An organoid dynamic culture device and system

Abstract

The application discloses an organoid dynamic culture device and system, which comprises a culture frame and a plurality of culture mechanisms. The culture mechanism comprises a driving assembly, a reactor and an upper cover assembly. The driving assembly is arranged in the culture frame. The upper cover assembly is located above the driving assembly and is connected with the culture frame. The upper cover assembly can move up and down relative to the culture frame. The reactor is located between the driving assembly and the upper cover assembly. The reactor comprises a cylindrical container, a container cover and a connecting shaft. The top end of the container extends into the container cover. The bottom end of the container is detachably connected with the driving assembly. The top end of the container cover is detachably connected with the upper cover assembly. The connecting shaft is located in the container. The bottom end of the connecting shaft is formed with an inverted conical frustum structure. The application can improve the consistency of organoid culture batches.

Description

Technical Field

[0001] This invention relates to the field of organoid in vitro culture technology, and specifically to an organoid dynamic culture device and system. Background Technology

[0002] Organoids, as primary cells cultured in a three-dimensional in vitro environment, can be used for disease modeling, drug screening, regenerative medicine, and precision medicine. With the development of engineered organoids (such as droplet organoids and multi-cell co-cultured organoids), culture systems have evolved from "small-scale, static, low-throughput" to "large-scale, dynamic, high-throughput, controllable mechanical microenvironment, and reproducible process windows." Dynamic culture can provide better conditions for material exchange (oxygen, nutrients, and metabolite removal) and can regulate organoid morphology and maturity through mechanical stimuli such as shearing.

[0003] Existing dynamic organoid culture devices typically employ stirred reactors. These reactors generally include a reactor body, a lid fitted to the top of the reactor body, a drive assembly located on the lid, and a stirring shaft positioned at the center of the reactor body. One end of the stirring shaft is close to the bottom of the reactor body, while the other end is connected to the drive assembly. The stirring shaft is equipped with blades. During dynamic culture of organoids (droplet organoids), culture medium is first added to the reactor body. Then, the organoids are placed in the area between one end of the stirring shaft and the bottom of the reactor body. The drive assembly then rotates the stirring shaft and blades, causing the blades to move the fluid composed of organoids and culture medium, generating shear force (also known as shear stress, which refers to the tangential force exerted by the fluid on a unit area of ​​the cell surface). This mixes the organoids and culture medium, continuously supplying oxygen and nutrients to the organoids while removing their metabolites. This maintains the activity and healthy growth of the organoids. Furthermore, the stimulation of this shear force can regulate the morphology and maturity of the organoids, thus achieving dynamic culture of organoids. However, the process of fluid flow driven by the blades can easily generate eddies, turbulence and shear peaks, which can easily damage organoids or cause abnormal organoid fusion. Under high-throughput culture, the consistency of organoid culture batches is reduced. Summary of the Invention

[0004] To overcome the shortcomings of the prior art, the present invention provides an organoid dynamic culture device and system, which can improve the consistency of organoid culture batches.

[0005] The technical solution adopted by this invention to solve its technical problem is: A first aspect of the present invention provides a dynamic organoid culture device, comprising a culture rack and a plurality of culture mechanisms. Each culture mechanism includes a drive assembly, a reactor, and a top cover assembly. The drive assembly is disposed within the culture rack. The top cover assembly is located above the drive assembly and connected to the culture rack. The top cover assembly is movable vertically relative to the culture rack. The reactor is located between the drive assembly and the top cover assembly. The reactor includes a cylindrical container, a container lid, and a connecting shaft. The top end of the container extends into the container lid, and the bottom end of the container is detachably connected to the drive assembly. The top end of the container lid is detachably connected to the top cover assembly. The connecting shaft is located within the container, and the bottom end of the connecting shaft forms an inverted frustum structure. The connecting shaft, the inverted frustum structure, and the container are coaxially arranged. The inverted frustum structure is close to the bottom of the container and forms a culture zone between the inverted frustum structure and the bottom of the container. The top end of the connecting shaft extends from the top end of the container and is connected to the container lid.

[0006] As a preferred technical solution, the angle between the inclined plane and the horizontal plane of the inverted truncated cone structure is 5 degrees to 15 degrees.

[0007] As a preferred technical solution, the driving assembly includes a driving component and a connecting plate. The driving component is disposed on one inner wall of the culture rack, and the connecting plate is sleeved on the outer periphery of the output shaft of the driving component. The bottom end of the container and the connecting plate are magnetically connected by a first magnetic attraction structure. The driving component is used to drive the connecting plate to rotate, thereby driving the container to rotate.

[0008] As a preferred technical solution, the first magnetic attraction structure includes a first magnet and a first attraction piece. The first magnet is disposed at the top of the connecting plate, and the first attraction piece is disposed at the bottom of the container. The first attraction piece and the first magnet are magnetically connected.

