Organ chip

Abstract

The utility model relates to the field of cell culture, in particular to an organ chip which comprises a bottom plate, a culture tank detachably connected to the bottom plate and a protective cover used for protecting a liquid flow channel and the culture tank. The culture tank comprises a containing part and a microporous membrane. The accommodating part is cylindrical, one end of the accommodating part is open, and the other end is closed by a microporous membrane; the bottom plate is provided with a liquid flow channel used for containing a culture medium. The liquid flow channel is provided with a matching part and a communicating part penetrating through the two sides of the matching part. The matching part is used for accommodating and constraining the culture tank, and the communicating part is used for adding and taking liquid into and out of the liquid flow channel. And when the culture tank is detachably sleeved on the inner side of the matching part, the culture tank is separated from the bottom of the liquid flow channel. The protective cover detachably covers the bottom plate. Through the detachable design, the difficulty of model sampling and cell inoculation is reduced, dynamic culture can be realized through shaking of the communication part, the operation difficulty and cost are reduced, and the practicability is improved.

Description

Technical Field

[0001] This utility model relates to the field of cell culture, and in particular to an organ-on-a-chip. Background Technology

[0002] With the rapid development of fields such as medicine, biology, and toxicology, the shortcomings of traditional experimental models have gradually become apparent. For example, animal models, due to species differences, struggle to accurately reflect the physiological and pathological responses of the human body, while two-dimensional cell culture models, due to their overly simplistic systems, cannot reproduce the complex dynamic microenvironment characteristics of in vivo tissues. These models are no longer sufficient to meet the needs of current applications, and there is an urgent need to develop in vitro models that better reflect the structure and functional characteristics of human tissues.

[0003] The emergence of organ-on-a-chip and organoid technologies has provided new strategies for constructing human-derived biomimetic in vitro models. Organ-on-a-chip technology offers advantages such as precise fluid control, multi-cell co-culture, and tissue barrier simulation, enabling highly controllable reproduction of complex dynamic culture microenvironments. Organoids are 3D cellular structures formed by the in vitro self-assembly of stem cells or tissue precursors, capable of mimicking the developmental processes and key structural and functional characteristics of the source tissues and organs to a certain extent. The Microphysiological System aims to combine organ-on-a-chip and organoid technologies to reconstruct the dynamic microenvironment of tissues and organs in vitro, simulating multi-organ interactions and establishing a reliable platform for life science and medical research.

[0004] Existing organ-on-a-chip and microphysiological systems are generally complex in structure, requiring connection to external pumps and various tubing, making them difficult to operate and with poor reproducibility. Moreover, most cell culture modules are sealed inside the system, which seriously affects the convenience of sample collection and subsequent offline characterization, resulting in high operational difficulty and making it difficult to be widely used in mass culture. Utility Model Content

[0005] The purpose of this invention is to provide an organ-on-a-chip that facilitates sample collection.

[0006] To achieve the above objectives, this utility model provides the following technical solution:

[0007] An organ-on-a-chip, comprising:

[0008] A culture tank includes a receiving part and a microporous membrane. The receiving part is cylindrical, with one end open and the other end closed through the microporous membrane.

[0009] The base plate has a liquid channel for containing culture medium. The liquid channel has a mating part and a connecting part that extends through both sides of the mating part. The mating part is used to contain and constrain the culture tank. The connecting part is used for adding and removing liquid from the liquid channel. When the culture tank is detachably fitted inside the mating part, the culture tank is separated from the bottom of the liquid channel.

[0010] A protective cover is placed on the base plate to protect the liquid flow channel and the culture tank.

[0011] Optionally, the organ-on-a-chip further includes a sealing plate connected to the base plate. The shape of the sealing plate is compatible with the base plate and the protective cover. The sealing plate has a mating part corresponding to the liquid flow channel and a through-hole-shaped constraint hole that fits into the outer wall of the culture tank. The sealing plate also has a through-hole-shaped injection hole corresponding to the connecting part of the liquid flow channel.

[0012] Optionally, multiple culture tanks are sequentially connected by several connectors to form a plug-in group, and the connectors are connected to the end of the receiving portion away from the microporous membrane. Multiple liquid channels on the base plate are arranged in an array, with multiple liquid channels arranged in a row along a first direction and multiple liquid channels arranged in a column along a second direction. The plug-in group is arranged parallel to the first direction and can be detached from multiple columns of liquid channels.

