Cell culture bottle working system

Abstract

The utility model provides a cell culture bottle working system. The cell culture bottle working system comprises a feeding assembly, a sampling assembly, a vertical oscillation assembly, a discharging assembly and a control unit, the feeding assembly is used for placing a to-be-processed culture bottle; the sampling assembly is used for conveying a culture bottle in the feeding assembly to the vertical oscillation assembly, and the vertical oscillation assembly is used for vertically oscillating and uniformly mixing the culture bottle, so that adherent cells in the culture bottle are oscillated to fall off; the discharging assembly is used for discharging the culture bottles which are vibrated and uniformly mixed by the vertical vibration assembly; the control unit is connected with the feeding assembly, the sampling assembly, the vertical oscillation assembly and the discharging assembly and used for controlling the working processes of all the assemblies. According to the cell culture bottle working system disclosed by the invention, adherent cells in the cell culture bottle can fall off within the shortest time under the action of the vertical oscillation assembly, and full-automatic control and operation equipment are adopted, so that the movement and the labor intensity of personnel are reduced, and the cleanness of a production environment is guaranteed.

Description

Technical Field

[0001] The utility model relates to the field of cell culture processing, in particular to a cell culture bottle working system. Background Art

[0002] With the continuous development of the cell therapy industry, the scale of cell culture continues to expand. For adherent cells, multi-layer cell culture flasks are often used for culture. During cell passage and digestion, the multi-layer cell culture flasks need to be manually shaken off the cells to obtain single cells for subsequent operations.

[0003] Existing cell culture flasks are divided into single-layer cell culture flasks and multi-layer cell culture flasks. When passaging adherent cells in single-layer cell culture flasks, cells can be blown off by pipetting with a pipette or a pipette gun, while when passaging adherent cells in multi-layer cell culture flasks, adherent cells need to be manually shaken off. Such manual shaking has the following disadvantages: 1. Manual shaking of cell culture flasks has a large amplitude, which is not conducive to maintaining a clean production area environment; 2. Manual shaking of cells can easily cause fatigue to operators, which is prone to errors in the production process; 3. When there are a large number of culture flasks, the operator will quickly consume physical energy due to operating too many flasks, resulting in the inability to completely detach cells from some culture flasks, causing waste; 4. When there are a large number of culture flasks, the selection of personnel to shake the cell culture flasks is greatly limited. Utility Model Content

[0004] The technical problem to be solved by the present disclosure is to overcome the defects in the prior art and provide a cell culture flask working system that can enable adherent cells to automatically complete cell shedding.

[0005] The present disclosure solves the above technical problems through the following technical solutions:

[0006] A cell culture bottle working system includes a loading component, a sampling component, a vertical oscillation component, a unloading component and a control unit;

[0007] The loading assembly is used to place the culture bottles to be processed;

[0008] The sampling component is used to take the culture bottle from the loading component and transport the culture bottle to the vertical shaking component.

[0009] The vertical shaking assembly is used to vertically shake the culture bottle to mix it evenly, so that the adherent cells in the culture bottle are shaken off;

[0010] The unloading component is used to unload the culture bottles after being shaken and mixed by the vertical shaking component;

[0011] The control unit is connected to the loading component, sampling component, vertical oscillation component and unloading component, and is used to control the work flow of each component.

[0012] Preferably, the sampling assembly includes a robot assembly, and the sampling assembly further includes a U-shaped oscillation assembly, and the U-shaped oscillation assembly realizes the U-shaped oscillation movement of the culture bottle.

[0013] Preferably, the robot assembly performs the U-shaped oscillating motion when grabbing the culture bottle from the loading assembly and transporting it to the vertical oscillating assembly.

[0014] Preferably, the loading assembly includes a plurality of loading stations, and each of the loading stations includes a capacitive proximity sensor for detecting whether the culture bottle is placed in place.

[0015] Preferably, the robot assembly includes a robotic arm, and the gripper portion of the robotic arm adopts a two-layer structure, including a hard material located on the outer layer and an elastic material located on the inner side.

[0016] Preferably, the vertical oscillation assembly includes a workbench and a fixed tooling installed on the workbench. The side of the fixed tooling is provided with a sensor for detecting whether the culture bottle is installed in place. The fixed tooling includes a locking mechanism for locking the culture bottle. The workbench performs reciprocating linear motion up and down.

