Automated passaging apparatus and cell passaging methods

Abstract

The embodiment of the present application provides a kind of automated passaging equipment and cell passaging method.The automated passaging equipment includes first work area, second work area and the cell culture area connected with first work area and second work area respectively, there is liquid handling position on first work area, first work area is provided with first working arm, first working arm is used to move the first bottle body containing cell to liquid handling position, and first bottle body is moved to cell culture area after processing, there is passaging position on second work area, second work area is provided with second working arm, second working arm is used to clamp first bottle body and at least one second bottle body to passaging position, to pass cell in first bottle body to at least one second bottle body in passaging position under passaging position.This can realize the automatic passaging operation of cell, effectively improve the scale and efficiency of cell passaging, also reduce human operation error and pollution risk, realize the automatic operation of cell passaging.

Description

Technical Field

[0001] This invention relates to the technical field of cell passage, specifically to an automated cell passage device and a cell passage method. Background Technology

[0002] In the industrial production of vaccines and cell culture, it is usually necessary to achieve large-scale expansion of cells through cell passage culture to obtain a sufficient and uniform cell population. Currently, cell passage culture is mainly carried out manually, requiring operators to perform the process manually inside a biosafety cabinet.

[0003] However, with the increasing scale and industrialization of vaccine preparation and cell culture, higher demands are being placed on the scale and efficiency of cell passaging. Currently, traditional manual culture methods are not only inefficient and labor-intensive, making large-scale culture and production difficult, but they are also prone to human error and contamination risks, affecting the stability and safety of cell passaging. Summary of the Invention

[0004] In order to at least partially solve the problems existing in the prior art, according to one aspect of the present invention, an automated transfer device is provided, the technical solution of which is as follows.

[0005] The automated passage device includes a first working area, a second working area, and a cell culture area connected to the first and second working areas respectively. The first working area has a liquid processing position and a first working arm. The first working arm is used to transfer a first bottle containing cells to the liquid processing position and, after processing, transfer the first bottle to the cell culture area. The second working area has a passage position and a second working arm. The second working arm is used to clamp the first bottle and at least one second bottle to the passage position so that the cells in the first bottle can be passaged to at least one second bottle at the passage position.

[0006] The automated passaging device of this invention has a first working arm that can clamp a first vial to a liquid processing position to process the cells in the first vial. Then, the first working arm clamps the processed first vial and transfers it to a cell culture zone for cell culture. After cell culture in the first vial is complete, a second working arm can clamp the first vial and at least one second vial and transfer them to a passaging position, where the cells in the first vial are passaged into at least one second vial. This achieves automated cell passaging, effectively increasing the scale and efficiency of cell passaging, reducing manual labor intensity, and meeting the production needs of large-scale, industrialized vaccine preparation and cell culture. It also reduces human error and contamination risks, improves the stability and safety of cell passaging, and automates the process. Furthermore, the automated passaging device has a simple structure, a rational layout, and fewer unsanitary areas, greatly ensuring its practicality.

[0007] For example, the automated transfer equipment also includes a first cap opening and closing mechanism and a liquid filling mechanism. The first cap opening and closing mechanism is disposed on the first working area, and the liquid filling mechanism is disposed at the liquid processing position. The first cap opening and closing mechanism is used to cooperate with the first working arm to open or close the cap of the first bottle, and the liquid filling mechanism is used to add processing liquid into the first bottle.

[0008] For example, the automated passage device further includes a first conveying mechanism, which is configured corresponding to the cell culture area and the first working area. The first conveying mechanism is at least used to convey the first bottle on the cell culture area to the first working area and to convey the processed first bottle to the cell culture area.

[0009] For example, a first partition is provided between the cell culture area and the first working area, a first delivery mechanism extends from the cell culture area through the first partition to the first working area, and a first opening and closing cover mechanism is provided on the first partition and is positioned on the side facing the first working area.

[0010] For example, the automated passage device also includes a second conveying mechanism, which is set corresponding to the cell culture area and the second working area. The second conveying mechanism is at least used to convey the cultured first bottle from the cell culture area to the second working area.

[0011] For example, a second opening and closing mechanism is provided on the second working area. The second opening and closing mechanism is used to cooperate with the second working arm to open or close the caps of the first bottle and / or the second bottle.

[0012] For example, a second partition is provided between the cell culture area and the second working area, a second delivery mechanism extends from the cell culture area through the second partition to the second working area, and a second opening and closing cover mechanism is provided on the second partition and is positioned on the side facing the second working area.

[0013] For example, the automated passage device also includes a placement mechanism disposed at the passage location. The placement mechanism has multiple placement positions, and the second working arm is used to place the first bottle and at least one second bottle in the corresponding placement positions, and to passage the cells in the first bottle to at least one second bottle through a pipette assembly.

[0014] For example, the pipette assembly includes a pipette and a pipette sleeve fitted over the pipette, with one end of the pipette having a connecting portion for connection with a second working arm.

[0015] For example, the straightness of the pipette is in the range of less than 0.5 mm.

[0016] For example, the automated transfer device also includes a second bottle feeding mechanism and a third conveying mechanism. The second bottle feeding mechanism is located next to the second working area, and the third conveying mechanism is located corresponding to the second bottle feeding mechanism and the second working area. The third conveying mechanism is used to convey at least one second bottle from the second bottle feeding mechanism to the second working area.