[0013] Optionally, each of the liquid flow channels includes a plurality of mating parts arranged along the second direction, and the plurality of mating parts of the same liquid flow channel are interconnected.

[0014] Optionally, the plug-in assembly is provided with a handle at at least one end in the first direction, and the handle extends to the outer side of the edge of the base plate. The protective cover is detachably provided on the top and side of the base plate, and the side of the protective cover is provided with a through groove corresponding to the handle.

[0015] The ratio of the number of columns of the liquid flow channels to the number of culture tanks in the plug-in group is 1 or 2.

[0016] Optionally, the surface of the sealing plate away from the base plate is formed with a limiting groove that mates with the connector and the handle, the limiting groove being used to constrain the plug assembly.

[0017] Optionally, a columnar positioning shaft is connected to the side of the sealing plate near the base plate, and at least one of the positioning shafts has a buckle on its surface. The side of the base plate near the sealing plate has a positioning hole that matches the positioning shaft, and the buckle is detachably connected to the corresponding positioning hole.

[0018] Optionally, the end of the receiving portion near the microporous membrane converges inward to form an annular step portion, and the microporous membrane is connected to the side of the step portion away from the opening of the receiving portion.

[0019] Optionally, a raised anti-slip frame is formed on the side of the base plate away from the protective cover, and a set of inserts that cooperate with the anti-slip frame are formed on the side of the protective cover away from the base plate. Multiple inserts are inserted into the inner side of the anti-slip frame to constrain another base plate placed above the protective cover.

[0020] Optionally, the inner diameter of the culture tank is any value between 3mm and 7mm, the outer diameter is any value between 6mm and 10mm, the height is any value between 6.5mm and 12mm, the depth of the liquid flow channel is any value between 7.5mm and 13mm, the maximum tilt angle of the organ-on-a-chip when it shakes is any value between 6° and 9°, and the angular velocity is any value between 5rpm and 15rpm.

[0021] The beneficial effects of this invention are as follows: By setting a microporous membrane, it is convenient to form models of sandwiched tissues or membraneless monolayer tissues through cell inoculation. Cell culture medium is injected into the liquid channel, and the culture tank is installed in the fitting part. Simply by shaking the base plate, the culture medium flows between the two ends of the connecting part of the liquid channel, thus keeping the culture medium in the fitting part in a flowing state, achieving dynamic culture of cells inoculated in the culture tank in a simple way. Since the culture tank is detachably connected to the base plate, it facilitates model sampling and allows for rapid continuation of the next culture after the first one is completed, helping to reduce operational difficulty and improve culture efficiency, thereby enhancing the practicality of organ-on-a-chip in situations with large culture demands.

[0022] 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

[0023] Figure 1 This is a structural disassembly diagram of the organ-on-a-chip shown in Embodiment 1 of this utility model;

[0024] Figure 2 This is a bottom view of the organ-on-a-chip shown in Embodiment 1 of this utility model;

[0025] Figure 3 for Figure 2 Cross-sectional view at point A-A'.

[0026] Legend: 1-Base plate, 11-Flow channel, 12-Liquid flow channel, 121-Matching part, 122-Connecting part, 13-Anti-slip frame, 141-First positioning hole, 142-Second positioning hole, 2-Sealing plate, 21-Constraint hole, 22-Injection hole, 231-First positioning shaft, 232-Snap fastener, 24-Limiting groove, 3-Plug-in group, 31-First plug-in group, 32-Second plug-in group, 33-Cultural tank, 331-Containing part, 332-Extension part, 333-Microporous membrane, 334-Step part, 34-Connector, 35-Handle, 4-Protective cover, 41-Through groove, 42-Insertion strip. Detailed Implementation

[0027] The technical solution of this utility model will now be clearly and completely described with reference to the accompanying drawings. Obviously, the described embodiments are only some, not all, of the embodiments of this utility model. Based on the embodiments of this utility model, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this utility model.

[0028] In the description of this utility model, it should be noted that the terms "center," "upper," "lower," "left," "right," "vertical," "horizontal," "inner," and "outer," etc., indicating the orientation or positional relationship, are based on the orientation or positional relationship shown in the accompanying drawings and are only for the convenience of describing this utility model and 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, and therefore should not be construed as a limitation of this utility model. Furthermore, the terms "first," "second," and "third" are used for descriptive purposes only and should not be construed as indicating or implying relative importance.