[0009] As a preferred technical solution, the bottom end of the container is provided with a positioning protrusion, and the connecting plate is provided with a positioning hole, wherein the positioning protrusion and the positioning hole cooperate with each other.

[0010] As a preferred technical solution, the upper cover assembly includes a lower connecting plate, an upper connecting plate, and at least two guide posts. The top of the container cover is magnetically connected to the lower connecting plate via a second magnetic attraction structure. The upper connecting plate is located above the culture rack and is equipped with an upper cover fastener. The two guide posts are symmetrically arranged about the center of the lower connecting plate. One end of each guide post is detachably connected to the lower connecting plate, and the other end of each guide post passes through a first groove at the top of the culture rack and a second groove at the top of the culture rack, and is detachably connected to the upper connecting plate. A plurality of gaskets are arranged around the outer periphery of the guide post, and the gaskets are stacked sequentially from bottom to top between the upper connecting plate and the top of the culture rack. A ring is formed at the bottom of the first groove, and the ring is fitted around the outer periphery of the guide post. The guide post can move up and down relative to the ring and the culture rack. An elastic element is fitted around the outer periphery of the ring and the guide post. One end of the elastic element is connected to one end of the guide post, and the other end of the elastic element is connected to the bottom of the first groove.

[0011] As a preferred technical solution, the second magnetic structure includes a second magnet and a second suction piece. The second magnet is disposed at the bottom end of the lower connecting plate, and the second suction piece is disposed at the top end of the container lid. The second suction piece and the second magnet are magnetically connected.

[0012] As a preferred technical solution, the top end of the connecting shaft is provided with a first mounting hole, the top end of the container cover is provided with a second mounting hole corresponding to the first mounting hole, a connecting fastener is installed in the first mounting hole and the second mounting hole, the head of the connecting fastener is located above the container cover, the lower connecting plate is provided with a positioning through hole that passes through its top and bottom ends, and the head of the connecting fastener cooperates with the positioning through hole.

[0013] As a preferred technical solution, the top end of the connecting shaft is provided with a positioning block, and the top of the container lid is provided with a positioning groove, the positioning block cooperating with the positioning groove.

[0014] A second aspect of the present invention provides an organoid dynamic culture system, including a control device and the organoid dynamic culture apparatus described in the above technical solution. The control device includes a housing, a control module, a power module, and a switch button. The housing is disposed on one side of the culture rack. The control module and the power module are both disposed inside the housing. The switch button is disposed at one end of the housing. The drive components of a plurality of culture mechanisms of the organoid dynamic culture apparatus, the power module, and the switch button are all electrically connected to the control module.

[0015] The beneficial effects of this invention are as follows: The organoid dynamic culture device of this invention includes a driving component, a reactor, and a cover component. The driving component drives the container of the reactor to rotate at a low speed relative to the container cover. This causes the fluid composed of culture medium and organoids within the container to flow around the axis of the connecting shaft and the inverted frustum-shaped structure, generating low shear force. This mixes the organoids and culture medium, continuously supplying oxygen and nutrients to the organoids while removing their metabolites. This maintains the activity and healthy growth of the organoids. Furthermore, the morphology and maturity of the organoids can be regulated by the stimulation of this shear force, thus achieving dynamic culture of organoids. In the dynamic culture of organoids, the inverted truncated cone structure remains stationary while the container rotates at a low speed, thus creating a Taylor-Couette flow field within the culture zone. By controlling the container's rotational speed and the viscosity of the culture medium to keep the Reynolds number below the turbulence threshold, the generation of eddies and turbulence can be reduced. Simultaneously, the inclined surface of the inverted truncated cone structure allows the structure and container to form a generalized cone-plate flow, resulting in a uniform shear force distribution within the culture zone. This maintains a laminar flow field, preventing shear spikes and thus avoiding damage to the organoids or abnormal organoid fusion. Under high-throughput culture, this improves the consistency of organoid culture batches. Attached Figure Description

[0016] The present invention will be further described below with reference to the accompanying drawings and embodiments.

[0017] Figure 1 This is a first-angle structural schematic diagram of an organoid dynamic culture system provided in an embodiment of the present invention; Figure 2 yes Figure 1 The diagram shows a second-angle structural schematic of the organoid dynamic culture system. Figure 3 yes Figure 1 The diagram shows the third-angle structural schematic of the organoid dynamic culture system. Figure 4 yes Figure 1 A first-angle cross-sectional view of the organoid dynamic culture system shown. Figure 5 yes Figure 1 A second-angle cross-sectional view of the organoid dynamic culture system shown. Figure 6 yes Figure 1 A cross-sectional view of the organoid dynamic culture device of the organoid dynamic culture system shown, after removing the top cover assembly. Figure 7 yes Figure 1 A cross-sectional schematic diagram of the top cover assembly and culture rack of the organoid dynamic culture device in the shown organoid dynamic culture system; Figure 8 This is a schematic diagram of the shear force versus position curve obtained through CFD simulation; Figure 9 This is a screenshot from a particle tracer experiment.

