Cell trap generation module for standardization and controllable regeneration of organoid

Abstract

The utility model relates to the technical field of biological tissue engineering, and discloses a cell trap generation module for standardization and controllable regeneration of organoid, which comprises a dehydration module, a first cell carrier, a second cell carrier, a first covered stent and a second covered stent, the first cell carrier is arranged in the first covered stent, a concave hole array is arranged on the first cell carrier, and cells are arranged in the concave hole array; the second cell carrier is arranged in the second covered stent; a dehydration channel is arranged in the dehydration module, at least part of the first cell carrier is exposed in the dehydration channel for dehydration, the second covered stent is arranged outside the first cell carrier, the second cell carrier is opposite to the concave hole array of the first cell carrier, and the second cell carrier enters the concave hole array and wraps cells to form a cell trap array. According to the cell trap generation module for the standardization and controllable regeneration of the organoid, the manufacturing process of the organoid can be simplified, and the controllability and the consistency of the regeneration process of the organoid can be improved.

Description

Technical Field

[0001] This invention relates to the field of biological tissue engineering technology, and in particular to a cell trap generation module for standardized and controllable regeneration of organoids. Background Technology

[0002] Organoids are tissue models that mimic the characteristics of corresponding organs in vivo, obtained by culturing adult stem cells or pluripotent stem cells in vitro. They have broad prospects in basic research, disease modeling, drug development, and precision treatment.

[0003] High-throughput culture of organoids can be achieved through culture systems such as microwell arrays and microfluidic droplets. However, the current organoid manufacturing process relies on complex manual operations by researchers, making automation and mass production difficult, and ensuring the controllability and consistency of the organoid regeneration process is challenging. Furthermore, the time cost for personnel involved in the culture process is extremely high due to the need for precise microscale manipulations during manufacturing.

[0004] Therefore, it is necessary to develop a cell trap generation module for the standardization and controllable regeneration of organoids, which would simplify the organoid manufacturing process and improve the controllability and consistency of the organoid regeneration process. Utility Model Content

[0005] The technical problem to be solved by this utility model is to provide a cell trap generation module for standardized and controllable regeneration of organoids, which simplifies the organoid manufacturing process and improves the controllability and consistency of the organoid regeneration process.

[0006] To solve the above-mentioned technical problems, this utility model provides a cell trap generation module for standardized and controllable regeneration of organoids, including a dehydration module, a first cell carrier, a second cell carrier, a first membrane-covered scaffold, and a second membrane-covered scaffold.

[0007] The first cell carrier is disposed within the first membrane-covered scaffold, and the first cell carrier is provided with an array of recessed holes, and cells are disposed within the array of recessed holes.

[0008] The second cell carrier is disposed within the second membrane-covered scaffold;

[0009] The dehydration module is provided with a dehydration channel. The first membrane-covered scaffold is detachably connected to the dehydration module. The first cell carrier is at least partially exposed in the dehydration channel for dehydration. The second membrane-covered scaffold is disposed outside the first cell carrier, and the second cell carrier is opposite to the concave array of the first cell carrier. The second cell carrier enters the concave array and encapsulates the cells to form a cell trap array.

[0010] As an improvement to the above scheme, the surface of the first cell carrier opposite to the concave array is exposed in the dehydration channel.

[0011] As an improvement to the above scheme, the first cell carrier and the first membrane-covered scaffold isolate the second cell carrier from the dehydration channel.

[0012] As an improvement to the above scheme, the top surface of the second cell carrier is covered by the second membrane scaffold.

[0013] As an improvement to the above solution, the first membrane-covered scaffold includes a scaffold body and a first supporting boss. The scaffold body has a through hole, and the first supporting boss is arranged circumferentially along the through hole. The first supporting boss is used to support the first cell carrier.

[0014] As an improvement to the above solution, the first film-coated support also includes a support arm disposed on the outer periphery of the support body;

[0015] The first end of the dehydration module is provided with a rotationally symmetrical mounting groove. The mounting groove extends spirally and is correspondingly arranged with the support arm. The support arm is arranged along the spiral direction of the mounting groove on the outer periphery of the bracket body. The support arm is screwed into the mounting groove, and the bracket body extends into the dehydration channel.