[0029] In the description of this utility model, it should be noted that, unless otherwise explicitly specified and limited, the terms "installation," "connection," and "joining" 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 utility model based on the specific circumstances.

[0030] Furthermore, the technical features involved in the different embodiments of this utility model described below can be combined with each other as long as they do not conflict with each other.

[0031] Please see Figure 1The organ-on-a-chip protected by this utility model includes a base plate 1, a culture tank 33 detachably connected to the base plate 1, and a protective cover 4 for protecting the liquid channel 12 and the culture tank 33. The culture tank 33 includes a receiving portion 331 and a microporous membrane 333. The receiving portion 331 is cylindrical, with one end open and the other end closed through the microporous membrane 333. The base plate 1 has a liquid channel 12 for receiving the culture medium. The liquid channel 12 has a fitting portion 121 and a connecting portion 122 penetrating both sides of the fitting portion 121. The fitting portion 121 is used to receive and constrain the culture tank 33, and the connecting portion 122 is used for adding and removing liquid from the liquid channel 12. When the culture tank 33 is detachably fitted inside the fitting portion 121, the culture tank 33 is separated from the bottom of the liquid channel 12. The protective cover 4 is detachably fitted onto the base plate 1.

[0032] By incorporating a microporous membrane 333, it is convenient to form models of membrane-bound or membrane-free monolayer tissues through cell seeding, and to facilitate the entry of culture medium into the culture tank 33. Cell culture medium is injected into the liquid channel 12, and the culture tank 33 is housed within the fitting part 121. Simply by shaking the base plate 1, the culture medium flows between the two ends of the connecting part 122 of the liquid channel 12, thus keeping the culture medium in the fitting part 121 in a flowing state. This simple method achieves dynamic culture of cells seeded in the culture tank 33, helping to reduce operational difficulty and culture costs. Since the culture tank 33 is detachably connected to the base plate 1, it facilitates model sampling and allows for rapid continuation of the next culture after the first one is completed, further reducing operational difficulty and improving culture efficiency. This enhances the practicality of organ-on-a-chip systems in situations with high culture demands.

[0033] In some embodiments, the organ-on-a-chip further includes a sealing plate 2 connected to the base plate 1. The sealing plate 2 is shaped to fit the base plate 1 and the protective cover 4. The sealing plate 2 has a mating portion 121 corresponding to the liquid flow channel 12 and a through-hole-shaped constraint hole 21 that fits the outer wall of the culture tank 33. The sealing plate 2 also has a through-hole-shaped injection hole 22 corresponding to the connecting portion 122 of the liquid flow channel 12. By providing the sealing plate 2, it helps to reduce the evaporation of the culture medium in the liquid flow channel 12 and facilitates the constraint of the position of the culture tank 33, preventing the culture tank 33 from shaking significantly relative to the base plate 1, thus helping to improve the culture quality.

[0034] In some embodiments, multiple culture tanks 33 are sequentially connected by several connectors 34 to form a plug-in group 3. The connectors 34 are connected to the end of the receiving portion 331 away from the microporous membrane 333. Multiple liquid channels 12 on the base plate 1 are arranged in an array. The multiple liquid channels 12 are arranged in a row along a first direction, and the multiple liquid channels 12 are arranged in a column along a second direction. The plug-in group 3 is arranged parallel to the first direction and is detachable from multiple columns of liquid channels 12. By setting up the plug-in group 3, the efficiency of installation and removal is improved. It is also used to connect substrates for building the same model, which facilitates model differentiation, thereby reducing the difficulty of operation and improving efficiency.

[0035] In some embodiments, each liquid flow channel 12 includes a plurality of mating parts 121 arranged along a second direction, and the plurality of mating parts 121 in the same liquid flow channel 12 are interconnected. By providing a plurality of interconnected mating parts 121, and by seeding different cells in a plurality of culture tanks 33 installed in the same liquid flow channel 12, the culture environments of different cells are interconnected, which facilitates the construction of a model simulating the interaction between organs.