[0017] For example, the second bottle feeding mechanism includes a frame and a pallet. A plurality of second bottles are stacked in the frame. The pallet is used to perform at least lifting and / or rotating movements to transfer at least one second bottle in the frame to a third conveying mechanism.

[0018] According to another aspect of the present invention, a cell passage method is also provided, applied to the automated passage device as described above. The automated passage device further includes a liquid addition mechanism and a placement mechanism. The liquid addition mechanism is disposed at the liquid processing position and is used to add processing liquid to a first vial. The placement mechanism is disposed at the passage position and has multiple placement positions. A second working arm is used to place the first vial and at least one second vial into corresponding placement positions, and to passage cells in the first vial to at least one second vial using a pipette assembly. The cell passage method includes:

[0019] Control the first working arm to move the first bottle containing cells to the liquid processing position;

[0020] The liquid dispensing mechanism is controlled to add treatment liquid into the first bottle located in the liquid treatment position;

[0021] Control the first working arm to pour out the processing solution and transfer the first bottle to the cell culture area;

[0022] The second working arm is controlled to transfer at least one second bottle and the first bottle located in the cell culture area to the placement mechanism respectively;

[0023] The placement mechanism works in conjunction with the second working arm to passage cells from the first vial into at least one second vial.

[0024] The above description is merely an overview of the technical solution of the present invention. In order to better understand the technical means of the present invention and to implement it in accordance with the contents of the specification, and in order to make the above and other objects, features and advantages of the present invention more apparent and understandable, specific embodiments of the present invention are described below. Attached Figure Description

[0025] The above and other objects, features, and advantages of the present invention will become more apparent from the more detailed description of the embodiments of the invention in conjunction with the accompanying drawings. The drawings are provided to further illustrate the embodiments of the invention and form part of the specification. They are used together with the embodiments of the invention to explain the invention and do not constitute a limitation thereof. In the drawings, the same reference numerals generally represent the same parts or steps.

[0026] Figure 1 A top view of an automated generation device according to an exemplary embodiment of the present invention is shown;

[0027] Figure 2 A front view of an automated generation device according to an exemplary embodiment of the present invention is shown;

[0028] Figure 3 A cross-sectional view of a pipette assembly according to an exemplary embodiment of the present invention is shown;

[0029] Figure 4 A flowchart of a cell passage method according to an exemplary embodiment of the present invention is shown.

[0030] The components indicated by the reference numerals in the figures are as follows:

[0031] 1. First working area; 11. Liquid processing position; 12. First working arm; 13. First cover opening and closing mechanism; 14. Liquid addition mechanism; 141. First liquid inlet; 142. Second liquid inlet; 2. Second working area; 21. Subculturing position; 22. Second working arm; 221. Clamping mechanism; 222. Liquid aspiration mechanism; 23. Second cover opening and closing mechanism; 24. Placement mechanism; 25. Culture medium addition mechanism; 26. Sampling device; 27. Fourth conveying unit 1. Mechanism; 28. Material rack; 3. Cell culture area; 31. Automated incubator; 4. First conveying mechanism; 5. First partition; 6. Second conveying mechanism; 7. Second partition; 8. Pipette assembly; 81. Pipette; 811. Connecting part; 82. Pipette sleeve; 9. Second bottle loading mechanism; 91. Frame; 92. Pallet; 10. Third conveying mechanism; 15. First bottle; 16. Second bottle; 17. Air outlet; 18. Negative pressure laminar flow equipment. Detailed Implementation

[0032] To make the objectives, technical solutions, and advantages of the present invention more apparent, exemplary embodiments according to the present invention will be described in detail below with reference to the accompanying drawings. Obviously, the described embodiments are merely a part of the embodiments of the present invention, and not all of the embodiments of the present invention. It should be understood that the present invention is not limited to the exemplary embodiments described herein. Based on the embodiments of the present invention described herein, all other embodiments obtained by those skilled in the art without inventive effort should fall within the protection scope of the present invention.

[0033] In the following description, numerous details are provided to enable a thorough understanding of the invention. However, those skilled in the art will appreciate that the following description merely illustrates preferred embodiments of the invention, and that the invention can be practiced without one or more of these details. Furthermore, to avoid obscuring the invention, some technical features well-known in the art have not been described in detail.

[0034] One embodiment of the present invention provides an automated passaging device that can automate cell passaging operations, effectively improving the scale and efficiency of cell passaging. The following will describe in detail an automated passaging device according to an embodiment of the present invention with reference to the accompanying drawings.

[0035] like Figure 1 and Figure 2As shown, the automated passage device includes a first working area 1, a second working area 2, and a cell culture area 3 connected to the first working area 1 and the second working area 2 respectively. The first working area 1 has a liquid processing position 11 and a first working arm 12. The first working arm 12 is used to transfer a first bottle 15 containing cells to the liquid processing position 11 and then transfer the first bottle 15 to the cell culture area 3 after processing. The second working area 2 has a passage position 21 and a second working arm 22. The second working arm 22 is used to clamp the first bottle 15 and at least one second bottle 16 to the passage position 21 so that the cells in the first bottle 15 can be passaged to at least one second bottle 16 at the passage position 21.

[0036] The first working area 1, the cell culture area 3, and the second working area 2 can each perform different functions. Specifically, the cell culture area 3 can be equipped with an automated incubator 31. The first working area 1 can be used for cell treatment before passage, the automated incubator 31 on the cell culture area 3 can be used for culturing the treated cells, and the second working area 2 can be used for passage of the cultured cells.

