

[0008] The utility model provides a culture plate, comprising a plate body, the plate body including a plurality of culture wells; and a cover body, the cover body being detachably arranged on the plate body to form a closed space, the culture wells being located within the closed space formed by the plate body and the cover body; wherein a layer of sealing gasket for independently sealing each of the culture wells is provided between the plate body and the cover body.

[0009] In some embodiments, the culture well includes a cell culture chamber, which includes a basement membrane, which is disposed at the bottom of the cell culture chamber; and a chamber support, which is disposed at the bottom of the cell culture chamber and is used to separate the culture well from the basement membrane.

[0010] In this implementation, by setting up a cell culture chamber in the culture well, it can be used to culture organoids and realize culture experiments simulating membrane-bound organoids to verify the material exchange function of the organoids.

[0011] In some implementations, the cell culture chamber further includes a pick-up ring, the top of the cell culture chamber is provided with the pick-up ring, and a side wall of the pick-up ring is hollowed out to provide a plurality of pick-up holes.

[0012] In some implementations, the sealing gasket includes a plurality of sealing rings positioned opposite to the culture holes, and the sealing rings abut against the plate body or the cell culture chamber so that the cell culture chamber is located in an independent closed cavity.

[0013] In some implementations, the sealing ring is interference fit with the outside or inside of the opening of the culture hole.

[0014] In some implementations, the sealing ring is interference-fitted with the outer side or inner side of the opening of the cell culture chamber.

[0015] In some implementations, the sealing gasket further includes a breathable membrane, and the breathable membrane is disposed on the inner side of the sealing ring.

[0016] In this implementation, by providing a breathable membrane, oxygen and carbon dioxide exchange can be provided to the cells during long-term transportation, thereby improving cell survival rate and cell activity. In some implementations, the sealing ring is not in contact with the cell culture chamber.

[0017] In some implementations, a portion of the cell culture chamber is located inside the sealing ring.

[0018] In some implementations, the maximum outer diameter of the sealing ring is larger than the inner diameter of the culture hole, and the radius difference between the sealing ring and the culture hole ranges from 0.2 mm to 1.5 mm.

[0019] In summary, a cover plate structure is adopted, and a sealing gasket is provided between the plate body and the cover body. Each culture well is sealed by the sealing gasket, which not only prevents contamination, but also the cavities in each culture well are not connected to each other, so that the culture plate can achieve effective sealing stability during transportation, which facilitates the transportation of cell culture plates between different laboratories. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 This is a schematic diagram of the overall explosion structure of an embodiment of the present utility model.

[0021] Figure 2 This is a schematic diagram of the cell culture chamber structure of an embodiment of the present utility model.

[0022] Figure 3 This is a schematic diagram of the connection structure between the sealing gasket and the plate body and an AA cross-sectional diagram of an embodiment of the present utility model.

[0023] Figure 4 for Figure 3 Schematic diagram of the enlarged portion B.

[0024] Figure 5 This is a schematic structural diagram of a sealing gasket according to an embodiment of the present utility model.

[0025] Figure 6 This is another structural schematic diagram of the sealing gasket according to an embodiment of the present utility model.

[0026] Figure 7 It is the overall structure and CC cross-sectional diagram of an embodiment of the present utility model.

[0027] Figure 8 for Figure 7 Enlarged schematic diagram of part D.

[0028] Markings in the figure:

[0029] 1. Plate body; 11. Culture wells;

[0030] 2. Cell culture chamber; 21. Chamber pillar; 22. Basement membrane; 23. Picking ring; 24. Picking hole

[0031] 3. Sealing pad; 31. Sealing ring; 32. Breathable membrane;

[0032] 4. Cover body. DETAILED DESCRIPTION

[0033] To make the purpose, technical solutions and advantages of the embodiments of the present invention more clear, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. The described embodiments are only part of the embodiments of the present invention, not all of the embodiments.

[0034] Therefore, the following detailed description of the embodiments of the present invention provided in the accompanying drawings is not intended to limit the scope of the claimed invention, but rather merely represents selected embodiments of the present invention. Based on the embodiments of the present invention, all other embodiments obtained by a person of ordinary skill in the art without creative effort are within the scope of protection of the present invention.

[0035] Example 1:

[0036] See also Figure 1 In this embodiment, a culture plate includes a plate body 1, which includes a plurality of culture wells 11; and a cover body 4, which is detachably arranged on the plate body 1 to form a closed space, and the culture wells 11 are located in the closed space formed by the plate body 1 and the cover body 4; wherein a sealing gasket 3 is provided between the plate body 1 and the cover body 4 for independently sealing each culture well 11.