[0036] In some embodiments, the plug-in assembly 3 is provided with a handle 35 at at least one end in the first direction, and the handle 35 extends to the outer edge of the base plate 1. The protective cover 4 is detachably provided on the top and side of the base plate 1, and the side of the protective cover 4 is provided with a through groove 41 corresponding to the handle 35. By providing the handle 35, the installation and removal of the plug-in assembly 3 are facilitated, which helps to reduce the difficulty of operation and improve practicality.

[0037] In some embodiments, the ratio of the number of columns of liquid flow channels 12 to the number of culture tanks 33 in the plug-in group 3 is 1 or 2, which facilitates the arrangement and installation of the plug-in group 3.

[0038] In some embodiments, the surface of the sealing plate 2 away from the base plate 1 is formed with a limiting groove 24 that matches the connector 34 and the handle 35. The limiting groove 24 is used to constrain the plug assembly 3 and prevent the plug assembly 3 from sliding significantly with the shaking of the base plate 1.

[0039] In some embodiments, a columnar positioning shaft is connected to the side of the sealing plate 2 near the base plate 1, and a buckle 232 is provided on the surface of at least one positioning shaft. The side of the base plate 1 near the sealing plate 2 is provided with a positioning hole that matches the positioning shaft, and the buckle 232 is detachably connected to the corresponding positioning hole, which facilitates the positioning and installation of the sealing plate 2.

[0040] In some embodiments, the end of the receiving portion 331 near the microporous membrane 333 converges inward to form an annular step portion 334. The microporous membrane 333 is connected to the side of the step portion 334 away from the opening of the receiving portion 331. The step portion 334 and the microporous membrane 333 form a groove with a small bottom area, which facilitates the formation of droplets of cell-gel mixture during three-dimensional gel culture or organoid model construction, thereby reducing the difficulty of operation and improving the culture quality.

[0041] In some embodiments, a raised anti-slip frame 13 is formed on the side of the base plate 1 away from the protective cover 4, and a set of inserts 42 that cooperate with the anti-slip frame 13 are formed on the side of the protective cover 4 away from the base plate 1. Multiple inserts 42 are inserted into the inner side of the anti-slip frame 13 to constrain another base plate 1 placed above the protective cover 4, preventing the multi-layered stacked organ-on-a-chip from becoming misaligned or even collapsing during shaking culture.

[0042] In some embodiments, the inner diameter of the culture tank 33 is any value from 3mm to 7mm, for example, any value from 3mm, 4mm, 5mm, 6mm, and 7mm; the outer diameter is any value from 6mm to 10mm, for example, any value from 6mm, 7mm, 8mm, 9mm, and 10mm; the height is any value from 6.5mm to 12mm, for example, any value from 6.5mm, 8mm, 9.5mm, 11mm, and 12mm; the depth of the liquid flow channel 12 is any value from 7.5mm to 13mm, for example, any value from 7.5mm, 9mm, 10.5mm, 12mm, and 13mm; the maximum tilt angle when the organ-on-a-chip shakes is any value from 6° to 9°, for example, any value from 6°, 7°, 8°, and 9°; and the angular velocity is any value from 5rpm to 15rpm, for example, any value from 5rpm, 7rpm, 9rpm, 11rpm, 13rpm, and 15rpm, which helps to prevent cell damage.

[0043] Please refer to the following examples for details.

[0044] Example 1:

[0045] Please see Figure 1 The organ-on-a-chip shown in a preferred embodiment of this application includes a base plate 1, a sealing plate 2, a plug-in group 3, and a protective cover 4.

[0046] Please see Figure 1 and Figure 2The base plate 1 is constructed as a rectangular plate, with one side surface protruding upwards to form a flow channel 11, giving the edge of the base plate 1 a stepped appearance. One corner of the flow channel 11 is chamfered to mark the orientation of the base plate 1. Liquid flow channels 12 for containing culture medium are formed on the surface of the flow channel 11 of the base plate 1. Multiple independent liquid flow channels 12 are arranged in an array, with six liquid flow channels 12 arranged parallel to a first direction forming a row, and two liquid flow channels 12 arranged parallel to a second direction forming a column, with the first and second directions parallel to the two edges of the base plate 1, respectively. Each liquid flow channel 12 includes a mating portion 121 and a connecting portion 122. Two identical circular mating portions 121 are arranged along the second direction, and a straight connecting portion 122 penetrates the center of both mating portions 121, with its two ends located on opposite sides of each mating portion 121, allowing the two mating portions 121 to communicate with each other. In this embodiment, the diameter of the mating part 121 is 12mm, the width of the connecting part 122 is 6mm, and the depth of the liquid flow channel 12 is 13mm. To save on raw material costs, all structures of the base plate 1 are formed by a thin shell structure. Therefore, the side of the base plate 1 away from the flow channel part 11 is hollowed out, and a rectangular frame-shaped anti-slip frame 13 is formed at the edge.

