Automated pharmaceutical processing and analysis and detection method and system

Abstract

An automated pharmaceutical processing and analysis and detection method, comprising the following steps: an extraction step, in which a transfer device transports a sample container containing a sample into a shaker of an extraction device, and the sample is subjected to oscillatory incubation using a cold maceration method; a preparation step, in which the transfer device transports the sample after the oscillatory incubation into at least one preparation device for preparation processing; and an analysis step, in which the transfer device transfers the sample after the preparation processing to an analysis device for testing and analysis. The present disclosure further provides an automated pharmaceutical processing and analysis and detection system.

Description

Pharmaceutical automated processing and analysis detection methods and systems

[0001] Cross-references

[0002] This disclosure claims priority to Chinese Patent Application No. 202411746331.X, filed on November 30, 2024, entitled "Automatic Processing and Analysis Detection Method and System for Pharmaceuticals", 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 automated equipment technology, and more specifically to a pharmaceutical automated processing and analysis detection method and a pharmaceutical automated processing and analysis detection system. Background Technology

[0004] Currently, in the field of pharmaceutical processing, the extraction, processing, detection, and analysis of sample components are mostly handled by a single module in conjunction with manual labor, making it impossible to automate a single process or the entire process. Summary of the Invention

[0005] This disclosure provides an automated pharmaceutical processing and analysis detection system and method, which can automate the entire process of sample extraction, processing, detection and analysis.

[0006] According to one aspect of this disclosure, an automated pharmaceutical processing and analysis method is provided, comprising the following steps: an extraction step, wherein a transfer device delivers a sample container containing a sample to the loading position of an extraction device, and a visual recognition module correspondingly positioned above the loading position identifies whether the sample container is located in an appropriate storage position on the loading position; the transfer device places the sample container in a corresponding position within the shaker of the extraction device for shaking incubation of the sample using a cold immersion method; a preparation step, wherein the transfer device delivers the shaken and incubated sample to at least one preparation device for preparation processing; and an analysis step, wherein the transfer device transfers the prepared sample to an analytical device for detection and analysis.

[0007] According to another aspect of this disclosure, an automated pharmaceutical processing and analysis system is provided, comprising: an extraction device that uses a shaker to incubate a sample contained in a sample container using a cold immersion method; multiple preparation devices that prepare the sample after incubation; an analysis device that detects and analyzes the prepared sample; and a transfer device that transfers the sample and the sample container within the extraction device, the preparation device, and the analysis device, and between the extraction device, the preparation device, and the analysis device, wherein when the sample container is fed into the extraction device for extraction, the sample container is placed on the loading position of the extraction device, and a visual recognition module correspondingly positioned above the loading position of the extraction device identifies whether the sample container is located in an appropriate storage position on the loading position, and the transfer device transfers the sample container to a corresponding position within the shaker of the extraction device for incubation.

[0008] Other features and advantages of this disclosure will be set forth in the description which follows, and will be apparent in part from the description, or may be learned by practicing the disclosure. The objects and other advantages of this disclosure may be realized and obtained by means of the structures particularly pointed out in the description, claims and drawings. Attached Figure Description

[0009] The accompanying drawings are provided to further understand the technical solutions of this disclosure and constitute a part of the specification. They are used together with the embodiments of this disclosure to explain the technical solutions of this disclosure and do not constitute a limitation on the technical solutions of this disclosure.

[0010] Figure 1 shows a schematic block diagram of a pharmaceutical automated processing and analysis detection system according to an embodiment of the present disclosure;

[0011] Figure 2 shows a top view of the layout of a pharmaceutical automated processing and analysis detection system according to an embodiment of the present disclosure;

[0012] Figure 3 shows a perspective view of the storage station of the material storage equipment of the pharmaceutical automated processing and analysis system according to an embodiment of the present disclosure;

[0013] Figure 4 shows a perspective view of the extraction device of the pharmaceutical automated processing and analysis detection system according to an embodiment of the present disclosure;

[0014] Figure 5 shows a perspective view of the dilution and reconstitution apparatus of a pharmaceutical automated processing and analysis system according to an embodiment of the present disclosure;

[0015] Figure 6a shows a perspective view of a centrifugal filtration device in a pharmaceutical automated processing and analysis system according to an embodiment of the present disclosure;

[0016] Figure 6b shows a top view of a centrifugal filtration apparatus of a pharmaceutical automated processing and analysis system according to an embodiment of the present disclosure;

[0017] Figure 7a shows a perspective view of the freeze-drying apparatus of a pharmaceutical automated processing and analysis system according to an embodiment of the present disclosure;

[0018] Figure 7b shows a top view of the freeze-drying apparatus of a pharmaceutical automated processing and analysis system according to an embodiment of the present disclosure;

[0019] Figure 8 shows a perspective view of a centrifugal concentration apparatus of a pharmaceutical automated processing and analysis system according to an embodiment of the present disclosure;

[0020] Figure 9 shows a perspective view of the dry sample loading apparatus of a pharmaceutical automated processing and analysis detection system according to an embodiment of the present disclosure;

[0021] Figure 10 shows a perspective view of a medium-pressure preparation and separation apparatus of a pharmaceutical automated processing and analysis detection system according to an embodiment of the present disclosure;

[0022] Figure 11 shows a top view of the high-pressure preparation and separation apparatus of a pharmaceutical automated processing and analysis detection system according to an embodiment of the present disclosure;

[0023] Figure 12 shows a perspective view of the LCMS analysis device of the pharmaceutical automated processing and analysis detection system according to an embodiment of the present disclosure;

[0024] Figure 13 shows a perspective view of the cell analysis apparatus of the analytical device of the pharmaceutical automated processing and analysis detection system according to the present disclosure; and

[0025] Figure 14 shows a flowchart of a pharmaceutical automated processing and analysis detection method according to an embodiment of the present disclosure. Detailed Implementation

[0026] To make the objectives, technical solutions, and advantages of the embodiments of this disclosure clearer, the specific implementation methods of this disclosure will be described in detail below with reference to the accompanying drawings. It should be understood that the specific implementation methods described herein are for illustration and explanation only and are not intended to limit this disclosure.

[0027] For ease of description, this specification uses directional terms such as "front", "back", "up", "down", "left", "right", "horizontal" and "vertical". These terms are used only to indicate the relative positions between devices or components and do not limit the installation or use orientation of the devices or components.

[0028] The pharmaceutical automated processing and analysis detection system and method disclosed herein automates the loading, temporary storage, handling, and transfer of materials and consumables between extraction equipment, preparation equipment, and analysis equipment by using transfer equipment, thereby assisting in the full-process automation of a series of operations such as sample extraction, processing, detection, and analysis.

[0029] Figure 1 shows a schematic block diagram of a pharmaceutical automated processing and analysis detection system 1 according to an embodiment of the present disclosure. Referring to Figure 1, the pharmaceutical automated processing and analysis detection system 1 according to an embodiment of the present disclosure includes: an extraction device 100, which incubates a sample contained in a sample container by shaking on a shaker; multiple preparation devices 110, which prepare the sample after shaking and incubation; an analysis device 120, which detects and analyzes the prepared sample; and a transfer device 130, which transfers the sample and sample container between the extraction device 100, the multiple preparation devices 110, and the analysis device 120. The sample container is transferred between the extraction device 100, multiple preparation devices 110, and analysis device 120. When the sample container is sent into the extraction device 100 for extraction, it is placed on the loading position 101 of the extraction device 100. The visual recognition module 106 of the extraction device 100, which is set directly above the loading position 101, identifies whether the sample container is in the appropriate storage position on the loading position 101. The transfer device 130 transfers the sample container to the corresponding set position in the shaker 103 of the extraction device 100 for shaking incubation.

[0030] This disclosure does not specifically limit the analytical equipment. For example, the analytical equipment includes equipment capable of performing at least one of the following analytical processing on pharmaceutical samples: automated high-performance liquid chromatography (HPLC) analysis of pharmaceutical samples, automated HPLC-MS analysis of pharmaceutical samples, and automated detection and analysis of cell activity and toxicity of pharmaceutical samples.

[0031] In some embodiments, the analytical apparatus includes at least one of the following: an apparatus for automated high-performance liquid chromatography (HPLC) analysis of pharmaceutical samples, an apparatus for automated high-performance liquid chromatography-mass spectrometry (HPLC-MS) analysis of pharmaceutical samples, and an apparatus for automated analysis of the cellular bioactivity and toxicity of pharmaceutical samples.

[0032] In some embodiments, the sample is a biological sample, a pharmaceutical sample, or a chemical sample. When the sample is a pharmaceutical sample, it can be a Western medicine sample, a traditional Chinese medicine sample, or other drug samples with medicinal effects. For example, traditional Chinese medicine samples include raw medicinal herbs, prepared slices of traditional Chinese medicine, proprietary Chinese medicines, semi-finished traditional Chinese medicines, and medicinal plants.

[0033] This disclosure automates each step and the entire process of sample extraction, treatment, and analysis by using appropriate equipment, greatly improving sample detection efficiency and reducing labor costs.

[0034] The specific devices included in the pharmaceutical automated processing and analysis detection system 1 according to an embodiment of the present disclosure will now be described in further detail with reference to FIG2.