[0018] Figure label: 100. Organoid dynamic culture device; 10. Culture rack; 11. Clearance hole; 12. First groove; 13. Ring; 20. Cultivation mechanism; 21. Drive assembly; 211. Drive component; 212. Connecting plate; 2121. Connecting plate mounting groove; 2122. Positioning hole; 213. First magnet; 214. First suction plate; 22. Reactor; 221. Container; 2212. Positioning protrusion; 222. Container lid; 2221. Connecting fastener; 2222. Positioning groove; 223. Connecting shaft; 2231. Positioning block; 224. Inverted frustum structure; 2241. Inclined surface 225. Cultivation area; 23. Upper cover assembly; 231. Lower connecting plate; 2311. First mounting position; 2312. First mounting fastener; 2313. Positioning through hole; 2314. Connecting plate mounting groove; 232. Upper connecting plate; 2321. Upper cover fastener; 2322. Third mounting position; 2323. Second mounting fastener; 233. Guide post; 234. Gasket; 235. Elastic element; 236. Second magnet; 237. Second suction plate; 200. Control device; 201. Housing; 202. Control module; 203. Switch button. Detailed Implementation

[0019] The following will clearly and completely describe the concept, specific structure, and technical effects of the present invention in conjunction with embodiments and accompanying drawings, so as to fully understand the purpose, features, and effects of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, not all of them. Other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are all within the scope of protection of the present invention. Furthermore, all connections / linkages involved in the patent do not simply refer to direct contact between components, but rather to the ability to form a better connection structure by adding or reducing connecting accessories according to specific implementation conditions. The various technical features in this invention can be combined interactively without contradicting each other.

[0020] Please refer to Figures 1 to 3 An embodiment of the present invention provides an organoid dynamic culture system, including an organoid dynamic culture device 100 and a control device 200.

[0021] Combination Figures 4 to 7As shown, the organoid dynamic culture device 100 includes a culture rack 10 and several culture mechanisms 20.

[0022] Several culture units 20 are arranged sequentially along the length of the culture rack 10. Each culture unit 20 includes a drive assembly 21, a reactor 22, and a cover assembly 23. The drive assembly 21 is disposed within the culture rack 10, and the cover assembly 23 is located above the drive assembly 21 and connected to the culture rack 10. The cover assembly 23 is movable vertically relative to the culture rack 10. The reactor 22 is located between the drive assembly 21 and the cover assembly 23. The culture rack 10 provides mounting support for the drive assembly 21 and the cover assembly 23.

[0023] The reactor 22 includes a cylindrical container 221, a container lid 222, and a connecting shaft 223. The container 221 has an open top; its volume can be adjusted according to specific requirements. The container lid 222 has an open bottom, with the top of the container 221 extending into it. The container 221 is used to hold organoids and culture medium. The lid 222 covers the top of the container 221, reducing the risk of contamination of the culture medium. The bottom of the container 221 is detachably connected to a drive assembly 21, which drives the container 221 to rotate at a low speed relative to the lid 222. The top of the lid 222 is detachably connected to a top cover assembly 23, which provides mounting support for the lid 222. The connecting shaft 223 has a T-shaped cross-section and is located inside the container 221. The bottom end of the connecting shaft 223 forms an inverted frustum-shaped structure 224. The connecting shaft 223, the inverted frustum-shaped structure 224, and the container 221 are coaxially arranged. The inverted frustum-shaped structure 224 is close to the bottom of the container 221, forming a culture zone 225 between them. The top end of the connecting shaft 223 extends from the top end of the container 221 and connects to the container cover 222. The container cover 222 provides mounting support for the connecting shaft 223. The up-and-down movement of the top cover assembly 23 moves the container cover 222 up and down, thereby moving the connecting shaft 223 and the inverted frustum-shaped structure 224 up and down. By detachably connecting the bottom end of the container 221 to the drive assembly 21 and the top end of the container cover 222 to the top cover assembly 23, it is convenient to disassemble and assemble the reactor 22, and to facilitate replacement and cleaning of the reactor 22.