[0047] The sealing plate 2 is constructed as a thin plate and is detachably connected to the flow channel surface of the base plate 1. The shape of the sealing plate 2 fits the flow channel portion 11 of the base plate 1, and multiple sets of constraint holes 21 corresponding to the mating portions 121 of the liquid flow channel 12 and through-hole-shaped injection holes 22 corresponding to the connecting portions 122 of the liquid flow channel 12 are formed thereon. The diameter of the constraint hole 21 is equal to the diameter of the mating portion 121, and the two injection holes 22 correspond to the two ends of the connecting portion 122, respectively, and their diameters are equal to the width of the connecting portion 122. Multiple positioning shafts are formed on the side of the sealing plate 2 near the base plate 1. The positioning shafts include a first positioning shaft 231 and a second positioning shaft. The first positioning shaft 231 is constructed as a rectangular column and is located at the four corners of the sealing plate 2, parallel to the first direction. The side of the first positioning shaft 231 away from the sealing plate 2 expands towards the outside of the sealing plate 2, forming a beveled buckle 232. A cylindrical second positioning shaft is disposed near two edges of the sealing plate 2 parallel to the first direction and located in the middle of the sealing plate 2. The base plate 1 has positioning holes that mate with the positioning shafts, wherein the first positioning shaft 231 corresponds to the first positioning hole 141, and the second positioning shaft corresponds to the second positioning hole 142. The second positioning height is greater than that of the first positioning shaft 231, facilitating positioning before the sealing plate 2 is detachably connected to the base plate 1.

[0048] Please see Figure 1 and Figure 3The plug-in group 3 includes two types: a first plug-in group 31 and a second plug-in group 32. Both plug-in groups 3 include three linearly arranged culture tanks 33, a connector 34 for connecting the culture tanks 33, and a handle 35. The culture tank 33 of the first plug-in group 31 includes a receiving portion 331, an extension portion 332, and a microporous membrane 333. The receiving portion 331 is vertically arranged and constructed as a cylinder open at both ends, with one end connected to the extension portion 332 and the other end connected to the microporous membrane 333. The microporous membrane 333 seals the end side of the receiving portion 331, making the receiving portion 331 closed on one side. The extension portion 332 is inclined and constructed as a long strip, with one end constructed as an arc shape to fit the receiving portion 331 and connected to the receiving portion 331, and the other end constructed as an arc shape concentric with the receiving portion 331 and with a larger diameter, fitting the constraint hole 21. Two extensions 332 are connected to the same receiving portion 331, and the horizontal direction of the extensions 332 is parallel to the arrangement direction of the culture tanks 33 in the same group. A flat connector 34 is connected to the end of each extension 332 away from the receiving portion 331. Adjacent connectors 34 in the same plug-in group 3 are connected to each other at the ends away from the culture tanks 33. A handle 35 is connected to the connector 34 located on the outer side of the culture tank 33 and extends horizontally away from each culture tank 33, with its width gradually increasing for easy gripping. In this embodiment, the inner diameter of the receiving portion 331 is 7 mm, the outer diameter is 10 mm, and the total height of the culture tanks 33 is 12 mm.

[0049] The only structural difference between the second plug-in group 32 and the first plug-in group 31 is that the end of its receiving portion 331 near the microporous membrane 333 converges inward to form a ring-shaped stepped portion 334, and the microporous membrane 333 is connected to the side of the stepped portion 334 away from the opening of the receiving portion 331. The stepped portion 334 and the microporous membrane 333 form a groove-like structure for seeding cells during three-dimensional gel culture or the construction of organoid models.

[0050] The plug-in assembly 3 is arranged parallel to the first direction, and each culture tank 33 within it passes through the constraint hole 21 and is partially embedded in the mating part 121 of the liquid flow channel 12. Since the outer diameter of the culture tank 33 is smaller than the inner diameter of the mating part 121, the fluidity of the culture medium within the liquid flow channel 12 is ensured. The end of the handle 35 furthest from each culture tank 33 is located outside the sealing plate 2 for easy gripping. A limiting groove 24 is formed on the surface of the sealing plate 2 furthest from the base plate 1, which mates with the connector 34 and the handle 35, for constraining the plug-in assembly 3.