[0035] Figure 2 illustrates an exemplary top view of the layout of a pharmaceutical automated processing and analysis system 1 according to an embodiment of the present disclosure. The pharmaceutical automated processing and analysis system 1 includes multiple preparation devices 110, including: a dilution and reconstitution device 200, a centrifugal filtration device 300, a lyophilization device 400, a centrifugal concentration device 500, a dry sample loading device 600, a medium-pressure preparation and separation device 700, and a high-pressure preparation and separation device 800.

[0036] The analytical equipment 120 of the pharmaceutical automated processing and analysis detection system 1 includes an LCMS (Liquid Chromatography-Mass Spectrometry) analytical device 900 and a cell analysis device 1000.

[0037] The transfer equipment 130 of the pharmaceutical automated processing and analysis testing system 1 includes a robotic arm and an AGV (Automated Guided Vehicle). The robotic arm includes both the robotic arm between various devices and the robotic arm inside each device used to perform various operations.

[0038] An AGV (Automated Guided Vehicle) is an intelligent logistics device that achieves autonomous movement based on automatic navigation technology. It is equipped with electromagnetic or optical automatic guidance devices, enabling it to travel along a predetermined guidance path. For example, the two robotic arms shown in Figure 2 are AGV composite robotic arms. An AGV composite robotic arm is an AGV equipped with robotic arms, capable of both autonomous movement and grasping operations. In some embodiments, the AGV can utilize various methods for navigation, including electromagnetic, laser, camera-based and AI algorithm-based vision solutions, gyroscope-based and encoder-based inertial solutions, and QR codes.

[0039] In some embodiments, AGVs can be used to transfer various materials, including samples and sample containers, between extraction equipment 100, multiple preparation equipment 110, and analysis equipment 130. A robotic arm can be used to deliver materials transferred from the AGV to the AGV exchange bin into the corresponding equipment in the extraction equipment 100, multiple preparation equipment 110, and analysis equipment 130. Material transfer is performed in the corresponding equipment, and the materials are taken out from the corresponding equipment and transferred into the AGV exchange bin for transfer by the AGV. The robotic arm transfers different materials by selecting the corresponding tool.

[0040] In addition, the pharmaceutical automated processing and analysis testing system 1 also includes a material storage device 1100 for storing the materials required in the process.

[0041] The pharmaceutical automated processing and analysis testing system 1 also includes a charging pile 1200, which is used to charge equipment such as the transfer equipment 130 that requires charging.

[0042] In some embodiments, as illustrated in FIG2, the layout of the pharmaceutical automated processing and analysis system 1 is generally arranged in two rows. The first row sequentially includes a cell analysis device 1000, a centrifugal filtration device 300, a charging station 1200, an LCMS analysis device 900, an extraction device 100, a charging station 1200, and a centrifugal concentration device 500. The second row sequentially includes a material storage device 1100, a high-pressure preparative separation device 800, a medium-pressure preparative separation device 700, a dry sample loading device 600, a dilution and reconstitution device 200, and a freeze-drying device 400. Two AGV composite robotic arms are also exemplarily shown shuttling between the devices to transport various items. Those skilled in the art can also modify the layout and number of devices in the pharmaceutical automated processing and analysis system 1 according to their needs.

[0043] The details of the pharmaceutical automated processing and analysis detection system 1 and its various devices according to embodiments of the present disclosure are described below with reference to Figures 3 to 11.

[0044] All the above-mentioned equipment in the pharmaceutical automated processing and analysis testing system 1 are equipped with AGV interactive gates and AGV positioning QR codes 12, which are used for material transportation between AGV vehicles and AGV exchange warehouses within the station.

[0045] In addition, each piece of equipment is usually equipped with: corresponding AGV exchange compartments or AGV interaction compartments for transferring materials and consumables transported by external AGV vehicles; various temporary storage positions for temporarily storing consumables or consumable trays; a cover opening and closing module for opening and closing sample containers; and a tool library for storing various corresponding tools.

[0046] Each piece of equipment is usually also equipped with various corresponding shelves for temporary storage or transfer of items.

[0047] The devices disclosed herein typically also include a ground rail module, which can be a single-rail design, a double-rail design, or any other suitable design. In some embodiments, a robotic arm is mounted on the ground rail module, wherein the robotic arm is capable of moving along the ground rail module. In some embodiments, the ground rail module includes only straight rails, or includes straight rails and curved rails, the curved rails being used to change the direction of travel of the track, for example, when the ground rail module is L-shaped or other shapes requiring turning. In some embodiments, the robotic arm has components that match the track on the ground rail module, allowing the robotic arm to move on the ground rail module while being braked and fixed upon reaching a designated position on the ground rail module, improving the operational stability of the robotic arm. In some embodiments, the robot can be used for the transfer of materials and consumables between various devices in a pharmaceutical automated processing and analysis testing system. In some embodiments, the robotic arm can include a movement mechanism having at least one degree of freedom in one direction, specifically, it can be a multi-degree-of-freedom robotic arm (such as a four-axis robotic arm, a six-axis robotic arm, etc.), or an XYZ three-axis linear movement mechanism. In some embodiments, the robotic arm can include hydraulic, pneumatic, and electric robotic arms, etc.

[0048] The samples mentioned in this disclosure include various reagents such as pharmaceuticals and chemicals, especially traditional Chinese medicine preparations. Additionally, in some embodiments, the sample containers mentioned in this disclosure, as devices for holding samples, may include shake flasks, centrifuge bottles, and concentration bottles. In some embodiments, the sample containers mentioned in this disclosure may include orifice plates, trays, and adapters. An adapter in this disclosure is a device used to connect bottles or containers of different sizes to facilitate operations such as dispensing, weighing, and centrifugation; examples include concentration bottle adapters and test tube adapters.

[0049] High-throughput automated separation and detection systems in the pharmaceutical field are generally designed for specific sample types (such as blood, cells, or swabs), and therefore are typically compatible with only a few types of consumables (such as blood collection tubes and microplates). However, the pharmaceutical automated processing and analysis system disclosed herein needs to meet the requirements for automated extraction and separation of different types and scales of traditional Chinese medicinal materials. It also needs to be able to automate the operation of various reagent bottles, tubes, HPLC vials, and chromatographic columns. Therefore, it requires the design and use of modules and grippers capable of automating the handling of various solvents to achieve automated operation of multiple containers within a limited space.

[0050] Material storage equipment

[0051] Referring first to Figure 3, an embodiment of the material storage device 1100 of the pharmaceutical automated processing and analysis system 1 is described. The material storage device 1100 includes a storage station 1110, which includes a storage station robotic arm 1120 and one or more storage stacks 1130. Each of the storage stacks 1130 includes multiple rows of storage racks 1140, each row of racks having the same height and a different number of storage layers depending on the volume of the consumables placed therein. Materials are transported from outside the material storage device 1100 to corresponding storage positions on the storage racks 1140 using an AGV (Automated Guided Vehicle) and the storage station robotic arm 1120. The AGV can transport materials to the material storage AGV exchange bin 1150 of the material storage device 1100, where the storage station robotic arm 1120 retrieves the materials and transports them to the appropriate location. The reverse operation can be performed when materials are retrieved from the material storage device 1100. Figure 2 illustrates an exemplary material storage device 1100 comprising two storage stations 1110, which can be satellite storage stations, transit storage stations, temporary storage stations, etc. Referring to Figure 3, each storage station 1110 includes a storage station robotic arm 1120 for loading and unloading materials and one or more storage stacks 1130 (four storage stacks are exemplarily shown in Figure 3). Each storage stack 1130 includes multiple storage racks 1140 (13 columns are exemplarily shown in Figure 3), each column of storage racks 1140 being of the same height, designed for easy disassembly, and allowing for different numbers of storage layers depending on the volume of the stored materials. Materials are placed on pallets, preferably standard pallets, and positioned in the corresponding storage locations within the storage stacks 1130. The pallets are designed for easy loading and unloading by the robotic arm and transport by AGVs. Storage station 1110 also includes a material storage AGV exchange compartment 1150. Before processing begins, sufficient materials can be prepared by AGV vehicles or by personnel. The materials are placed on the corresponding pallets, and the pallets containing the materials are placed in the corresponding pallet storage positions of the single-row storage rack 1140.

[0052] The material storage device 1100 disclosed herein automates material loading and retrieval by using a warehouse robotic arm 1120 and an AGV vehicle to exchange materials at the material storage AGV exchange warehouse 1150. The storage stack 1130 is designed for easy disassembly, and the pallet for loading materials is designed for easy gripping and handling by the robotic arm, thereby helping to achieve automation.