[0037] A first working arm 12 can be installed on the first working area 1. The working range of the first working arm 12 can fully cover the first working area 1, thereby ensuring that any operating position within the first working area 1 can be effectively reached and the work performed by the first working arm 12. Similarly, a second working arm 22 can be installed on the second working area 2. The working range of the second working arm 22 can also fully cover the second working area 2, which will not be elaborated further here.

[0038] The first working area 1 may have a liquid processing position 11, and the first working arm 12 may clamp the first bottle 15 and transfer the first bottle 15 to the liquid processing position 11. At the liquid processing position 11, the automated passage device may process the cells in the first bottle 15, thereby enabling the cells in the first bottle 15 to meet the requirements of cell culture operations.

[0039] The second working area 2 may have a passage position 21, and the second working arm 22 may clamp the first bottle 15 and at least one second bottle 16 and transfer them to the passage position 21. At the passage position 21, the second working arm 22 may also passage the cells in the first bottle 15 into at least one second bottle 16.

[0040] Understandably, the first bottle 15 can be a mother bottle, i.e., a bottle containing cells to be passaged. The second bottle 16 can be a daughter bottle, i.e., a bottle that receives cells from the mother bottle after passage, for further cell culture or expansion.

[0041] Air outlets 17 can be respectively installed at the edges of the first working area 1 and the second working area 2. A negative pressure laminar flow device 18 can be installed above the first working area 1 and the second working area 2, supplying clean air to both areas. After flowing through the first working area 1 and the second working area 2, the clean air can be discharged through the air outlets 17. This creates and maintains a Class A unidirectional laminar flow environment within the first working area 1 and the second working area 2. By forming a directional, stable, and uniform clean airflow curtain, air infiltration between the two working areas and the external environment is effectively blocked, ensuring that air does not leak from the two working areas and that air from the external environment does not intrude, thereby greatly guaranteeing the reliability and safety of the transmission operation.

[0042] The automated cell passage device of the present invention includes a first working arm 12 that can clamp a first vial 15 to a liquid processing position 11 to process the cells within the first vial 15. The first working arm 12 then clamps the processed first vial 15 and transfers it to a cell culture zone 3 for cell culture. After cell culture in the first vial 15 is complete, a second working arm 22 can clamp the first vial 15 and at least one second vial 16 and transfer them to a passage position 21, where the cells from the first vial 15 are passaged into at least one second vial 16. This automated cell passage operation effectively improves the scale and efficiency of cell passage, reduces manual labor intensity, and meets the production needs of large-scale, industrialized vaccine preparation and cell culture. It also reduces human error and contamination risks, improves the stability and safety of cell passage, and achieves automated cell passage. In addition, the automated transfer equipment has a simple structure, reasonable layout, and fewer dead corners for hygiene, which greatly ensures the practicality of the automated transfer equipment.

[0043] In some embodiments, such as Figure 1 and Figure 2 As shown, the automated transfer equipment also includes a first cap opening and closing mechanism 13 and a liquid adding mechanism 14. The first cap opening and closing mechanism 13 is disposed on the first working area 1, and the liquid adding mechanism 14 is disposed on the liquid processing position 11. The first cap opening and closing mechanism 13 is used to cooperate with the first working arm 12 to open or close the cap of the first bottle 15, and the liquid adding mechanism 14 is used to add processing liquid into the first bottle 15.

[0044] The aforementioned first cap opening and closing mechanism 13 can cooperate with the first working arm 12 to open or close the cap of the first bottle 15. Specifically, the first working arm 12 can clamp the first bottle 15 and extend the cap of the first bottle 15 into the first cap opening and closing mechanism 13. The first cap opening and closing mechanism 13 can clamp the cap and drive the cap to rotate, thereby opening or closing the cap of the first bottle 15.

[0045] It is understood that the first cover opening and closing mechanism 13 can simultaneously perform the functions of clamping the cover and rotating the cover. Specifically, the first cover opening and closing mechanism 13 may include a first cylinder, a first rotary motor, and multiple first grippers. Each first gripper can be connected to the first cylinder, so that it can move away from or towards each other under the drive of the first cylinder. The first cylinder can also be connected to the rotating shaft of the first rotary motor. When the multiple first grippers cooperate to clamp the cover under the drive of the first cylinder, the rotating shaft of the first rotary motor can drive the first cylinder to rotate, thereby driving the multiple first grippers to rotate the cover.

[0046] The aforementioned liquid addition mechanism 14 may have a first liquid addition port 141 and a second liquid addition port 142. The first liquid addition port 141 can be used to add phosphate-buffered saline (PBS) solution to the first bottle 15. The PBS solution can remove residual culture medium components, cell metabolic waste, and cell debris from the first bottle 15. The second liquid addition port 142 can be used to add trypsin to the first bottle 15. Trypsin can break down intercellular junction proteins, causing the cells in the first bottle 15 to disperse into individual cells, thereby facilitating subsequent passage operations.