[0017] Preferably, it also includes a frame and a working platform, and a shell arranged on the frame.

[0018] The working platform is arranged in the frame, and the loading assembly, sampling assembly, oscillating assembly and unloading assembly are all arranged on the working platform;

[0019] The housing includes a transparent portion.

[0020] Preferably, it further comprises an air filtration system, which is arranged above the working platform.

[0021] Preferably, the blanking assembly comprises a stacking assembly, and the stacking assembly can be automatically popped out.

[0022] Preferably, the culture bottle comprises a multi-layer structure extending in the vertical length and width directions of the bottle body, the multi-layer structure being stacked along the thickness direction of the culture bottle, the bottle mouth of the culture bottle being disposed horizontally within the vertical oscillation assembly, and the multi-layer structure being disposed vertically. The above-mentioned preferred conditions may be arbitrarily combined, consistent with common knowledge in the art, to obtain preferred embodiments of the present disclosure.

[0023] The positive progress of the present disclosure is that the cell culture flask working system disclosed in the present disclosure, through the action of the vertical oscillation component, can remove the adherent cells in the cell culture flask in the shortest possible time. For example, the loading and unloading of a single culture flask can be completed within 45 seconds, and the vertical oscillation time is only 15 seconds. It can also effectively prevent excessive cell digestion from affecting the cell state. The use of fully automatic control and operating equipment reduces the movement of personnel, ensures the cleanliness of the production environment, and reduces the labor intensity of personnel. The setting of the U-shaped oscillation component further improves the mixing efficiency of the digestive fluid, saves overall time, and improves work efficiency. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 A schematic diagram of a cell culture flask working system provided by an exemplary embodiment of the present disclosure;

[0025] Figure 2 A side view of a culture bottle provided as an exemplary embodiment of the present disclosure;

[0026] Figure 3 A top view of a cell culture flask working system provided by an exemplary embodiment of the present disclosure;

[0027] Figure 4 A schematic diagram of a robot assembly of a cell culture flask working system according to an exemplary embodiment of the present disclosure;

[0028] Figure 5 A schematic diagram of a gripper portion of a robot assembly of a cell culture flask working system according to an exemplary embodiment of the present disclosure;

[0029] Figure 6 A schematic diagram of a fixing tool in a vertical oscillation assembly provided as an exemplary embodiment of the present disclosure. DETAILED DESCRIPTION

[0030] The present disclosure is further illustrated below by way of examples, but the present disclosure is not limited to the scope of the examples.

[0031] In the embodiments of the present disclosure, prefixes such as "first" and "second" are used only to distinguish different description objects, and have no limiting effect on the position, order, priority, quantity or content of the described objects. In the embodiments of the present disclosure, the use of prefixes such as ordinal numbers to distinguish description objects does not constitute a limitation on the described objects. For the statement of the described objects, please refer to the description in the context of the claims or embodiments, and no unnecessary limitations should be constituted due to the use of such prefixes. In addition, in the description of this embodiment, unless otherwise specified, the meaning of "plurality" is two or more.

[0032] The cell culture flask working system of this application, such as Figure 1As shown, it includes a loading component 1, a sampling component 2, a vertical oscillation component 3, a unloading component 4 and a control unit 5.

[0033] The loading assembly 1 is used to place the culture bottles to be processed; the sampling assembly 2 is used to take the culture bottles in the loading assembly and transport the culture bottles to the vertical shaking assembly 3, and the vertical shaking assembly 3 vertically shakes and mixes the culture bottles to shake and fall off the adherent cells in the culture bottles;

[0034] The unloading component 4 is used to unload the culture bottles after being shaken and mixed by the vertical oscillation component 3; the control unit 5 is connected to the loading component 1, sampling component 2, vertical oscillation component 3 and unloading component 4, and is used to control the work flow of each component.

[0035] The vertical oscillation assembly 3 is used to vibrate the culture bottle 100 up and down. The sampling assembly 2 includes a robot assembly 20, which also includes a U-shaped oscillation assembly. Preferably, the U-shaped oscillation assembly is located within the robot assembly 20. The U-shaped oscillation assembly performs a U-shaped oscillation motion on the culture bottle. By performing the U-shaped oscillation motion, the digestive fluid in the culture bottle is fully mixed while the sampling assembly 2 transports the culture bottle.