[0024] In practical application, first, move the top cover assembly 23 upward to the predetermined position and separate the container cover 222 of the reactor 22 from the top cover assembly 23. Then, separate the container 221 of the reactor 22 from the drive assembly 21. Next, remove the entire reactor 22 and remove it from the culture rack 10. Then, remove the container cover 222, connecting shaft 223, and inverted frustum structure 224 from the container 221. Then, add culture medium into the container 221 and add the organoids (the organoids are droplet organoids, such as droplet organoids from the HepaRG cell line or primary mouse lung organoids). (etc.) Place the connecting shaft 223 and the inverted frustum structure 224 into the container 221, ensuring the top of the container 221 is inside the container cover 222, and make the connecting shaft 223, the inverted frustum structure 224, and the container 221 coaxial. Then move the top cover assembly 23 upward to the predetermined position. Next, move the reactor 22 into the culture rack 10, and install the bottom of the container 221 and the drive assembly 21 together. Then slowly lower the top cover assembly 23, and install the top of the container cover 222 and the top cover assembly 23 together. Figures 1 to 6 As shown, the container 221 is then driven to rotate at a low speed by the drive component 21. Since the inverted frustum structure 224 and the connecting shaft 223 are stationary, the rotation of the container 221 causes the fluid composed of culture medium and organoids inside the container 221 to flow around the axis of the connecting shaft 223 and the inverted frustum structure 224, generating low shear force. This mixes the organoids and culture medium, continuously delivering oxygen and nutrients to the organoids and removing their metabolites, thus maintaining the activity and healthy growth of the organoids. Furthermore, the morphology and maturity of the organoids can be regulated by the stimulation of this shear force, thereby achieving dynamic culture of the organoids. During the culture of the organoids, half of the culture medium is removed each day and new culture medium is added to meet the culture requirements.

[0025] During the dynamic culture of organoids, since the inverted frustum structure 224 is stationary while the container 221 rotates at a low speed, a Taylor-Couette flow field can be formed within the culture zone 225. By controlling the rotational speed of the container 221 and the viscosity of the culture medium, the Reynolds number is kept below the turbulence threshold, thereby reducing the generation of eddies and turbulence. Simultaneously, the inclined surface 2241 of the inverted frustum structure 224 allows the inverted frustum structure 224 and the container 221 to form a generalized cone-plate flow. According to the cone-plate flow shear rate calculation formula γ˙ (shear rate) = ω (angular velocity at a point, which is equal to the angular velocity of the container 221 and can be calculated from the rotational speed of the container 221) / tan ( Given the angle A between the inclined plane 2241 of the inverted truncated cone structure 224 and the horizontal plane, it can be seen that the shear rate at a certain point in the culture zone 225 is only related to the angular velocity of the container 221 and the angle A between the inclined plane 2241 and the horizontal plane, and is independent of the rotation radius of the point. According to the shear force calculation formula τ (shear force) = μ (culture medium viscosity) * γ˙ (shear rate), it can be seen that the shear force at a certain point in the culture zone 225 is only related to the viscosity of the culture medium, the angular velocity of the container 221, and the angle A between the inclined plane 2241 and the horizontal plane. Since the viscosity of the culture medium, the angular velocity of the container 221, and the angle A between the inclined plane 2241 and the horizontal plane are constant, the shear force distribution in the culture zone 225 is uniform, which keeps the flow field in a laminar state and prevents shear peaks. This avoids damage to organoids or abnormal organoid fusion, and improves the consistency of organoid culture batches under high-throughput culture.

[0026] In this embodiment, the viscosity of the culture medium is 1-1.05 cP (centipoise), the rotation speed of the container 221 is 0.25-2 r / s (revolutions per second), and the angle A between the inclined surface 2241 of the inverted truncated cone structure 224 and the horizontal plane is 5 degrees-15 degrees, preferably 10 degrees. This value can reduce the generation of eddies and turbulence, generate low shear force, and form a generalized cone-plate flow.

[0027] In this embodiment, the minimum depth of the culture zone 225 is 0.5 mm to 2.5 mm, and it is suitable for organoids with diameters of 400 micrometers to 600 micrometers. Understandably, the depth of the culture zone 225 can be set according to actual conditions.

[0028] Figure 8 This is a schematic diagram of the shear force versus position obtained from CFD (Computational Fluid Dynamics) simulation. The horizontal axis represents the distance from the center of the bottom surface of the inverted frustum-shaped structure 224 to the inner wall of the container 221, in meters; the vertical axis represents the magnitude of the shear force, in Pascals. Figure 8 It can be seen that the shear force in the culture zone 225 is basically consistent, presenting a plateau region. The shear force is evenly distributed and low, with no shear peaks. The shear force in the region between the inverted frustum structure 224 and the inner wall of the container 221 shows a gradient change, which can be regarded as the boundary effect region. Figure 9 Screenshot of particle tracer experiment, by Figure 9 It can be seen that the fluid composed of culture medium and organoids in culture zone 225 did not exhibit eddies or turbulence, but rather laminar flow characteristics.

[0029] The bottom end of container 221 is detachably connected to drive assembly 21: Specifically, drive assembly 21 includes drive component 211 and connecting plate 212. Drive component 211 is disposed on one inner wall of culture rack 10. Connecting plate 212 has a T-shaped cross-section and is fitted around the outer periphery of the output shaft of drive component 211. The bottom end of container 221 and connecting plate 212 are magnetically connected by a first magnetic attraction structure. Using magnetic connection, disassembling and assembling reactor 22 is simpler and saves time and effort. Drive component 211 is used to drive connecting plate 212 to rotate, thereby driving container 221 to rotate.

[0030] The drive element 211 is preferably an electric motor. Understandably, the drive element 211 can also be other types, such as a rotary cylinder.