[0037] Specifically, in this embodiment, a culture well 11 is provided in the plate body 1 of the culture plate. The culture well 11 is a round hole with a flat bottom. Six culture wells 11 are distributed on the plate body 1 in an array of two rows and three columns, and the distance between two adjacent culture wells 11 is equal. The cover body 4 is adapted to the plate body 1. The cover body 4 can cover the upper end of the plate body 1. The edge of the upper surface of the plate body 1 is stepped, and the cover body 4 can be fixed to the plate body 1 by means including but not limited to a slot, static friction, etc. A closed space is formed between the cover body 4 and the plate body 1. The culture well 11 is located on the plate body 1. The opening of the culture well 11 faces the cover body 4, and the internal space of the culture well 11 is connected to the above-mentioned closed space. The sealing gasket 3 is arranged between the plate body 1 and the cover body 4. The sealing gasket 3 is used to seal the culture wells 11 and covers the openings of each culture well 11. A closed cavity is formed between the sealing gasket 3 and the culture well 11. Each closed cavity is independent of each other, thereby ensuring that the interior of the culture well 11 can have a certain stable culture environment, avoiding leakage of the cell culture fluid in the culture well 11 during transportation, preventing cross contamination, and reducing the possibility of overall contamination.

[0038] The plate 1 features a beveled right corner, and the cover 4 closes in one direction, ensuring a single orientation for placement. The plate 1 and culture cover 4 can be injection molded using thermoplastic. The sealing gasket 3 is made of medical silicone and can be reused repeatedly under high-temperature sterilization, improving both cost-effectiveness and safety.

[0039] In some embodiments, cells for culture are placed in culture wells 11, and sealing gaskets 3 are placed between the plate body 1 and the cover body 4. The culture wells 11 are squeezed and sealed by covering the cover body 4 with the plate body 1. Each culture well 11 is not connected to each other and is isolated from each other to ensure that the internal liquids are not mixed and contaminated. The sealing gaskets 3 cover the openings of each culture well 11 to seal each independent culture well 11 to form a closed cavity, thereby ensuring that the interior of the culture well 11 can have a certain stable culture environment, which has a sealing effect during transportation and solves the problem of easy transfer and leakage of culture plates for cell culture.

[0040] In some embodiments, the sealing gasket 3 and the cover body 4 can be integrated, and the sealing gasket 3 is fixed to the inner side of the cover body 4. Opening and closing the cover body 4 can seal the cavity between the sealing gasket 3 and the culture well 11, making the operation more convenient. In other embodiments, the sealing gasket 3 and the cover body 4 can also be separate. When the cover body 4 is opened, the sealing gasket 3 can be used as a cover to cover the opening of the culture well 11. In some embodiments, the sealing gasket 3 can be designed to carry out a separate experimental operation by lifting a corner of the sealing gasket 3, and the remaining culture wells 11 will not be disturbed by the outside as much as possible. The cavities of each culture well 11 are independent of each other, and the sealing gasket 3 covering the upper end of the plate body 1 can play a good protective effect, solving the problems of bacterial contamination risk and cross-contamination of cell culture. Of course, the sealing gasket 3 can also be designed to enable each culture well 11 to be completely opened when it is lifted, and this application does not limit this.

[0041] Example 2:

[0042] See Figure 2 , the figure shows the structure of the cell culture chamber of an embodiment of the present utility model.

[0043] In some embodiments, the culture well 11 includes a cell culture chamber 2, which is a container with its opening facing upward. The cell culture chamber 2 includes a basement membrane 22, which is disposed at the bottom of the cell culture chamber 2; and a chamber support 21, which is disposed at the bottom of the cell culture chamber 2. The chamber support 21 is used to separate the culture well 11 from the basement membrane 22.

[0044] Specifically, the cell culture chamber 2 is placed in the culture well 11. When sealed, there are no other contact points except the chamber pillars 21. The basement membrane 22 is arranged at the bottom of the cell culture chamber 2. When conducting experimental cell exchange experiments, the matching cell culture chamber 2 is used, and different types of basement membranes 22 are selected, such as PET membranes, PC membranes, etc. The chamber pillars 21 connected to the bottom of the cell culture chamber 2 are optional but not limited to three. The chamber pillars 21 are evenly distributed along the circumference. The chamber pillars 21 and the cell culture chamber 2 can be separate structures, or the two can be formed as one body, which is used to prevent the cell culture chamber 2 from contacting the bottom of the culture well 11 where it is located, to avoid contact affecting the cultivation. The three chamber pillars 21 are used to ensure the flatness of the basement membrane 22.