[0051] The protective cover 4 is detachably mounted on the top and side of the flow channel 11 and the sealing plate 2 of the base plate 1, and its structure fits the flow channel 11 to protect the liquid flow channel 12 and the culture tank 33. The bottom of the protective cover 4 is supported by a stepped structure below the flow channel 11, and its outer wall fits the anti-slip frame 13. The side of the protective cover 4 has through grooves 41 that fit the handles 35 of each plug-in assembly 3, so that the protective cover 4 can still be mounted on the base plate 1 when the base plate 1 is fully loaded with plug-in assemblies 3. The four corners of the top outer wall of the protective cover 4 have protruding inserts 42, which extend along the edge of the protective cover 4, and their outer walls fit the inner wall of the anti-slip frame 13, which facilitates the positioning and limiting of organ-on-a-chip when multiple layers are stacked.

[0052] In this embodiment, the main body of the organ-on-a-chip is constructed of polycarbonate (PC), and the various components are fabricated through machining. The microporous membrane 333 is constructed of polyethylene terephthalate (PET), and the pore size is 2 μm.

[0053] In this embodiment, when constructing the organ-on-a-chip model, endothelial cells are first concentrated on the side of the microporous membrane 333 of the second plug-in group 32 away from the receiving part 331. Then, the organoids, along with the matrix gel, are seeded in the culture tank 33 within the groove formed by the step part 334 and the microporous membrane 333. The culture is then incubated in an incubator until the matrix gel solidifies. Endothelial cell culture medium is added to the liquid channel 12, and the sealing plate 2 is installed on the base plate 1. The second plug-in group 32 is then installed on the sealing plate 2 and the base plate 1, and organoid culture medium is added to the second plug-in group 32. The protective cover 4 is then closed. The organ-on-a-chip is placed on a shaker for culture. The shaker rotates along the central axis in a vertical plane, and the horizontal direction of the shaker's movement is parallel to the second direction. The maximum tilt angle of the shaker is 6°, and the angular velocity is 15 rpm. As a large amount of culture medium in the liquid channel 12 evaporates over time, culture medium is replenished into the liquid channel 12 through the injection hole 22. After culturing a set of samples, the same second plug-in group 32 can be put back in after the second plug-in group 32 is removed to continue culturing, which helps to improve efficiency.

[0054] Example 2:

[0055] The difference between this embodiment and Embodiment 1 is that:

[0056] In this embodiment, the organ-on-a-chip is made of polyethylene terephthalate (PET), and the components are manufactured by injection molding. The diameter of the mating portion 121 of the liquid flow channel 12 on the base plate 1 is 8 mm, the width of the connecting portion 122 is 4 mm, and the depth of the liquid flow channel 12 is 7.5 mm. One plug-in assembly 3 includes six culture tanks 33, the inner diameter of the receiving portion 331 is 3 mm, the outer diameter is 6 mm, the total height of the culture tanks 33 is 6.5 mm, and the microporous membrane 333 is made of PC material with micropores having a pore size of 8 μm.

[0057] During model construction, epithelial and endothelial cells were seeded on both sides of the microporous membrane 333 of the second plug-in group 32 of the culture insert, and incubated statically in an incubator until the cells were completely adhered. Endothelial cell culture medium was added to the liquid channel 12, and the sealing plate 2 was installed on the base plate 1. The second plug-in group 32 was then installed on the sealing plate 2 and the base plate 1, and epithelial cell culture medium was added to the second plug-in group 32. The protective cap 4 was then closed. The organ-on-a-chip was placed on a shaker for culture, with a maximum tilt angle of 9° and an angular velocity of 5 rpm.

[0058] The technical features of the above embodiments can be combined in any way. For the sake of brevity, not all possible combinations of the technical features in the above embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0059] The embodiments described above are merely illustrative of several implementations of this utility model, and while the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the utility model patent. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of this utility model, and these all fall within the protection scope of this utility model. Therefore, the protection scope of this utility model patent should be determined by the appended claims.