[0047] A waste liquid collection mechanism can also be installed in the first working area 1. The movement process within the first working area 1 is described below: The first working arm 12 can cooperate with the first opening and closing mechanism 13 to open the cap of the first bottle 15; subsequently, the first working arm 12 can move the first bottle 15 to below the first liquid inlet 141, and add phosphate buffered saline (PBS) solution into the first bottle 15 through the first liquid inlet 141. Afterwards, it cooperates with the first opening and closing mechanism 13 again to close the cap, and shakes the first bottle 15 to allow the phosphate buffered saline solution to mix with the cells in the first bottle 15. After initial contact with the cells, shake well and open the cap to pour the phosphate buffer solution in the first bottle 15 into the waste collection mechanism. Next, the first working arm 12 moves the first bottle 15 to below the second inlet 142, adding trypsin into the first bottle 15 through the second inlet 142. Then, the cap is sealed using the first opening and closing mechanism 13, and the first bottle 15 is shaken again to ensure sufficient contact between the trypsin and the cells. After contact is complete, the cap is opened, and the trypsin is poured into the waste collection mechanism. Finally, the cap of the first bottle 15 is sealed and transferred to the cell culture area 3. It is understood that the number of times the phosphate buffer solution and trypsin are added can be determined based on actual needs, and this application does not impose specific limitations on this.

[0048] In the above embodiments, the first opening and closing cap mechanism 13 and the liquid adding mechanism 14 can cooperate with the first working arm 12 respectively to complete the cell treatment operation before the cell passage operation in the first bottle 15. This realizes the integration and standardization of the cell treatment process and steps, effectively shortens the cell treatment cycle in the first bottle 15, improves the treatment efficiency, and ensures the stability and reliability of cell treatment.

[0049] In some embodiments, such as Figure 2 As shown, the automated passage device also includes a first conveying mechanism 4, which is set in relation to the cell culture area 3 and the first working area 1. The first conveying mechanism 4 is used at least to convey the first bottle 15 on the cell culture area 3 to the first working area 1 and to convey the processed first bottle 15 to the cell culture area 3.

[0050] The first conveying mechanism 4 and the first opening and closing cover mechanism 13 can be disposed on one side of the first working arm 12, and the liquid adding mechanism 14 can be disposed on the other side of the first working arm 12.

[0051] The aforementioned first conveying mechanism 4 can specifically be a conveyor belt. The first conveying mechanism 4 can be configured corresponding to the cell culture area 3 and the first working area 1. The operator can place the first bottle 15 on the first conveying mechanism 4, so that the first bottle 15 is conveyed from the cell culture area 3 to the first working area 1 via the first conveying mechanism 4, thereby allowing the first working arm 12 to process the cells within the first bottle 15. After processing, the first working arm 12 can place the first bottle 15 back on the first conveying mechanism 4, and then convey the first bottle 15 to the automated incubator 31 in the cell culture area 3 via the first conveying mechanism 4, for culturing the cells within the first bottle 15.

[0052] In the above embodiments, the first conveying mechanism 4 can realize the automated connection between the cell culture area 3 and the first working area 1, so that the first bottle 15 can be smoothly transferred between the cell culture area 3 and the first working area 1 with the assistance of the first working arm 12. This achieves a seamless connection between cell passage pretreatment and cell culture process, reduces the risks brought about by manual intervention, and effectively improves the continuity and efficiency of the overall automated passage operation.

[0053] In some embodiments, such as Figure 2 As shown, a first partition 5 is provided between the cell culture area 3 and the first working area 1. The first conveying mechanism 4 extends from the cell culture area 3 through the first partition 5 to the first working area 1. The first opening and closing cover mechanism 13 is provided on the first partition 5 and is positioned facing the first working area 1.

[0054] The aforementioned first partition 5 can be disposed between the cell culture area 3 and the first working area 1, thereby dividing the cell culture area 3 and the first working area 1 into two independent operating areas. Furthermore, a first through hole can be formed on the first partition 5 at the position corresponding to the first conveying mechanism 4, allowing the first conveying mechanism 4 to extend from the cell culture area 3 through the first through hole on the first partition 5 to the first working area 1, thus achieving automated connection between the cell culture area 3 and the first working area 1.

[0055] The aforementioned first switch cover mechanism 13 can be mounted on the first partition 5 and positioned facing the first working area 1. This greatly frees up space in the first working area 1, providing ample space for the installation of the first working arm 12 and the liquid adding mechanism 14.

[0056] Furthermore, the first switch cover mechanism 13 can be tilted at 45 degrees toward the first working area 1. In this way, when cleaning the first switch cover mechanism 13 with cleaning fluid, the cleaning fluid can drip onto the first working area 1 under the action of gravity, which greatly facilitates the cleaning of the first switch cover mechanism 13.

[0057] In the above embodiments, the first partition 5 can divide the cell culture area 3 and the first working area 1 into two independent operating areas. On the one hand, it can effectively block the cross-flow of airflow and particles between the two working areas, improving the cleanliness and safety of the cell culture environment. On the other hand, it can also realize the partitioned operation between different processes, avoiding mutual interference between different processes. Furthermore, the first opening and closing cover mechanism 13 can be set on the first partition 5, thereby optimizing the layout of the first working area 1. It can not only improve the space utilization of the first working area 1, but also facilitate the coordinated cooperation with the first working arm 12, significantly improving the structural compactness and operational convenience of the first working area 1.

[0058] In some embodiments, such as Figure 2 As shown, the automated passage device also includes a second conveying mechanism 6, which is set in relation to the cell culture area 3 and the second working area 2. The second conveying mechanism 6 is used at least to convey the cultured first bottle 15 from the cell culture area 3 to the second working area 2.

