Cell culture apparatus
By setting up clearly defined operating cabinets, culture cabinets, and consumable cabinets in the cell culture equipment, and combining them with liquid storage modules, liquid supply modules, and pipetting modules, the problem of unsuitable liquid storage and supply in cell culture equipment is solved, achieving efficient and reliable liquid management and automated cell culture.
Patent Information
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- LEAD HEALTHCARE TECHNOLOGY (GUANGZHOU) CO LTD
- Filing Date
- 2024-12-09
- Publication Date
- 2026-06-11
AI Technical Summary
Existing cell culture equipment suffers from poor cell culture consistency, cell growth damage due to unsuitable liquid storage and supply, easy failure and low efficiency in the pipetting process, and insufficient unattended operation capability.
A cell culture device was designed, comprising an operating cabinet, a culture cabinet, and a consumables cabinet, with clearly defined zones. It includes a liquid storage module for storing liquids at different temperatures, a liquid supply module for heating liquids to a suitable temperature, and a pipetting module that uses a robotic arm to drive the pipetting head for efficient and reliable pipetting operations. It is also equipped with highly automated modules such as a robotic arm, a barcode scanning unit, and a sterilization module.
It achieves efficient and reliable liquid supply and storage, improves the automation level of cell culture, ensures normal cell growth and culture consistency, reduces human intervention, and enhances the unattended operation capability of the equipment.
Smart Images

Figure CN2024137925_11062026_PF_FP_ABST
Abstract
Description
Cell culture equipment
[0001] This application claims priority to Chinese Patent Application No. 202411791839.1, filed with the Chinese Patent Office on December 6, 2024, the entire contents of which are incorporated herein by reference. Technical Field
[0002] This application relates to the field of life science instrument technology, such as a cell culture device. Background Technology
[0003] With the advancement of precision medicine, more and more research is being conducted based on individual cells, such as antibody drug development, anticancer drug development, and drug toxicology studies. As a result, the demand for cell culture equipment is increasing.
[0004] In related cell culture equipment, operation is primarily manual, leading to issues such as poor consistency between batches of cells and a lack of standardization in the culture process. Furthermore, unsuitable storage and supply temperatures for various liquids required for cell culture can impair cell growth, and the pipetting process is prone to malfunctions and inefficient. Additionally, these problems result in poor unattended operation capabilities for cell culture equipment. Summary of the Invention
[0005] Based on the above, this application provides a cell culture device that can store and supply liquids required for cell culture at different temperatures, while the pipetting process is more efficient and reliable, the partitioning is more reasonable, and the degree of automation is higher.
[0006] This application provides a cell culture device, comprising:
[0007] An operating cabinet is provided, comprising a working area and a non-working area. The working area includes a robotic arm, a liquid supply module, a liquid transfer module, and at least two operating modules. The non-working area includes a liquid storage module and a waste area. The liquid storage module stores liquid at a preset storage temperature. The liquid supply module is connected to the liquid storage module and is used to heat a preset amount of liquid to a preset operating temperature. The working area also includes a support base. The liquid transfer module has a pipette head, which is detachably mounted on the support base. The robotic arm can selectively grip and drive the pipette head to perform liquid transfer. The robotic arm can move between the liquid transfer module and two or more of the operating modules. The waste area is selectively connected to the working area.
[0008] The culture cabinet and the consumable cabinet are respectively located on both sides of the operating cabinet and can be selectively connected to the operating cabinet. The culture cabinet is used for cell culture, and the consumable cabinet is used to hold consumables.
[0009] In some implementations, the pipetting module is further provided with a cable supply assembly, which includes an adjustable-length cable, one end of which is disposed on the support base and the free end is connected to the pipetting head.
[0010] In some implementations, the liquid storage module includes a storage tank, multiple liquid storage bottles, and a detection unit. The storage tank is equipped with a refrigeration unit, the cold end of which is connected to the inner cavity of the storage tank to provide a preset storage temperature to the inner cavity. The multiple liquid storage bottles are disposed in the inner cavity and can selectively connect to the main liquid pipe. The detection module is disposed in the inner cavity and corresponds to each of the liquid storage bottles to detect the remaining liquid level in the bottles.
[0011] In some implementations, the liquid supply module includes a preheating unit, which includes a heating component and a consumable bag. The consumable bag includes a bag body, an outlet tube, and an inlet tube. One end of the outlet tube is connected to the bag body, and the other end is connected to the pipetting module. One end of the inlet tube is connected to the bag body, and the other end is connected to the liquid storage module. The end of the inlet tube away from the bag body is also connected to an air tube. The inlet tube can selectively connect to the liquid storage module and the air tube.
[0012] In some implementations, the control cabinet is equipped with an operating table, which is used to separate the working area and the non-working area. The operating table is equipped with a waste outlet and an isolation door. The isolation door can selectively block the waste outlet to selectively connect the waste area and the working area.
[0013] In some implementations, the waste area is further provided with a waste carrier, a waste switch door, and a sliding assembly. The waste carrier is disposed on the sliding assembly, and the sliding assembly is used to move the waste carrier out of the waste switch door.
[0014] In some implementations, the operation module includes a capping unit for opening centrifuge tubes and / or culture flasks; and / or the operation module includes an incubation unit for providing a preset incubation temperature.
[0015] In some implementations, the operation module further includes a filtration unit for filtering and circulating air within the working area; and / or the operation module includes a barcode scanning unit for scanning the feature codes and / or feature chips of culture flasks and / or centrifuge tubes.
[0016] In some implementations, the incubator is equipped with a sterilization module for providing hydrogen peroxide fumigation.
[0017] In some implementations, the cell culture apparatus further includes a handling robot for transporting materials between the culture cabinet, the operating cabinet, and the consumables cabinet.
[0018] This application utilizes an operating cabinet, a culture cabinet, and a consumables cabinet for operation, culture, and consumables storage, respectively. The culture cabinet and consumables cabinet are located on opposite sides of the operating cabinet and can selectively communicate with it. This allows the three cabinets to be connected or disconnected as needed. When connected, they are used for material transfer; when disconnected, they maintain relative independence, ensuring suitable environments for separate operations. The operating cabinet is divided into a working area, a non-working area, and a waste area, resulting in more rational zoning and reducing interference between different modules within each area. The liquid storage module in the non-working area stores liquid at a preset storage temperature to ensure its activity and effectiveness. The liquid supply module heats a preset amount of liquid to a preset operating temperature to ensure normal cell growth. The pipetting module's pipetting head detaches from the support base under the drive of a robotic arm for pipetting, making the process more reliable and efficient. Furthermore, the robotic arm can move between multiple modules for corresponding operations, offering good compatibility and high utilization. Attached Figure Description
[0019] Figure 1 is a schematic diagram of the cell culture equipment provided in this application;
[0020] Figure 2 is a schematic diagram of the control cabinet of the cell culture equipment provided in this application from one perspective.