Claims

1. An organ-on-a-chip, characterized in that, include: The culture tank (33) includes a receiving part (331) and a microporous membrane (333). The receiving part (331) is cylindrical, with one end open and the other end closed through the microporous membrane (333). The base plate (1) has a liquid channel (12) for containing culture medium. The liquid channel (12) has a mating part (121) and a connecting part (122) penetrating both sides of the mating part (121). The mating part (121) is used to contain and constrain the culture tank (33). The connecting part (122) is used for adding and removing liquid from the liquid channel (12). When the culture tank (33) is detachably fitted inside the mating part (121), the culture tank (33) is separated from the bottom of the liquid channel (12). A protective cover (4) is placed on the base plate (1) to protect the liquid flow channel (12) and the culture tank (33).

2. The organ-on-a-chip as described in claim 1, characterized in that, It also includes a sealing plate (2) connected to the base plate (1). The shape of the sealing plate (2) is matched with the base plate (1) and the protective cover (4). The sealing plate (2) has a mating part (121) corresponding to the liquid flow channel (12) and a through-hole-shaped constraint hole (21) that fits the outer wall of the culture tank (33). The sealing plate (2) also has a through-hole-shaped injection hole (22) corresponding to the connecting part (122) of the liquid flow channel (12).

3. The organ-on-a-chip as described in claim 2, characterized in that, Multiple culture tanks (33) are connected in sequence by several connectors (34) to form a plug-in group (3), and the connectors (34) are connected to the end of the receiving part (331) away from the microporous membrane (333). Multiple liquid channels (12) on the base plate (1) are arranged in an array. Multiple liquid channels (12) are arranged in a row along the first direction, and multiple liquid channels (12) are arranged in a column along the second direction. The plug-in group (3) is set parallel to the first direction and can be detached from multiple columns of liquid channels (12).

4. The organ-on-a-chip as described in claim 3, characterized in that, Each of the liquid flow channels (12) includes a plurality of mating parts (121) arranged along the second direction, and the plurality of mating parts (121) of the same liquid flow channel (12) are interconnected.

5. The organ-on-a-chip as described in claim 3, characterized in that, The plug-in assembly (3) is provided with a handle (35) at at least one end in the first direction, and the handle (35) extends to the outer side of the edge of the base plate (1). The protective cover (4) is detachably covered on the top and side of the base plate (1), and the side of the protective cover (4) is provided with a through groove (41) corresponding to the handle (35). The ratio of the number of columns of the liquid flow channel (12) to the number of culture tanks (33) in the plug-in group (3) is 1 or 2.

6. The organ-on-a-chip as described in claim 5, characterized in that, The sealing plate (2) has a limiting groove (24) formed on the surface away from the base plate (1) that matches the connector (34) and the handle (35). The limiting groove (24) is used to constrain the plug assembly (3).

7. The organ-on-a-chip as described in claim 2, characterized in that, The sealing plate (2) is connected to a columnar positioning shaft on the side near the base plate (1). At least one of the positioning shafts is provided with a buckle (232) on its surface. The base plate (1) is provided with a positioning hole that matches the positioning shaft on the side near the sealing plate (2). The buckle (232) is detachably connected to the corresponding positioning hole.

8. The organ-on-a-chip as described in claim 1, characterized in that, The receiving portion (331) near the end of the microporous membrane (333) converges inward to form an annular stepped portion (334), and the microporous membrane (333) is connected to the side of the stepped portion (334) away from the opening of the receiving portion (331).

9. The organ-on-a-chip as described in claim 1, characterized in that, The base plate (1) has a raised anti-slip frame (13) on the side away from the protective cover (4), and the protective cover (4) has a set of inserts (42) that cooperate with the anti-slip frame (13) on the side away from the base plate (1). A plurality of inserts (42) are inserted into the inside of the anti-slip frame (13) to constrain another base plate (1) placed above the protective cover (4).

10. The organ-on-a-chip according to any one of claims 1 to 9, characterized in that, The inner diameter of the culture tank (33) is any value between 3mm and 7mm, the outer diameter is any value between 6mm and 10mm, the height is any value between 6.5mm and 12mm, the depth of the liquid flow channel (12) is any value between 7.5mm and 13mm, the maximum tilt angle of the organ-chip when it shakes is any value between 6° and 9°, and the angular velocity is any value between 5rpm and 15rpm.

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