[0045] In order to make the cell culture chamber 2 more convenient to clamp, in some embodiments, the cell culture chamber 2 further includes a picking ring 23 . The top of the cell culture chamber 2 is provided with the picking ring 23 , and the side wall of the picking ring 23 is hollowed out to provide a plurality of picking holes 24 .

[0046] Specifically, the picking ring 23 is set on the top of the cell culture chamber 2, and the multiple picking holes 24 hollowed out on the side wall of the picking ring 23 can solve the problem that the cell culture chamber 2 is difficult to be clamped with tweezers, making it convenient to transfer the cell culture chamber 2 in the laboratory.

[0047] The culture plate of the present invention has a cell culture chamber 2 disposed within its culture well 11, and each culture well 11 is independently sealed and does not interfere with each other. The cell culture chamber 2 is supported by a chamber support 21, and a basement membrane 22 is disposed at the bottom of the cell culture chamber 2. The chamber support 21 supports and separates the culture well 11 from the basement membrane 22 to avoid interference with the cultivation experiment. A pick-up ring 23 is disposed at the top of the cell culture chamber 2. For easy clamping, a hollow pick-up hole 24 is provided on the side wall of the pick-up ring 23. The independent cell culture chamber 2 facilitates observation of the growth status and appearance of the cell culture process, and also facilitates the experimenter to remove the individual cell culture chamber 2 for operation, thereby achieving independent cultivation and research and reducing the risk of cross contamination.

[0048] It is understandable that the above-mentioned implementation of the cell culture chamber 2 is only for example, and in actual application, other implementations of the cell culture chamber 2 can also be used to facilitate the use of the culture plate, and this application does not limit this.

[0049] Example 3:

[0050] The difference between this embodiment and embodiment 1 is that this embodiment optimizes the sealing gasket of the culture plate of the utility model, see Figures 3 to 8 .

[0051] The sealing gasket 3 of this embodiment includes several sealing rings 31 located opposite to the culture holes 11 . The sealing rings 31 abut against the plate 1 or the cell culture chamber 2 to achieve relative sealing, so that the cell culture chamber 2 is located in an independent closed cavity.

[0052] Specifically, a plurality of sealing rings 31 are provided on the sealing gasket 3, which are arranged relative to the position of the culture hole 11. The sealing ring 31 can be an embedded groove or a snap-fit ​​seal, or a protrusion can be provided on the sealing ring 31 toward the wall of the culture hole 11 for static friction sealing connection. The sealing ring 31 can abut against the plate body 1 to form a closed cavity in the culture hole 11, so that the cell culture chamber 2 is located in an independent closed cavity. The sealing ring 31 can also abut against the cell culture chamber 2 for sealing, so that the cell culture chamber 2 is also located in an independent closed cavity. Of course, the specific sealing method, such as what form of sealing ring 31 to use and how to seal the culture hole 11, can be determined according to the actual situation, as long as it can achieve the ability to independently seal each cell culture sample.

[0053] In order to ensure the sealing of the cell culture chamber 2 during transportation, in some embodiments, the sealing ring 31 is interference-fitted with the outer side or inner side of the opening of the culture hole 11 .

[0054] Specifically, the sealing ring 31 can be wrapped around the culture hole 11 and tightly attached to the outer wall of the opening of the culture hole 11 to achieve sealing, or it can be embedded in the culture hole 11 and tightly attached to the inner wall of the opening of the culture hole 11 to achieve sealing. It can be connected by static friction. The sealing ring 31 and the culture hole 11 are both interference fit to ensure the stability of the seal.

[0055] In some embodiments, as Figure 4 As shown, combined with Figure 3 The sealing gasket 3 covers the culture hole 11 of the plate body 1, and the sealing ring 31 on the sealing gasket 3 has an interference fit with the inner side of the culture hole 11. The sealing ring 31 provided on the sealing gasket 3 can make each culture hole 11 sealed independently, and when a single culture hole 11 is opened, the inside of the other culture holes 11 can continue to maintain a sealed state and will not be disturbed by the external environment.

[0056] In order to ensure the sealing of the cell culture chamber 2 during transportation, in some embodiments, the sealing ring 31 is interference-fitted with the outer side or inner side of the opening of the cell culture chamber 2 .