[0021] Figure 3 is a schematic diagram of the control cabinet of the cell culture equipment provided in this application from another perspective;
[0022] Figure 4 is a schematic diagram of the internal working cabinet of the cell culture equipment provided in this application;
[0023] Figure 5 is a schematic diagram of the control cabinet of the cell culture equipment provided in this application from another perspective;
[0024] Figure 6 is a schematic diagram of the pipetting module provided in this application;
[0025] Figure 7 is a schematic diagram of the pipetting components of the pipetting module provided in this application from one perspective;
[0026] Figure 8 is a schematic diagram of the pipetting components of the pipetting module provided in this application from another perspective;
[0027] Figure 9 is a schematic diagram of the liquid storage module provided in this application;
[0028] Figure 10 is a schematic diagram of the liquid storage module provided in this application;
[0029] Figure 11 is a cross-sectional view of the liquid storage module provided in this application;
[0030] Figure 12 is a schematic diagram of the liquid supply module provided in this application;
[0031] Figure 13 is a cross-sectional view of the liquid supply module provided in this application;
[0032] Figure 14 is a schematic diagram of the consumable bag for the liquid supply module provided in this application.
[0033] In the picture:
[0034] 1000. Control Cabinet; 1001. Work Area; 1011. Robotic Arm; 1016. Pipette Head; 1017. Filtration Unit; 1018. 96-Channel Pipette; 1019. Information Recognition Area; 1020. Centrifuge Tube Consumables Set; 1021. Culture Bottle Consumables Set; 1022. Incubation Unit; 1023. Well Plate Tip Box; 1024. Pipette Tip Box; 1025. Consumables Cabinet Transfer station; 1026, Disinfectant dispensing device; 1027, Transfer station; 1002, Non-working area; 1100, Frame; 1300, First window; 1400, Second window; 1500, Cap opening unit; 1510, Electric suction cup cap opener; 1520, Rotary cap opener; 1600, Microscope; 1701, Waste carrier; 1800, Centrifuge; 1900, Waste outlet;
[0035] 2000, incubator;
[0036] 3000, Consumables Cabinet;
[0037] 4100, Pipetting assembly; 4110, Pipetting body; 4111, Snap-fit female connector; 4112, Limiting plate; 4114, Snap-fit male connector; 4300, Clamping assembly; 4400, Cable supply assembly; 4410, Cable reel;
[0038] 5100 Storage box; 5101 Inner cavity; 5110 Refrigeration unit; 5111 Cold end; 5112 Hot end; 5113 Cooling fan; 5120 Temperature equalization fan; 5131 Inner layer; 5132 Outer layer; 5133 Insulation layer; 5200 Liquid storage bottle; 5210 Main liquid pipe; 5211 Peristaltic pump; 5300 Detection unit; 5310 Weighing platform; 5311 Tray; 5312 Weight sensor; 5400 Preheating unit; 5500 Control valve assembly; 5510 Switch valve;
[0039] 6100, Heating body; 6110, Locking assembly; 6120, Insulation layer; 6130, Hinge; 6200, Consumable bag; 6210, Bag body; 6220, Outlet pipe; 6230, Inlet pipe; 6240, Liquid pipe; 6250, Air pipe; 6300, Heating assembly; 6310, Heating element; 6320, Heat-conducting block. Detailed Implementation
[0040] Embodiments of this application are described in detail below. Examples of these embodiments are illustrated in the accompanying drawings, wherein the same or similar reference numerals denote the same or similar elements or elements having the same or similar functions throughout. The embodiments described below with reference to the accompanying drawings are exemplary and intended to explain this application.
[0041] In the description of this application, the terms "center," "upper," "lower," "left," "right," "vertical," "horizontal," "inner," and "outer," etc., indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings. These terms are used for ease of description and simplification, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation. Furthermore, the terms "first" and "second" are used for descriptive purposes only and should not be construed as indicating or implying relative importance. Specifically, the terms "first position" and "second position" refer to two different positions.
[0042] Unless otherwise expressly specified and limited, the terms "installation," "connection," "linking," and "fixing" should be interpreted broadly. For example, they can refer to fixed connections or detachable connections; mechanical connections or electrical connections; direct connections or indirect connections through an intermediate medium; and connections within two components or interactions between two components. Those skilled in the art can understand the meaning of these terms in this application as appropriate.
[0043] In this application, unless otherwise expressly specified and limited, "above" or "below" the second feature can include direct contact between the first and second features, or contact between the first and second features through another feature between them. Furthermore, "above," "over," and "on top" of the second feature includes the first feature being directly above or diagonally above the second feature, or simply indicates that the first feature is at a higher horizontal level than the second feature. "Below," "below," and "under" the second feature includes the first feature being directly below or diagonally below the second feature, or simply indicates that the first feature is at a lower horizontal level than the second feature.
[0044] The technical solution of this application will be described below with reference to the accompanying drawings and specific embodiments.
[0045] As shown in Figures 1-5, this embodiment provides a cell culture device, which includes an operation cabinet 1000, a culture cabinet 2000, and a consumable cabinet 3000. The operation cabinet 1000 is provided with a working area 1001 and a non-working area 1002. The working area 1001 is equipped with a robotic arm 1011, a liquid supply module, a liquid transfer module, and at least two operation modules. The non-working area 1002 is equipped with a liquid storage module and a waste area. The liquid storage module is used to store liquid at a preset storage temperature. The liquid supply module is connected to the liquid storage module and is used to heat a preset amount of liquid to a preset operating temperature. The area 1001 is also equipped with a support base, and the pipetting module is equipped with a pipetting head 1016. The pipetting head 1016 is detachably mounted on the support base. The robotic arm 1011 can selectively grip and drive the pipetting head 1016 to perform pipetting. The robotic arm 1011 can move and operate between the pipetting module and two or more operation modules. The waste area is selectively connected to the work area 1001. The culture cabinet 2000 and the consumable cabinet 3000 are respectively located on both sides of the operation cabinet 1000 and can selectively connect to the operation cabinet 1000. The culture cabinet 2000 is used for cell culture, and the consumable cabinet 3000 is used to hold consumables.
[0046] By setting up an operation cabinet 1000, a cultivation cabinet 2000, and a consumables cabinet 3000, respectively used for operation, cultivation, and storage of consumables, the operation cabinet 1000 and the consumables cabinet 3000 are respectively located on both sides of the operation cabinet 1000 and can selectively communicate with the operation cabinet 1000. This allows the three cabinets to be connected or disconnected as needed. When connected, they are used to transfer materials; when disconnected, they are used to maintain a relatively independent relationship, so as to maintain a suitable environment for separate operations. The operation cabinet 1000 is divided into a working area 1001, a non-working area 1002, and a waste area, which makes the zoning more reasonable and reduces the impact between different modules in each area. The liquid storage module in the non-working area 1002 is used to store liquid at a preset storage temperature to ensure the activity and effectiveness of the liquid; the liquid supply module is used to heat a preset amount of liquid to a preset operating temperature to ensure normal cell growth; the pipetting head 1016 of the pipetting module is driven by the robotic arm 1011 to detach from the carrier to perform pipetting, making the pipetting process more reliable and efficient; at the same time, the robotic arm 1011 can also move between multiple modules to perform corresponding operations, with good compatibility and high utilization.
[0047] Optionally, the control cabinet 1000, the incubation cabinet 2000, and the consumables cabinet 3000 can operate independently or be controlled via a bus. The three cabinets can be connected or separated into one unit through electrically controlled doors.
[0048] The culture cabinet 2000 provides a suitable environment for cell growth, such as providing appropriate temperature and carbon dioxide fields. It also includes a sterilization module for hydrogen peroxide fumigation. Furthermore, the culture cabinet 2000 can be equipped with a motion mechanism to transfer cell culture containers within it to specific locations. The culture cabinet 2000 is compatible with T75 cells, well plates, and culture dishes. Optionally, these cell culture containers can be made compatible with the motion mechanism via an intermediate transfer tray 5311, which restricts the cell culture containers' freedom of movement in the planar direction. In particular, the culture cabinet 2000 can also be used for culturing cells after the addition of drugs or viruses.