[0016] As an improvement to the above solution, it also includes an array mold and a support assembly. The first membrane-coated support is detachably connected to the dehydration module. The first membrane-coated support and the support assembly cooperate to form a receiving cavity. An inert gel is provided in the receiving cavity. The inert gel is pressed into the concave array by the array mold to form the first cell carrier. The first cell carrier can be removed from the support assembly along with the first membrane-coated support.

[0017] As an improvement to the above solution, the support assembly includes a petri dish and a support. The support is disposed in the petri dish and includes a base and a second support boss formed on the base. The second support boss is adapted to the through hole and extends from the bottom through the through hole to form the receiving cavity.

[0018] As an improvement to the above solution, a dehydration platform is also included. The dehydration platform is provided with a heat source cavity, an installation cavity, and a dehydration hole. The installation cavity is used to accommodate the dehydration module, and the dehydration hole is used to connect the heat source cavity and the dehydration channel so that the heat source of the heat source cavity flows to the dehydration channel.

[0019] As an improvement to the above solution, the side wall of the mounting cavity is provided with a first limiting groove and a second limiting groove. The second limiting groove is connected to the bottom end of the first limiting groove, and the second limiting groove extends from the first limiting groove to the circumference of the mounting cavity. The second end of the dehydration module is provided with a mounting protrusion protruding outward from the outer wall. The mounting protrusion is inserted from the top end of the first limiting groove and screwed into the second limiting groove.

[0020] Implementing this utility model has the following beneficial effects:

[0021] This invention discloses a cell trap generation module for standardized and controllable regeneration of organoids. By setting a concave array on a first cell carrier and placing cells within the concave array, the first cell carrier is at least partially exposed in the dehydration channel for dehydration. During the dehydration process, the concave array structure on the first cell carrier allows the opposing second cell carrier to both enter the concave array and encapsulate the cells within it, and also achieve dehydration. The dehydration of the second cell carrier causes the side opposite to the concave array to form an entangled state. The entangled part formed by dehydration will increase its physical strength, changing from a very soft state to a relatively hard solid state, making it easier to separate from the first cell carrier, thereby leaving the cells in the second cell carrier to form a cell trap array.

[0022] Because the first and second cell carriers are easier to separate after dehydration, the process of manufacturing organoids is simplified.

[0023] Since the first membrane-covered scaffold is detachably connected to the dehydration module, and the first cell carrier is at least partially exposed in the dehydration channel when it is installed on the dehydration module, the first membrane-covered scaffold can be used directly as a dehydration carrier and is easy to move. A concave array can be formed directly on the first membrane-covered scaffold, which simplifies the fabrication and transfer of the first cell carrier.

[0024] The array of recessed holes on the first cell carrier provides a space for the implanted cells to grow in a controlled manner, preventing the cells from expanding outward in the horizontal direction and improving the consistency of the cell regeneration process.

[0025] The second cell carrier encapsulates and wraps the cells in the concave array to form a cell trap array. Each cell trap on the second cell carrier is a multi-cell system. Because each cell is mutually constrained with other cells, the temporal and spatial characteristics of its cell signal activation will gradually stabilize, and it has a certain resistance to external disturbances, which can help improve the controllability and consistency of the organoid regeneration process. Attached Figure Description

[0026] Figure 1 This is a schematic diagram of an embodiment of a cell trap generation module for standardized and controllable regeneration of organoids according to this utility model;

[0027] Figure 2 This is a schematic diagram of the assembly structure of the first membrane-covered scaffold with the first cell carrier and the dehydration module;

[0028] Figure 3 yes Figure 2 Side view;

[0029] Figure 4 yes Figure 3 A schematic diagram of the CC section structure;

[0030] Figure 5 yes Figure 1 This is a schematic diagram of the array mold, support components and first membrane scaffold of another embodiment of the cell trap generation module for standardized and controllable regeneration of organoids according to this utility model.

[0031] Figure 6 This is a schematic diagram of the structure of the first covered stent;

[0032] Figure 7 This is a schematic diagram of the support structure;

[0033] Figure 8 This is a schematic diagram of the assembly structure of the dehydration platform and dehydration module;

[0034] Figure 9 yes Figure 8 Top view;

[0035] Figure 10 yes Figure 9 A schematic diagram of the DD cross-section structure.