[0036] The cell culture flask 100, such as Figure 2 As shown, the multi-layer structure 101 generally includes a multi-layer structure extending along the vertical length and width of the bottle body, and the multi-layer structure 101 is stacked along the thickness direction of the culture bottle. The culture bottle is placed horizontally with the bottle mouth inside the vertical oscillation assembly 3, and the multi-layer structure is arranged vertically, so that the vertical vibration of the vertical oscillation assembly 3 can drive the culture bottle to move up and down.

[0037] During cell culture, adherent cells cling tightly to the attachment layer within the culture flask. The digestion step requires the digestive fluid to separate the adherent cells from the attachment layer within the culture flask. Adherent cells have a strong ability to adhere to the flask, so the digestive fluid's ability to digest and separate the adherent cells is crucial. This requires the combined action of external force and the digestive fluid, which allows the adherent cells to be detached from the culture plate within the culture flask. Therefore, the vertical reciprocating motion of the vertical oscillating assembly 3, combined with the physical flushing power of the digestive fluid, allows the adherent cells to be completely separated from the culture plate within the shortest possible digestion time.

[0038] Feeding component 1, such as Figure 3 As shown, the system includes multiple loading stations 11, each of which includes a capacitive proximity sensor located at its bottom to detect whether a culture bottle is placed on the station. Preferably, the capacitive proximity sensor has a detection distance of 2-8 mm. When a culture bottle is placed on a loading station 11, its bottom contacts the capacitive proximity sensor, triggering the induction.

[0039] The sampling assembly 2 includes a robot assembly, wherein the U-shaped oscillation assembly is provided in the sampling assembly, and the U-shaped oscillation assembly realizes the U-shaped oscillation of the culture bottle. The robot assembly realizes the U-shaped oscillation when grabbing the culture bottle from the loading assembly and transporting it to the vertical oscillation assembly. Figure 4 As shown, a U-shaped oscillation as shown by the arrow is achieved.

[0040] Of course, those skilled in the art can also understand that the sampling component can also be other structures that transport the culture bottles on the loading station 11 to the vertical oscillation component 3, and the sampling component 2 can include a U-shaped oscillation component to achieve U-shaped oscillation action during the transportation process.

[0041] In this embodiment, Figure 3 、 4 As shown, the robot assembly performs a U-shaped oscillating motion when grabbing the culture bottle from the loading station 11 and transporting it to the vertical oscillating assembly 3.

[0042] like Figure 5 As shown, the robot assembly includes a robot arm 21, and the gripper portion 22 of the robot arm 21 adopts a two-layer structure, including a hard material located on the outer layer and an elastic material located on the inner layer. Figure 4 As shown, the gripper portion 22 includes a bracket 221, a slide rail 222 mounted on the bracket 221, and a slider 223 that moves along the slide rail 222. The slider 223 can move in various directions along the slide rail 222 to move away from or grasp the culture bottle. The slider 223 comprises an outer hard material and an inner elastic material. The elastic material contacts the culture bottle, ensuring the bottle's integrity while gripping it.

[0043] like Figure 1As shown, the vertical oscillation component 3 includes a workbench 31 and a fixed fixture 32 provided on the workbench 31, and the fixed fixture 32 is used to clamp the culture bottle 100. The side of the fixed fixture is provided with a sensor for detecting whether the culture bottle is installed in place, and a locking mechanism for locking the culture bottle. After the locking mechanism locks the culture bottle, the fixed fixture 32 oscillates up and down along the track on the workbench 31, completing the reciprocating motion at a predetermined frequency, and has corresponding position sensing at the highest point and the lowest point, and the position of the highest point and the lowest point is confirmed. The time of the reciprocating motion is obtained from a large amount of experimental data. This time takes into account comprehensive considerations such as the digestion effect of the adherent cells in the entire culture bottle, the noise during the operation of the workstation, and the vibration maintenance during the operation of the workstation. The moving part adopts heavy-duty linear guides and adopts medium preload to ensure that the repeat positioning accuracy is between ±0.5mm. In the numerical oscillation component, the mouth of the culture bottle is horizontal and the multi-layer structure is set numerically, so that the digestive fluid in the culture bottle can be evenly distributed to the bottom of each culture plate of the culture bottle. When the vertical oscillation component subsequently moves back and forth, the digestive fluid in each layer of the culture bottle can be used to evenly flush the adherent cells on the culture plate, thereby achieving the purpose of uniform flushing and shedding of all adherent cells.