[0049] The consumables cabinet 3000 can hold consumables for culture containers, well plates, and disposable pipette tips. Optionally, the consumables cabinet 3000 can be installed independently outside the incubator; it can be housed within the operating cabinet 1000 or operate independently of it. Considering the throughput of the cell culture equipment, the consumables cabinet 3000 can optionally be located outside the operating cabinet 1000. The consumables cabinet 3000 also has specific locations for docking with external automated feeding equipment. There can be one or more such locations, located on the side of the consumables cabinet 3000, with the highest point of each location 800mm-1200mm from the ground. Several workstations for placing consumables are arranged on the worktable of the work area 1001, and workstations for placing consumables are also mounted on the walls of the work area 1001. For example, centrifuge tube consumables set 1020, culture flask consumables set 1021, well plate pipette box 1023, and pipette box 1024.
[0050] Furthermore, the control cabinet 1000 and the consumable cabinet 3000 are connected via an electrically operated door. The consumable cabinet 3000 also includes a device for transferring and feeding materials, as well as an automated electrically controlled door located on the side of the consumable cabinet 3000 closest to the control cabinet 1000, which opens and closes in conjunction with the device for transferring and feeding materials. The electrically controlled door can be a rotary door or a swing door; in this embodiment, a swing door is used. The sliding electrically controlled door can be opened directly by a linear screw drive or by a rack and pinion transmission.
[0051] The control cabinet 1000 is equipped with a rack 1100, a first window 1300 communicating with the incubator 2000, and a second window 1400 communicating with the consumables cabinet 3000. The control cabinet 1000 is divided into a working area 1001 and a non-working area 1002. The control module also includes a filter unit 1017 for filtering and circulating the air within the working area 1001 to ensure the cleanliness of the working area 1001. Optionally, a high-efficiency particulate air (HEAP) filter may be used.
[0052] The operation module includes a capping unit 1500 for opening centrifuge tubes and / or culture flasks. Optionally, one or more capping units 1500 are provided in the working area 1001. Some capping units 1500 are used for opening centrifuge tubes, and others are used for opening culture flasks. The ratio of capping units 1500 for centrifuge tubes to capping units 1500 for culture flasks is 1:1 or 2:1. Optionally, the capping units 1500 can perform Z-axis movement, partial rotation, and movement functions for opening centrifuge tubes and culture flasks. Centrifuge tubes and culture flasks can be placed inside a well plate, which can be a 96-well plate or a 382-well plate, etc. Optionally, the capping unit 1500 includes an electric suction cup capping machine 1510 and a rotary capping machine 1520 for different capping scenarios.
[0053] The operation module includes a barcode scanning unit for scanning the feature codes and / or feature chips of culture flasks, which improves the informatization level of cell culture equipment and facilitates traceability. Optionally, 1-3 sets of barcode scanning units can be arranged, which can be configured as scanning docks, cameras, etc.
[0054] The operating module includes a centrifuge 1800 for centrifugation operations. The centrifuge 1800 can be an angle rotor centrifuge or a basket centrifuge with temperature control.
[0055] The operating module includes a microscope 1600 for observing cells, as well as for cell status and counting.
[0056] The operation module includes an incubation unit 1022, which provides a preset incubation temperature. The incubation unit 1022 has multiple stations and can provide constant temperature incubation for culture flasks, petri dishes, or well plates. The incubation temperature can be 37°C or other set temperatures.
[0057] It is worth noting that the robotic arm 1011 can move consumables such as cell culture containers, 96-well plates, and centrifuge tubes in space. The range of motion of the robotic arm 1011 can cover more than 90% of the work area 1001. For example, when the robotic arm 1011 is set as a 6-axis robotic arm 1011, the length of the work area 1001 is 1.5-2 times the extended length of the robotic arm 1011. Optionally, multiple robotic arms 1011 can be provided.
[0058] As shown in Figures 6-8, the pipetting module also includes a cable supply assembly 4400, which comprises an adjustable-length cable. One end of the cable is mounted on the support, and the free end is connected to the pipetting head 1016. By providing the cable supply assembly 4400 and connecting one end of the adjustable-length cable to the pipetting assembly 4100, the cable length can be adjusted according to the distance between the pipetting assembly 4100 and the support when the pipetting assembly 4100 is detached from the support for pipetting, effectively reducing the entanglement of various leads of the pipetting assembly 4100 with other wires.
[0059] Optionally, the pipette tip 1016 can be a component used for aspirating and dispensing liquids. In one embodiment, the pipette tip 1016 can be configured as a separate pipetting pump, in which case the pipetting pump requires a power cord for power supply and signal transmission; in other embodiments, the pipette tip 1016 can also be a stainless steel pipette tip, in which case the stainless steel pipette tip needs to be connected to a tubing for aspiration and dispensing. Optionally, the pipette tip 1016 can be configured as an ADP pipette.
[0060] Optionally, the pipette tip 1016 is detachably equipped with a disposable tip, which is replaced after each pipette operation to ensure the sterility of each pipette operation and avoid contamination caused by repeated pipetting.
[0061] Furthermore, the cable can also be retracted or stretched by other elastic components. For example, the cable supply assembly 4400 includes a cable reel 4410, with one end of the cable wound around it and the other end fixedly connected to a pipetting assembly 4100. The pipetting assembly 4100 is provided with an electric wire or tubing, which is fixedly connected to the cable. The other end of the cable is connected to the pipetting assembly 4100. The cable reel 4410 can automatically wind and unwind the cable and the electric wire or tubing by adapting to the distance between the support and the pipetting assembly 4100 as the pipetting assembly 4100 moves, reducing tangling between the leads. Optionally, the cable is made of SUS stainless steel.
[0062] In other embodiments, the cable may also be a spiral or spring wire that can retract under its own elasticity and be stretched under external force. For example, the cable may be a spring wire, which is an electrical wire used to power the pipette head 1016; or the spring wire may be a liquid tube connected to the pipette head 1016.
[0063] Understandably, the longest retractable length of the cable is not less than the maximum distance between the pipetting assembly 4100 and the carrier.
[0064] Of the support and the pipetting body 4110, one is provided with a snap-fit male connector 4114 and the other with a snap-fit female connector 4111. The snap-fit male connector 4114 can snap into the snap-fit female connector 4111 to achieve the connection between the support and the pipetting body 4110. Optionally, the snap-fit male connector 4114 is provided with a wedge-shaped protrusion, and the snap-fit female connector 4111 is provided with a corresponding groove. At the same time, a ball is provided inside the groove. When the wedge-shaped protrusion is placed in the groove, the ball can confine the snap-fit male connector 4114 within the snap-fit female connector 4111. It is understood that the preload force of the ball is not less than the weight of the pipetting assembly 4100 to ensure that the pipetting assembly 4100 can be stably placed in the support. In other embodiments, the connection structure can also be set as a dovetail protrusion and a dovetail groove that can snap into each other, or other elastic structures that can snap into each other.
[0065] Optionally, the support base is provided with a limiting stage, and the pipetting body 4110 is provided with a limiting plate 4112. When the male connector 4114 and the female connector 4111 are engaged, the limiting plate 4112 can be placed on the limiting stage. By providing the mutually cooperating limiting stage and limiting plate 4112, the pipetting assembly 4100 is supported, the force between the male connector 4114 and the female connector 4111 is reduced, and the reliability of the pipetting assembly 4100 placed on the support base is improved.