[0053] extraction equipment

[0054] Referring to Figure 4, an embodiment of the extraction device 100 of the pharmaceutical automated processing and analysis system 1 is described below. The extraction device 100 utilizes a shaker-based cold immersion method to incubate samples through shaking. The extraction device 100 includes: a loading station 101 on which a sample container containing the sample is placed; a vision recognition module 106 for identifying whether the sample container is located in the appropriate storage position on the loading station 101; an extraction robotic arm 104 for grasping and transporting the sample container; and a shaker 103 for incubating the sample through shaking. The extraction device 100 also includes an extraction device AGV exchange compartment 102 and a barcode scanner (also referred to as a "scanning device") 105. The shaker 103 includes multiple shake flask storage positions, each equipped with an automated clamp for securing the shake flasks. The loading station 101 includes multiple shake flask openings; in some embodiments, the number of shake flask storage positions is the same as the number of shake flask openings. In some embodiments, as exemplarily shown in FIG4, two loading positions are provided, but the number of loading positions can be changed as needed. In some embodiments, the AGV places the sample container on the loading position 101. In some embodiments, interactive doors are provided on both sides of the loading position. Personnel have the authority to open the interactive doors, allowing manual placement of the shake flasks directly into the corresponding shake flask openings on the loading position before processing begins. A QR code label is provided on each shake flask, containing material information and processing method for each flask. A barcode scanner 105 is used to scan the QR code labels on the shake flasks and read the relevant material information and / or processing method information. In FIG4, a vision recognition module 106 is exemplarily positioned directly above the two loading positions 101 to accurately identify the storage information of the shake flask openings after loading, preventing human error from causing the robotic arm to miss its target.

[0055] At the start of processing, the shaking table door automatically opens, and the extraction robotic arm 104 picks up the shaker bottles from the loading position 101 and transfers them to the barcode scanner 105 for barcode recognition. After confirming the barcode information, the shaker bottles are placed in the corresponding clamping holes within the shaking table 103. This process continues until the extraction robotic arm 104 has retrieved and placed all the required shaker bottles according to the above procedure. The shaking table door automatically closes, and based on the material information and / or processing method information obtained from the barcode scanner 105, appropriate parameters are set for the shaking table 103, and vibration incubation continues until the processing is complete. The shaking table door automatically reopens, and the extraction robotic arm 104 removes the shaker bottles from the shaking table 103 and places them in the AGV exchange compartment 102 of the extraction equipment, awaiting transfer by the AGV to the next device for subsequent processes.

[0056] The extraction apparatus 100 disclosed herein performs the extraction operation by shaking and incubating the sample using a shaker cold immersion method. This shaker cold immersion method reduces energy consumption because it does not require heating. In addition, more than one solvent can be added to extract polar and non-polar extracts separately, thus achieving standardization and improving extraction efficiency.

[0057] In addition, the extraction device 100 disclosed herein automates loading and handling by employing an extraction robotic arm 104 and an AGV vehicle, ensures correct placement at the loading position 101 by using a vision recognition module 106, and confirms sample container information by using a barcode scanner by setting a QR code label on the sample container, thereby achieving full automation of the shaker extraction process.

[0058] Dilution and Reconstitution Equipment

[0059] Referring to Figure 5, an embodiment of the dilution and reconstitution device 200 of the pharmaceutical automated processing and analysis system 1 is introduced. Specifically, the dilution and reconstitution device 200 includes: a liquid addition module 216 for adding liquid to sample containers (also referred to as "consumables"); a pipetting module 218 for transferring at least a portion of the sample from one sample container to another; an ultrasonic vibration module 238 for ultrasonically vibration of the sample containers; a first visual inspection module 239 for detecting whether the sample in the ultrasonically vibrated sample container is completely dissolved; and a test tube centrifugation module 222 for centrifuging the ultrasonically vibrated sample container when the sample container is a test tube.

[0060] In the dilution and reconstitution device 200, when the amount of liquid in the test tube is relatively small, it is necessary to ensure that the liquid can be completely aspirated during pipetting. The centrifugation operation of the test tube centrifugation module 222 can cause the liquid on the test tube wall to be thrown to the bottom of the test tube, so as to ensure that the liquid can be completely aspirated during pipetting.

[0061] The oscillation module 238 is used to ultrasonically oscillate the sample container. It can perform ultrasonication and oscillation simultaneously, or in any order. This oscillation operation is to accelerate the dissolution of the sample.

[0062] In some embodiments, the dilution and reconstitution equipment 200 further includes a dilution and reconstitution AGV exchange compartment 210, a transfer storage position 212, a shaker flask cap switch module 214, a concentration flask cap switch module 220, a pouring and merging position 224, a robot rail module 226, a dilution and reconstitution robotic arm 236, a long consumable shelf 234, a short consumable shelf 235, an ultrasonic cleaning module 237, and a dilution and reconstitution tool library. The dilution and reconstitution tool library includes a pallet handling tool 231, a concentration flask handling tool 232, and a test tube handling tool 233; wherein, the ultrasonic cleaning module 237 is used to ultrasonically clean sample containers containing residual samples; the pouring and merging position 224 is used to merge liquids from multiple concentration flasks by pouring.

[0063] In the preparation stage before processing, an external AGV transfers the tray / shaking flask to the dilution and reconstitution AGV exchange compartment 210. The dilution and reconstitution robotic arm 236 selects the corresponding handling tool (tray handling tool 231 or concentrate bottle handling tool 232) to transfer the tray (containing test tubes / concentrate bottles) / shaking flask on the dilution and reconstitution AGV exchange compartment 210 to the transfer storage location 212, the long consumable shelf 234, or the short consumable shelf 235. After all the required consumables are delivered to the long consumable shelf 234 or the short consumable shelf 235, the dilution and reconstitution robotic arm 236 selects the corresponding handling tool (test tube handling tool 233 or concentrate bottle handling tool 232) to transfer the test tubes / concentrate bottles / shaking flasks to the shake bottle cap opening module 214 or the concentrate bottle cap opening module 220 for opening. Then, the dilution and reconstitution robotic arm 236 transfers the opened consumables to the liquid addition module 216 for liquid addition. After the liquid addition is complete, the dilution and reconstitution robotic arm 236 transfers the shake flask back to the transfer storage location 212, the long consumable shelf 234, or the short consumable shelf 235 at an appropriate time as needed, and transfers other consumables to the shaking module 238. Depending on the processing requirements, it can be selected to sonicate and shake simultaneously, or sonicate first and then shake. After sonication and shaking for a certain period of time, the dilution and reconstitution robotic arm 236 transports the consumables to the first vision inspection module 239, which detects whether the sample in the consumables is completely dissolved. If the consumables used are test tubes, the dilution and reconstitution robotic arm 236 first transports the test tubes to the test tube centrifugation module 222 for centrifugation. After centrifugation for a certain time and speed, the test tubes are then transferred to the pipetting module 218, which transfers the liquid in the test tubes to the designated test tubes / concentrators. If the consumables used are concentration bottles, centrifugation is not required; the liquid is directly transferred to the pipetting module 218, which transfers the liquid in the concentration bottle to the designated test tubes / concentrators. According to the processing requirements, when the liquid volume in the test tubes / concentration bottles is small, the liquids in multiple test tubes / concentration bottles can be combined using the pipetting module 218. When the liquid volume in the concentration bottle is large, the concentration bottle can be transferred to the pouring and merging station 224 during merging. The dilution and reconstitution robotic arm 236 then pours the liquids from the concentration bottles to be merged into another designated concentration bottle, thereby improving the efficiency of liquid merging. After the test tubes / concentration bottles have completed the corresponding liquid addition, shaking, and merging operations, the dilution and reconstitution robotic arm 236 transfers the test tubes / concentration bottles to their corresponding shaker / cap switch module 214 or concentration bottle cap switch module 220 for capping. The capped test tubes / concentration bottles are then returned to their corresponding trays and stored in the long consumable shelf 234 or short consumable shelf 235. After all samples have been processed, the dilution and reconstitution robotic arm 236 transfers all samples sequentially to the dilution and reconstitution AGV exchange chamber 210. The external AGV then delivers the samples from the dilution and reconstitution AGV exchange chamber 210 to the subsequent equipment for further processing.

[0064] The dilution and reconstitution equipment 200 disclosed herein automates the loading, temporary storage, handling, and transfer of consumables between processing modules by employing a dilution and reconstitution robotic arm 236, an AGV vehicle, and various handling tools. It automates the opening and closing of test tubes / concentration bottles / shaking flasks by employing a cap-opening module, ensures complete dissolution of samples within consumables by employing a first vision detection module 239, and automates merging operations by employing a pipetting module 218 and the dilution and reconstitution robotic arm 236. Thus, it achieves full automation of the dilution and reconstitution process while ensuring the dissolution effect.

[0065] Centrifugal filtration equipment

[0066] Referring to Figures 6a and 6b, an embodiment of the centrifugal filtration device 300 of the pharmaceutical automated processing and analysis system 1 is described. Specifically, the centrifugal filtration device 300 includes: a filtration module 316 for performing at least one of coarse and fine filtration on a sample to obtain a filtered sample; a centrifuge 324 for centrifuging a sample container containing the filtered sample to separate the supernatant and residue; and a weighing and pipetting device for balancing multiple sample containers; and a transfer device 130 for performing transfer operations required for filtration, centrifugation, and balancing operations by changing different tools to assist in completing the filtration, centrifugation, and balancing operations. The weighing and pipetting device consists of a weighing module 328 and a pipetting device 342 for balancing multiple sample containers. The weighing module 328 is used to weigh multiple sample containers containing the filtered sample sequentially. The pipetting device 342 is used to transfer a portion of the sample from a sample container containing more sample to another sample container.