[0036] Figure 11 This is a schematic diagram of an automated manufacturing system for cell trap arrays based on a cell trap generation module and featuring human-computer interaction.

[0037] Figure 12 yes Figure 11 A structural diagram of the workbench, robotic arm, and industrial camera; Detailed Implementation

[0038] To make the objectives, technical solutions and advantages of this utility model clearer, the utility model will be described in further detail below with reference to the accompanying drawings.

[0039] like Figures 1 to 4As shown, this utility model discloses an embodiment of a cell trap generation module for standardized and controllable regeneration of organoids, including a dehydration module 14, a first cell carrier b, a second cell carrier c, a first membrane scaffold 12, and a second membrane scaffold 15. The first cell carrier b is disposed within the first membrane scaffold 12, and the first cell carrier b has a concave array b1, with cells disposed within the concave array b1. The second cell carrier c is disposed within the second membrane scaffold 15. The dehydration module 14 has a dehydration channel 141, and the first membrane scaffold 12 is detachably connected to the dehydration module 14. The first cell carrier b is at least partially exposed in the dehydration channel 141 for dehydration. The second membrane scaffold 15 is disposed outside the first cell carrier b, and the second cell carrier c is opposite to the concave array b1 of the first cell carrier b. The second cell carrier c enters the concave array b1 and encapsulates the cells to form a cell trap array.

[0040] In this embodiment, the first cell carrier b is made of an inert gel a, preferably an agarose gel. The second cell carrier c is a biohydrogel such as matrix gel, collagen, or fibrinogen-thrombin; in this embodiment, matrix gel, commonly used in organoid culture, is preferred. The matrix gel encapsulates the cultured cells, resulting in a more uniform surrounding environment and preventing polarity reversal due to differences in the micro-surrounding polarity, thus maximally mimicking the in vivo environment. The second membrane-covered scaffold 15 is preferably the first culture dish. The top surface of the second cell carrier c is covered by the first culture dish, and the first cell carrier b and the first membrane-covered scaffold 12 isolate the second cell carrier c from the dehydration channel 141. When the first culture dish containing matrix gel is placed on the agarose gel with the concave array b1, the matrix gel adheres to the first culture dish.

[0041] Due to its inert chemical properties, agarose gel cannot form covalent bonds with all current bio-hydrogels. During the research process, this invention discovered that many bio-hydrogels used for manufacturing organoids, including matrix gels, can form entangled states through dehydration, providing gels with strength exceeding that of cross-linked structures in a short time. Therefore, the second cell carrier c does not form chemical bonds after contact with the first cell carrier b. Furthermore, in this embodiment, the second cell carrier c within the second membrane scaffold 15 is positioned opposite the pore array b1. During the dehydration of the first cell carrier b, the first cell carrier b and the first membrane scaffold 12 isolate the second cell carrier c from the dehydration channel 141. Although the second cell carrier c is not directly exposed to the dehydration channel 141, the pore array b1 structure on the first cell carrier b allows the second cell carrier c to also dehydrate, resulting in an entangled state on the side of the second cell carrier c opposite to the pore array b1. In this embodiment, as the second cell carrier c enters the concave array b1 and encapsulates the cells, the matrix gel, after dehydration and forming an entangled portion, increases its physical strength, transforming from a very soft state into a relatively hard solid, making it easier to separate from the first cell carrier b. When the side of the second cell carrier c opposite to the concave array b1 is dehydrated and entangled, the side of the second cell carrier c in contact with the first culture dish retains its original state; that is, the top of the second cell carrier c is adsorbed onto the first culture dish. A gentle pull by hand is sufficient to completely detach the matrix gel from the agarose gel, leaving the cell-encapsulated matrix gel on the first culture dish, thus completing the fabrication of the cell trap array.

[0042] The first cell carrier b has a concave array b1 for implanting cells, which provides a controllable space for the implanted cells to grow, preventing the cells from expanding outward in the horizontal direction and improving the consistency of the cell regeneration process. The second cell carrier c encloses and wraps the cells in the concave array b1 to form a cell trap array. Each cell trap on the second cell carrier c is a multi-cell system. Each cell in the system is mutually constrained with other cells, and the temporal and spatial characteristics of its cell signal activation will gradually stabilize, and it has a certain resistance to external disturbances.