[0066] It is worth noting that the cell culture equipment is also equipped with a control system, and the drive components and detection components are all communicatively connected to the control system. Optionally, the control system can adopt PID closed-loop control. The control system mainly consists of a memory, sensors, a power source, and motion units of control components. The memory can be considered as the central processing unit of the equipment, which can monitor the status of all positions of the equipment, the culture status of cell culture flasks, etc., including the culture time of the corresponding culture flask in the cell culture equipment, and the cell culture status obtained at the previous moment through methods such as microscope 1600. Sensors can include temperature sensors, flow sensors, position optocouplers, etc., the power source can be a motor, pump, etc., and the control components can be valves, position switches, etc.
[0067] The working process of the above-mentioned pipetting module is as follows: During operation, when the cell culture equipment receives an instruction that a cell culture flask needs to be passaged, the digested cell culture flask is placed in the transfer position and tilted at a certain angle to accommodate the pipetting tip 1016; at the same time, the opened centrifuge tube is placed in the corresponding position. At this time, the robotic arm 1011 moves the clamping component 4300 close to the pipetting component 4100 and clamps the pipetting body 4110. The machine moves horizontally or vertically to remove the pipetting component 4100 from the support. Then, the pipetting tip 1016 is replaced with a disposable pipette tip. Afterward, the machine moves the pipetting component 4100 to the cell culture flask position and performs liquid aspiration. When a certain amount of liquid has been aspirated, the machine moves the pipetting component 4100 to a nearby centrifuge tube and dispenses the liquid. When the cell culture flask contains a large amount of liquid or there are multiple cell culture flasks of the same type that need to be aspirated, the above actions can be repeated to complete the aspiration. After the suction action is completed, the machine moves the pipetting assembly 4100 to the solid waste area, performs a disposable suction nozzle removal, and finally puts the pipetting assembly 4100 back into the carrier.
[0068] It is worth noting that the movement of the pipette tip 1016 can also be achieved by a multi-degree-of-freedom mechanism, such as an XYZ component. Furthermore, the process of pipetting in centrifuge tubes and cell culture flasks can also involve fixing the pipette tip 1016 in place, while the robotic arm 1011 picks up the culture flask or centrifuge tube and moves it to the pipette tip 1016 to aspirate and transfer the liquid. If multiple cell culture flasks or centrifuge tubes are operated on at the same time, the robotic arm 1011 needs to continuously switch hands to change different containers and move them to the pipette tip 1016 for aspiration and collection.
[0069] Furthermore, the pipette head 1016 of the pipetting module is located in the working area 1001 of the control cabinet 1000, while the power components of the pipette head 1016, such as the pump and valve, can be placed in the non-working area 1002. If the pipeline is connected to a container containing disinfectant at the pump inlet, the pipetting module can supply disinfectant to the container in the working area 1001. When the pump inlet is connected to a waste liquid container, the pipetting module can perform waste liquid aspiration. Furthermore, a sensor can be installed at the inlet of the pipette head 1016 to monitor the presence or absence of liquid in the pipeline.
[0070] The control cabinet 1000 can also house a well plate pipetting device, which can perform 96-well plate pipetting, 384-well plate pipetting, and other functions. Specifically, the well plate pipetting device can be a single-channel pipetting pump, an 8-channel pipetting pump, or a 96-channel or 384-channel pipetting assembly. The pipetting volume of a single channel is between 5ul and 500ul, optionally 300ul. This well plate pipetting device can be placed in a separate space with air filtration, or in the aforementioned work area 1001. Optionally, this module is a 96-channel well plate pipetting assembly, and the 96-channel well plate pipetting assembly is installed in work area 1001.
[0071] Outside the non-working area 1002, a cell monitoring device for cell fluorescence detection and activity detection is also arranged. The sample inlet of the cell monitoring device is located in the working area 1001, or the inlet can be connected to a transfer container, which is located in the working area 1001. The liquid pipeline between the inlet and the cell culture device is equipped with components such as solenoid valves and pumps. The solenoid valve is used to monitor the cell monitoring device to close the liquid pipeline during non-working hours to prevent bacteria and other contaminants in the liquid pipeline from entering the working area 1001 of the cell culture device.
[0072] As shown in Figures 9-11, the liquid storage module includes a storage tank 5100, multiple liquid storage bottles 5200, and a detection unit 5300. A cooling unit 5110 is installed inside the storage tank 5100. The cold end 5111 of the cooling unit 5110 is connected to the inner cavity 5101 of the storage tank 5100 so that the inner cavity 5101 has a preset storage temperature. Multiple liquid storage bottles 5200 are installed in the inner cavity 5101 and can selectively connect to the main liquid pipe 5210. The detection module is installed in the inner cavity 5101 and is set one-to-one with the liquid storage bottles 5200 to detect the remaining liquid in the liquid storage bottles 5200.
[0073] By setting up a storage box 5100 with an inner cavity 5101 to accommodate multiple liquid storage bottles 5200, each capable of storing one or more reagents, the quantity and variety of reagents stored can be increased. Simultaneously, each liquid storage bottle 5200 can selectively connect to the main liquid pipe 5210 to ensure liquid supply. Furthermore, a detection unit 5300 is configured one-to-one with each liquid storage bottle 5200, enabling real-time detection of the remaining reagent level in each bottle. This allows for selective connection or disconnection of the reagent bottle and main liquid pipe 5210 based on the remaining reagent level, increasing the possibility of unattended operation of the liquid storage and supply device, thereby reducing the need for periodic manual reagent replenishment, improving supply efficiency, and lowering labor costs. By connecting the cold end 5111 of the refrigeration unit 5110 to the inner cavity 5101, a low-temperature storage environment is provided.
[0074] Optionally, the cold end 5111 of the cooling unit 5110 is disposed on the side wall of the inner cavity 5101. The cooling unit 5110 also includes a hot end 5112 and a cooling fan 5113. The hot end 5112 is connected to the cold end 5111 and is located on the outside of the storage box 5100, that is, the cooling unit 5110 passes through the side wall of the storage box 5100. The cooling unit 5110 is installed with screws, which is convenient for installation and easy to replace. The cooling fan 5113 located on the outside of the storage box 5100 can be used to dissipate heat from the hot end 5112, thereby ensuring the cooling effect of the cold end 5111. Optionally, the cooling unit 5110 is configured as a semiconductor cooler.
[0075] Furthermore, to prevent the temperature near the cold end 5111 of the refrigeration unit 5110 from becoming too low, which could cause the reagent in the storage bottle 5200 near the cold end 5111 to freeze, a temperature equalization fan 5120 is installed inside the storage box 5100 to accelerate the gas flow inside the inner cavity 5101 and equalize the temperature inside the inner cavity 5101. Optionally, the temperature equalization fan 5120 is an axial flow fan.
[0076] For example, the preset storage temperature is set to 4℃-8℃; the preset operating temperature is set to 30℃-37℃. Optionally, the cold end 5111 of the cooling unit 5110 is set to a temperature not lower than 1.5℃ to prevent the reagent from freezing due to excessively low temperature inside the cavity 5101.