[0031] like Figure 6 As shown, the first magnetic attraction structure includes a first magnet 213 and a first attraction piece 214. The first magnet 213 is disposed at the top of the connecting plate 212, and the first attraction piece 214 is disposed at the bottom of the container 221. The first attraction piece 214 and the first magnet 213 are magnetically connected. The first attraction piece 214 is a magnetic sheet. By separating the first magnet 213 and the first attraction piece 214, the container 221 and the drive assembly 21 can be disassembled. By magnetically connecting the first magnet 213 and the first attraction piece 214, the container 221 and the connecting plate 212 can be installed together, thereby enabling the container 221 and the drive assembly 21 to be installed together.

[0032] In this embodiment, the connecting plate 212 has a connecting plate hole that passes through its top and bottom ends. The connecting plate 212 is sleeved on the output shaft of the driving component 211 through the connecting plate hole. The top end of the connecting plate 212 has a connecting plate mounting groove 2121 at the position corresponding to the connecting plate hole. The connecting plate mounting groove 2121 communicates with the connecting plate hole. The first magnet 213 is a ring magnet. The first magnet 213 is disposed in the connecting plate mounting groove 2121 and is arranged around the outer periphery of the end of the output shaft. The top end of the first magnet 213 is flush with the top end of the connecting plate 212. The bottom end of the container 221 has a container mounting groove that corresponds to the connecting plate mounting groove 2121. The first suction piece 214 is disposed in the container mounting groove. The bottom end of the first suction piece 214 is flush with the bottom end of the container 221.

[0033] The bottom end of the container 221 has a positioning protrusion 2212, and the connecting plate 212 has positioning holes 2122. The positioning protrusion 2212 and the positioning holes 2122 cooperate with each other. The positioning protrusion 2212 and the positioning holes 2122 play a positioning role in the process of installing the container 221 and the drive assembly 21 together, which makes the installation simple. In this embodiment, there are two positioning protrusions 2212, and the first suction piece 214 is located between the two positioning protrusions 2212. The number of positioning holes 2122 corresponds to the number of positioning protrusions 2212, which is also two. The connecting plate mounting groove 2121 is located between the two positioning holes 2122. It can be understood that the number of positioning holes 2122 and positioning protrusions 2212 can be set according to the actual situation.

[0034] The top of the container lid 222 is detachably connected to the upper cover assembly 23. Specifically, the upper cover assembly 23 includes a circular lower connecting plate 231, an upper connecting plate 232, and two hollow guide posts 233. The top of the container lid 222 is magnetically connected to the lower connecting plate 231 via a second magnetic attraction structure. This magnetic connection method simplifies the assembly and disassembly of the reactor 22, saving time and effort. The upper connecting plate 232 is located above the culture rack 10 and is threaded with an upper cover fastener 2321, such as a screw. The head of the upper cover fastener 2321 is located above the upper connecting plate 232, and the tail end is located below the upper connecting plate 232. The top of the culture rack 10 is provided with a clearance hole 11 for avoiding the upper cover fastener 2321. The upper cover fastener 2321 facilitates the up-and-down movement of the upper connecting plate 232. Two guide posts 233 are symmetrically arranged about the center of the lower connecting plate 231. One end of the guide post 233 is detachably connected to the lower connecting plate 231 for easy assembly and disassembly. The other end of the guide post 233 passes through the first groove 12 at the top of the culture rack 10 and the second groove at the top of the culture rack 10 and is detachably connected to the upper connecting plate 232 for easy assembly and disassembly. Several gaskets 234 are arranged around the outer periphery of the guide post 233. The gaskets 234 are stacked from bottom to top between the upper connecting plate 232 and the top of the culture rack 10. By increasing or decreasing the number of gaskets 234, the distance between the upper connecting plate 232 and the top of the culture rack 10 can be adjusted, thereby adjusting the distance between the inverted frustum structure 224 and the bottom of the container 221, and thus adjusting the depth of the culture area 225. This allows for the adaptation to organoids of different diameters and has a wide range of applications. The bottom of the first groove 12 has a ring 13, which extends into the culture rack 10 and is fitted around the outer periphery of the guide post 233. The guide post 233 can move up and down relative to the ring 13 and the culture rack 10. The up and down movement of the upper connecting plate 232 can drive the two guide posts 233 and the lower connecting plate 231 to move up and down. Understandably, the guide posts 233 can also be, for example, three or four, and can be set according to the actual situation. There are two gaskets 234 on the outer periphery of the guide post 233. Understandably, the number of gaskets 234 can be set according to the actual situation.