[0067] In some embodiments, the centrifugal filtration device 300 further includes a centrifugal filtration AGV exchange chamber 310, a shake flask storage position 312, a centrifuge bottle / concentrate bottle storage position 313, a centrifugal filtration switch cover module 314, a loading rack 318, a unloading rack 320, a cleaning module 322, a centrifugal filtration robotic arm 326, a tray transfer unit 330, and a centrifugal filtration tool library 340. The centrifugal filtration tool library 340 includes tray grippers, concentrate bottle grippers, and pipetting devices 342, etc. In some embodiments, the pipetting device 340 is a 5ml pipette.

[0068] The loading rack 318 is used to store new sieves. The unloading rack 320 is used to store used sieves. The centrifugal filtration robotic arm 326 assists in completing the filtration, centrifugation, and balancing operations by changing different tools and performing the necessary transfer operations. The cleaning module 322 is used to clean the sample container after filtration to remove any remaining solid sample. The tray transfer unit 330 is used to transfer trays within the equipment. Additionally, during the process of holding the bottle with the concentrate bottle grippers and pouring the sample from the bottle onto the sieve for filtration, fluid dripping may occur, contaminating the equipment; therefore, an anti-contamination design is provided on the concentrate bottle grippers to prevent such contamination. In some embodiments, a replaceable adhesive tape is attached to the bottle grippers. This allows any fluid remaining at the container opening to flow onto the tape during pouring, preventing contamination of other components; the tape can be replaced manually or automatically after filtration of a fluid; the tape can be, for example, Teflon tape or cloth-based tape.

[0069] During the preparation phase before the experiment, an external AGV transfers the shake flask / centrifuge bottle / concentrate bottle tray to the centrifugal filtration AGV exchange chamber 310. The centrifugal filtration robotic arm 326 selects the appropriate handling tool to transfer the shake flasks from the centrifugal filtration AGV exchange chamber 310 to the shake flask temporary storage position 312, and transfers the centrifuge bottle / concentrate bottle tray to the centrifuge bottle / concentrate bottle temporary storage position 313. Clean screens are placed on the loading rack 318 manually or via the robotic arm, and the tip head tray is placed in the tray transfer section 330. At the start of the experiment, the centrifugal filtration robotic arm 326 uses different tools to move the shake flasks to the centrifugal filtration switch cover module 314 for opening. Then, the centrifuge bottle tray is moved from the centrifuge bottle / concentrate bottle temporary storage position 313 to the tray transfer section 330. The centrifuge bottles are removed and sent to the centrifugal filtration switch cover module 314 for opening. After opening, the centrifuge bottles are sent to the liquid receiving position in the filtration module 316. Move the clean coarse sieve from the loading rack 318 to the filtration module 316. Move the shaking flask above the filtration module 316 and tilt it, simultaneously completing the filtration process by drawing a vacuum from the top. After filtration, place the shaking flask back into the centrifugal filter switch cover module 314 and close the cover, then move it to the shaking flask storage position 312. Move the used coarse sieve to the unloading rack 320. Move the centrifuge bottle to the centrifugal filter switch cover module 314, close the cover, and then move it to the weighing module 328 for weighing. Repeat the above operation until multiple filtered centrifuge bottles are collected and the weight difference between them is confirmed to be within the allowable range, then place them in the centrifuge 324 for centrifugation. If the weight difference exceeds the allowable range, move the centrifuge bottle back to the centrifugal filter switch cover module 314, open the cover, move the centrifuge bottle to the weighing module 328, and balance it using the pipetting device 342. After balancing, move the centrifuge bottle back to the centrifugal filter switch cover module 314, close the cover, and then place it in the centrifuge 324. After centrifugation, remove the centrifuge bottle and move it to the centrifuge filter switch cover module 314 to open the cover. Move the concentration bottle to the liquid receiving position in the filter module 316. Place a clean fine sieve into the filter module 316, and then pour out the centrifuge bottle to complete the filtration process. After filtration, move the centrifuge bottle to the centrifuge filter switch cover module 314, close the cover, and then place it back into the tray transfer section 330. Return the used fine sieve to its original position, place the concentration bottle back into the tray transfer section 330, and finally use an AGV to remove the shake flask / centrifuge bottle tray / concentration bottle tray from the equipment through the centrifuge filter AGV exchange chamber 310.

[0070] Furthermore, centrifugation of the sample is not mandatory; a judgment step is performed before centrifugation. In some embodiments, the judgment step determines whether centrifugation is necessary based on the sample type. If the sample is determined to be pulverized, centrifugation is required; if the sample is determined not to be pulverized, only filtration is performed without centrifugation. That is, in some embodiments of this disclosure, if the sample is a blocky, uncrushed mass, centrifugation is not performed; if the sample is a blocky, pulverized powder, centrifugation is performed. In some embodiments, the need for centrifugation can be determined based on information recorded on the sample label, but other methods known in the art are also feasible. In some embodiments, the need for centrifugation can be determined by software based on rules.

[0071] In some embodiments, during the determination step, the need for centrifugation is determined based on whether the sample is clear. If the sample is not clear, centrifugation is required; if the sample is clear, centrifugation is not required. That is, in some embodiments of this disclosure, if the sample is clear after the first filtration step, centrifugation is unnecessary. This determination can be based on a visual analysis module, which can employ any suitable camera known in the art. Its specific structure and installation location are not limited, as long as it can determine the clarity of the sample.

[0072] The centrifugal filtration device 300 disclosed herein automates the loading, temporary storage, handling, and transfer of consumables between processing modules by employing a centrifugal filtration robotic arm 326, an AGV vehicle, and various handling tools. It also automates the opening and closing of test tubes / concentrate flasks / shaking flasks by employing a cap-opening module, and achieves automatic balancing operations without manual intervention by employing a weighing module 328 and a pipetting device 342. Thus, it can realize the full automation of a series of operations, including filtration, centrifugation, weighing, and balancing, in the centrifugal filtration process of samples.

[0073] freeze drying equipment

[0074] Referring to Figures 7a and 7b, an embodiment of the freeze-drying apparatus 400 of the pharmaceutical automated processing and analysis system 1 is described. The freeze-drying apparatus 400 of the pharmaceutical automated processing and analysis system 1 includes: a weighing module for weighing sample containers before and after freeze-drying; a freeze dryer 422 for freeze-drying and concentrating samples in the sample containers; a labeling module 426 for labeling the sample containers; and a freeze-drying robotic arm 410, which uses a quick-change device to change different grippers to transfer different types of sample containers between the weighing module, the freeze dryer, and the labeling machine to assist in completing the weighing, freeze-drying, and labeling operations. In some embodiments, the labeling module 426 can label the sample containers according to sample information recorded in the pharmaceutical automated processing and analysis system 1. In some embodiments, the weighing module may include a 1 / 1000 weighing module 418 and a 1 / 10,0000 weighing module 420.

[0075] In some embodiments, the freeze-drying equipment 400 further includes a ground rail 412, a freeze-drying AGV exchange compartment 414, a temporary test tube rack 416 within the station, a label printing module 424, a manual feeding rack 428, a labeling transfer rack 430, a barcode scanner 432, and a freeze-drying tool library 440. The barcode scanner 432 includes a weighing barcode scanner 433 and a labeling barcode scanner 434. The freeze-drying tool library 440 includes, for example, tray grippers 442, concentration bottle grippers 444, and test tube grippers 446.

[0076] The freeze-drying robotic arm 410 moves back and forth on the ground rail 412. Its end effector is equipped with a quick-change device, which can connect to quick-change devices on three end effectors located in the freeze-drying tool magazine 440: tray gripper 442, concentration bottle gripper 444, and test tube gripper 446. This allows for quick changes to suit different working scenarios. The connection between the freeze-drying robotic arm 410 and the tray gripper 442 enables operations such as gripping and transferring trays, and pulling out and pushing in the material rack of the freeze dryer 422. The connection between the freeze-drying robotic arm 410 and the concentration bottle gripper 444 enables operations such as lifting concentration bottles from the tray to the 1% weighing module 418 for weighing, and lifting concentration bottles to the fully automatic labeling machine for labeling. The connection between the freeze-drying robotic arm 410 and the test tube gripper 446 enables operations such as lifting test tubes from the tray to the 0.01% weighing module 420 for weighing, and lifting test tubes to the labeling machine for labeling.

[0077] The temporary test tube rack 416 is equipped with multiple tray storage positions. The freeze-drying robotic arm 410 picks up various sample containers from the freeze-drying AGV exchange chamber 414, such as... test tube, Trays of test tubes and 250ml concentrate bottles, and transfer them to temporary test tube rack 416.

[0078] When weighing, place the test tube (e.g.) test tube, The test tubes are transferred to the 0.01% weighing module 420 for weighing, and the concentrate bottles (e.g., 250ml concentrate bottles) are transferred to the 0.1% weighing module 418 for weighing. The top outer door of the balance in both the 0.1% and 0.01% weighing modules 418 and 420 opens and closes automatically. When weighing is required, the top outer door automatically opens; after placing the material on the balance, it closes again for weighing. After weighing, the top outer door automatically opens to remove the material and then automatically closes again. The top outer door remains closed when weighing is not required.