[0077] In this embodiment, the detection unit 5300 includes a weighing platform 5310, and a liquid storage bottle 5200 is disposed on the weighing platform 5310. Optionally, the weighing platform 5310 includes a tray 5311 and a weight sensor 5312 disposed below the tray 5311, and the liquid storage bottle 5200 can be placed inside the tray 5311. Optionally, the tray 5311 is also provided with a drainage hole for draining condensate water inside the tray 5311, so as to reduce the interference of condensate water on weight detection and ensure the accuracy of reagent balance detection.
[0078] In other embodiments, the detection unit 5300 includes a liquid level detection element to detect the liquid level in the storage bottle 5200, thereby determining the remaining reagent level in the storage bottle 5200. The liquid level can be detected by infrared or ultrasonic methods.
[0079] To achieve selective connectivity between multiple liquid storage bottles 5200 and the main liquid pipe 5210, the liquid storage and supply device further includes a control valve assembly 5500. The control valve assembly 5500 includes multiple switching valves 5510, each corresponding to one of the multiple liquid storage bottles 5200. When a switching valve 5510 is in the open position, it can connect the liquid storage bottle 5200 to the main liquid pipe 5210. It is understood that the switching valve 5510 is communicatively connected to the detection unit 5300 of the corresponding liquid storage bottle 5200, so that the switching valve 5510 can selectively open and close based on the reagent balance detected by the detection unit 5300. In other embodiments, the control valve assembly 5500 can also be configured as a multi-way valve, with the valve body positioned in different positions to achieve selective connectivity between the multiple liquid storage bottles 5200 and the main liquid pipe 5210.
[0080] Furthermore, the main liquid pipe 5210 is equipped with a peristaltic pump 5211, which is located upstream of the preheating unit 5400 and is used to extract the reagent in the storage bottle 5200 when the storage bottle 5200 is connected to the main liquid pipe 5210.
[0081] Optionally, to ensure the storage temperature of the inner cavity 5101, the storage box 5100 is configured with two layers, and the inner layer 5131 is configured as a heat insulation layer to reduce the outward diffusion of low temperature from the inner cavity 5101. At the same time, a heat insulation layer 6120 is provided between the outer layer 5132 and the inner layer 5131 to further improve the heat preservation effect on the low temperature environment of the inner cavity 5101. For example, the heat insulation layer 6120 is configured as heat insulation cotton. Furthermore, the upper storage box is also provided with a door to facilitate the access and placement of the liquid storage bottle 5200; and the door is also provided with a heat insulation structure.
[0082] This embodiment also discloses a cell culture apparatus, including a liquid storage and supply device as described in any of the above embodiments. In a cell culture apparatus equipped with the aforementioned liquid storage and supply device, reagents can be stored in a low-temperature environment, and the influence between multiple storage bottles 5200°C is minimal, ultimately providing reagents with a preset operating temperature.
[0083] The operation of the above-mentioned liquid supply module is as follows: When the liquid supply module is in operation, since the cooling unit 5110 is controlled by a PID control algorithm, the minimum temperature of the cooling unit 5110 will not be lower than the set threshold temperature (1.5℃); at the same time, since there is a temperature equalization fan 5120 in the inner cavity 5101, it can be used to realize the air circulation in the inner cavity 5101, so the temperature of the inner cavity 5101 is relatively uniform. When the detection unit 5300 of a certain liquid storage bottle 5200 detects that the reagent residue in the corresponding liquid storage bottle 5200 is lower than the set threshold, then in the next test liquid addition, the liquid storage bottle 5200 is disconnected from the main liquid pipe 5210, and the other liquid storage bottle 5200 is connected to the main liquid pipe 5210.
[0084] For example, cell culture equipment typically requires the presence of at least two types of liquids for cell culture. For instance, culture of adherent cells requires trypsin solution and cell culture medium solution. Considering cell passage and medium replacement, the capacity of a single reagent bottle is usually no less than 1L. Therefore, the liquid storage and supply device can maintain unattended operation for at least 2 days. If unattended culture for a longer period, such as 1 week, is required, the corresponding reagent storage capacity needs to be increased. For example, by placing 5-6 storage bottles 5200 in the storage box 5100, the detection unit 5300 and control valve group 5500 can be set up accordingly.
[0085] As shown in Figures 12-14, the liquid supply module includes a preheating unit 5400, which includes a heating component 6300 and a consumable bag 6200. The consumable bag 6200 includes a bag body 6210, an outlet pipe 6220, and an inlet pipe 6230. One end of the outlet pipe 6220 is connected to the bag body 6210, and the other end is connected to the liquid transfer module. One end of the inlet pipe 6230 is connected to the bag body 6210, and the other end is connected to the liquid storage module. The end of the inlet pipe 6230 away from the bag body 6210 is also connected to the air pipe 6250. The inlet pipe 6230 can selectively connect to the liquid storage module and the air pipe 6250.
[0086] A consumable bag 6200 is provided to hold the liquid to be preheated. A heating body 6100 is provided to heat the liquid to be preheated inside the bag body 6210. Optionally, the heating body 6100 is provided with a heating element 6310 and a heat-conducting block 6320. The heating element 6310 is used to provide high temperature, and the heat-conducting block 6320 is located between the heating element 6310 and the bag body 6210 to uniformly heat the liquid and reduce the problem of liquid failure caused by excessive local temperature. The heat-conducting block 6320 is provided with a placement groove. When the two heating bodies 6100 are fastened together, the two placement grooves are fastened together to form a placement space that can completely cover the bag body 6210. The circumferential heating can effectively ensure sufficient and uniform heating, and at the same time, the heating efficiency is higher. The bag body 6210 is provided with an inlet pipe 6230 and an outlet pipe 6220 at both ends for the entry and exit of the liquid to be heated. The inlet pipe 6230 is also connected to a liquid pipe 6240 and an air pipe 6250. When the liquid pipe 6240 is connected to the inlet pipe 6230, it is used to inject the liquid to be preheated into the bag body 6210. When the air pipe 6250 is connected to the inlet pipe 6230, it is used to drain the liquid in the bag body 6210, the inlet pipe 6230 and the outlet pipe 6220 to avoid waste.
[0087] For example, the heating element 6310 is configured as a PI heating film. The bag body 6210 has a thickness of 0.1mm-1mm and a volume range of 1ml-20ml, optionally a 10ml volume. The bag body 6210 can be made of PP film, PP composite film, or can be provided with an aluminum layer. Optionally, a PP composite film with an attached aluminum layer can be used.
[0088] Optionally, the inlet pipe 6230, outlet pipe 6220, and air pipe 6250 can be made of PVC, silicone, PU, etc. The air pipe 6250 is equipped with a filter to filter the air entering the consumable bag 6200 when the liquid is drained through the air pipe 6250 and inlet pipe 6230, preventing contamination of the liquid inside the bag body 6210. A sensor can be installed on the outlet pipe 6220 to detect whether liquid is passing through it; the sensor can be an ultrasonic flow sensor or an optical flow sensor, etc. Additionally, a peristaltic pump 5211 is installed on the inlet pipe 6230 to pump the liquid to be preheated into the bag body 6210.
[0089] Optionally, one end of the two heating bodies 6100 is rotatably connected to facilitate opening and closing operations. For example, the rotatable connection is achieved by a hinge 6130. The other end of the two heating bodies 6100 is provided with a locking component 6110 for locking the two heating bodies 6100 after they are engaged.