[0035] An elastic element 235, which is a spring, is fitted around the outer periphery of the ring 13 and the guide post 233. One end of the elastic element 235 is connected to one end of the guide post 233, and the other end is connected to the bottom of the first groove 12. During the rotation of the container 221, when the container cover 222, the inverted truncated cone structure 224, the connecting shaft 223, and the lower connecting plate 231 tend to move upward under the influence of the culture medium and the organoids, the elastic force of the elastic element 235 will exert a downward reaction force on the lower connecting plate 231. This restricts the upward movement of the container cover 222, the inverted truncated cone structure 224, the connecting shaft 223, and the lower connecting plate 231, ensuring the stability of the fluid environment inside the container 221 and preventing fluctuations. This avoids damage to the organoids or abnormal organoid fusion. The ring 13 and guide post 233 can provide guiding support and installation support for the elastic element 235 respectively, and the ring 13 also limits the guide post 233, so that the guide post 233 can only move up and down.

[0036] like Figure 7 As shown, the guide post 233 is detachably connected to the lower connecting plate 231 in the following manner: the bottom end of the lower connecting plate 231 is provided with a first mounting position 2311, the top end of the lower connecting plate 231 is provided with a second mounting position, the bottom of the first mounting position 2311 is provided with a first mounting hole, the first mounting hole communicates with the second mounting position, one end of the guide post 233 cooperates with the second mounting position, and the first mounting fastener 2312, such as a screw, is threadedly installed in the first mounting hole and one end of the guide post 233, and the head of the first mounting fastener 2312 is accommodated in the first mounting position 2311.

[0037] The other end of the guide post 233 is detachably connected to the upper connecting plate 232 in the following manner: The upper connecting plate 232 has a third mounting position 2322 at its top and a fourth mounting position at its bottom. The bottom of the third mounting position 2322 has a second mounting hole that communicates with the fourth mounting position. The other end of the guide post 233 mates with the fourth mounting position. A second mounting fastener 2323, such as a screw, is threaded into the second mounting hole and the other end of the guide post 233, with the head of the second mounting fastener 2323 housed within the third mounting position 2322. By assembling and disassembling the first mounting fastener 2312 and the second mounting fastener 2323, the lower connecting plate 231, the upper connecting plate 232, and the guide post 233 can be disassembled and assembled. The other end of the guide post 233 is detachably connected to the upper connecting plate 232 to facilitate the addition or reduction of the number of gaskets 234. For example, when it is necessary to reduce the number of gaskets 234, the second mounting fastener 2323 can be removed first, then the upper connecting plate 232 can be removed, then one of the gaskets 234 on the outer periphery of the guide post 233 can be removed from the guide post 233, then the other end of the guide post 233 can be engaged with the fourth mounting position, then the second mounting fastener 2323 can be installed in the second mounting hole and the other end of the guide post 233, and the head of the second mounting fastener 2323 can be accommodated in the third mounting position 2322. Similarly, when it is necessary to increase the number of gaskets 234, the second mounting fastener 2323 can be removed first, then the upper connecting plate 232 can be removed, then one gasket 234 can be placed around the outer periphery of the guide post 233 and stacked on the remaining gaskets 234, then the other end of the guide post 233 can be matched with the fourth mounting position, then the second mounting fastener 2323 can be installed in the second mounting hole and the other end of the guide post 233, and the head of the second mounting fastener 2323 can be accommodated in the third mounting position 2322.

[0038] like Figure 5 As shown, the second magnetic structure includes a second magnet 236 and a second suction piece 237. The second magnet 236 is disposed at the bottom end of the lower connecting plate 231, and the second suction piece 237 is disposed at the top end of the container lid 222. The second suction piece 237 and the second magnet 236 are magnetically connected. The second suction piece 237 is a magnetic sheet. By separating the second magnet 236 and the second suction piece 237, the container lid 222 and the upper lid assembly 23 can be disassembled. By magnetically connecting the second magnet 236 and the second suction piece 237, the container lid 222 and the lower connecting plate 231 can be installed together, thereby enabling the container lid 222 and the upper lid assembly 23 to be installed together.

[0039] In this embodiment, the bottom end of the lower connecting plate 231 is provided with a connecting plate mounting groove 2314. The second magnet 236 is a ring magnet, which is disposed in the connecting plate mounting groove 2314, and the bottom end of the second magnet 236 is flush with the bottom end of the lower connecting plate 231. The top end of the container lid 222 is provided with a container lid mounting groove corresponding to the connecting plate mounting groove 2314. The second suction piece 237 is disposed in the container lid mounting groove, and the top end of the second suction piece 237 is flush with the top end of the container lid 222.

[0040] There are two second magnets 236, which are symmetrically arranged about the center of the lower connecting plate 231. The number of connecting plate mounting slots 2314, second suction pieces 237, and container lid mounting slots corresponds to the number of second magnets 236, which are also two each. Understandably, the number of second magnets 236 and second suction pieces 237 can be set according to the actual situation.

[0041] The connection between the top end of the connecting shaft 223 and the container cover 222 is as follows: the top end of the connecting shaft 223 has a first mounting hole, and the top end of the container cover 222 has a second mounting hole corresponding to the first mounting hole. The second mounting hole communicates with the interior of the container cover 222. Fasteners 2221, such as screws, are threaded into both the first and second mounting holes. Figure 3 , Figure 4 , Figure 6 As shown. By disassembling and assembling the fastener 2221, the connecting shaft 223 and the container cover 222 can be disassembled and assembled, making it easy to replace the container cover 222, the connecting shaft 223, and the inverted truncated cone structure 224.