[0059] The second conveying mechanism 6 can be a conveyor belt. The second conveying mechanism 6 can be set up corresponding to the cell culture area 3 and the second working area 2. After the cell culture in the first bottle 15 is completed, the second conveying mechanism 6 can transport the first bottle 15 from the cell culture area 3 to the second working area 2, so that the second working arm 22 on the second working area 2 can clamp the first bottle 15 and transfer it to the passage position 21.

[0060] In the above embodiments, the second conveying mechanism 6 can realize the automated connection between the cell culture area 3 and the second working area 2, achieving seamless connection between cell culture and cell passage processes, reducing the risks brought about by manual intervention, and further improving the continuity and efficiency of the overall automated passage operation.

[0061] In some embodiments, such as Figure 1 and Figure 2 As shown, a second opening and closing mechanism 23 is provided on the second working area 2. The second opening and closing mechanism 23 is used to cooperate with the second working arm 22 to open or close the lid of the first bottle 15 and / or the second bottle 16.

[0062] The aforementioned second cap-opening mechanism 23 can cooperate with the second working arm 22 to open or close the caps of the first bottle 15 and / or the second bottle 16. Specifically, the second working arm 22 can clamp the first bottle 15 and / or the second bottle 16 and extend the caps of the first bottle 15 and / or the second bottle 16 into the second cap-opening mechanism 23. The second cap-opening mechanism 23 can clamp the caps and rotate them, thereby opening or closing the caps of the first bottle 15 and / or the second bottle 16.

[0063] It is understandable that the second cover opening and closing mechanism 23 can simultaneously perform the functions of clamping the cover and rotating the cover. Specifically, the second cover opening and closing mechanism 23 can have multiple clamping positions, each clamping position can be respectively provided with multiple second grippers, and correspondingly provided with a second cylinder and a second rotary motor. The multiple second grippers on each clamping position can be respectively connected to the corresponding second cylinder, so that they can move away from or towards each other under the drive of the second cylinder. The second cylinder can also be connected to the rotating shaft of the corresponding second rotary motor, so that when the multiple second grippers cooperate to clamp the cover under the drive of the second cylinder, the rotating shaft of the second rotary motor can drive the second cylinder to rotate, thereby driving the multiple second grippers to cooperate in rotating the cover.

[0064] It is understandable that the multiple clamping positions on the second opening and closing mechanism 23 can be used to simultaneously accommodate the cap of the first bottle 15 and the cap of the second bottle 16, thereby realizing separate clamping and rotation operations for different bottles.

[0065] In the above embodiments, the second opening and closing mechanism 23 can cooperate with the second working arm 22 to open or close the caps of the first bottle 15 and / or the second bottle 16, thereby realizing the integration and standardization of the cell passage process and steps, effectively shortening the cell passage cycle, improving the passage efficiency, and ensuring the stability and reliability of cell passage.

[0066] In some embodiments, such as Figure 2 As shown, a second partition 7 is provided between the cell culture area 3 and the second working area 2. The second conveying mechanism 6 extends from the cell culture area 3 through the second partition 7 to the second working area 2. The second opening and closing cover mechanism 23 is provided on the second partition 7 and is positioned facing the second working area 2.

[0067] The aforementioned second partition 7 can be disposed between the cell culture area 3 and the second working area 2, thereby dividing the cell culture area 3 and the second working area 2 into two independent operating areas. Furthermore, a second through hole can be formed on the second partition 7 at the position corresponding to the second conveying mechanism 6. The second conveying mechanism 6 can extend from the cell culture area 3 through the second through hole on the second partition 7 to the second working area 2, thus achieving automated connection between the cell culture area 3 and the second working area 2.

[0068] The aforementioned second switch cover mechanism 23 can be mounted on the second partition 7 and positioned facing both sides of the second working area 2. This greatly frees up space in the second working area 2, providing ample space for the installation of the second working arm 22 and the placement mechanism 24 (described in detail below).

[0069] Furthermore, the second switch cover mechanism 23 can be tilted at 45 degrees toward the second working area 2. In this way, when cleaning the second switch cover mechanism 23 with cleaning fluid, the cleaning fluid can drip onto the second working area 2 under the action of gravity, which greatly facilitates the cleaning of the second switch cover mechanism 23.

[0070] In the above embodiment, the second partition 7 divides the cell culture area 3 and the second working area 2 into two independent operating regions. On the one hand, it effectively blocks the cross-contamination of airflow and particles between the two working areas, improving the cleanliness and safety of the cell passage environment. On the other hand, it also enables zoned operation between different processes, avoiding mutual interference between different processes. Furthermore, the second opening and closing cover mechanism 23 can be disposed on the second partition 7, thereby optimizing the layout of the second working area 2. This not only improves the space utilization of the second working area 2 but also facilitates its coordination with the second working arm 22, significantly improving the structural compactness and operational convenience of the second working area 2.

[0071] In some embodiments, such as Figure 1 and Figure 2 As shown, the automated passage device also includes a placement mechanism 24 disposed at passage position 21. The placement mechanism 24 has multiple placement positions. The second working arm 22 is used to place the first bottle 15 and at least one second bottle 16 in the corresponding placement positions, and to passage the cells in the first bottle 15 to at least one second bottle 16 through the pipette assembly 8.

[0072] The second working arm 22 may be integrated with a clamping mechanism 221 and a suction mechanism 222. The clamping mechanism 221 can be used to clamp the first bottle 15 and the second bottle 16. The suction mechanism 222 can be connected to the pipette assembly 8 to aspirate cells from the first bottle 15 and transfer them to the second bottle 16.

