Automated cell analysis device, method and system

Abstract

An automated cell analysis device, an automated cell analysis method, and an automated cell analysis system. The automated cell analysis device comprises: a workbench; functional modules arranged on the workbench, wherein the functional modules are used for cell culture, analysis and / or detection; and a rail-mounted transfer robot arranged on the workbench, wherein the rail-mounted transfer robot comprises a rail and a robot, and the robot is arranged on the rail and can move along the rail to transfer a material between the functional modules.

Description

Automated cell analysis equipment, methods and systems

[0001] Cross-references

[0002] This disclosure claims priority to Chinese Patent Application No. 202411746916.1, filed on November 30, 2024, entitled "Automated Cell Analysis Device, Method and System", the entire contents of which are incorporated herein by reference. Technical Field

[0003] This disclosure relates to the field of automated equipment technology, specifically to the field of pharmaceutical and chemical automated equipment technology, and more specifically, to an automated cell analysis device, an automated cell analysis method, and an automated cell analysis system. Background Technology

[0004] In biological research, pharmaceutical research, and development applications, cellular-level analysis and detection are required. Currently, cell culture, analysis, and detection consume a significant amount of time and effort from laboratory personnel, resulting in high labor costs and low operational efficiency. Summary of the Invention

[0005] This disclosure provides an automated cell analysis device, comprising: a workbench; functional modules disposed on the workbench, the functional modules being used for cell culture, analysis, and / or detection; a ground-rail transfer robot disposed on the workbench, wherein the ground-rail transfer robot includes a ground rail and a robot, the robot being disposed on the ground rail and capable of moving along the ground rail to transfer materials between the functional modules; the automated cell analysis device further comprises at least one of the following modules: an interaction rack for exchanging materials with an external source; a labeling machine for labeling materials; and a material storage module for storing materials.

[0006] This disclosure also provides an automated cell analysis system, which includes a mobile device and the aforementioned automated cell analysis device. The mobile device is used to pick up and place materials in the interactive shelf of the automated cell analysis device.

[0007] This disclosure also provides an automated cell analysis method applied to the aforementioned automated cell analysis equipment. The automated cell analysis method includes: transferring cells to a pipetting module within a functional module using a ground-rail transfer robot; adding detection reagents in the pipetting module; transferring the cells with added detection reagents to a cell culture incubator within the functional module using a ground-rail transfer robot for incubation; and transferring the incubated cells to an ELISA reader and / or a high-content analysis module within the functional module using a ground-rail transfer robot for analysis and detection. Attached Figure Description

[0008] Figure 1 shows a perspective view of an automated cell analysis apparatus according to some embodiments of the present disclosure.

[0009] Figure 2 shows a perspective view of an automated cell analysis apparatus according to some embodiments of the present disclosure.

[0010] Figure 3 shows a perspective view of an automated cell analysis apparatus according to some embodiments of the present disclosure.

[0011] Figure 4 shows a schematic flowchart of a cell dispensing process according to some embodiments of the present disclosure.

[0012] Figure 5 shows a schematic flow diagram of a fraction dilution and addition process according to some embodiments of the present disclosure.

[0013] Figure 6 shows a schematic flowchart of a cell detection process according to some embodiments of the present disclosure.

[0014] Figure 7 shows a schematic flowchart of a microplate labeling process according to some embodiments of the present disclosure.

[0015] Figure 8 shows a perspective view of a labeling machine according to some embodiments of the present disclosure.

[0016] Figure 9 shows a perspective view of the labeling mechanism of a labeling machine according to some embodiments of the present disclosure. Detailed Implementation

[0017] The following embodiments are intended to enable those skilled in the art to fully understand this disclosure, but do not limit this disclosure in any way.

[0018] Some workstations are equipped with robotic arms for material handling. Typically, taller modules are positioned further away from the robotic arm to prevent interference and collisions. This limits module layout, unnecessarily increasing material handling distances and reducing efficiency.

[0019] The automated cell analysis equipment disclosed herein can be used in fields such as biological research and pharmaceutical research. For example, it can be used in the field of traditional Chinese medicine research. The automated cell analysis equipment disclosed herein aims to achieve full automation and unmanned operation of the cell culture analysis process, solving the problem of cumbersome manual operation steps in cell culture analysis and detection. By designing an integrated device to achieve automated cell culture analysis, it can significantly improve experimental efficiency and the degree of automation.

[0020] Figures 1 to 3 show perspective views of an automated cell analysis apparatus according to some embodiments of the present disclosure. Referring to Figures 1 to 3, the automated cell analysis apparatus includes a workbench 11, functional modules, and a ground-rail transfer robot 7. In some embodiments, the workbench 11 may be formed of suitable materials such as stainless steel and resin, but the present disclosure is not limited thereto. In some embodiments, as shown in Figures 1 and 2, a top cover may be formed on the workbench 11, so that the workbench 11 and the top cover form a relatively independent receiving space, which is beneficial for the maintenance of the operating environment. In some embodiments, the shape and size of the workbench 11 may be designed according to actual needs, and is generally rectangular, but the present disclosure is not limited thereto.