[0090] Optionally, a heat insulation layer 6120 is provided on the side of the heating element 6310 away from the heat-conducting block 6320. The heat insulation layer 6120 can wrap the heat-conducting block 6320, while only exposing the side of the heat-conducting block 6320 with the placement groove. After the consumable bag 6200 is installed into the heat-conducting block 6320, the two heating bodies 6100 are interlocked, so that the bag body 6210 of the consumable bag 6200 is basically completely wrapped for heating, resulting in better heating effect. The two heating bodies 6100 have the same structure. In other embodiments, one of the heating bodies 6100 can be set with the above structure, and the other heating body 6100 can be set as a combination of a metal plate, heat insulation cotton, or other plastic parts with heat insulation function.
[0091] Furthermore, the heat-conducting block 6320 is provided with multiple placement slots spaced along its length to simultaneously heat multiple consumable bags 6200, thereby increasing the liquid heating and supply device's ability to supply more liquid at the same time and adapting to more usage scenarios. It is understood that the width of the placement slots is adapted to the width of the consumable bags 6200 after liquid is added. Moreover, the multiple placement slots are independent of each other and do not affect each other.
[0092] Optionally, the preheating unit 5400 is further equipped with a temperature detection element, which is used to detect the temperature of the placement space, and by detecting the temperature of the placement space, the temperature of the liquid inside the consumable bag 6200 is determined. Optionally, the temperature detection element can be located within the heat-conducting block 6320 of one of the heating bodies 6100. The temperature of the placement space can be set to 37°C.
[0093] In this embodiment, to enable the inlet pipe 6230 to selectively connect with the liquid pipe 6240 and the air pipe 6250, the consumable bag 6200 also includes a three-way valve. The three-way valve is connected to the inlet pipe 6230, the liquid pipe 6240 and the air pipe 6250 respectively. The opening and closing of the liquid pipe 6240 and the air pipe 6250 can be achieved by controlling the position of the valve body of the three-way valve. Alternatively, the consumable bag 6200 also includes two switching valves 5510. The two switching valves 5510 are respectively set on the liquid pipe 6240 and the air pipe 6250. The opening and closing of the liquid pipe 6240 and the air pipe 6250 can be achieved by controlling the opening and closing of the switching valves 5510 respectively.
[0094] The liquid volume in the inlet pipe 6230 is a, the liquid volume in the bag body 6210 is b, the liquid volume in the outlet pipe 6220 is c, and the required liquid volume is d. When d≤a+b+c, the liquid volume d in the consumable bag 6200 is directly discharged through the outlet pipe 6220. When d>a+b+c, first, a liquid volume of 1.5 (dabc) is injected into the consumable bag 6200 through the inlet pipe 6230 and heated, and then the liquid volume d in the consumable bag 6200 is discharged through the outlet pipe 6220.
[0095] The liquid supply method of the aforementioned liquid supply module effectively solves the problem of liquid waste caused by the preheating liquid volume exceeding the actual required liquid volume in related technologies. Based on the structure of the liquid supply module, by determining the required liquid volume and comparing it with the total liquid volume in the bag body 6210, inlet pipe 6230, and outlet pipe 6220, the amount of liquid injected into the consumable bag 6200 is controlled. This ensures that when the liquid volume in the bag body 6210, inlet pipe 6230, and outlet pipe 6220 is sufficient for one-time supply, liquid supply is performed directly; when the liquid volume in the bag body 6210, inlet pipe 6230, and outlet pipe 6220 is insufficient for one-time supply, liquid is first injected into the consumable bag 6200, and then liquid supply is performed. A certain safety margin is set for the injected liquid volume to ensure the accuracy of liquid addition.
[0096] The above-mentioned liquid supply module is used as follows: Set the temperature of the placement space to a constant temperature, such as 37°C, and install the consumable bag 6200 into the placement slot, then fasten and lock the heating body 6100. When a liquid injection command is received, the liquid pipe 6240 and the inlet pipe 6230 are connected, and the peristaltic pump 5211 starts to rotate, drawing liquid from a bottle and allowing it to flow through the inlet pipe 6230 into the bag body 6210 located in the placement space, and then out to the outlet pipe 6220. When the control system determines that the current liquid addition test is the last test, it will perform liquid addition according to the liquid supply method. During liquid addition, the inlet pipe 6230 and the air pipe 6250 are connected, and the peristaltic pump 5211 rotates, allowing air to flow into the inlet pipe 6230 after passing through the filter. Then, the liquid in the consumable bag 6200 is added to the corresponding container. If the remaining liquid in the consumable is less than or equal to the required amount, the liquid pipe 6240 and the inlet pipe 6230 are first connected, and the peristaltic pump 5211 rotates to extract a certain amount of liquid. After extraction, the inlet pipe 6230 and the air pipe 6250 are connected, and the peristaltic pump 5211 continues to rotate, allowing air to flow into the inlet pipe 6230 through the filter. After the liquid addition is completed, all remaining liquid is discharged into the waste liquid area.
[0097] Typically, a cell workstation only cultures one type of cell per batch. Therefore, the growth rate and growth pattern of cells within specific culture containers are known in advance. These known parameters include: the required culture environment temperature for primary cell culture, carbon dioxide concentration, the time required for primary cells to reach passage age, the time required for the second passage after the first, the frequency of medium changes, and the amount of reagents to be added. The control system can then predict the number of passages and medium changes needed each day, thereby calculating the required amounts of various liquids to be added.
[0098] The control cabinet 1000 is equipped with an operating platform, which separates the working area 1001 from the non-working area 1002. The operating platform is equipped with a waste outlet 1900 and an isolation door. The isolation door can selectively block the waste outlet 1900 to selectively connect the waste area and the working area 1001. Furthermore, the waste area is also equipped with a waste carrier 1701, a waste switch door, and a sliding assembly. The waste carrier 1701 is disposed on the sliding assembly, which is used to move the waste carrier 1701 out of the waste switch door.
[0099] Waste outlet 1900 is used to discharge solid waste and liquid waste liquid. Below waste outlet 1900 is a waste carrier 1701 for receiving waste (waste carrier 1701 is located in non-working area 1002). Optionally, waste carrier 1701 is placed on a retractable drawer, which can be further equipped with an electric device to enable the drawer to extend and retract.
[0100] The waste inlet 1900 is equipped with a waste switch door, which can be opened under the drive of an electric device. Furthermore, the waste switch door can be rotated open or moved open. A sealing strip is provided on the other side of the waste switch door at the mating position to prevent air from the waste carrier 1701 from flowing into the working area 1001. Specifically, when a rotating door is used, the waste switch door rotates towards the direction of the robotic arm 1011. The waste inlet 1900 is designed as a funnel-shaped constriction opening, through which waste can flow out to the waste carrier 1701 under gravity. Specifically, a switch valve for controlling the on / off of the pipeline is provided in the waste carrier 1701 and the funnel-shaped constriction opening. Liquid and solid waste can be disposed of in the same waste carrier 1701 or in different waste carriers 1701. Furthermore, a sensor located below the waste carrier 1701 is used to detect the full load status of the material inside the waste carrier 1701. This signal can be used to dispatch a handling robot to replace the waste carrier 1701, or it can be used for early warning of the waste full load status. The sensor can be a weighing sensor. The waste carrier 1701 can be configured as a waste bin.