[0073] The aforementioned placement mechanism 24 is rotatably mounted on the transfer position 21. The placement mechanism 24 may have multiple placement positions. The clamping mechanism 221 on the second working arm 22 may clamp the first bottle 15 after opening or the second bottle 16 after opening and transfer it to any one of the multiple placement positions.

[0074] The second working area 2 may also be provided with a culture medium adding mechanism 25. The culture medium adding mechanism 25 may be located next to the placement mechanism 24. When the placement mechanism 24 rotates the placement position of the first bottle 15 to below the culture medium adding mechanism 25, the culture medium adding mechanism 25 may add culture medium into the first bottle 15.

[0075] The movement process within the second working area 2 can be described below: The second working arm 22 can cooperate with the second opening and closing mechanism 23 to open the caps of the first bottle 15 and the second bottle 16. Then, the first bottle 15 and the second bottle 16 are placed on the placement mechanism 24. The placement mechanism 24 can then rotate the first bottle 15 to a position below the culture medium adding mechanism 25 to add culture medium into the first bottle 15. The second working arm 22 can connect to the pipette assembly 8 and move above the placement mechanism 24. The placement mechanism 24 can then move the first bottle 15 and the second bottle 16 sequentially below the second working arm 22 to transfer the cells from the first bottle 15 to the second bottle 16. It is understood that during this process, the second working arm 22 can drive the pipette assembly 8 to move vertically without horizontal displacement. This effectively avoids cell fluid spillage due to shaking and inertia during horizontal movement of the pipette assembly 8, thus significantly reducing the risk of cell fluid dripping and contamination.

[0076] like Figure 2 As shown, when the first bottle 15 and the second bottle 16 are placed in their respective positions, they can be tilted to allow the cell culture medium inside to collect at the bottom, facilitating the extraction by the pipette assembly 8. Furthermore, the cells in the first bottle 15 can be adherent cells, meaning they can attach to the inner wall of the first bottle 15. This allows the pipette assembly 8 to extract the culture medium from the first bottle 15 and spray it onto the inner wall, causing the cells adhering to the inner wall to fall to the bottom of the first bottle 15 under the flushing action of the culture medium, thus ensuring the cell count during passage.

[0077] The second working area 2 may also be equipped with a sampling device 26 and a fourth transport mechanism 27. The fourth transport mechanism 27 can be configured to correspond to the sampling device 26 and a cell counter (not shown in the figure). Before the passage operation, the second working arm 22 can draw a small amount of cell fluid through the pipette assembly 8 and place it on the sampling device 26. The fourth transport mechanism 27 can transfer the sampling device 26 to the cell counter to determine the number of cells in the second bottle 16 based on the counting results of the cell counter.

[0078] In the above embodiments, the placement mechanism 24 can cooperate with the second working arm 22 to transfer cells in the first bottle 15 to at least one second bottle 16, thereby realizing automated cell passage and further improving the scale and efficiency of cell passage.

[0079] In some embodiments, such as Figure 3As shown, the pipette assembly 8 includes a pipette 81 and a pipette sleeve 82 sleeved outside the pipette 81. One end of the pipette 81 is provided with a connecting part 811 for connecting to the second working arm 22.

[0080] A material rack 28 can also be provided on the second working area 2. The pipette assembly 8 can be placed in the material rack 28 and engaged with the material rack 28. The liquid suction mechanism 222 of the second working arm 22 can be connected to the connection part 811 of the pipette 81, so that while the pipette 81 is pulled away from the pipette sleeve 82, the pipette sleeve 82 is also prevented from being pulled up along with it.

[0081] The liquid suction mechanism 222 of the second working arm 22 and the connection part 811 of the pipette 81 can be connected by plug-in or threaded connection. Plug-in connection is preferred to ensure the connection strength between the two while simplifying the connection steps.

[0082] In the above embodiments, the pipette sleeve 82 can be fitted over the outside of the pipette 81. On the one hand, it provides rigid protection for the pipette 81, thereby preventing damage or breakage when subjected to external forces. On the other hand, it also prevents the pipette 81 from direct contact with the external environment, thus ensuring the cleanliness and hygiene of the pipette 81. Furthermore, the pipette 81 can have a connecting part 811 that connects to the second working arm 22, which greatly facilitates the extraction of the pipette 81 and effectively improves the ease of use of the pipette 81.

[0083] In some embodiments, the straightness of the pipette 81 is less than 0.5 mm.

[0084] The straightness of the pipette 81 can be less than 0.5 mm, for example, 0.1 mm, 0.2 mm, 0.3 mm, 0.4 mm, etc.

[0085] In the above embodiments, the pipette 81 can have a straightness within the above-mentioned range. When the pipette 81 is inserted into the first bottle 15 to extract the culture medium in the first bottle 15 and rinse the cells on the inner wall of the first bottle 15, the pipette 81 with a high degree of straightness can avoid contact with the bottle mouth of the first bottle 15, thereby effectively preventing the pipette 81 from scratching the bottle mouth and causing contamination or even damage, and effectively ensuring the stability and safety of the pipetting operation.

[0086] In some embodiments, such as Figure 2As shown, the automated transfer equipment also includes a second bottle feeding mechanism 9 and a third conveying mechanism 10. The second bottle feeding mechanism 9 is located on the side of the second working area 2, and the third conveying mechanism 10 is located corresponding to the second bottle feeding mechanism 9 and the second working area 2. The third conveying mechanism 10 is used to convey at least one second bottle 16 on the second bottle feeding mechanism 9 to the second working area 2.