[0021] In some embodiments, functional modules are arranged on the workbench 11. In some embodiments, the functional modules are used for cell culture, analysis, and / or detection to perform cellular-level analysis and detection of substances extracted from traditional Chinese medicine. In some embodiments, depending on the processing design, any suitable number of functional modules can be arranged on the workbench 11. In some embodiments, a ground-rail transfer robot 7 is arranged on the workbench 11. In some embodiments, the ground-rail transfer robot 7 includes a ground rail and a robot, the robot being arranged on the ground rail and capable of moving along the ground rail to transfer materials between functional modules. In some embodiments, the ground rail can be a single-rail design, a double-rail design, or any other suitable design. In some embodiments, the ground rail includes only straight rails, or includes straight rails and curved rails, the curved rails being used to change the direction of travel of the rail, for example, the ground rail is L-shaped or other shapes that require turning. In some embodiments, the robot has components that match the rails on the ground rail, allowing the robot to move on the ground rail and brake and fix itself when reaching a designated position on the ground rail, thereby improving the robot's operational stability. In some embodiments, the ground-rail transfer robot 7 can be used for material transfer between various modules on an automated cell analysis device. In some embodiments, the robot can include a three-axis robot, a four-axis robot, or a six-axis robot, but this disclosure is not limited thereto.

[0022] The robot is fixed at a certain position on the workbench 11, and various modules are arranged around the robot. In this case, the taller modules are positioned further away from the robot to prevent interference and collision between the robot's robotic arm and the modules. However, this restricts the layout of the modules. For example, if two modules with frequent material transfers are positioned far apart due to height constraints, the material transfer distance is unnecessarily increased, reducing material transfer efficiency. This disclosure reduces the problem of interference and collision between the fixed robot and modules during operation by setting up a ground-rail transfer robot 7, which moves along a ground rail, without reducing the compactness of the automated cell analysis equipment. In addition, this also reduces the operational complexity of the robot, as it can interact with various functional modules at a closer distance. Therefore, the automated cell analysis equipment of this disclosure improves work efficiency and reduces labor costs, while reducing the possibility of interference and collision between the robot and functional modules through the setting of the ground-rail transfer robot 7, thereby expanding the freedom of setting the functional modules and further improving material transfer efficiency.

[0023] In some embodiments, the automated cell analysis device of this disclosure may further include at least one or more of the following: an exchange rack 1, a labeling machine 2, and a material storage module 10. In some embodiments, the exchange rack 1 is used for exchanging materials with external systems. For example, the exchange rack 1 can be used to place materials transported by an external automated guided vehicle (AGV). Additionally, materials processed by the automated cell analysis device can also be placed in the exchange rack 1, after which the external AGV can transport the processed materials to other suitable processing equipment for further processing. In some embodiments, to facilitate material placement by the external AGV, a positioning sensor can be installed in the exchange rack 1 to allow the AGV to identify the position of the exchange rack 1 for correct material placement.

[0024] As shown in Figure 1, in some embodiments, the interaction rack 1 is located at the edge of one side of the automated cell analysis device. This allows for convenient material exchange between the external AGV and the interaction rack 1. In some embodiments, the interaction rack 1 may include at least two compartments (a first compartment and a second compartment), where the first compartment receives materials delivered by the external AGV, and the second compartment holds materials to be delivered from the automated cell analysis device. In some embodiments, both the first and second compartments are equipped with sensors. Once materials delivered by the external AGV are placed in the first compartment, a notification is sent to the ground-rail transfer robot 7, informing it that there are materials to be handled or transferred in the first compartment; once materials to be retrieved by the external AGV are placed in the second compartment, a notification is sent to the external AGV, informing it that there are materials to be retrieved in the second compartment. In some embodiments, both the first and second compartments may be equipped with positioning elements, such as step pins, connecting posts, or elastic clips, to cooperate with and fix the orifice plate bracket, preventing the materials from slipping or falling. Figure 3 shows an interactive rack 1 with four shelves, but this is merely exemplary and not intended to limit the present disclosure. For example, in the case of an interactive rack 1 with four shelves, the first and second shelves can serve as first storage locations, and the third and fourth shelves can serve as second storage locations, but this is merely exemplary and not intended to limit the present disclosure.

[0025] In some embodiments, the automated cell analysis device further includes a top cover that cooperates with the workbench 11 to form a receiving space. The side of the top cover has an opening corresponding to the interaction frame, such as the AGV interaction window 13 shown in Figure 1. Therefore, the interaction frame 1 is positioned close to the AGV interaction window 13 to facilitate the external AGV in picking up and placing materials on the interaction frame 1, enabling interaction between the automated cell analysis device and an external system. In some embodiments, the opening or AGV interaction window 13 is provided with an automatic lifting door. In some embodiments, the automatic lifting door may be equipped with a sensor that automatically opens when an object is detected approaching and automatically closes when the object leaves. This enables automatic lifting and closing of the door. In some embodiments, the automatic lifting door may include a door frame, a lifting mechanism, a drive mechanism, and a door body. In some embodiments, the lifting mechanism is slidably connected to the door frame. For example, the lifting mechanism may include two lifting units, which are arranged opposite each other and slidably connected to the door frame. The door body is placed between and connected to the two lifting units, and the two lifting units simultaneously drive the door body to slide relative to the door frame. In some embodiments, a drive mechanism is mounted on the door frame and connected to the lifting mechanism, and the drive mechanism is used to drive the lifting mechanism to slide relative to the door frame.