[0043] The first coated support 12 in this embodiment specifically includes a support body 121 and a first support boss 122. The support body 121 has a through hole 123, and the first support boss 122 is arranged circumferentially along the through hole 123. The first coated support 12 is disposed within a support assembly. The support assembly has a second support boss 161, which is adapted to the through hole 123. The second support boss 161 extends from the bottom of the through hole 123 and forms a receiving cavity with the through hole 123. The inert gel a in the receiving cavity contacts the first support boss 122.

[0044] In this embodiment, after agarose is poured into the cavity, the agarose forms an agarose gel. The agarose gel covers the first support protrusion 122, so that the first support protrusion 122 can be embedded in the agarose gel and form a stable support for it.

[0045] The bottom of the array mold 11 has a raised array corresponding to the concave array b1. The array mold 11 can directly press the concave array b1 onto the top surface of the inert gel a, or press it onto the top of the poured agarose. After solidification, the array mold 11 is removed to obtain an agarose gel with the concave array b1. When the array mold 11 presses the surface of the agarose gel, the raised array is opposite to the second support protrusion 161 and offset from the first support protrusion 122. After pressing, the array mold 11 is pulled out to form the concave array b1 in the middle area of ​​the agarose gel surface. The agarose gel in the middle area has good uniformity in thickness, which is beneficial to improving the consistency of the cell trap. The agarose gel forming the concave array b1 is the first cell carrier b. By moving the first membrane scaffold 12, the first cell carrier b can be transferred to the cell seeding area B for cell seeding.

[0046] The protrusions of the array mold 11 are conical, and the concave array b1 structure formed by the array mold 11 with this structure makes it easier for the second cell carrier c to detach the wrapped cells from the first cell carrier b.

[0047] To facilitate the movement of the first membrane-covered scaffold 12 and the first cell carrier b on it, the first membrane-covered scaffold 12 in this embodiment is also provided with a support arm 124, which is arranged in an array along the outer periphery of the scaffold body 121.

[0048] The support assembly in this embodiment specifically includes a second petri dish 17 and a support 16 disposed within the second petri dish 17. The support 16 includes a base 162, a limiting boss 163, and the aforementioned second supporting boss 161. Both the second supporting boss 161 and the limiting boss 163 are formed on the top of the base 162. The limiting boss 163 is arranged in an array around the outer periphery of the second supporting boss 161. The support body 121 is disposed between the limiting boss 163 and the second supporting boss 161, and the support arm 124 is disposed between two adjacent limiting bosses 163. The second petri dish 17 can collect substances overflowing during agarose casting. The structure of the support 16 allows for the directional placement of the first coated support 12, facilitating rapid positioning and pressing of the array mold 11, and facilitating the formation of the concave hole array b1. Furthermore, by designing a support 16 with second support protrusions 161 of varying heights, the height at which the second support protrusions 161 extend into the through hole 123 can be altered, thereby changing the thickness of the agarose gel and adapting to different organoid culture needs. The support 16, in conjunction with the first covered scaffold 12, forms a cavity for containing agarose, enabling the production of agarose gels of different thicknesses without the need for separately designing different models of the first covered scaffold 12.

[0049] In this embodiment, the first end of the dehydration module 14 is provided with a rotationally symmetrical mounting groove 142, and the second end of the dehydration module 14 is connected to the dehydration platform 13. The mounting groove 142 extends spirally and is correspondingly positioned with the support arm 124, which is arranged along the spiral direction of the mounting groove 142 on the outer periphery of the support body 121. When cell seeding or dehydration is performed, with the concave array b1 facing upwards, the support arm 124 of the first membrane-covered support 12 is screwed into the mounting groove 142, and the support body 121 extends into the dehydration channel 141. At this time, the through hole 123 is coaxial with the dehydration channel 141, and the surface of the first cell carrier b opposite to the concave array b1 is exposed in the dehydration channel 141, achieving rapid dehydration of the first cell carrier b. Simultaneously, the second cell carrier c is dehydrated through the concave array; the top surface of the second cell carrier c is covered by the second membrane-covered support 15, maintaining a large adsorption area between the second cell carrier c and the second membrane-covered support 15, facilitating subsequent separation of the second cell carrier c from the first cell carrier b.