[0087] The aforementioned third conveying mechanism 10 can specifically be a conveyor belt. The third conveying mechanism 10 can be set up corresponding to the second bottle feeding mechanism 9 and the second working area 2. The third conveying mechanism 10 can convey at least one second bottle 16 to the second working area 2, so that the second working arm 22 on the second working area 2 can clamp the second bottle 16 and transfer it to the placement mechanism 24.

[0088] In the above embodiments, the third conveying mechanism 10 can realize the automated connection between the second bottle feeding mechanism 9 and the second working area 2, realize the automated feeding of the second bottle 16, reduce the risks caused by manual intervention, and effectively improve the automation level of the automated transfer equipment.

[0089] In some embodiments, such as Figure 2 As shown, the second bottle loading mechanism 9 includes a frame 91 and a tray 92. A plurality of second bottles 16 are stacked inside the frame 91. The tray 92 is used to perform at least lifting and / or rotating movements to transfer at least one second bottle 16 inside the frame 91 to the third conveying mechanism 10.

[0090] The aforementioned frame 91 can be constructed as a frame structure, and operators can stack multiple second bottles 16 sequentially within the frame structure. The frame structure 91 allows the tray 92 to easily extend into the frame 91.

[0091] The aforementioned tray 92 can be plate-shaped. The plate-shaped tray 92 can move upwards and extend below the first second bottle 16 from top to bottom among the plurality of second bottles 16, thus allowing it to continue moving upwards to move the second bottle 16 away from the frame 91. Then, the tray 92 can drive the second bottle 16 downwards and rotate it, so that the second bottle 16 can align with the third conveying mechanism 10 and be placed on the third conveying mechanism 10.

[0092] In the above embodiment, the pallet 92 can transfer the second bottle 16 in the frame 91 to the third conveying mechanism 10, thereby realizing the continuous feeding of the second bottle 16. This not only ensures the continuity of the transfer operation and improves the transfer efficiency of the automated transfer equipment, but also further improves the automation level of the automated transfer equipment.

[0093] According to another aspect of the invention, such as Figure 4 As shown, a cell passage method is also provided, which is applied to the automated passage device described above. The automated passage device further includes a liquid addition mechanism 14 and a placement mechanism 24. The liquid addition mechanism 14 is located at the liquid processing position 11 and is used to add processing liquid into the first bottle 15. The placement mechanism 24 is located at the passage position 21 and has multiple placement positions. The second working arm 22 is used to place the first bottle 15 and at least one second bottle 16 into the corresponding placement positions, and to passage the cells in the first bottle 15 into at least one second bottle 16 through the pipette assembly 8. The cell passage method includes steps S101 to S105.

[0094] Step S101: Control the first working arm 12 to move the first bottle 15 containing cells to the liquid processing position 11.

[0095] Step S102: Control the liquid adding mechanism 14 to add treatment liquid into the first bottle 15 located in the liquid treatment position 11.

[0096] Step S103: Control the first working arm 12 to pour out the processing solution and transfer the first bottle 15 to the cell culture area 3.

[0097] Step S104: Control the second working arm 22 to transfer at least one second bottle 16 and the first bottle 15 in the cell culture area 3 to the placement mechanism 24 respectively.

[0098] Step S105: Control the placement mechanism 24 to cooperate with the second working arm 22 to passage the cells in the first bottle 15 into at least one second bottle 16.

[0099] In the automated cell passaging equipment employing the aforementioned method, the first working arm 12 can clamp the first vial 15 to the liquid processing position 11, where a processing solution is added to the first vial 15. Then, the first working arm 12 clamps the processed first vial 15 and transfers it to the cell culture zone 3, where the cells within the first vial 15 are cultured. After cell culture in the first vial 15 is complete, the second working arm 22 can clamp the first vial 15 and at least one second vial 16 and transfer them to the passaging position 21. At the passaging position 21, the cells in the first vial 15 are then passaged to at least one second vial 16 using a pipette assembly 8. This automated cell passaging operation effectively improves the scale and efficiency of cell passaging, reduces manual labor intensity, and meets the production needs of large-scale, industrialized vaccine preparation and cell culture. It also reduces human error and contamination risks, improves the stability and safety of cell passaging, and achieves automated cell passaging.

[0100] To fully understand the embodiments of the present invention, detailed structures will be presented in the following description. Obviously, the implementation of the embodiments of the present invention is not limited to the specific details familiar to those skilled in the art. Preferred embodiments of the present invention are described in detail below; however, in addition to these detailed descriptions, the present invention may have other embodiments.

[0101] Although exemplary embodiments have been described herein with reference to the accompanying drawings, it should be understood that the above exemplary embodiments are merely illustrative and are not intended to limit the scope of the invention. Various changes and modifications can be made therein by those skilled in the art without departing from the scope and spirit of the invention. All such changes and modifications are intended to be included within the scope of the invention as claimed in the appended claims.

[0102] For ease of description, the term "connection" may be used herein to describe the relationship between one or more elements or features shown in the figure and other elements or features. It should be understood that "connection" may include direct connections or indirect connections via other elements or features, and this document is intended to encompass all such cases.