[0044] like Figure 6 The figure shows a schematic diagram of the specific structure of the fixture 32 on the vertical oscillation assembly. The fixture 32 is provided with a horizontal and vertically extending groove 321 for accommodating the culture bottle to be processed. The groove 321 surrounds the culture bottle from all sides, preventing it from falling out of the groove. A spring clip 322 is provided at one end of the groove 321 of the fixture 32, which is used to clamp the bottle's neck, thereby securing one end of the bottle. The other end of the groove 321 is provided with a push rod fixture. This push rod fixture includes a bracket 324 and a push rod 323 mounted on the bracket 324, which can move horizontally to block the culture bottle from one side. The push rod 323 is horizontally movable and works in conjunction with the robotic arm 21. When the culture bottle is placed in the groove 321, the robotic arm 21 pushes the push rod 323 horizontally from the outside, causing the push rod 323 to block the other end of the culture bottle from one side, cooperating with the spring clip 322 to prevent the culture bottle from falling out of the groove 321. After the culture bottle has completed its oscillation within the fixture 32, the robotic arm 21 first pushes the push rod 323 to move horizontally, thereby unlocking the culture bottle and removing it from the fixture 32. The spring clip 322 and the push rod fixture constitute the locking mechanism of the fixture 32. This locking mechanism has a simple structure and can be used in conjunction with the robotic arm, eliminating the need for complex operations. Of course, those skilled in the art will also appreciate that other locking mechanisms can also be used in conjunction with the robotic arm 21 to lock and unlock the culture bottle.

[0045] The vertical oscillation assembly is powered by a servo motor. Combined with a cam linkage and Hiwin linear guides, a two-in-one configuration drives two oscillating fixtures in reciprocating linear motion, achieving vertical oscillation. The rotating shaft is constructed of 40Cr, a high-quality medium-carbon alloy steel. The shaft undergoes high-frequency surface hardening, resulting in high surface hardness and strength, while the core maintains excellent rigidity, preventing fatigue damage and brittle fracture during high-speed rotation. After heat treatment, the surface is hard-chrome plated for excellent wear resistance and rust resistance. The connecting rod is constructed of 7075 aviation aluminum, boasting a high specific height, light weight, and high strength. This robust design significantly reduces rotational inertia and vibration, ensuring long-term, continuous operation with a lifespan of up to one year. Dowel pins are used to connect all components to ensure accurate positioning. The moving parts utilize Hiwin HG series heavy-duty linear guides with a medium preload, ensuring repeatable positioning accuracy within ±0.5mm. A locking mechanism, consisting of a leaf spring and latch, secures the culture flask during oscillation.

[0046] The material discharge assembly 4 comprises a stack assembly, which can automatically eject the material when the number of culture bottles on the stack assembly reaches a preset number.

[0047] The control unit 5 of this system is connected to the loading component 1, sampling component 2, vertical oscillation component 3 and unloading component 4, and is used to control the work flow of each component. For example, the proximity sensor on the loading component is connected to transmit the signal on the loading station to the sampling component 2, and is also connected to the robot component 20 of the sampling component. The gripper part of the mechanical arm of the robot component 20 is provided with pre-pressure. When the gripper part grasps the culture bottle, the pre-pressure is within the normal range. If the pre-pressure is abnormal, it means that the culture bottle is not grasped, or the culture bottle is broken during transportation, or a fault occurs, etc. The vertical oscillation component 3 is connected to the control unit, and the control unit is used to control the start and timed end of the vertical oscillation. At the same time, the signal of the end of the oscillation is sent to the sampling component, and the sampling component transports the culture bottle after oscillation to the stacking component.

[0048] like Figure 1 、 2 As shown, the cell culture flask working system also includes a frame 200 and a work platform 300 disposed within the frame 200. The loading assembly 1, sampling assembly 2, vertical oscillation assembly 3, and unloading assembly 4 are all disposed on the work platform. The control unit 5 includes a controller and input / output modules, which can be located outside the work platform 300 and the frame 200. The work platform includes a stainless steel perforated plate for ventilation and drainage, among other functions.

[0049] A housing is provided around the frame 200 to enclose the above components. The housing includes a transparent portion for easy observation. Preferably, a portion of the housing is a manually flip-up glass door, a suspended glass door, or a glass door that can be opened and closed in other ways, so as to facilitate observation of the entire operation and manual troubleshooting.