[0050] The dehydration channel 141 includes a recessed platform 144. The first membrane-coated support 12 is spirally connected to the dehydration module 14. After the support body 121 extends into the dehydration channel 141, it abuts against the recessed platform 144, sealing the dehydration channel 141 and isolating the second cell carrier c from it. The first membrane-coated support 12 not only facilitates movement and positioning but also controls the flow of heat sources.

[0051] The dehydration module 14 can be equipped with two or more dehydration channels 141, and the top of each dehydration channel 141 is connected to the first membrane support 12 to achieve higher throughput cell seeding.

[0052] In this embodiment, the first cell carrier b is supported by the first membrane support 12. The support arm 124 structure of the first membrane support 12 cooperates with the spiral mounting groove 142 of the dehydration module 14, which facilitates the assembly and disassembly of the first membrane support 12 and the dehydration module 14. The through hole 123 structure of the first membrane support 12 can promote the dehydration of the first cell carrier b and the second cell carrier c.

[0053] The dehydration platform 13 is provided with an installation cavity 132 and a dehydration hole 133. The installation cavity 132 is used to accommodate the dehydration module 14, and the dehydration hole 133 is used to connect the heat source cavity 131 and the dehydration channel 141 so that the hot air in the heat source cavity 131 flows to the dehydration channel 141. The side wall of the installation cavity 132 is provided with a first limiting groove 134 and a second limiting groove 135. The second limiting groove 135 is connected to the bottom end of the first limiting groove 134, and the second limiting groove 135 extends from the first limiting groove 134 into the circumference of the installation cavity 132. The second end of the dehydration module 14 is provided with an installation protrusion 143 protruding outward from the wall. The installation protrusion 143 is inserted into the second limiting groove 135 from the top end of the first limiting groove 134.

[0054] See Figures 1 to 12This utility model also discloses an embodiment of an automated manufacturing system for cell trap arrays based on a cell trap generation module with human-computer interaction, including a workbench 1, a robotic arm 2, an industrial camera 3, and a control module 4. The workbench 1 has an array fabrication area A and a cell inoculation area B. The array fabrication area A has an array mold 11, a support assembly, and a first coating scaffold 12. The first coating scaffold 12 cooperates with the support assembly to form a receiving cavity, in which an inert gel a is placed. The inert gel a is formed by pressing a concave array b1 into the surface of the array mold 11, forming a first cell carrier b. The first cell carrier b can be removed from the support assembly along with the first coating scaffold 12. The cell inoculation area B has a dehydration platform 13 and a dehydration module 14. The dehydration module 14 has a dehydration channel 141, and the dehydration platform 13 has a heat source cavity 131 for providing hot air to the dehydration channel 141. The dehydration channel 141 is connected to the heat source cavity 131. The first coating scaffold 12 carrying the first cell carrier b is detachably connected to the dehydration module 14. An industrial camera 3 is positioned above the cell seeding area B to visually image the concave array b1 in the cell seeding area B and obtain an image of the position of the concave array b1. A control module 4 is electrically connected to the robotic arm 2 and the industrial camera 3. The drive end of the robotic arm 2 is equipped with a pipette 21. The control module 4 controls the robotic arm 2 to drive the pipette 21 to implant cells into the concave array b1 corresponding to the position image of the concave array b1 based on the image fed back by the industrial camera 3. After cell seeding and culture, a second membrane-covered scaffold 15 is placed outside the first cell carrier b. A second cell carrier c is placed inside the second membrane-covered scaffold 15, positioned opposite the concave array b1. The first cell carrier b is at least partially exposed in the dehydration channel 14 for dehydration. The second cell carrier c enters the concave array b1 and encapsulates the cells, forming a cell trap array.