[0057] Specifically, the sealing ring 31 can be positioned so as to fit snugly against the outer wall of the opening of the cell culture chamber 2, or it can be embedded within the cell culture chamber 2 and snugly against the inner wall of the opening of the cell culture chamber 2. Both arrangements employ an interference fit, connected by static friction to ensure a stable seal. The direct contact of the sealing ring 31 with the cell culture chamber 2 mitigates impact during transport and reduces the possibility of leakage of liquid within the cell culture chamber 2.

[0058] In order to ensure air permeability of the cell culture chamber 2 during transportation, in some embodiments, the sealing pad 3 further includes a breathable membrane 32 , which is disposed on the inner side of the sealing ring 31 .

[0059] In some embodiments, as Figure 5 As shown, Figure 5 It is a porous sealing gasket 3 with a breathable membrane 32 on the inner side of the sealing ring 31. The breathable membrane 32 of different specifications can be matched as needed to allow the air pressure of the cell culture chamber 2 in the culture hole 11 to exchange gas with the external environment, ensuring sufficient permeability for long-term cell survival during transportation.

[0060] In other embodiments, Figure 6 As shown, Figure 6 The fully sealed gasket 3 has no breathable membrane 32 on the inner side of the sealing ring 31 and can be used for storage and preservation.

[0061] To facilitate picking up the cell culture chamber 2, in some embodiments, the sealing ring 31 does not contact the cell culture chamber 2. Specifically, the cell culture chamber 2 does not contact the sealing ring 31, so that when the sealing gasket 3 is opened, the cell culture chamber 2 is not affected by external forces and is thus carried out of the culture well 11 by the sealing ring 31, reducing operational risks.

[0062] To facilitate stable transportation of the cell culture chamber 2 , in some embodiments, the cell culture chamber 2 is at least partially located inside the sealing ring 31 .

[0063] Specifically, in this embodiment, Figure 8 As shown, combined with Figure 7 The top part of the cell culture chamber 2 is located on the inner side of the sealing ring 31. During transportation, the cell culture chamber 2 is located in the culture well 11. Due to the surrounding and protection of the sealing ring 31, the cell culture chamber 2 is prevented from directly colliding with the culture well 11, which can reduce vibration during transportation and reduce the possibility of leakage of the cell culture chamber 2.

[0064] In order to ensure reliable sealing performance between the sealing ring 31 on the sealing gasket 3 and the culture hole 11, in some embodiments, as shown in FIG. Figure 7 and 8 As shown, the maximum outer diameter of the sealing ring 31 is larger than the inner diameter of the culture hole 11, and the radius difference between the sealing ring 31 and the culture hole 11 ranges from 0.2 mm to 1.5 mm.

[0065] Specifically, when the maximum outer diameter of the sealing ring 31 is larger than the inner diameter of the culture well 11, the sealing ring 31 is inserted into and covers the opening of the culture well 11. The outward protrusion on the sealing ring 31 contacts the inner wall of the culture well 11, so that the sealing ring 31 can be fixed at the opening of the culture well 11 by static friction, making it more sealed. When the outer diameter of the outward protrusion on the sealing ring 31 is 0.5mm to 1.5mm larger than the inner diameter of the culture well 11, it can be fixed by static friction and is not easy to fall off. When using the required cell culture chamber 2 for operation, only one corner of the sealing gasket 3 can be lifted, the sealing ring 31 at the opening of the corresponding culture well 11 can be pulled out, and the corresponding cell culture chamber 2 can be taken out separately for operation, while the other culture wells 11 are still in a state of being sealed by the sealing gasket 3, thereby protecting the stability of the internal environment of the other cell culture chambers 2. In this embodiment, the outer diameter of the sealing ring 31 is 0.5 mm larger than the inner diameter of the culture well 11, and the silicone hardness is 30 Shore A. Tests have confirmed that this fit not only ensures reliable sealing performance but also facilitates press-fit installation. It is understood that the outer diameter of the sealing ring 31 and its dimensional relationship with the culture well 11 can be determined based on actual conditions and are not limited herein.

[0066] The culture plate of the present invention is provided with a sealing ring 31 on the sealing gasket 3. According to experimental verification, under the condition that the sealing and convenient pressing and installation are satisfied, a sealing ring 31 is provided at the position of the sealing gasket 3 of each culture well 11. The outer diameter of the sealing ring 31 is larger than the inner diameter of the culture well 11, and the size difference is preferably 0.5mm. The silicone hardness is preferably Shore A 30 degrees. During transportation, the cell culture chamber 2 is in the culture well 11. Due to the surrounding and protection of the sealing ring 31, the cell culture chamber 2 is not easily affected by impact and leakage. The sealing gasket 3 is made of medical materials and can be reused continuously under high-temperature sterilization, thereby improving its economy and safety. By arranging a breathable membrane 32 on the inner side of the sealing gasket 3, the air permeability in the cell culture chamber 2 is improved, making the simulation more natural. The breathable membrane 32 of different specifications can be matched as needed to ensure good air permeability during transportation and avoid being contaminated by the outside world while satisfying the air permeability.