[0026] In some embodiments, the labeling machine 2 is used to label materials. For example, in some embodiments, the labeling machine 2 can automatically label four sides of a perforated plate to identify samples in the perforated plate. In some embodiments, as shown in FIG8, the labeling machine 2 includes a marking instrument 21, a labeling mechanism 22, a bracket 23, and a barcode scanner 24, wherein the marking instrument 21 is used to print labels, the bracket 23 is used to place materials (e.g., perforated plates) to be labeled, and the labeling mechanism 22 is used to affix the labels printed by the marking instrument 21 to the materials to be labeled. In some embodiments, as shown in FIG9, the labeling mechanism 22 includes a rotating component 221, a translation component 222 disposed on the rotating component 221, and a suction cup 223 disposed on the translation component 222. In some embodiments, the suction cup 223 is used to pick up the label printed by the marking device 21, the translation component 222 is used to move the suction cup 223 closer to or further away from the marking device 21, and the rotation component 222 is used to move the suction cup 223 on the rotation component 222 to switch positions between the marking device 21 and the bracket 23. In some embodiments, the bracket 23 can be raised, lowered, and rotated to apply labels to any side of the perforated plate. By using the labeling machine 2 of this disclosure, it is possible to label materials of different specifications (e.g., perforated plates) and all four sides of the perforated plate, and to perform fast and convenient automated labeling, thereby improving labeling efficiency and the overall efficiency of the equipment.

[0027] In some embodiments, the rotating component 221 is a rotary motor, and the translation component 222 is a translation slide. The rotary motor and the translation slide are fixedly connected by a connector, and the suction cup 223 is fixed on the translation component 222. In some embodiments, the suction cup 223 is used to pick up the label printed by the marking instrument 21 and affix the label to the material to be labeled on the bracket. The translation component 222 is used to move the suction cup 223 closer to or away from the marking instrument 21, and the rotating component 221 is used to move the suction cup 223 between the marking instrument 21 and the bracket 23 to switch positions. In some embodiments, the suction cup 223 can form a suction cup assembly with an electric diaphragm pump. Both the electric diaphragm pump and the suction cup are mounted on the translation slide, and the electric diaphragm pump is connected to the suction cup. Specifically, the suction cup 223 is provided with a first connector 224, and the electric diaphragm pump is provided with a second connector 225. The first connector 224 and the second connector 225 are connected by an air pipe. To improve the suction cup's adhesion to the label, five suction nozzles are provided. Furthermore, to ensure uniform air supply or extraction from the multiple nozzles on the suction cup by the electric diaphragm pump, two first connectors 224 are provided on the suction cup, both connected to second connectors 225. It should be understood that the above quantities are merely exemplary and not intended to limit this disclosure.

[0028] In some embodiments, the bracket 23 is used to hold perforated plates and is liftable and rotatable to enable labeling of perforated plates of different sizes and all four sides of the perforated plates. In some embodiments, the lifting and rotation of the bracket 23 is specifically implemented as follows: a lifting slide and a rotary motor are provided below the bracket 23. The rotary motor is located on the lifting slide, the bracket 23 is connected to the rotary motor and can be driven to rotate by the rotary motor, and the lifting slide can drive the rotary motor on it and the bracket 23 to lift together. In some embodiments, the barcode scanner 24 is used to scan the labels on the perforated plates after labeling.

[0029] In some embodiments, after the label is printed by the marking machine 21, the perforated plate is placed on the bracket 23. The rotary motor drives the suction nozzle of the suction cup toward the label outlet of the marking machine 21, and the translational slide moves the suction nozzle toward the label. When the label contacts the suction nozzle, the electric diaphragm pump operates to draw air inward from the suction cup, adsorbing the label onto the suction nozzle. Then, the rotary motor drives the suction nozzle toward the bracket, the lifting slide adjusts the bracket to a suitable height, and the translational slide moves the suction nozzle toward the perforated plate. When the label contacts the perforated plate, the electric diaphragm pump operates to blow air outward from the suction cup, causing the label to detach from the suction nozzle and adhere to the perforated plate. The bracket is adjusted, and the above operation is repeated to label all four sides of the perforated plate. After labeling, the perforated plate is transferred to the barcode scanner 24 to scan and record the labels on the perforated plate.

[0030] In some embodiments, the material storage module 10 is used to store materials. In this disclosure, a stacked material storage module can be used; therefore, the material storage module 10 can also be referred to as a material storage stack 10. In some embodiments, the material storage stack 10 stores consumables for cell culture testing, well plates, etc., and can be provided with a standard storage of 9 columns and 16 layers. It should be understood that this is merely exemplary, and other suitable storage structures with varying numbers and arrangements can be used. In some embodiments, a ground-rail transfer robot 7 replaces manual operation, thereby automating the operation of the automated cell analysis equipment. Alternatively, materials can be manually retrieved and placed on the material storage stack 10 via a manual door 12. By employing the stacked material storage module 10, the space occupied by the workbench 11 can be saved, improving the compactness of the automated cell analysis equipment.

[0031] In some embodiments, the material storage module 10 further includes an information management system electrically connected to the detection component. The information management system receives and manages the information detected by the detection component. The information management system serves as the backend for the material storage device and manages the material operation of the device. The information management system may consist of hardware such as a computer and suitable software; this disclosure does not specifically limit its composition. The electrical connection between the information management system and the detection component can be wired or wireless, without limitation. The information detected by the detection component is input to the information management system, which processes the information to obtain information such as the material's operating status and location; specific details are not limited in this disclosure.