[0103] It should be noted that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit the exemplary embodiments according to this application. As used herein, the singular form is intended to include the plural form as well, unless the context clearly indicates otherwise. Furthermore, it should be understood that when the terms "comprising" and / or "including" are used in this specification, they indicate the presence of features, steps, operations, parts, components, and / or combinations thereof.

[0104] It should be noted that the terms "first," "second," etc., used in the specification, claims, and accompanying drawings of this application are used to distinguish similar objects and are not necessarily used to describe a specific order or sequence. It should be understood that such data can be interchanged where appropriate so that the embodiments of this application described herein can be implemented in sequences other than those illustrated or described herein.

[0105] The present invention has been described through the above embodiments. However, it should be understood that the above embodiments are for illustrative purposes only and are not intended to limit the invention to the scope of the described embodiments. Furthermore, those skilled in the art will understand that the present invention is not limited to the above embodiments, and many more variations and modifications can be made based on the teachings of the present invention, all of which fall within the scope of protection claimed by the present invention. The scope of protection of the present invention is defined by the appended claims and their equivalents.

Claims

1. An automated generation device, characterized in that, The system includes a first working area, a second working area, and a cell culture area connected to both the first and second working areas. The first working area has a liquid processing position and a first working arm. The first working arm is used to transfer a first bottle containing cells to the liquid processing position and, after processing, to transfer the first bottle to the cell culture area. The second working area has a passage position and a second working arm. The second working arm is used to clamp the first bottle and at least one second bottle to the passage position so that the cells in the first bottle can be passaged to at least one second bottle at the passage position.

2. The automated transfer equipment according to claim 1, characterized in that, The automated transfer equipment further includes a first cap opening and closing mechanism and a liquid adding mechanism. The first cap opening and closing mechanism is disposed on the first working area, and the liquid adding mechanism is disposed at the liquid processing position. The first cap opening and closing mechanism is used to cooperate with the first working arm to open or close the cap of the first bottle, and the liquid adding mechanism is used to add processing liquid into the first bottle.

3. The automated generation equipment according to claim 2, characterized in that, The automated passage device further includes a first conveying mechanism, which is configured corresponding to the cell culture area and the first working area. The first conveying mechanism is at least used to convey the first bottle on the cell culture area to the first working area and to convey the processed first bottle to the cell culture area.

4. The automated generation equipment according to claim 3, characterized in that, A first partition is provided between the cell culture area and the first working area. The first conveying mechanism extends from the cell culture area through the first partition to the first working area. The first opening and closing cover mechanism is provided on the first partition and is positioned facing the first working area.

5. The automated transfer equipment according to claim 1, characterized in that, The automated passage device further includes a second conveying mechanism, which is configured to correspond to the cell culture area and the second working area. The second conveying mechanism is at least used to convey the cultured first bottle from the cell culture area to the second working area.

6. The automated generation equipment according to claim 5, characterized in that, The second working area is provided with a second opening and closing mechanism, which is used to cooperate with the second working arm to open or close the caps of the first bottle and / or the second bottle.

7. The automated transfer equipment according to claim 6, characterized in that, A second partition is provided between the cell culture area and the second working area. The second conveying mechanism extends from the cell culture area through the second partition to the second working area. The second opening and closing cover mechanism is provided on the second partition and is positioned facing the second working area.

8. The automated transfer equipment according to claim 6, characterized in that, The automated passage device further includes a placement mechanism disposed at the passage location. The placement mechanism has multiple placement positions. The second working arm is used to place the first bottle and at least one second bottle in the corresponding placement positions, and to passage the cells in the first bottle to at least one second bottle through a pipette assembly.

9. The automated transfer equipment according to claim 8, characterized in that, The pipette assembly includes a pipette and a pipette sleeve fitted over the pipette, with one end of the pipette having a connecting part for connecting to the second working arm.

10. The automated generation equipment according to claim 9, characterized in that, The straightness of the pipette is less than 0.5 mm.

11. The automated generation equipment according to claim 9, characterized in that, The automated transfer equipment also includes a second bottle feeding mechanism and a third conveying mechanism. The second bottle feeding mechanism is located next to the second working area, and the third conveying mechanism is located corresponding to the second bottle feeding mechanism and the second working area. The third conveying mechanism is used to convey at least one second bottle from the second bottle feeding mechanism to the second working area.

12. The automated generation equipment according to claim 11, characterized in that, The second bottle feeding mechanism includes a frame and a pallet. Multiple second bottles are stacked in the frame. The pallet is used to perform at least lifting and / or rotating movements to transfer at least one second bottle in the frame to the third conveying mechanism.

13. A cell passage method, applied to the automated passage device as described in any one of claims 1 to 12, characterized in that, The automated passage device further includes a liquid addition mechanism and a placement mechanism. The liquid addition mechanism is located at the liquid processing position and is used to add processing liquid to the first bottle. The placement mechanism is located at the passage position and has multiple placement positions. The second working arm is used to place the first bottle and at least one second bottle into the corresponding placement positions, and passage the cells in the first bottle into at least one second bottle using a pipette assembly. The cell passage method includes: Control the first working arm to move the first bottle containing cells to the liquid processing position; The liquid adding mechanism is controlled to add treatment liquid into the first bottle located at the liquid treatment position; Control the first working arm to pour the processing solution and transfer the first bottle to the cell culture area; The second working arm is controlled to transfer at least one second bottle and the first bottle located in the cell culture area to the placement mechanism respectively; The placement mechanism is controlled to cooperate with the second working arm to passage cells from the first vial to at least one second vial.

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