[0067] In this utility model, unless otherwise specified or limited, the terms "installed," "connected," "connect," "fixed," etc. should be understood in a broad sense. For example, they can refer to fixed connection, detachable connection, or integration; mechanical connection, electrical connection; direct connection, indirect connection through an intermediate medium, internal communication between two components, or interaction between two components. Those skilled in the art will understand the specific meanings of the above terms in this utility model based on specific circumstances.

[0068] In the description of this utility model, it should be noted that the terms "center," "upper," "lower," "left," "right," "vertical," "horizontal," "inner," and "outer" and the like, indicating orientations or positional relationships, are based on the orientations or positional relationships shown in the accompanying drawings, or are the orientations or positional relationships in which the utility model product is typically placed when in use. These terms are intended solely to facilitate the description of this utility model and to simplify the description, and are not intended to indicate or imply that the device or component referred to must have a specific orientation, be constructed, or operate in a specific orientation. Therefore, they should not be construed as limitations on this utility model. Furthermore, the terms "first," "second," and "third," etc., are used solely to distinguish descriptions and should not be construed as indicating or implying relative importance.

[0069] Furthermore, terms such as "horizontal," "vertical," and "overhanging" do not necessarily imply that a component must be absolutely horizontal or overhanging, but rather that it 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 rather that it can be slightly tilted.

[0070] In the present invention, unless otherwise expressly specified or limited, a first feature being above or below a second feature may include the first and second features being in direct contact, or may include the first and second features being in contact not directly but through another feature between them. Furthermore, a first feature being above, above, and above the second feature includes the first feature being directly above and obliquely above the second feature, or simply means that the first feature is higher in level than the second feature. A first feature being below, below, and below the second feature includes the first feature being directly below and obliquely below the second feature, or simply means that the first feature is lower in level than the second feature.

[0071] Although the present invention has been described with reference to the above specific embodiments, it is obvious that those skilled in the art can make many substitutions, modifications and variations based on the above content. Therefore, all such substitutions, modifications and variations are included within the spirit and scope of the appended claims.

Claims

1. A culture plate, characterized in that include a plate body, the plate body comprising a plurality of culture wells; and a cover body, the cover body being detachably disposed on the plate body to form a closed space, the culture well being located in the closed space formed by the plate body and the cover body; Wherein, a sealing gasket is provided between the plate body and the cover body for independently sealing each of the culture wells.

2. A culture plate according to claim 1, characterized in that, The culture well includes a cell culture chamber, and the cell culture chamber includes: a basement membrane disposed at the bottom of the cell culture chamber; and The chamber pillar is arranged at the bottom of the cell culture chamber, and is used to separate the culture hole and the basement membrane.

3. A culture plate according to claim 2, characterized in that, The cell culture chamber further comprises a pick-up ring, which is arranged on the top of the cell culture chamber and has a side wall of the pick-up ring which is hollowed out and provided with a plurality of pick-up holes.

4. A culture plate according to claim 2, characterized in that, The sealing gasket includes a plurality of sealing rings opposite to the culture holes, and the sealing rings abut against the plate body or the cell culture chamber so that the cell culture chamber is located in an independent closed cavity.

5. A culture plate according to claim 4, characterized in that, The sealing ring is interference-fitted with the outer side or inner side of the opening of the culture hole.

6. A culture plate according to claim 4, characterized in that, The sealing ring is interference-fitted with the outer side or inner side of the opening of the cell culture chamber.

7. A culture plate according to claim 4, characterized in that: The sealing gasket further comprises a breathable membrane, and the breathable membrane is arranged on the inner side of the sealing ring.

8. A culture plate according to claim 5, characterized in that: There is no contact between the sealing ring and the cell culture chamber.

9. A culture plate according to claim 5, characterized in that: Part of the cell culture chamber is located inside the sealing ring.

10. A culture plate according to claim 8 or 9, characterized in that: The maximum outer diameter of the sealing ring is larger than the inner diameter of the culture hole, and the radius difference between the sealing ring and the culture hole ranges from 0.2 mm to 1.5 mm.

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