[0032] In some embodiments, the interactive rack 1 is adjacent to the labeling machine 2 and the material storage module 10, and is located between the labeling machine 2 and the material storage module 10. This facilitates the labeling machine 2 in conveniently affixing labels to materials from the interactive rack 1, and also facilitates the quick and convenient storage of materials from the interactive rack 1 in the material storage module 10.

[0033] In some embodiments, the functional modules include at least one or more of the following: a microplate reader 3, a centrifuge 4, a plate washer 5, a pipetting module 6, a high-content analysis module 8, and a cell culture incubator 9. In some embodiments, the microplate reader 3 is used for enzyme-labeled detection of samples. Typically, the microplate reader can be used for enzyme-linked immunosorbent assay (ELISA), and in this disclosure, it can be used for cell target detection. In some embodiments, the microplate reader 3 may include a light source, a filter / monochromator, a microplate rack, a photodetector, and a data collection module, etc. In some embodiments, the microplate reader typically uses halogen lamps, LEDs, or lasers as light sources, which can provide stable light output suitable for different detection modes; filters / monochromators are used to select light of a specific wavelength to match the absorption or emission characteristics of the analyte. The filters are fixed, while the monochromators can be adjusted to select different wavelengths; microplate holders are used to hold microplates, which are typically available in sizes such as 96 wells, 384 wells, or 1536 wells, and can be selected according to experimental needs; photodetectors (e.g., photomultiplier tubes (PMTs) or photodiodes) are used to receive light transmitted or reflected / scattered by the sample and convert it into an electrical signal.

[0034] In this embodiment of the disclosure, by setting up a ground-rail transfer robot on the workbench, automated cell sample transfer is achieved, which improves work efficiency. A cell sample can be used for enzyme labeling detection in the ELISA reader 3 and for high-content analysis in the high-content analysis module 8. In other words, a cell sample can be reused.

[0035] In some embodiments, centrifuge 4 is used for centrifugation operations, typically performing centrifugation operations on a maximum of two well plates at a time. In some embodiments, centrifuge 4 is used for centrifuging liquids in well plates. In some embodiments, centrifuge 4 may include a centrifuge body, safety mechanisms, and cooling mechanisms. In some embodiments, the centrifuge body may include a motor, rotor, and housing. The motor provides rotational power and is typically a brushless DC motor, characterized by high efficiency and low noise. The rotor is mounted on the motor shaft and is used to load sample tubes. The type and design of the rotor vary depending on the sample characteristics and separation requirements; common types include horizontal rotors and angle rotors. The rotor can be used to fix microplates of different sizes (such as 96-well plates, 384-well plates, etc.). The housing protects the internal mechanical components and also serves for sound insulation and heat dissipation. In some embodiments, the safety mechanisms may include a door lock, imbalance detection, and overheat protection. The door lock ensures that the lid is closed during centrifuge operation to prevent accidental opening and potential danger. The imbalance detection checks whether the rotor is balanced during operation and immediately stops the machine if an imbalance is detected. When the motor or circuit temperature is too high, the overheat protection automatically cuts off the power supply to avoid damaging the module. In some embodiments, the cooling mechanism may include a cooling unit and a fan. The cooling unit keeps the sample in a low-temperature environment, suitable for temperature-sensitive samples; the fan helps dissipate heat and maintain the normal operating temperature of the module.

[0036] In some embodiments, the plate washer 5 is used for automated cleaning of materials (e.g., well plates). In some embodiments, the plate washer 5 may include a microplate support platform, a liquid dispensing system, a liquid aspiration system, a control module, and a safety module. In some embodiments, the microplate support platform is used to hold the microplates to be cleaned; the platform is typically designed to be height and position adjustable to accommodate microplates of different sizes. In some embodiments, the liquid dispensing system may include a reservoir, a pump, and a nozzle. The reservoir stores the cleaning solution; common cleaning solutions include phosphate-buffered saline (PBS) and Tris buffer. The pump delivers the cleaning solution from the reservoir to the nozzle. The nozzle is typically mounted on top of the washer and can precisely add cleaning solution to each well of the microplate. In some embodiments, the liquid aspiration system may include a suction head, a vacuum pump, and a waste collection tank. The suction head is located below the microplate and is used to aspirate waste liquid from the wells. The suction head is typically designed to be replaceable to accommodate microplates with different pore sizes; a vacuum pump provides negative pressure, allowing waste liquid to be drawn away through the suction head; a waste liquid collection tank is used to collect and store the waste liquid. In some embodiments, a control module is responsible for controlling the entire cleaning process, ensuring the accuracy and repeatability of the operation. In some embodiments, a safety module may include an emergency stop button and sensors. In the event of a malfunction or accident, the emergency stop button can immediately stop the operation of the plate washer, and the sensors are used to detect the position and status of the microplate, ensuring the safety and accuracy of the operation.