[0050] The frame 200 also includes an air filtration system, located above the work platform 300. This system includes a fan that draws cleanroom air from top to bottom through a HEPA filter and into the top of the system. The clean air then flows evenly through a flow-distributing membrane beneath the HEPA filter to the work platform below, where it is exhausted through the platform's stainless steel perforated plate. After passing through this air filtration system, the system's internal air supply environment meets Class A standards.

[0051] The frame 200 also includes lighting and ultraviolet lamps. The lighting lamps can provide an effective lighting environment during the operation of the system. Preferably, the lighting area can reach 3 to 8 m 2 , illumination>300lux; the ultraviolet lamp can be turned on after the internal cleaning of the equipment to play a sterilization role.

[0052] The cell culture flask working system disclosed in the present invention can remove the adherent cells in the cell culture flask in the shortest possible time through the action of the vertical oscillation component. For example, the loading and unloading of a single culture flask can be completed within 45 seconds, and the vertical oscillation time is only 15 seconds. It can also effectively prevent excessive cell digestion from affecting the cell state. The use of fully automatic control and operating equipment reduces the movement of personnel, ensures the cleanliness of the production environment, and reduces the labor intensity of personnel. The setting of the U-shaped oscillation component further improves the mixing efficiency of the digestive fluid, saves overall time, and improves work efficiency.

[0053] While specific embodiments of the present disclosure have been described above, those skilled in the art will appreciate that these are merely illustrative and that the scope of protection of the present disclosure is defined by the appended claims. Those skilled in the art may make various changes or modifications to these embodiments without departing from the principles and essence of the present disclosure, and such changes and modifications are intended to fall within the scope of protection of the present disclosure.

Claims

1. A cell culture flask working system, characterized in that: It includes a loading component, a sampling component, a vertical oscillation component, a unloading component and a control unit; The loading assembly is used to place the culture bottles to be processed; The sampling component is used to take the culture bottle from the loading component and transport the culture bottle to the vertical shaking component. The vertical shaking assembly is used to vertically shake the culture bottle to mix it evenly, so that the adherent cells in the culture bottle are shaken off; The unloading component is used to unload the culture bottles after being shaken and mixed by the vertical shaking component; The control unit is connected to the loading component, sampling component, vertical oscillation component and unloading component, and is used to control the work flow of each component.

2. The cell culture flask working system according to claim 1, characterized in that: The sampling component includes a robot component, and the sampling component also includes a U-shaped oscillation component, and the U-shaped oscillation component realizes the U-shaped oscillation action of the culture bottle.

3. The cell culture flask working system according to claim 2, wherein: The robot assembly realizes the U-shaped oscillating motion when grabbing the culture bottle from the loading assembly and transporting it to the vertical oscillating assembly.

4. The cell culture flask working system according to claim 1, wherein: The loading assembly includes a plurality of loading stations, and each loading station includes a capacitive proximity sensor for detecting whether the culture bottle is placed in place.

5. The cell culture flask working system according to claim 2, wherein: The robot assembly includes a robotic arm, and the gripper portion of the robotic arm adopts a two-layer structure, including a hard material located on the outer layer and an elastic material located on the inner layer.

6. The cell culture flask working system according to claim 2, wherein: The vertical oscillation assembly includes a workbench and a fixed tooling installed on the workbench. The side of the fixed tooling is provided with a sensor for detecting whether the culture bottle is installed in place. The fixed tooling includes a locking mechanism for locking the culture bottle. The workbench performs reciprocating linear motion up and down.

7. The cell culture flask working system according to claim 1, wherein: It also includes a frame and a working platform, as well as a shell arranged on the frame. The working platform is arranged in the frame, and the loading assembly, sampling assembly, oscillating assembly and unloading assembly are all arranged on the working platform; The housing includes a transparent portion.

8. The cell culture flask working system according to claim 7, wherein: It also includes an air filtration system, which is arranged above the working platform.

9. The cell culture flask working system according to claim 1, wherein: The blanking assembly includes a stacking assembly, and the stacking assembly can be automatically popped out.

10. The cell culture flask working system according to claim 2, wherein: The culture bottle is a multi-layer structure extending along the vertical length and width directions of the bottle body, and the multi-layer structure is stacked along the thickness direction of the culture bottle. The bottle mouth of the culture bottle is arranged horizontally in the vertical shaking assembly, and the multi-layer structure is arranged vertically.

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