[0055] In this embodiment, the workbench 1 is modularly partitioned, with an array fabrication area A and a cell seeding area B. In the array fabrication area A, an inert gel a and its top surface concave array b1 are formed using an array mold 11, a support component, and a first membrane scaffold 12 to obtain a first cell carrier b that can be detached from the support component along with the first membrane scaffold 12. In the cell seeding area B, the first membrane scaffold 12 carrying the first cell carrier b is detachably connected to a dehydration module 14. An industrial camera 3 above the cell seeding area B performs visual imaging of the concave array b1 to obtain a position image of the concave array b1. The control module 4 controls the robotic arm 2 to drive the pipette 21 to implant cells into the concave array b1 based on the position image of the concave array b1 fed back by the industrial camera 3. After the first cell carrier b with implanted cells is detached from the dehydration module 14 along with the first membrane scaffold 12, it can be placed in a culture environment for cell culture. The concave array b1 provides a physical boundary for the growth of cell spheres or organoids, allowing the first cell carrier b to obtain cell spheres or organoids of controllable type, quantity, and density. After the cell carrier b completes self-assembly, the first membrane scaffold 12 carrying the first cell carrier b is detachably connected to the dehydration module 14, exposing the surface of the first cell carrier b opposite to the concave array b1 to the dehydration channel 141. A second membrane scaffold 15 is set outside the first cell carrier b, with the second cell carrier c inside the second membrane scaffold 15 facing the concave array b1. The second cell carrier c will enter the concave array b1 and encapsulate the cells. Simultaneously, under the action of hot air in the dehydration channel 141, the first cell carrier b is rapidly dehydrated, and the second cell carrier c easily separates from the first cell carrier b, leaving the cells in the second cell carrier c to form a cell trap array. In this embodiment, a human-machine interactive robotic arm 2 is set up in conjunction with an industrial camera 3 to assist the operator's fine movements. At the same time, the structural cooperation between the dehydration platform 13, dehydration module 14, first membrane scaffold 12, array mold 11, support components, and second membrane scaffold 15 on the workbench 1 simplifies the high-throughput manufacturing process of organoids and improves the controllability and consistency of the organoid regeneration process.

[0056] The first membrane-covered scaffold 12 can be used in the array fabrication area A for forming the concave array b1, and can also be directly moved to the cell seeding area B as a dehydration carrier, which helps to simplify the fabrication and transfer of the first cell carrier b.

[0057] The heat source in the heat source chamber 131 is provided by an air compressor 5 and a gas heater 6, which are connected in sequence. The air compressor 5 draws air from the environment and pressurizes it to a certain pressure. The pressurized air is heated to a certain temperature by the gas heater 6 and then input into the heat source chamber 131 of the dehydration platform 13 to provide hot convection air for the dehydration module 14. The gas heater 6 includes a cooling module and a heating module to achieve an adjustable temperature. The dehydration channel 141 of the dehydration module 14 is connected to the cooling module and the heating module to provide hot convection air with an adjustable temperature to the dehydration channel 141. The dehydration platform 13 is provided with an air inlet 136 and an air outlet 137 that are connected to the heat source chamber 131. The pressurized air is heated to a certain temperature by the gas heater 6 and then input into the heat source chamber 131 through the air inlet 136.

[0058] The workbench 1 is provided with an installation plate 18 for installing the dehydration platform 13. The installation plate 18 is provided with an assembly groove 181 and a positioning groove 182. The assembly groove 181 is adapted to the dehydration platform 13 and the assembly groove 181 communicates with the positioning groove 182. The positioning groove 182 is provided with an elastic positioning element (not shown in the figure) for elastically abutting against the side wall of the dehydration platform 13 in the assembly groove 181, so as to realize the quick positioning and installation of the dehydration platform 13.

[0059] The dehydration modules 14 on the dehydration platform 13 not only provide dehydration channels 141 during the dehydration process, but also serve to fix the first membrane-coated scaffold 12 during cell seeding. To achieve higher throughput cell seeding, this embodiment arranges multiple dehydration modules 14 in an array on the dehydration platform 13 in the cell seeding area B, so that multiple first membrane-coated scaffolds 12 with first cell carriers b are installed in the cell seeding area B. Each dehydration module 14 can be individually detached from the dehydration platform 13, making experiments more convenient.

[0060] In addition, the cell seeding area B is equipped with an XY motorized translation stage 19, and a dehydration platform 13 is located on top of the XY motorized translation stage 19. This platform drives the dehydration platform 13 to move laterally and longitudinally, allowing the first cell carriers b on different dehydration modules 14 to fall into the visual range of the industrial camera 3. The robotic arm 2 drives the pipette 21 to implant cells into the concave array b1 on the first cell carriers b that have fallen into the visual range of the industrial camera 3. The cell types in the pipette 21 can be set as needed, and the number of cells implanted in the concave array b1 can be controlled by the pipette 21. Cells can be implanted into concave arrays at different intervals by controlling the robotic arm 2 or the XY motorized translation stage 19, thus controlling the cell density distribution of the concave array b1.