[0079] The freeze dryer 422 is equipped with a pull-out rack, which is multi-layered and has multiple tray placement positions. The freeze dryer door is an automatic door. When a tray is placed into the freeze dryer 422, the freeze dryer door opens automatically, and the freeze-drying robotic arm 410 connects with the tray gripper 442 to pull out the pull-out rack of the freeze dryer 422 to the tray placement and transfer position. Then, it picks up the tray from the temporary test tube rack 416 and transfers it to the pull-out rack of the freeze dryer 422 to complete the tray transfer. Then, the pull-out rack of the freeze dryer 422 is pushed forward to the freeze-drying position. The freeze dryer door closes automatically, and the freeze dryer starts the freeze-drying process.

[0080] The labeling machine consists of a label printing module 424 and a rotary labeling module (also called a "labeling module") 426. The label printing module 424 is used to print labels. The label scanner 434 is used to scan the labels on the labeled objects after labeling.

[0081] At the start of the experiment, the freeze-drying robotic arm 410 transfers the trays transported from the previous step by the AGV to the freeze-drying AGV exchange compartment 414 to the horizontal frame on the bottom inner side of the temporary test tube rack 416. The freeze-drying robotic arm 410 switches its end grippers (concentration flask gripper 444 or test tube gripper 446) to pick up the corresponding sample containers (concentration flasks or test tubes) on the tray, labels them with a labeling machine, and then transfers them to the weighing barcode scanner 433 for barcode scanning. After scanning, the samples are placed in the corresponding weighing module for weighing to obtain the initial weighing result. The weighed sample containers are then returned to the tray. The initial weighing result is automatically recorded by the software and matched with the barcode information of the test tubes in the information system, that is, the initial weighing result is recorded in association with the barcode information of the test tube. After weighing all the sample containers on the trays, the door of the freeze dryer 422 is automatically opened. The freeze-drying robotic arm 410 switches to the tray gripper 442, which pulls out the pull-out rack inside the freeze dryer 422 and places the tray in the corresponding tray position, completing the tray transfer. Then, the tray gripper 442 pushes the pull-out rack back to its original position. The freeze dryer 422 door automatically closes. Processing information corresponding to the recorded barcode information is retrieved from the information system, and appropriate parameters are set for the freeze dryer 422 based on this information for freeze-drying concentration. After freeze-drying, the freeze dryer 422 door automatically opens, and the freeze-drying robotic arm 410's tray gripper 442 pulls out the pull-out tray inside the freeze dryer 422 and transfers it to the bottom inner crossbar of the temporary test tube rack 416. The freeze-drying robotic arm 410 switches to its end gripper, picks up the sample container, and places it in the weighing barcode scanner 433 for barcode scanning. The container is then transferred to the corresponding weighing module for weighing, and after weighing, it is returned to the tray. The initial weighing result and the weighing result after freeze-drying are subtracted from the mass of the empty bottle recorded in the information system to calculate the initial mass and the mass of the freeze-dried product. The initial mass, freeze-dried product mass data, and other information are used to calculate the subsequent dissolution method parameters using a rule formula, and this is recorded in the information system. After each freeze-dried sample is weighed, the freeze-drying robotic arm 410 transfers the tray to the freeze-drying AGV exchange chamber 414, where the AGV vehicle transfers it to the next process for further processing. The freeze-drying AGV exchange chamber 414 has multiple tray storage positions, and precise positioning of the trays is achieved through pin positioning on the freeze-drying AGV exchange chamber 414.

[0082] Sample containers can be labeled at any suitable time as needed. When labeling is required, the freeze-drying robotic arm 410 connects to the tray gripper 442, picking up the tray to be labeled from the temporary test tube rack 416 and transferring it to the labeling transfer rack 430. The freeze-drying robotic arm 410 switches to the test tube gripper 446, which picks up the test tube and places it close to the labeling module 426, causing the sixth axis of the freeze-drying robotic arm 410 to rotate parallel to the horizontal direction, thus completing the test tube labeling. The freeze-drying robotic arm 410 picks up the labeled test tube and places it at the labeling scanner 434 for information binding. After labeling and scanning are completed, the test tube is returned to the labeling transfer rack 430. The freeze-drying robotic arm 410 picks up the tray and transfers it to the freeze-drying AGV exchange bin 414, where it is picked up by the AGV and transferred to the next device. When labeling concentrate bottles, the freeze-drying robotic arm 410 switches to the concentrate bottle gripper 444 and performs the above processing similarly. In some embodiments, manual loading can be supported to transfer test tubes to the manual loading rack 428 for automatic labeling. The system can have side door opening permissions, allowing manual access to open the side door and load the tray containing the test tubes to be labeled into the manual loading rack 428. After loading is complete, the side door is closed, and the system starts the automatic labeling and scanning process. After the automatic labeling process is completed, the system provides two unloading methods: first, the tray can be transferred to the freeze-drying AGV exchange compartment 414, where it is picked up by the AGV and transferred to the next device; second, the tray can be transferred to the manual loading rack 428 for manual unloading.

[0083] The freeze-drying equipment 400 disclosed herein automates the loading, temporary storage, handling, and transfer of consumables between processing modules by employing a freeze-drying robotic arm 410, an AGV vehicle, and various handling tools. Furthermore, it automates the freeze-drying and labeling operations by employing a freeze dryer 422 and a labeling machine, thereby enabling full automation of the freeze-drying process for samples.

[0084] Centrifugal Concentration Equipment

[0085] Two centrifugal concentration devices 500 are shown exemplary in the top view of Figure 2.

[0086] Referring to Figure 8, an embodiment of a centrifugal concentration device 500 of a pharmaceutical automated processing and analysis system 1 is described. The centrifugal concentration device 500 includes: a centrifugal concentrator 510 (five are shown exemplary in Figure 8, but the number can be set according to specific needs), which performs centrifugal concentration operations on samples in multiple sample containers, and the centrifugal concentrator 510 has an imbalance detection sensor; and a balancing and weighing module, which balances the samples in the multiple sample containers when the imbalance detection sensor detects that the weight difference between the multiple sample containers exceeds a predetermined threshold; wherein, a centrifugal concentration robotic arm 524 uses a quick-change device to change different grippers, transferring different types of gripped objects between the centrifugal concentrator 510 and the balancing and weighing module to assist in completing the centrifugal concentration.

[0087] In some embodiments, the balancing and weighing module of the centrifugal concentration apparatus 500 includes a weighing module 518 and a liquid addition module 520. During the liquid addition and balancing operation, the centrifugal concentration robotic arm 524 moves each sample container into the weighing module 518 for weighing. Based on the weighing results, the centrifugal concentration robotic arm 524 moves the sample containers that need to be added weight into the liquid addition module 520 to add the required amount of liquid for balancing.

[0088] The centrifugal concentrator 500 includes pallet racks 512 (two are shown exemplarily in Figure 8), a pallet transfer station 514, an adapter rack 516, a weighing module 518, a liquid dispensing module 520, a centrifugal concentrator AGV exchange compartment 522, a ground rail module 526, and a centrifugal concentrator tool library 530. The centrifugal concentrator tool library 530 includes pallet grippers, adapter grippers, and bottle grippers.

[0089] Pallet rack 512 is configured with multiple layers, such as 5 layers, for temporary storage of pallets during processing. Adapters include, for example, 250ml concentrate bottle adapters. test tube adapter and Test tube adapter.

[0090] At the start of the experiment, the AGV transports the required materials to the centrifugal concentration AGV exchange compartment 522. Then, the centrifugal concentration robotic arm 524, in conjunction with pallet grippers, transfers the pallet from the exchange compartment 522 to the pallet rack 512, simultaneously transferring the corresponding adapter to the rack. The end effector of the centrifugal concentration robotic arm 524 switches to a bottle gripper, which transfers the bottles from the pallet to the adapter. The end effector of the centrifugal concentration robotic arm 524 then switches to an adapter gripper, which places the adapter into the centrifugal concentrator 510. The centrifugal concentrator 510 has an automatically opening and closing door. When centrifugal concentration is required, the door of the centrifugal concentrator 510 automatically opens. After the centrifugal concentration robotic arm 524 has placed the adapter, the door of the centrifugal concentrator 510 automatically closes. Appropriate centrifugal concentration parameters are set, and processing begins. The centrifugal concentrator 510 has an imbalance detection sensor. When the imbalance detection sensor detects that the weight difference of the bottles in the adapter reaches a certain threshold, the centrifugal concentrator 510 automatically stops, and the door of the centrifugal concentrator 510 automatically opens. The adapter is removed by the centrifugal concentrator robotic arm 524 and transferred to the weighing module 518 for weighing. Based on the weighing result, the liquid addition module 520 adds liquid to the bottles inside the adapter to balance the weight. After balancing, the centrifugal concentrator robotic arm 524 places the adapter into the centrifugal concentrator 510 for further concentration. After concentration, the centrifugal concentrator robotic arm 524 removes the adapter and places it on the pallet rack 512. The end effector of the centrifugal concentrator robotic arm 524 switches the bottle gripper, transfers the bottle to the pallet, and then the centrifugal concentrator robotic arm 524 switches the pallet gripper to transfer the pallet to the centrifugal concentrator AGV exchange compartment 522.