[0037] In some embodiments, the pipetting module 6 is used for liquid transfer, such as performing automated precision pipetting operations on a well plate. In some embodiments, the pipetting module 6 may include a pipetting tip (e.g., a tip), a drive mechanism, a displacement sensor, a pressure sensor, and a controller. The pipetting tip is the part that directly contacts the liquid and is typically designed to be replaceable, disposable, or reusable. The size and shape of the pipetting tip vary depending on the volume of liquid to be processed. The drive mechanism controls the up-and-down movement of the pipetting tip to achieve aspiration and dispensing actions. The drive mechanism can be a stepper motor, a servo motor, or a pneumatic system, the specific choice depending on the required accuracy and speed. The displacement sensor is used to accurately measure the position of the pipetting tip, ensuring that the expected volume is achieved with each aspiration and dispensing. The pressure sensor detects pressure changes during pipetting, helping to determine if there are air bubbles or blockages. The controller includes a microprocessor and related software to parse user commands, control the entire pipetting process, and process data from the sensors to ensure operational accuracy.

[0038] In some embodiments, the high-content analysis module 8 can be used for cell imaging analysis and detection. In some embodiments, the high-content analysis module 8 can be used for cell phenotype detection and cell target detection. In some embodiments, the high-content analysis module 8 may include a microscope system, an imaging system, an automated sample processing system, and a data management and analysis system. In some embodiments, the microscope system may include an optical microscope, a fluorescence light source, and filters. The optical microscope is used to acquire cell images, and common types include inverted microscopes and upright microscopes. The fluorescence light source is used for fluorescence imaging, and common types include mercury lamps, LED light sources, and lasers. The filters are used to select light of specific wavelengths to observe specific fluorescent markers. In some embodiments, the imaging system may include a camera and an image acquisition card. The camera is used to capture images under the microscope, and common types include charge-coupled device (CCD) cameras and complementary metal-oxide-semiconductor (CMOS) cameras, which have high resolution and high sensitivity. The image acquisition card transmits the image data captured by the camera to a computer for processing. In some embodiments, the automated sample processing system may include a sample stage and a sample transport module. The sample stage is used to place microplates or other sample containers and is typically designed to be automatically movable to accommodate samples in different locations. The sample transport module is used to automatically move the microplates from the storage location to the imaging location, enabling high-throughput processing. In some embodiments, the data management and analysis system can be used to automatically identify and analyze cell images and extract various cell parameters, such as cell number, morphology, and fluorescence intensity.

[0039] In some embodiments, the cell culture chamber 9 provides a cell culture environment for cell culture. In some embodiments, the cell culture chamber 9 may include a chamber body, a temperature control system, a humidity control system, a gas control system, a ventilation system, and a safety module. In some embodiments, the chamber body may include an outer shell and an inner liner. The outer shell is typically made of stainless steel or coated steel plate, providing good corrosion resistance and heat insulation. The internal space of the inner liner is used to place cell culture flasks, culture dishes, or microplates, and is typically made of stainless steel or plastic for easy cleaning and sterilization. In some embodiments, the temperature control system may include a heating element, a temperature sensor, and a temperature controller. The heating element (e.g., a heating wire or heating plate) provides stable heat; the temperature sensor (e.g., a resistance temperature detector or thermocouple) monitors the temperature inside the chamber in real time; the temperature controller controls the power of the heating element to ensure a constant temperature inside the chamber, typically set to 37°C. In some embodiments, the humidity control system may include a humidifier, a humidity sensor, and a water tray. The humidifier maintains a suitable relative humidity inside the chamber using a steam generator or ultrasonic humidifier; the humidity sensor monitors the humidity inside the chamber in real time; the water tray is typically placed inside the chamber to increase humidity through evaporation. In some embodiments, the gas control system may include a CO2 supply system, a gas mixer, a gas sensor, and a gas flow meter. The CO2 supply system provides a certain concentration of carbon dioxide to the chamber through a gas cylinder and a pressure reducing valve to maintain the pH value of the culture medium. The gas mixer is used to mix air and CO2 to ensure a stable gas ratio. The gas flow meter is used to regulate the gas flow rate to ensure a constant gas concentration inside the chamber. The gas sensor is used to monitor the CO2 concentration inside the chamber in real time. In some embodiments, the ventilation system may include a fan and a filter. The fan is used to evenly distribute the temperature and gas inside the chamber to ensure consistent conditions in all parts. The filter is used to filter the air entering the chamber to prevent microbial contamination. In some embodiments, the safety module may include an over-temperature protection and alarm system. When the temperature exceeds a set value, the over-temperature protection automatically cuts off the power to prevent overheating damage. When the temperature, humidity, or gas concentration deviates from the set value, the alarm system issues an audible and visual alarm.

[0040] In some embodiments, the cell culture chamber 9 is located between the material storage module 10 and the high-content analysis module 8. The cell culture chamber 9 is frequently used in cell analysis and detection. Positioning it between the material storage module 10 and the high-content analysis module 8 facilitates rapid physical interaction between the two modules and allows for convenient transfer of cells cultured in the cell culture chamber 9 to the high-content analysis module 8 for analysis. In some embodiments, the cell culture chamber 9 is positioned near the center of the ground rail of the ground-rail transfer robot 7. This allows the robot to more easily transport and transfer cells and other materials within the cell culture chamber 9. Furthermore, the presence of the ground rail allows the relatively tall cell culture chamber 9 to be positioned closer to the ground-rail transfer robot 7 without height constraints.