[0061] In this embodiment, the control module 4 uses a computer as the control center of the entire system to process information from various parts and issue control commands.

[0062] In this embodiment, the workbench 1 is modularly distributed. In addition to the array fabrication area A and the cell seeding area B mentioned above, a robotic arm 2 module area and a microscopic vision area are also provided. The robotic arm 2 is located in the robotic arm 2 module area of ​​the workbench 1, and the industrial camera 3 is located in the microscopic vision area of ​​the workbench 1. The modules are connected together by a base plate to form an integral structure.

[0063] The robotic arm 2 is equipped with an electric gripper 22 at its drive end, which holds the pipette 21. The robotic arm 2 can achieve multi-degree-of-freedom, high-speed, and high-precision movements. Working in conjunction with the electric gripper 22, it can grasp objects over a wide range, at high speed, and with high precision, moving them to the appropriate position and enabling human-machine interaction. Using the electric gripper 22 to hold the pipette 21 allows for rapid, accurate, and stable cell seeding.

[0064] The microscopic vision area includes an industrial camera 3, a lens, a light source, and a mounting bracket. The lens and light source are both mounted on the industrial camera 3. The light source's supplementary illumination and the lens's focusing help obtain clearer images. The industrial camera 3 is fixedly mounted on the worktable 1 via the mounting bracket. The industrial camera 3 captures images of the positions of the concave aperture array b1 on the first cell carrier b. After computer image processing, the robotic arm 2 and the XY motorized translation stage 19 are controlled to move accordingly. By translating the XY motorized translation stage 19 along the X and Y directions, the industrial camera 3 can observe the different concave aperture arrays b1 on the first cell carrier b under a microscope.

[0065] In addition to fixing the robotic arm 2 and industrial camera 3 on the workbench 1, the industrial camera 3 can also be fixed on the drive end of the robotic arm 2 to automate recognition and operation through computer vision technology.

[0066] To ensure a clean experimental environment, a biosafety cabinet 7 is also installed on the workbench 1 in this embodiment. The biosafety cabinet 7 is equipped with a working area, a ventilation system, a filtration system, a UV lamp, a protective barrier, etc. The workbench 1 is located in the working area of ​​the biosafety cabinet 7, so that the organoid array can be manufactured in the working area of ​​the biosafety cabinet to minimize contamination.

[0067] In addition, depending on specific needs, equipment modules such as vibrators, centrifuges, and PCR instruments can also be installed on workbench 1.

[0068] The working process of this utility model is as follows: The support 16 is placed in the second culture dish 17, then the first coated scaffold 12 is placed on the corresponding support 16. Agarose is poured into the first coated scaffold 12, and then the array mold 11 is pressed onto the first coated scaffold 12. After the agarose solidifies, the array mold 11 is removed, resulting in the first cell carrier b solidified on the first coated scaffold 12. The first coated scaffold 12 is placed on the dehydration module 14. Under the visual guidance of the industrial camera 3, the experimenter controls the robotic arm 2 and the electric gripper 22 to grasp the pipette 21 and move it above the dehydration platform 13. By controlling the XY electric translation stage 19, the dehydration module 14 is precisely moved below the pipette 21. Cells are seeded sequentially in the concave array b1 of the first cell carrier b. After seeding, the first coated scaffold 12 is removed and placed in the second culture dish 17 or a six-well plate for culture, thus rapidly creating a cell array with controllable cell type, quantity, and density. After the cells complete self-assembly in the first cell carrier b, the first membrane-covered scaffold 12 is removed from the second culture dish 17 or a six-well plate and placed on the dehydration module 14. The second culture dish 17, with a substrate gel evenly coated on the bottom, is then placed over the first cell carrier b. At this time, the substrate gel enters the concave array b1, encapsulating the cultured cell spheres or organoids. Simultaneously, constant-temperature air generated by the air compressor 5 and the gas heater 6 convects with the first cell carrier b, causing the water on the first cell carrier b and the side of the second cell carrier c opposite to the concave array b1 to be quickly removed. The second cell carrier c, made of substrate gel, forms an entangled state during the dehydration process and can be easily physically separated from the first cell carrier b. Therefore, the second culture dish 17 and the second cell carrier c inside it can be easily removed. The cell spheres or organoids in the concave array b1 are then transferred to the second cell carrier c inside the second culture dish 17, thereby rapidly creating an organoid array with controllable cell types, numbers, and densities.