[0091] The centrifugal concentration equipment 500 disclosed herein automates the loading, temporary storage, transportation, and transfer of consumables between processing modules by employing a centrifugal concentration robotic arm 524, an AGV vehicle, and various handling tools. Furthermore, it automates centrifugal concentration and automatic balancing operations through a centrifugal concentrator 510, a weighing module 518, and a liquid addition module 520, thereby enabling full automation of the centrifugal concentration process for samples.

[0092] Dry sample loading equipment

[0093] Referring to Figure 9, an embodiment of the dry sample loading device 600 of the pharmaceutical automated processing and analysis detection system 1 is described. A dry sample loading apparatus 600 according to an embodiment of the present disclosure includes: a powder addition module 612 for quantitatively adding powder to a sample loading column and a rotary evaporation column; a rotary evaporation module 626 for rotary drying the sample in the rotary evaporation column; a powder scraping tool for scraping powder from the rotary evaporation column; a scraper cleaning module 622 for cleaning and wiping the scraper of the scraper tool used for scraping powder; a powder leveling module 614 for leveling the powder in the sample loading column; a cover opening and closing and powder scraping rotation module 624 for fixing and rotating the column when opening the cover of the rotary evaporation column and the sample loading column, and for fixing and rotating the rotary evaporation column when scraping powder from the column; and a second visual inspection module 616 for detecting the state of the sample inside the rotary evaporation column.

[0094] In some embodiments, the dry sample loading apparatus 600 further includes a sample loading robotic arm 610, a docking track 618, a loading rack module 620, and a sample loading tool library 630. The sample loading tool library 630 includes, for example, handling tools, pouring tools, and powder scraping tools. The loading rack module 620 includes, for example, a powder bucket rack 642, a funnel rack 644, a rotary evaporation column rack 646, and a sample loading column rack 648.

[0095] The sample loading robotic arm 610 is used for quick-connect connection with various tools in the tool library (such as handling tools, pouring tools, powder scraping tools, etc.) to perform corresponding operations. The second vision inspection module 616 detects the state of the sample inside the rotary evaporation column, including detecting whether the sample inside the column is dried and whether the powder inside the column has been completely scraped off. The second vision inspection module 616 can use any suitable device for image collection; in one embodiment, a CCD vision module can be used to collect images of the rotary evaporation column. The docking track 618 allows the sample loading robotic arm 610 to move. The loading rack module 620 is used for the interaction of materials and consumables between an external AGV vehicle and this equipment; that is, it can interact with powder bucket trays, funnel trays, rotary evaporation column trays, sample loading column trays, etc. The cover opening / closing and powder scraping rotation module 624 is used in conjunction with the handling tools when opening / closing the rotary evaporation column and sample loading column, and in conjunction with the powder scraping tool when scraping powder from the rotary evaporation column. The sample loading tool library 630 is used to temporarily store various tools such as handling tools, pouring tools, and powder scraping tools. Handling tools are used to handle various containers, such as sample loading columns, rotary evaporation columns, powder buckets, funnels, etc. Pouring tools are used to handle various containers and pour powder. Powder scraping tools are used to scrape powder samples from the side walls and bottom of the rotary evaporation column.

[0096] Before processing begins, the necessary materials (powder bucket, funnel, rotary evaporator column, sample loading column), etc., are manually placed in the corresponding compartments of the loading rack module 620. The rotary evaporator column may also be derived from the product combined by the dilution and reconstitution equipment 200. In some embodiments, an AGV (Automated Guided Vehicle) can also place the necessary materials in the corresponding compartments of the loading rack module 620. The sample loading robot arm 610 switches to a handling tool to place the powder bucket containing silica powder and the rotary evaporator column into the powder adding module 612, which quantitatively adds silica powder to the rotary evaporator column. The sample loading robot arm 610 transfers the powder-added rotary evaporator column to the rotary evaporation module 626, which performs rotary evaporation on the column. The sample loading robot arm 610 transfers the rotary evaporator column after rotary evaporation to the second vision inspection module 616, which takes a picture and analyzes it to determine whether the sample in the rotary evaporator column has been dried. After confirming that the rotary evaporation column has dried, the loading robotic arm 610 transfers the column to the opening / closing and scraping rotation module 624, and changes the scraping tool to scrape powder from the column. After scraping, the robotic arm 610 moves the scraping tool to the scraper cleaning module 622 for cleaning. The robotic arm 610 then switches to a handling tool to transfer the scraped column back to the second vision inspection module 616, which takes pictures and analyzes them to check the state of the contents (mixed silica gel). The robotic arm 610 then transfers the loading column to the opening / closing and scraping rotation module 624 to open the lid. The robotic arm 610 places the funnel at the opening of the loading column, switches to a pouring tool to pour the powder from the rotary evaporation column into the loading column, and then switches back to the handling tool to return the funnel to the loading rack module 620. The loading robotic arm 610 transfers the loading column to the powder leveling module 614 for powder leveling, then transfers the powder container and loading column to the powder adding module 612 for powder addition, and finally transfers the powder-added loading column to the cover opening and closing module 624 for cover closing. An AGV then transfers the loading column to the next device (e.g., a medium-pressure preparation and separation device). In some embodiments, quartz sand is added during powder addition. Quartz sand serves two main purposes: first, to level the sample, ensuring the surface of the sample mixed with silica gel after rotary drying is flush (so that it can contact the reagents simultaneously during subsequent component separation); second, to reduce excess space in the loading column. Quartz sand is an inert substance and will not react with or dissolve in the sample or reagents. However, quartz sand is only one example; other materials may be added as needed.

[0097] The dry sample loading equipment disclosed herein automates the loading, temporary storage, handling, and transfer of consumables between processing modules by employing a sample loading robotic arm 610, an AGV vehicle, and various handling tools. Furthermore, it automates sample loading, detection, cleaning, and cap opening / closing operations through a powder adding module 612, a second vision inspection module 616, a powder leveling module 614, a scraper cleaning module 622, a cap opening / closing and powder scraping rotation module 624, and a rotary evaporation module 626. Thus, it enables full automation of the dry sample loading process.

[0098] Medium-pressure preparation and separation equipment

[0099] Referring to Figure 10, an embodiment of a medium-pressure preparative separation device 700 of a pharmaceutical automated processing and analysis system 1 is described. The medium-pressure preparative separation device 700 according to an embodiment of this disclosure includes: a column loading module 716 for connecting a chromatographic column and a sample loading column; a sample loading and syringe cleaning module 718 for performing sample loading and syringe cleaning operations on a sample container containing the transferred sample; and a medium-pressure fraction collection module 722 (two are exemplary shown in Figure 10, but the number can be set as needed) for collecting fractions condensed at different time periods or temperatures for subsequent analysis or use. The pump and valve module 720 (two are shown exemplary in Figure 10, but the number can be set as needed) is used for pumping liquid and related analytical processing; and the mobile phase buffer module 724 is used to buffer and hold the mobile phase required for processing; wherein, the pump and valve module 720 is connected to the sample loading and liquid addition and needle cleaning module 718, column packing module 716, medium-pressure fraction collection module 722, and mobile phase buffer module 724 through pipelines, providing power for liquid transfer between the above modules.

[0100] In some embodiments, the medium-pressure preparation and separation device 700 further includes a medium-pressure preparation and separation exchange chamber 710, a medium-pressure preparation and separation robotic arm 712, a ground rail module 714, a transfer buffer 726 (three of which are shown exemplarily in FIG10), a cleaning column module 728, an upper plug placement module 730, and an end gripper 732.

[0101] In column packing module 716, the chromatographic column and sample loading column are transferred here for column connection. Sample loading and needle cleaning module 718 performs sample loading and needle cleaning operations; the sample container containing the sample is transferred to sample loading and needle cleaning module 718. Medium-pressure fraction collection module 722 is compatible with multiple trays and buffers different containers for collecting fractions condensed at different time periods or temperatures for subsequent analysis or use. Mobile phase buffer module 724, used to buffer the mobile phase required for the experimental process, can contain multiple mobile phase storage tanks, each containing a different mobile phase. A cleaning column module 728 is located on one side of the column loading module 716 and is used to buffer and place multiple cleaning columns. The cleaning column module 728 can be considered as a placement seat that can hold multiple cleaning columns, such as four. The cleaning columns are used in conjunction with the column loading module 716. When the column loading module 716 needs to clean its tubing or chromatographic / loading columns, the medium-pressure preparative separation robotic arm 712 removes the cleaning column from the placement seat and installs it into the column loading module 716 to achieve cleaning of the tubing or chromatographic / loading columns of the column loading module 716. Additionally, the cleaning column can also be used as a connecting tubing when the chromatographic / loading columns are packed and eluted separately. An upper plug placement module 730 is used to buffer and place upper plugs for various chromatographic and loading columns.