[0041] In some embodiments, the microplate reader 3 is located between the labeler 2 and the centrifuge 4, and the centrifuge 4 is located between the microplate reader 3 and the plate washer 5. This facilitates microplate reader testing of labeled plates and also improves the convenience of centrifugation and plate washing before or after microplate reader testing.

[0042] In some embodiments, as shown in FIG2, a laminar flow hood is disposed on top of the top cover, which continuously blows clean air into the containment space. In some embodiments, the laminar flow hood protects the containment space of the automated cell analysis equipment from contamination by generating unidirectional flow of clean air. In some embodiments, the laminar flow hood is a vertical laminar flow hood, but this disclosure is not limited thereto. In some embodiments, the laminar flow hood may include a pre-filter, a high-efficiency filter, and a blower, etc. In some embodiments, the high-efficiency filter is the core component of the laminar flow hood, capable of filtering out more than 99.97% of particles larger than 0.3 micrometers in the air, ensuring that the output air is extremely clean; the pre-filter is located before the high-efficiency filter and is used to capture larger dust particles to extend the service life of the high-efficiency filter; the blower provides sufficient airflow to form a stable laminar flow state after the air passes through the filter.

[0043] In some embodiments, multiple ultraviolet lamps are disposed inside the laminar flow hood to sterilize the environment within the containment space. Thus, a substantially sterile environment can be created within the containment space of the automated cell analysis device of this disclosure, which helps ensure that the cells within the automated cell analysis device are free from contamination, thereby improving the accuracy of cell analysis and detection.

[0044] In some embodiments, since the UV lamp of this disclosure provides sterilization, and the camera, other cables, or plastic parts of the high content analysis module are not resistant to UV light, sheet metal parts can be used to cover the structures that are not resistant to UV light. Therefore, in some embodiments, a sheet metal part is provided on the top side of the camera of the high content analysis module. In some embodiments, common sheet metal parts include, but are not limited to, cold-rolled steel sheets, hot-rolled steel sheets, stainless steel sheets, aluminum sheets, etc. In some embodiments, the sheet metal parts have various shapes and can be made into various forms such as flat, curved, and folded according to design requirements. In some embodiments, the connection between sheet metal parts or with other components can be achieved by welding, riveting, bolting, etc.

[0045] In some embodiments, the automated cell analysis device is also equipped with a sterile protective cover, which places the inside of the automated cell analysis device in a sterile environment, further ensuring that the cells inside the device are not contaminated, thereby improving the accuracy of cell analysis and detection, and extending the effective duration of cell samples, which is beneficial for the reuse of a single cell sample.

[0046] In some embodiments, a recycling mechanism may be provided within the base of the workbench 11, passing through the workbench 11 to collect waste solutions, containers, tip heads, filter heads, etc. In some embodiments, the base of the workbench 11 is a hollow shell, and the internal space can house the control and electrical modules of the robot and functional modules, such as an electrical box, computer host, or robotic arm control box. Additionally, the base may also be equipped with multiple cooling fans to dissipate heat from the electrical control modules within the base; the controllers for these cooling fans may also be located within the base.

[0047] In some embodiments, positioning sensors are installed on the ground rail. For example, corresponding positioning sensors are installed on the ground rail for the material storage module and each functional module. When the robot needs to exchange materials with the corresponding functional module, the robot can quickly locate the corresponding position, improving the material transfer efficiency.

[0048] In some embodiments, the ground-rail transfer robot 7 is equipped with an image recognition module to facilitate its positioning and operation. For example, in some embodiments, the ground-rail transfer robot 7 may be equipped with a camera to acquire surrounding images for image analysis. This image analysis can help locate the corresponding functional modules for material exchange and can also improve operational accuracy. For example, the robot's pose can be adjusted in real time based on the acquired images to exchange materials with the corresponding functional modules.

[0049] In some embodiments, as shown in Figures 1 and 2, the automated cell analysis equipment further includes a top cover that mates with the workbench 11 to form a receiving space. The sides of the top cover have openings corresponding to the labeling machine 2, the plate washer 5, and the pipetting module 6, respectively. Manual doors 12 can be installed on these openings. Thus, manual material handling and machine maintenance can be performed through these manual doors 12, such as replacing the labeling paper in the labeling machine 2, replenishing the cleaning solution in the plate washer 5, and replenishing the solution in the pipetting module 6.

[0050] In some embodiments, as shown in Figures 1 and 2, a display screen or operation panel 15 is provided on the outer side of the top cover for displaying and operating parameters. This display screen facilitates understanding of the overall operating status of the automated cell analysis equipment and allows for manual intervention in certain situations.

[0051] In some embodiments, this disclosure also provides an automated cell analysis system, which includes a mobile device and the aforementioned automated cell analysis equipment. The mobile device is used to pick up and place materials in the interaction rack of the automated cell analysis equipment. In some embodiments, the mobile device may include an AGV (Automated Guided Vehicle), which can transfer materials between the automated cell analysis equipment and other external devices. The mobile device can be any mobile device in the prior art capable of performing the above functions, such as, but not limited to, a mobile AGV or a mobile robot.

[0052] The workflow of the automated cell analysis apparatus of this disclosure is briefly described below to better understand this disclosure. It should be understood that this is merely exemplary and not intended to limit this disclosure.