[0069] The above-disclosed embodiment is merely a preferred embodiment of the present utility model and should not be construed as limiting the scope of the present utility model. Therefore, any equivalent variations made in accordance with the claims of the present utility model shall still fall within the scope of the present utility model.

Claims

1. A cell trap generation module for standardized and controllable regeneration of organoids, characterized in that, It includes a dehydration module, a first cell carrier, a second cell carrier, a first membrane-covered scaffold, and a second membrane-covered scaffold; The first cell carrier is disposed within the first membrane-covered scaffold, and the first cell carrier is provided with an array of recessed holes, with cells disposed within the array of recessed holes. The second cell carrier is disposed within the second membrane-covered scaffold; The dehydration module is provided with a dehydration channel. The first membrane-covered scaffold is detachably connected to the dehydration module. The first cell carrier is at least partially exposed in the dehydration channel for dehydration. The second membrane-covered scaffold is disposed outside the first cell carrier, and the second cell carrier is opposite to the concave array of the first cell carrier. The second cell carrier enters the concave array and encapsulates the cells to form a cell trap array.

2. The cell trap generation module for standardized and controllable regeneration of organoids as described in claim 1, characterized in that, The first cell carrier and the first membrane-covered scaffold isolate the second cell carrier from the dehydration channel.

3. The cell trap generation module for standardized and controllable regeneration of organoids as described in claim 1 or 2, characterized in that, The top surface of the second cell carrier is covered by the second membrane-covered scaffold.

4. The cell trap generation module for standardized and controllable regeneration of organoids as described in claim 1, characterized in that, The surface of the first cell carrier opposite the array of pores is exposed in the dehydration channels.

5. The cell trap generation module for standardized and controllable regeneration of organoids as described in claim 1, characterized in that, The first membrane-covered scaffold includes a scaffold body and a first supporting boss. The scaffold body has a through hole, and the first supporting boss is arranged circumferentially along the through hole. The first supporting boss is used to support the first cell carrier.

6. The cell trap generation module for standardized and controllable regeneration of organoids as described in claim 5, characterized in that, The first film-coated support also includes a support arm disposed on the outer periphery of the support body; The first end of the dehydration module is provided with a rotationally symmetrical mounting groove. The mounting groove extends spirally and is correspondingly arranged with the support arm. The support arm is arranged along the spiral direction of the mounting groove on the outer periphery of the bracket body. The support arm is screwed into the mounting groove, and the bracket body extends into the dehydration channel.

7. The cell trap generation module for standardized and controllable regeneration of organoids as described in claim 1, characterized in that, It also includes an array mold and a support assembly. The first membrane-coated support is detachably connected to the dehydration module. The first membrane-coated support and the support assembly cooperate to form a receiving cavity. The receiving cavity is provided with an inert gel. The inert gel is pressed into the concave array by the array mold to form the first cell carrier. The first cell carrier can be removed from the support assembly along with the first membrane-coated support.

8. The cell trap generation module for standardized and controllable regeneration of organoids as described in claim 7, characterized in that, The support assembly includes a petri dish and a support. The support is disposed in the petri dish and includes a base and a second support boss formed on the base. The second support boss is adapted to the through hole and extends from the bottom through the through hole to form the receiving cavity.

9. The cell trap generation module for standardized and controllable regeneration of organoids as described in claim 7, characterized in that, It also includes a dehydration platform, which has a heat source cavity, an installation cavity and a dehydration hole. The installation cavity is used to accommodate the dehydration module and the dehydration hole is used to connect the heat source cavity and the dehydration channel so that the heat source of the heat source cavity flows to the dehydration channel.

10. The cell trap generation module for standardized and controllable regeneration of organoids as described in claim 9, characterized in that, The side wall of the mounting cavity is provided with a first limiting groove and a second limiting groove. The second limiting groove is connected to the bottom end of the first limiting groove and extends from the first limiting groove to the circumference of the mounting cavity. The second end of the dehydration module is provided with a mounting protrusion protruding outward from the outer wall. The mounting protrusion is inserted from the top end of the first limiting groove and screwed into the second limiting groove.

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