[0102] Before processing begins, an external AGV transfers a tray containing empty test tubes to the medium-pressure preparation and separation exchange chamber 710. The medium-pressure preparation and separation robotic arm 712 and the ground track module 714 use the end gripper 732 of the medium-pressure preparation and separation robotic arm 712 to move the tray containing empty test tubes from the medium-pressure preparation and separation exchange chamber 710 to the transfer buffer position 726. After processing begins, the medium-pressure preparation and separation robotic arm 712 and the ground track module 714 move the corresponding chromatographic column and sample loading column to the column loading module 716. In some embodiments, after the columns are connected, the medium-pressure preparation and separation robotic arm 712 and the ground track module 714 use the end gripper 732 of the medium-pressure preparation and separation robotic arm 712 to move the tray containing empty test tubes from the transfer buffer position 726 to the medium-pressure fraction collection module 722, thus completing the preparation work. An external AGV transfers a tray containing test tubes of samples to the medium-pressure preparation and separation exchange chamber 710. The medium-pressure preparation and separation robotic arm 712 and the ground rail module 714 use the end gripper 732 of the medium-pressure preparation and separation robotic arm 712 to move the tray containing test tubes of samples from the medium-pressure preparation and separation exchange chamber 710 to the sample loading and liquid addition and needle cleaning module 718. Then, the medium-pressure preparation and separation robotic arm 712 and the ground rail module 714 use the end gripper 732 of the medium-pressure preparation and separation robotic arm 712 to move the tray of empty test tubes from the transfer buffer position 726 to the medium-pressure fraction collection module 722. Thus, the separation and purification of sample components are achieved through the medium-pressure preparation and separation equipment 700.

[0103] The medium-pressure preparation and separation equipment disclosed herein automates the loading, temporary storage, handling, and transfer of consumables between processing modules by employing a medium-pressure preparation and separation robotic arm 712, an AGV vehicle, and various handling tools. Furthermore, it automates the medium-pressure preparation, separation, purification, and collection operations through a column loading module 716, a sample loading and liquid addition and needle cleaning module 718, a pump and valve module 720, a medium-pressure fraction collection module 722, a mobile phase buffer module 724, and a cleaning column module 728.

[0104] High-pressure preparation and separation equipment

[0105] Referring to Figure 11, an embodiment of a high-pressure preparation separation device 800 of a pharmaceutical automated processing and analysis system 1 is described. The high-pressure preparation separation device 800 according to an embodiment of this disclosure includes a high-pressure preparation separation station 820 and a detection filtration station 850. The detection filtration station 850 includes: a positive pressure filtration module 858 for filtering samples before high-pressure processing; a sieve filtration module 860 for filtering samples before either high-pressure processing or wet loading processing; and a pipetting module 862 (e.g., a 1 ml pipetting module) for transferring samples from one sample container to another for subsequent analytical procedures.

[0106] The high-pressure preparation separation station 820 includes: a high-pressure preparation sample inlet / outlet module 810, used to perform high-pressure preparation separation on samples that have passed through either the positive pressure filtration module 858 or the sieve filtration module 860 and transfer them to a pipetting module 862; a mobile phase buffer 814, used to introduce the sample from the high-pressure preparation sample inlet / outlet module and to introduce a predetermined mobile phase into the mobile phase buffer 814 according to the introduced sample, thereby mixing the sample with the predetermined mobile phase to obtain a second mixture; and a pump valve analysis module 812, used to perform pumping and analysis-related processing, wherein the pump valve analysis module 812 separates the components of the second mixture, analyzes each component, and then exports the different components to the high-pressure preparation sample inlet / outlet module 810 for fraction collection.

[0107] The filtration inspection station 850 also includes: a filtration inspection robotic arm 852, a filtration inspection AGV exchange compartment 854, a main rack 856, and a buffer rack 864.

[0108] The detection and filtration robotic arm 852 is used to move various trays and consumables inside the high-pressure preparation and separation equipment 800. The detection and filtration AGV exchange compartment 854 is used to transfer trays transported by external AGV vehicles. The main rack 856 is used to store trays transported by external AGV vehicles. The positive pressure filtration module 858, used for filtration before high-pressure treatment of samples, is used to filter small volumes of sample liquid, such as sample liquid contained in a filter column. The sieve filtration module 860 is used for filtration before high-pressure treatment of samples, and for filtering large volumes of sample liquid, such as sample liquid contained in a solvent bottle; additionally, the sieve filtration module 860 is also used for filtration before wet medium-pressure treatment. The pipetting module 862 is used to transfer samples from test tubes to other containers for subsequent analytical procedures. The buffer rack 864 is used to temporarily store funnel trays and concentration bottle trays used for sieve filtration.

[0109] In the pre-processing preparation stage, an external AGV transfers the pallet to the AGV exchange compartment 854 for testing and filtration, and the robotic arm 852 moves the pallet to the main shelf 856. When the sample begins to be filtered before high-pressure filtration, especially for small amounts of sample liquid, the robotic arm 852 transfers the test tube tray and filter column tray from the main shelf 856 to the positive pressure filtration module 858 for filtration. The robotic arm 852 automatically grips the filter column. The filter column contains the sample liquid to be filtered and is equipped with a plugging mechanism, such as a plug, to prevent premature leakage. The robotic arm 852 removes the plug, punctures the filter head, and inserts a tip into the filter head outlet. If the sample volume is small (e.g., 0-2 ml), the sample is punctured and filtered into a liquid chromatography vial; if the sample volume is large (e.g., 2-30 ml), it is filtered into a test tube. When filtering large volumes of sample liquid, the detection and filtration robotic arm 852 transfers the concentration bottle tray and filter funnel tray from the main shelf 856 to the buffer shelf 864. The robotic arm 852 then takes an empty concentration bottle and filter funnel and places them in the corresponding positions within the screen filter module 860, and also takes a concentration bottle containing the sample and places it in the corresponding position within the screen filter module 860. The sample is poured into the filter funnel, causing the sealing plate of the screen filter module 860 to automatically press down, thus pressurizing the funnel to complete the filtration. After a batch of high-pressure fractions has been collected, the detection and filtration robotic arm 852 pulls out the fraction drawer and places the test tube tray in the corresponding position within the pipetting module 862. The pipetting module 862 inserts a tip and draws the sample from the fraction test tube, transferring the sample to a liquid chromatography vial for subsequent operations.

[0110] The high-pressure preparation sample inlet / outlet module 810 is used for high-pressure preparation and separation of samples. During the process, after filtration in the positive pressure filtration module 858 or the sieve filtration module 860, the sample is transferred to the high-pressure preparation sample inlet / outlet module 810, and then the sample processed in the high-pressure preparation sample inlet / outlet module 810 is transferred to the aforementioned pipetting module 862. The pump valve analysis module 812 is connected to the high-pressure preparation sample inlet / outlet module 810 via a pipeline (not shown) and is used for pumping and analysis-related processing. In some embodiments, two high-pressure preparation sample inlet / outlet modules 810 are provided, and two corresponding pump valve analysis modules 812 are provided (as exemplarily shown in FIG11). The mobile phase buffer 814 is also connected to the pump valve analysis module 812 via a pipeline (not shown) and is used to introduce the sample in the high-pressure preparation sample inlet / outlet module 810 through the pipeline, i.e., a set of samples in the high-pressure preparation sample inlet / outlet module 810, and then introduce a predetermined mobile phase into the mobile phase buffer 814 according to the introduced sample, thereby mixing the sample with the predetermined mobile phase. The mobile phase buffer 814 disclosed herein serves to store a large volume of mobile phase liquid. This mobile phase buffer 814 can be considered a box structure with a flip-top door on the outer shell. Inside, a large-capacity container (e.g., 30L) of mobile phase liquid is placed. When the liquid in the container is insufficient, the flip-top door can be manually opened to remove the container and add liquid. The container is connected to the pump-valve analysis module 812 via a pipe through a through-hole on the outer shell. In related technologies, mobile phase buffers have relatively small capacities and require frequent manual replenishment. The pump-valve analysis module 812 separates the components of the mixture, analyzes each component, and then pipes the different components to the high-pressure preparation sample inlet / outlet module 810 for fraction collection. That is, multiple sets of fractions are collected in the aforementioned high-pressure preparation sample inlet / outlet module 810.

[0111] When the wet medium-pressure filtration of the sample begins, the filtration robot arm 852 transfers the concentration bottle tray and filter funnel tray from the main shelf 856 to the buffer shelf 864. The robot arm 852 then picks up an empty concentration bottle and filter funnel and places them in the corresponding positions in the screen filter module 860, and also picks up a concentration bottle containing the sample and places it in the corresponding position in the screen filter module 860. The sample is poured into the filter funnel, causing the sealing plate of the screen filter module 860 to automatically press down, thereby pressurizing the funnel to complete the filtration. The filtration robot arm 852 returns the filter funnel and concentration bottle to their respective trays and then returns the trays to the main shelf 856. The sample filtered before the wet medium-pressure process can then be transferred to the medium-pressure preparation and separation equipment 700 for wet medium-pressure treatment.