[0053] Figure 4 illustrates a schematic flowchart of a cell dispensing process according to some embodiments of the present disclosure. Referring to Figure 4, in the cell dispensing step, consumables (e.g., pipette tips, microplates, etc.) can be placed into the material storage module 10 manually (e.g., through the manual door 12 on the opening corresponding to the material storage module 10). It should be understood that consumables can also be delivered to the interaction rack 1 via an external AGV, and then placed into the material storage module 10 by a robot. Alternatively, cell culture medium can be placed into the cell culture incubator 9 manually (e.g., through the manual door 12 on the opening corresponding to the cell culture incubator 9). It should be understood that consumables can also be delivered to the interaction rack 1 via an external AGV, and then placed into the cell culture incubator 9 by a robot. Afterward, the robotic arm of the ground-rail transfer robot 7 can transfer the consumables and cells to the pipetting module 6, where cell dispensing is performed. Finally, the remaining consumables are returned to the material storage module 10 by the robotic arm of the ground-rail transfer robot 7, and the dispensed cells are placed into the cell culture incubator 9.

[0054] Figure 5 illustrates a schematic flowchart of a fraction dilution and addition process according to some embodiments of the present disclosure. Referring to Figure 5, in the fraction dilution and addition step, an external AGV places the fraction to be detected into the interaction rack 1. Alternatively, consumables (e.g., pipette tips, etc.) can be placed into the material storage module 10 manually (e.g., through the manual door 12 on the opening corresponding to the material storage module 10). It should be understood that consumables can also be delivered to the interaction rack 1 via an external AGV, and then placed into the material storage module 10 by a robot. Afterwards, the consumables, the cultured cells in the cell culture incubator 9, and the fraction from the interaction rack 1 are transferred to the pipetting module 6 by the robotic arm of the ground-rail transfer robot 7, where the fraction is diluted and added to the cells. Finally, the remaining consumables are returned to the material storage module 10 by the robotic arm of the ground-rail transfer robot 7, and the cells with added fraction are placed into the cell culture incubator 9.

[0055] Figure 6 illustrates a schematic flowchart of a cell detection process according to some embodiments of the present disclosure. Referring to Figure 6, in the cell detection step, the cultured cells with added fractions are located in the cell culture incubator 9. Consumables (e.g., pipette tips, etc.) can be placed into the material storage module 10 manually (e.g., through a manual door 12 on the opening corresponding to the material storage module 10). It should be understood that consumables can also be delivered to the interaction rack 1 via an external AGV, and then placed into the material storage module 10 by a robot. Then, the consumables and cells are transferred to the pipetting module 6 by the robotic arm of the ground-rail transfer robot 7, where detection reagents (e.g., traditional Chinese medicine extracts, etc.) are added. Afterwards, the cells with added detection reagents are transferred to the cell culture incubator 9 for incubation by the robotic arm of the ground-rail transfer robot 7. After incubation, the incubated cells are transferred to the plate washer 5 for plate washing by the robotic arm of the ground-rail transfer robot 7. Next, the robotic arm of the ground-rail transfer robot 7 transfers a portion of the cells to the high-content analysis module 8 for imaging detection; another portion of the cells is transferred to the cell culture incubator 9, chromogenic solution is added, and the cells are transferred to the ELISA reader 3 for ELISA detection.

[0056] Figure 7 illustrates a flowchart of a microplate labeling process according to some embodiments of the present disclosure. Referring to Figure 7, in the microplate labeling step, consumables (e.g., microplates, etc.) can be placed into the material storage module 10 manually (e.g., through a manual door 12 on the opening corresponding to the material storage module 10). It should be understood that consumables can also be delivered to the interaction rack 1 via an external AGV, and then placed into the material storage module 10 by a robot. Then, the microplate is transferred to the labeling machine 2 by the robotic arm of the ground-rail transfer robot 7, where it is labeled. Finally, the labeled microplate is transferred back to the material storage module 10 by the robotic arm of the ground-rail transfer robot 7.

[0057] The automated cell analysis device disclosed herein utilizes a ground-rail transfer robot to transfer materials between integrated functional modules, achieving full automation and reducing labor costs. For example, this device can automate plate storage, labeling, cell pipetting, culture, centrifugation, enzyme-linked immunosorbent assay (ELISA), and high-content analysis, minimizing manual operation. Furthermore, this automated cell analysis device can communicate with external modules via local area network, Bluetooth, Wi-Fi, etc., enabling timely and efficient transmission of data generated within the automated cell analysis device to external databases for analysis and processing.

[0058] Furthermore, this disclosure reduces the likelihood of interference and collisions between a stationary robot and functional modules during operation by using a ground-rail transfer robot that moves along a ground rail. This is because the robot moves to the appropriate position on the ground rail before performing operations, without compromising the compactness of the automated cell analysis equipment. Additionally, this reduces the robot's operational complexity, as it can interact with various functional modules at closer range. Therefore, the automated cell analysis equipment of this disclosure improves work efficiency and reduces labor costs. The ground-rail transfer robot further reduces the possibility of interference and collisions between the robot and functional modules, thereby expanding the freedom of placement for functional modules and further improving material handling efficiency. For example, two closely interacting functional modules can be positioned adjacent to each other, rather than being separated by module height.