[0042] The head of the connecting fastener 2221 is located above the container cover 222. The lower connecting plate 231 has a positioning through hole 2313 passing through its top and bottom ends. The head of the connecting fastener 2221 mates with the positioning through hole 2313. The connecting fastener 2221 and the positioning through hole 2313 serve a positioning function during the installation of the container cover 222 and the lower connecting plate 231 together, simplifying installation. In this embodiment, there are two first mounting holes, which are symmetrically arranged about the axis of the connecting shaft 223. The number of second mounting holes, connecting fasteners 2221, and positioning through holes 2313 corresponds to the number of first mounting holes, also being two each. It can be understood that the number of first mounting holes, second mounting holes, connecting fasteners 2221, and positioning through holes 2313 can be set according to actual conditions.

[0043] Furthermore, a positioning block 2231 is provided at the top of the connecting shaft 223, such as... Figure 6As shown, a positioning groove 2222 is provided at the top inside the container cover 222, and a positioning block 2231 cooperates with the positioning groove 2222. The positioning block 2231 and the positioning groove 2222 play a positioning role in the process of installing the connecting shaft 223 and the container cover 222 together, making the installation simple.

[0044] In practical applications, when it is necessary to remove the reactor 22 from the drive assembly 21 and the top cover assembly 23, first fix the container cover 222 by hand, and then pull the top cover fastener 2321 upward, which can drive the upper connecting plate 232, the two guide pillars 233, and the lower connecting plate 231 to move upward to the predetermined position, so that the second suction piece 237 separates from the corresponding second magnet 236 and the connecting fastener 2221 separates from the positioning through hole 2313. At this time, do not loosen the top cover fastener 2321, the elastic element 235 is compressed, and then the reactor 22 is lifted as a whole, so that the first suction piece 214 separates from the corresponding first magnet 213 and the positioning protrusion 2212 separates from the positioning hole 2122. Then the reactor 22 can be removed as a whole and taken out of the culture rack 10. Then release the top cover fastener 2321. The reset elastic force of the elastic element 235 can drive the upper connecting plate 232, the two guide pillars 233, and the lower connecting plate 231 to move downward to the initial position. When it is necessary to install the reactor 22, first pull the upper cover fastener 2321 upward, which will drive the upper connecting plate 232, the two guide columns 233, and the lower connecting plate 231 to move upward to the predetermined position. Then, move the reactor 22 into the culture rack 10 as a whole. Then, mate the positioning protrusion 2212 of the container 221 with the positioning hole 2122 of the connecting plate 212 and magnetically connect the first suction piece 214 with the first magnet 213. In this way, the reactor 22 is installed together with the drive assembly 21. Then, slowly lower the upper cover fastener 2321, which will allow the upper cover assembly 23 to be lowered as a whole. Then, mate the connecting fastener 2221 with the positioning through hole 2313 and magnetically connect the second suction piece 237 and the second magnet 236. In this way, the reactor 22 is installed together with the upper cover assembly 23. Thus, the installation of the reactor 22 is completed.

[0045] In this embodiment, there are four culture units 20, which enables the present invention to dynamically culture batches of organoids at once, improving culture efficiency. Furthermore, using this type of culture unit 20 ensures the consistency of organoid culture batches. It is understood that the number of culture units 20 can also be, for example, one, two, three, five, six, etc., and can be set according to actual needs.

[0046] like Figure 3 and Figure 5As shown, the control device 200 includes a housing 201, a control module 202, a power module, and a switch button 203. The housing 201 is located on one side of the culture rack 10. The control module 202 and the power module are both located inside the housing 201, and the switch button 203 is located at one end of the housing 201. The drive components 211 of the drive assemblies 21 of the several culture mechanisms 20, the power module, and the switch button 203 are all electrically connected to the control module 202. By pressing the switch button 203, the control module 202 can control the drive component 211 of the drive assembly 21 to work, thereby driving the container 221 to rotate at a low speed. By pressing the switch button 203 again, the control module 202 can control the drive component 211 of the drive assembly 21 to stop working, thereby stopping the rotation of the container 221. The power module provides power to the control module 202. One end of the housing 201 is provided with a power interface, which is electrically connected to the control module 202. The power interface is used to connect to an external power source through a power cord, so that the power module can be charged by the external power source.

[0047] In this embodiment, the drive component 211 is electrically connected to the control module 202 via a connecting wire, and one inner wall of the culture rack 10 has a wire-passing hole for the connecting wire to pass through. In this embodiment, there are multiple culture mechanisms 20, and the operation of the drive component 211 of each culture mechanism 20 can be individually controlled by the control module 202. The control device 200 enables the linkage of several culture mechanisms 20, thereby achieving unified, efficient, and stable batch culture of organoids.