[0101] The cell culture equipment also includes a handling robot for moving materials between the culture cabinet 2000, the operating cabinet 1000, and the consumables cabinet 3000. The handling robot has moving parts and a mobile arm component. The mobile arm can be a commercially available 6-axis robotic arm 1011 or a collaborative robot. The handling robot can replenish consumables or move and refresh waste bins in accordance with the control commands of the cell culture equipment or the operator's instructions. The handling robot can also dock with the laboratory's biosafety transfer window and designated docking stations on the cell culture equipment. Furthermore, the number of docking stations on the cell culture equipment is no less than the sum of the number of feeding docking mechanisms in the consumables cabinet 3000, the number of waste bin stations, and the total number of operating stations in the operating cabinet 1000. For example, if the consumables cabinet 3000 has 2 feeding docking mechanisms, 1 waste bin station, and 1 biosafety transfer window station, then the mobile robot can dock with no fewer than 4 stations.
[0102] For example, the cell culture equipment described above can perform the following operations:
[0103] Cell Culture: During operation, when the cell culture flasks inside the culture cabinet 2000 need to be changed, the flask retrieval mechanism of the culture cabinet 2000 will remove the cell culture flasks from the chamber inside the culture cabinet 2000. At this time, the sealed door on the side of the culture cabinet 2000 near the operating cabinet 1000 needs to be opened, and then the cell culture flasks are sent to the first window 1300 of the operating cabinet 1000 that connects with the culture chamber. A barcode scanning unit is arranged on the side of the first window 1300. When the cell culture flasks are sent out, the barcode scanning unit can identify the barcode or RFID chip on the cell culture flasks to record the status of the cell culture flasks. After the culture flasks are sent out, the multi-degree-of-freedom motion mechanism, such as the 6-axis robotic arm 1011, located in the operating cabinet 1000, will be driven to the position of the cell culture flasks to grip them. The end of the 6-axis robotic arm 1011 is equipped with an actuator. After gripping the culture flasks, the flasks are then moved to the bottom of the capping unit 1500 to open the caps of the culture flasks. After opening, the cell culture flask cap is retained in the clamp of the capping unit 1500. At this time, the robotic arm 1011 moves the culture flask to the liquid waste disposal position and emptys the culture flask. Simultaneously, the solenoid valve and pump located below the waste inlet 1900 are activated to suck away the waste liquid. The work area 1001 is also equipped with a liquid filling module. Then, the robotic arm 1011 moves the cell culture flask below the liquid filling module to add fresh culture medium to the cells. At this time, the pump and solenoid valve on the corresponding pipeline of the liquid filling module are activated to pump out the refrigerated culture medium from the storage tank 5100 and drive the liquid to flow through the preheating unit 5400. Then, the corresponding volume of culture medium is added to the cell culture flask. After the operation is completed, the robotic arm 1011 moves the culture flask below the corresponding capping unit 1500, closes the cap, and then sends it back to the designated position of the first window 1300 where the operating cabinet 1000 is connected to the incubator. The culture flask is then sent back to the incubator 2000 for continued incubation and growth.
[0104] Subculturing: When the cell culture flask reaches the corresponding subculturing time, the incubator sends the corresponding cell culture flask from the incubator to the designated position of the first window 1300 of the control cabinet 1000 that is connected to the incubator. At this time, the barcode scanner or RFID sensor of the barcode scanning unit will read the information of the culture flask. Then, the robotic arm 1011 will move the culture flask to the observation stage of the microscope 1600. The microscope 1600 reads the cell status in the culture flask. When the software determines that the cells in the cell culture flask have reached the subculturing conditions, the robotic arm 1011 will take out the culture flask to the capping unit 1500 and open the cap. Then, the culture flask is transferred to the waste port 1900 to pour out the waste liquid. At the same time, the pump and solenoid valve for pumping out the waste liquid are opened to suck up the waste liquid. Next, the robotic arm 1011 moves the culture flask to the corresponding filling port of the liquid filling module, adds cell culture medium to wash the cells for residual liquid, and pours out the washed liquid again. The number of washings can be once or multiple times, depending on the actual needs. Then, the robotic arm 1011 moves the culture flask to the bottom of the cap opening unit 1500, closes the cap, and then places the culture flask in the incubation unit 1022 located in the work area 1001 of the operation cabinet 1000 for incubation.
[0105] Cell growth observation: Next, robotic arm 1011 retrieves another cell culture flask from incubator 2000, repeating the above steps. The flask is then placed in the second position of incubation unit 1022. It is important to note that during the observation phase, if the microscope 1600 reads that the cell growth in the flask does not meet the passage conditions, the flask will be returned to incubator 2000 for continued incubation. Incubation unit 1022 has at least two incubation positions, optionally four, designated as #1, #2, #3, and #4.
[0106] Digestion and Termination of Digestion: Robotic arm 1011 removes the cell culture flask from incubation position #1, performs actions such as opening the cap and pouring the liquid, then moves to the liquid dispensing device to add digestive enzymes. After the digestive enzymes are added, the cell culture flask is closed and returned to incubation area #1. Next, it removes the cell culture flask from incubation position #2, performs actions such as opening the cap and pouring the liquid, adds digestive enzymes in the same way, and returns it to incubation area #2 after the liquid dispensing is complete. When the digestion time is up, robotic arm 1011 sequentially opens the caps of the cell culture flasks, moves them to the corresponding positions on the liquid dispensing device to terminate the digestion solution dispensing, closes the caps, shakes the culture flasks, and then returns them to their respective incubation areas.
[0107] Centrifuge tube preparation: At this time, the robotic arm 1011 can go to the centrifuge tube consumable position to pick up new centrifuge tubes. After picking up the centrifuge tubes, it is moved to the bottom of the capping unit 1500 to open the centrifuge tube caps. Then the centrifuge tubes are transferred to the liquid transfer position of the centrifuge tubes. Considering that multiple flasks of cells can be passaged, the same number of centrifuge tubes as the cell culture flasks that need to be passaged can be picked up at the same time and placed in the liquid transfer position.
[0108] Cell culture flask transfer: Place the cell culture flask from incubation unit 1022 into the culture flask transfer position, and change the gripping method of the robotic arm 1011 on the cell culture flask. Then, open the cap of the culture flask and place it near the liquid aspiration position of the pipette tip 1016. Note that the liquid aspiration position of the cell culture flask has a certain angle to ensure that when the pipette tip 1016 moves vertically into the flask, the tip of the pipette tip 1016 can reach the lowest point inside the flask. If there are multiple culture flasks, this operation can be performed sequentially.
[0109] Pipetting: The robotic arm 1011 grips the pipette tip 1016 and holds the pipette tip 1016. Then, the liquid in the culture flask is transferred to the centrifuge tube. After the liquid transfer is completed, the pipette tip 1016 is hung back in its original position (carrier).
[0110] Centrifuge tube centrifugation: Cap each centrifuge tube individually and place it in the corresponding port of centrifuge 1800. Note that if there is an odd number of centrifuge tubes, centrifuge 1800 needs to be balanced. While waiting for centrifugation, robotic arm 1011 can move an old cell culture flask to the underside of the disinfectant dispensing port 1026 and add liquids such as alcohol or 84 disinfectant. Then, cap the flask and discard it into the waste bin. Alternatively, one old cell culture flask can be left in the pipetting position to collect the supernatant from the centrifuge tubes after centrifugation.
[0111] Cell resuspension and fluid transfer after centrifugation: After centrifugation, robotic arm 1011 grips the centrifuge tube and opens the cap, then places it back into the transfer position 1027. The supernatant is then transferred to the old culture flask, the pipette tip 1016 is reattached, and the old culture flask is added with disinfectant, capped, and discarded. The centrifuge tube is then gripped again and moved to the fluid filling device to add the appropriate culture medium for resuspension. Finally, the centrifuge tube is returned to the transfer position.