[0059] This disclosure improves work efficiency and reduces labor costs by installing a track-guided transfer robot on the workbench. The track design also reduces the likelihood of interference and collisions between the robot and functional modules, thereby expanding the freedom of module placement and further enhancing material transfer efficiency. This disclosure solves the problem of cumbersome manual operations in cell culture analysis and detection, achieving automated cell culture analysis and significantly improving experimental efficiency and automation.

[0060] Those skilled in the art should understand that the above embodiments are merely exemplary embodiments, and various changes, substitutions, and modifications can be made without departing from the spirit and scope of this disclosure.

Claims

1. An automated cellular analysis apparatus, characterized by, include: Workbench; A functional module is provided on the workbench, and the functional module is used for cell culture, analysis and / or detection; as well as A ground-rail transfer robot is set on the workbench, wherein the ground-rail transfer robot includes a ground rail and a robot, the robot is set on the ground rail and is able to move along the ground rail to transfer materials between the functional modules; The automated cell analysis equipment further includes at least one of the following modules: an interaction rack for exchanging materials with external sources; a labeling machine for labeling materials; and a material storage module for storing materials.

2. The automated cellular analysis apparatus of claim 1, wherein, The interactive rack is located at the edge of one side of the automated cell analysis equipment, adjacent to the labeling machine and the material storage module, and between the labeling machine and the material storage module.

3. The automated cellular analysis apparatus of claim 1, wherein, The interactive frame is equipped with positioning components to secure the materials on it.

4. The automated cellular analysis apparatus according to claim 1 or 2, characterized in that, The automated cell analysis equipment also includes a top cover that cooperates with the workbench to form a receiving space. The side of the top cover is provided with an opening corresponding to the interactive frame, and the opening is provided with an automatic lifting door.

5. The automated cellular analysis apparatus according to claim 1 or 2, characterized in that, The labeling machine includes a labeling device, a labeling mechanism, and a bracket. The labeling device is used to print labels, the bracket is used to place materials to be labeled, and the labeling mechanism is used to paste the labels printed by the labeling device onto the materials to be labeled.

6. The automated cellular analysis apparatus of claim 5, wherein, The labeling mechanism includes a rotating component, a translation component disposed on the rotating component, and a suction cup disposed on the translation component. The suction cup is used to pick up the label printed by the marking instrument. The translation component is used to move the suction cup closer to or away from the marking instrument. The rotating component is used to move the suction cup on the rotating component to switch positions between the marking instrument and the bracket.

7. The automated cell analysis apparatus according to any one of claims 1 to 3, 5, and 6, characterized in that, The functional modules include at least one or more of the following: An enzyme-linked immunosorbent assay (ELISA) reader is used for enzyme-linked detection of samples. Centrifuge, used for centrifugation operations; A plate washing machine is used for automatic cleaning of materials; A pipetting module for transferring liquids; High-content analysis module, used for cell imaging analysis and detection; as well as A cell culture incubator is used for cell culture.

8. The automated cellular analysis apparatus of claim 7, wherein, The automated cell analysis equipment also includes a top cover that cooperates with the worktable to form a receiving space, and the sides of the top cover are provided with openings corresponding to the plate washer and the pipetting module, respectively.

9. The automated cellular analysis apparatus of claim 7, wherein, The cell culture chamber is located between the material storage module and the high-content analysis module, the enzyme-linked immunosorbent assay (ELISA) reader is located between the labeling machine and the centrifuge, and the centrifuge is located between the ELISA reader and the plate washer.

10. The automated cellular analysis apparatus of claim 8, wherein, A laminar flow hood is provided on the top of the top cover, and the laminar flow hood blows clean air into the containing space; Multiple ultraviolet lamps are installed inside the laminar flow hood to sterilize the environment within the containment space; The camera of the high-content analysis module has a sheet metal part on its top side.

11. The automated cellular analysis apparatus according to claim 4 or 8, characterized by A display screen is provided on the outer side of the top cover for displaying and operating parameters.

12. The automated cell analysis apparatus according to any one of claims 1 to 11, characterized in that, The robot is equipped with an image recognition module to facilitate its positioning and operation.

13. An automated cell analysis system, characterized by The automated cell analysis system includes a mobile device and an automated cell analysis device according to any one of claims 1 to 12, wherein the mobile device is used to pick up and place materials in the interactive shelf of the automated cell analysis device.

14. An automated cell analysis method, characterized by, The automated cell analysis method is applied to the automated cell analysis apparatus according to any one of claims 1 to 12, wherein the automated cell analysis method comprises: Cells are transferred to the pipetting module within the functional module using a ground-rail transfer robot; The detection reagent is added in the pipetting module; The cells containing the detection reagents are transferred to the cell culture chamber in the functional module for incubation using the ground-rail transfer robot. The incubated cells are transferred to the ELISA reader and / or high-content analysis module in the functional module by the ground-rail transfer robot for analysis and detection.

15. The automated cell analysis method of claim 14, wherein, The automated cell analysis method also includes: Cells are dispensed into the pipetting module; The pre-packaged cells are transferred to the cell culture chamber using the ground-rail transfer robot.

16. The automated cell analysis method of claim 14, wherein, The automated cell analysis method also includes: The fraction to be tested is transferred to the pipetting module by the ground-rail transfer robot; The distillation unit performs fraction dilution and adds the diluted fraction to the cells; The cells with added fractions are transferred to the cell culture chamber by the ground-rail transfer robot.

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