[0048] The above is a detailed description of the preferred embodiments of the present invention. However, the present invention is not limited to the embodiments described. Those skilled in the art can make various equivalent modifications or substitutions without departing from the spirit of the present invention. All such equivalent modifications or substitutions are included within the scope defined by the claims of this application.

Claims

1. A dynamic organoid culture device, characterized in that, The device includes a culture rack and several culture mechanisms. Each culture mechanism includes a drive assembly, a reactor, and a top cover assembly. The drive assembly is disposed within the culture rack. The top cover assembly is located above the drive assembly and connected to the culture rack. The top cover assembly is movable vertically relative to the culture rack. The reactor is located between the drive assembly and the top cover assembly. The reactor includes a cylindrical container, a container lid, and a connecting shaft. The top end of the container extends into the container lid, and the bottom end of the container is detachably connected to the drive assembly. The top end of the container lid is detachably connected to the top cover assembly. The connecting shaft is located within the container, and the bottom end of the connecting shaft forms an inverted frustum structure. The connecting shaft, the inverted frustum structure, and the container are coaxially arranged. The inverted frustum structure is close to the bottom of the container and forms a culture zone between the inverted frustum structure and the bottom of the container. The top end of the connecting shaft extends from the top end of the container and is connected to the container lid.

2. The organoid dynamic culture device according to claim 1, characterized in that, The angle between the inclined plane and the horizontal plane of the inverted frustum structure is 5 degrees to 15 degrees.

3. The organoid dynamic culture device according to claim 1, characterized in that, The driving assembly includes a driving component and a connecting plate. The driving component is disposed on one inner wall of the culture rack, and the connecting plate is sleeved on the outer periphery of the output shaft of the driving component. The bottom end of the container and the connecting plate are magnetically connected by a first magnetic attraction structure. The driving component is used to drive the connecting plate to rotate, thereby driving the container to rotate.

4. The organoid dynamic culture device according to claim 3, characterized in that, The first magnetic attraction structure includes a first magnet and a first attraction piece. The first magnet is disposed at the top of the connecting plate, and the first attraction piece is disposed at the bottom of the container. The first attraction piece and the first magnet are magnetically connected.

5. The organoid dynamic culture device according to claim 3, characterized in that, The bottom of the container has a positioning protrusion, and the connecting plate has a positioning hole, with the positioning protrusion and the positioning hole cooperating.

6. The organoid dynamic culture device according to claim 1, characterized in that, The upper cover assembly includes a lower connecting plate, an upper connecting plate, and at least two guide posts. The top of the container cover is magnetically connected to the lower connecting plate via a second magnetic attraction structure. The upper connecting plate is located above the culture rack and is equipped with an upper cover fastener. The two guide posts are symmetrically arranged about the center of the lower connecting plate. One end of the guide post is detachably connected to the lower connecting plate, and the other end of the guide post passes through the first groove at the top of the culture rack and the second groove at the top of the culture rack and is detachably connected to the upper connecting plate. A plurality of gaskets are arranged around the outer periphery of the guide post. The gaskets are stacked sequentially from bottom to top between the upper connecting plate and the top of the culture rack. A ring is formed at the bottom of the first groove. The ring is fitted around the outer periphery of the guide post, and the guide post can move up and down relative to the ring and the culture rack. An elastic element is fitted around the outer periphery of the ring and the guide post. One end of the elastic element is connected to one end of the guide post, and the other end of the elastic element is connected to the bottom of the first groove.

7. The organoid dynamic culture device according to claim 6, characterized in that, The second magnetic attraction structure includes a second magnet and a second attraction piece. The second magnet is disposed at the bottom end of the lower connecting plate, and the second attraction piece is disposed at the top end of the container lid. The second attraction piece and the second magnet are magnetically connected.

8. The organoid dynamic culture device according to claim 6, characterized in that, The top end of the connecting shaft is provided with a first mounting hole, and the top end of the container lid is provided with a second mounting hole corresponding to the first mounting hole. A connecting fastener is installed in the first mounting hole and the second mounting hole. The head of the connecting fastener is located above the container lid. The lower connecting plate is provided with a positioning through hole that passes through its top and bottom ends. The head of the connecting fastener cooperates with the positioning through hole.

9. The organoid dynamic culture device according to claim 8, characterized in that, The top of the connecting shaft is provided with a positioning block, and the top of the container lid is provided with a positioning groove, the positioning block cooperating with the positioning groove.

10. A dynamic organoid culture system, characterized in that, The device includes a control unit and an organoid dynamic culture apparatus as described in any one of claims 1-9. The control unit includes a housing, a control module, a power module, and a switch button. The housing is disposed on one side of the culture rack. The control module and the power module are both disposed inside the housing. The switch button is disposed at one end of the housing. The drive components, power module, and switch button of a plurality of culture mechanisms of the organoid dynamic culture apparatus are all electrically connected to the control module.

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