[0112] New culture flask preparation: Pick up the new culture flask from the culture flask consumables area and identify the information. Then open the cap of the culture flask and move it to the pipetting device to add culture medium. Then place it on the pipetting transfer position 1027. Pick up the number of new culture flasks according to the actual needs.
[0113] Cell resuspension mixing and dispensing: The robotic arm 1011 grips the pipette tip 1016 to aspirate the mixed liquid from the centrifuge tube and transfers the entire mixture to the same centrifuge tube. The liquid is then agitated several times, and a certain amount of the mixed liquid is transferred to a new culture flask. Furthermore, a new pipette tip 1016 can be used when transferring new cell mixtures.
[0114] After passage, the cells are returned to the culture flask: The culture flasks containing the cells are capped and transferred to the transfer position of the first window 1300 where the operating cabinet 1000 is connected to the incubator. Then the cell culture flasks are sent back to the incubator 2000.
[0115] Drug transfer and culture: When cells grow to a certain extent, the cell mixture in the culture flask needs to be transferred to a well plate. First, remove the single-well plate from the consumables cabinet 3000 and place it in the culture flask transfer position. Then, pour the digested and dedigested cell solution onto the single-well plate. Next, transfer the single-well plate to the working position of the pipetting module and activate the 96-channel pipetting device 1018 to aspirate the solution. After aspiration, transfer the single-well plate to the disinfectant inlet, add a certain amount of disinfectant, and then discard the entire single-well plate. Next, the 96-well plate containing the drug solution is transferred from the consumable cabinet 3000 or via a transport robot to the cell culture flask hand-changing position in the operating cabinet 1000. The robotic arm 1011 picks up the 96-well plate and moves the information recognition area 1019 to read and record the plate's information. Then, it moves to the underside of the electric suction cup cap opener 1510 to open the 96-well plate's cap. The plate is then placed in the corresponding pipetting position, and cell culture medium is added to the drug-containing well. The liquid can be gently agitated. Finally, the plate is picked up and moved to the electric suction cup cap opener 1510, the cap is closed, and the plate is transferred to the culture cabinet 2000. Furthermore, when performing drug screening or virus culture, the culture conditions in the culture cabinet 2000 can be set according to actual conditions. In this case, the mixed liquids in the cell culture flasks inside the culture cabinet 2000 need to be transferred to the corresponding well plates.
[0116] Consumable replenishment: When the remaining consumables in the consumable cabinet 3000 are insufficient, a signal can be sent to remind staff to replenish the consumables. Furthermore, the consumables can be replenished manually or by a handling robot, which can retrieve the consumables from the designated laboratory transfer window and transfer them to the designated consumable transfer location in the consumable cabinet 3000 to complete the replenishment.
[0117] Waste bin handling: When the waste bin is low on capacity, the equipment can send a signal to remind staff to replace the waste bin. Alternatively, the waste bin can be replenished manually or by a handling robot that retrieves a new waste bin from a designated laboratory transfer window or other location and places it on the equipment to complete the waste bin replacement.
Claims
1. Cell culture equipment, including: An operating cabinet (1000) is provided, which includes a working area (1001) and a non-working area (1002). The working area (1001) is provided with a robotic arm (1011), a liquid supply module, a liquid transfer module, and at least two operating modules. The non-working area (1002) is provided with a liquid storage module and a waste area. The liquid storage module is configured to store liquid at a preset storage temperature. The liquid supply module is connected to the liquid storage module and is configured to heat a preset amount of liquid to a preset operating temperature. The working area (1001) is also provided with a support base, and the pipetting module (1013) is provided with a pipetting head (1016). The pipetting head (1016) is detachably mounted on the support base. The robotic arm (1011) can selectively grip and drive the pipetting head (1016) to perform pipetting. The robotic arm (1011) can move and operate between the pipetting module (1013) and two or more of the operating modules. The waste area is selectively connected to the working area (1001). The culture cabinet (2000) and the consumable cabinet (3000) are respectively located on both sides of the operation cabinet (1000) and can selectively communicate with the operation cabinet (1000). The culture cabinet (2000) is configured for cell culture, and the consumable cabinet (3000) is configured to hold consumables.
2. The cell culture apparatus according to claim 1, wherein, The pipetting module (1013) is also provided with a cable supply assembly (4400), which includes an adjustable-length cable, one end of which is disposed on the support base and the free end is connected to the pipetting head (1016).
3. The cell culture apparatus according to claim 1, wherein, The liquid storage module includes a storage tank (5100), multiple liquid storage bottles (5200), and a detection unit (5300). A refrigeration unit (5110) is provided inside the storage tank (5100). The cold end (5111) of the refrigeration unit (5110) is connected to the inner cavity (5101) of the storage tank (5100) so that the inner cavity (5101) has a preset storage temperature. Multiple liquid storage bottles (5200) are disposed in the inner cavity (5101), and the liquid storage bottles (5200) can selectively communicate with the main liquid pipe (5210). The detection module is disposed in the inner cavity (5101) and is configured one-to-one with the liquid storage bottles (5200) to detect the remaining liquid in the liquid storage bottles (5200).
4. The cell culture apparatus according to claim 1, wherein, The liquid supply module includes a preheating unit (5400), which includes a heating component (6300) and a consumable bag (6200). The consumable bag (6200) includes a bag body (6210), an outlet tube (6220), and an inlet tube (6230). One end of the outlet tube (6220) is connected to the bag body (6210), and the other end is connected to the pipetting module (1013). One end of the inlet tube (6230) is connected to the bag body (6210), and the other end is connected to the liquid storage module. The end of the inlet tube (6230) away from the bag body (6210) is also connected to an air tube (6250). The inlet tube (6230) can selectively connect to the liquid storage module and the air tube (6250).
5. The cell culture apparatus according to claim 1, wherein, The control cabinet (1000) is equipped with an operating table, which is configured to separate the working area (1001) and the non-working area (1002). The operating table is equipped with a waste outlet (1900) and an isolation door. The isolation door can selectively block the waste outlet (1900) to selectively connect the waste area and the working area (1001).
6. The cell culture apparatus according to claim 5, wherein, The waste area is also provided with a waste carrier (1701), a waste switch door and a sliding assembly. The waste carrier (1701) is disposed on the sliding assembly, and the sliding assembly is configured to move the waste carrier (1701) out of the waste switch door.
7. The cell culture apparatus according to claim 1, wherein, The operation module includes a cap-opening unit (1500) configured to open centrifuge tubes and / or culture flasks; and / or the operation module includes an incubation unit (1022) configured to provide a preset incubation temperature.
8. The cell culture apparatus according to claim 1, wherein, The operation module further includes a filtration unit (1017) configured to filter and circulate the air in the working area (1001); and / or the operation module includes a barcode scanning unit configured to scan the feature codes and / or feature chips of culture flasks and / or centrifuge tubes.
9. The cell culture apparatus according to claim 1, wherein, The incubator (2000) is equipped with a sterilization module, which is configured to provide hydrogen peroxide fumigation.
10. The cell culture apparatus according to any one of claims 1-9 further includes a handling robot for transporting between the culture cabinet (2000), the operation cabinet (1000), and the consumable cabinet (3000).