[0112] The high-pressure preparation and separation equipment disclosed herein automates the loading, temporary storage, handling, and transfer of consumables between processing modules by employing a detection and filtration robotic arm 852, an AGV vehicle, and various handling tools. Furthermore, it automates high-pressure preparation, separation, purification, collection, and filtration operations through the high-pressure preparation and separation workstation 820 and the detection and filtration workstation 850.

[0113] Analytical equipment

[0114] LCMS analysis device

[0115] Referring to Figure 12, an embodiment of the LCMS analysis device 900 of the analytical apparatus of the pharmaceutical automated processing and analysis detection system 1 is described. The LCMS analysis device 900 of the analytical apparatus according to this disclosure includes: a first mass spectrometer 912 for performing relatively simple analyses of samples; a second mass spectrometer 914 for performing complex sample analyses; a fraction collection module 920 for receiving fractions output from analyses performed by at least one of the first mass spectrometer 912 and the second mass spectrometer 914; and an autosampler 922 (two are exemplary shown in Figure 12, but their number can be specifically set as needed) for automatically feeding samples into either the first mass spectrometer 912 or the second mass spectrometer 914.

[0116] The LCMS analysis apparatus 900 of the analytical device according to this disclosure employs different mass spectrometers to perform LCMS analysis from different aspects, and also includes a robotic arm and ground rail module 910, an LCMS analysis AGV exchange bin 916, and a temporary storage rack 918 (three of which are shown exemplary in Figure 12).

[0117] The first mass spectrometer 912 is used to perform simpler analyses on the sample, such as molecular weight analysis. The second mass spectrometer 914 is used to perform complex sample analyses, such as molecular structure analysis. In some embodiments, the simpler and complex sample analyses can be automatically determined by the system based on preset information, or they can be set by the operator.

[0118] For example, in one exemplary embodiment, the first mass spectrometer 912 can be a single-bar mass spectrometer, and the second mass spectrometer 914 can be a QTOF (Quadrupole Time-of-Flight Mass Spectrometer) mass spectrometer, so that the device can independently perform HPLC (High Performance Liquid Chromatography) and QTOF analysis. However, the first mass spectrometer 912 and the second mass spectrometer 914 can be selected from various mass spectrometers known in the art, such as quadrupole mass spectrometers, ion trap mass spectrometers, time-of-flight mass spectrometers, and magnetic mass spectrometers, as needed. By using different first mass spectrometers 912 and second mass spectrometers 914, different analyses can be performed on the sample simultaneously and independently, thereby shortening the overall processing time and improving the efficiency of separation and analysis.

[0119] Before processing begins, an AGV (Automated Guided Vehicle) places the trays to be tested and the trays for collecting fractions into the LCMS (Liquid Crystal Mass Analyzer) AGV exchange compartment 916. The robotic arm and ground rail module 910 then deliver the trays to be tested to the first mass spectrometer 912 and / or the second mass spectrometer 914 for LCMS analysis, according to the testing requirements. This allows for direct acquisition of test results and uploading of test reports. Conversely, the fractions output from the LCMS analysis are received by the corresponding fraction collection module 920 and then transported by the robotic arm and ground rail module 910 to the LCMS analysis AGV exchange compartment 916, where they are transferred by the AGV to the next process step.

[0120] The LCMS analysis apparatus 900 disclosed herein automates the loading, temporary storage, handling, and transfer of consumables between processing modules by employing a robotic arm and ground rail module 910, an AGV vehicle, and various handling tools. Furthermore, it automates operations such as LCMS analysis by employing a first mass spectrometer 912, a second mass spectrometer 914, a fraction collection module 920, and an autosampler 922, and can simultaneously perform different LCMS analyses on samples as needed.

[0121] Cell analysis device

[0122] Referring to Figure 13, an embodiment of the cell analysis device 1000 of the analytical apparatus of the pharmaceutical automated processing and analysis detection system 1 is described. The cell analysis device 1000 of the analytical apparatus according to this disclosure includes: a pipetting workstation 1010, which performs automated precision pipetting operations on well plates for holding cells; a plate washer 1012, which automatically cleans the well plates; a cell culture incubator 1024, which provides a cell culture environment; an analytical centrifuge 1014, which performs centrifugation operations on the well plates; an enzyme-linked immunosorbent assay (ELISA) reader 1016, which performs enzyme-linked immunosorbent assay (ELISA) target detection on well plates containing cultured cells; a labeling device 1018, which automatically labels the well plates; and a high-content imaging analysis module 1026, which performs cell imaging analysis on the cultured cells in the well plates.

[0123] The cell analysis device 1000 also includes an AGV interaction frame 1020, a storage stack 1022, and a robotic arm and ground rail module 1028.

[0124] Typically, the analytical centrifuge 1014 performs centrifugation of up to two wells at a time; in some embodiments, the centrifuge 1014 is used for centrifuging the liquid in the wells. The ELISA reader 1016, typically used for enzyme-linked immunosorbent assays (ELISA), can be used for cell target detection in this disclosure. The labeling device 1018 can automatically label, for example, four sides of the wells. The AGV interaction rack 1020 enables interaction between the cell analysis device 1000 and other parts of the overall pharmaceutical automated processing and analysis system 1; the cell analysis device 1000 has a manual door around its perimeter for manual maintenance. The storage stack 1022 stores consumables for culturing and detecting cells, and wells; in some embodiments, it has nine rows of 16-layer standard well plate storage positions. The cell culture incubator 1024 provides a cell culture environment. In some embodiments, the high-content imaging analysis module 1026 can be used for cell phenotypic detection and cell target detection. The robotic arm and ground rail module 1028 are used to transfer and connect the various functional modules.

[0125] In some embodiments, the following analytical process can be performed: Cells or samples are added to well plates in the cell analysis device 1000 as needed, and the well plates are transferred to a cell culture incubator 1024 for incubation via a robotic arm and ground rail module 1028. After incubation, the incubated cells are transferred to a plate washer 1012 for washing. Next, a portion of the cells is transferred to a high-content imaging analysis module 1026 for imaging detection; another portion of the cells is transferred to the cell culture incubator 1024, chromogenic buffer is added, and the cells are transferred to a microplate reader 1016 for enzyme-linked immunosorbent assay (ELISA) detection. In this way, a single cell sample can be simultaneously analyzed using both high-content and ELISA techniques.

[0126] In the cell analysis device 1000 disclosed herein, the loading, temporary storage, handling, and transfer of consumables between processing modules are automated by replacing manual operation with a robotic arm and a ground rail module 1028, an AGV vehicle, and various handling tools. Furthermore, automated cell analysis is achieved through a plate washer 1012, an analytical centrifuge 1014, an ELISA reader 1016, a labeling device 1018, a cell culture incubator 1024, and a high-content imaging analysis module 1026.

[0127] In addition, this disclosure also provides an automated pharmaceutical processing and analysis method.

[0128] Referring to Figure 14, an automated pharmaceutical processing and analysis method according to an embodiment of the present disclosure includes the following steps: an extraction step S100, in which a transfer device 130 delivers a sample container containing the sample to the loading position 101 of the extraction device 100, and identifies whether the sample container is located in an appropriate storage position on the loading position 101 by a visual recognition module 106 correspondingly set above the loading position 101, and the transfer device 130 transfers the sample container to the corresponding setting position in the shaker 103 of the extraction device for shaking incubation of the sample by cold immersion method; a preparation step S102, in which the transfer device 130 delivers the shaken and incubated sample to at least one preparation device for preparation processing; and an analysis step S104, in which the transfer device 130 transfers the prepared sample to the analysis device 120 for detection and analysis.

[0129] This disclosure does not specifically limit the analytical equipment. For example, the analytical equipment includes equipment capable of performing at least one of the following analytical processing on pharmaceutical samples: automated high-performance liquid chromatography (HPLC) analysis of pharmaceutical samples, automated HPLC-MS analysis of pharmaceutical samples, and automated analysis of the cellular biological activity and toxicity of pharmaceutical samples.

[0130] In some embodiments, the analytical apparatus includes at least one of the following: an apparatus for automated high-performance liquid chromatography (HPLC) analysis of pharmaceutical samples, an apparatus for automated HPLC-MS analysis of pharmaceutical samples, and an apparatus for automated analysis of the cell activity and toxicity of pharmaceutical samples.

[0131] The pharmaceutical automated processing and analysis detection system and method disclosed herein automates the loading, temporary storage, handling, and transfer of materials and consumables between extraction equipment, preparation equipment, and analysis equipment by using transfer equipment, thereby assisting in the full-process automation of a series of operations such as sample extraction, processing, detection, and analysis.

[0132] In some embodiments, the AGV vehicle of the transfer device 130 transfers various materials, including samples and sample containers, between the extraction device, at least one preparation device, and the analysis device; the robotic arm of the transfer device 130 delivers the materials transferred from the AGV vehicle to the AGV exchange bin into the corresponding devices in the extraction device, at least one preparation device, and the analysis device, performs material transfer in the corresponding devices, and removes the materials from the corresponding devices and transfers them into the AGV exchange bin for transfer by the AGV vehicle.

[0133] In some embodiments, the robotic arm transfers different materials by selecting appropriate tools.

[0134] In some embodiments, during the extraction step, the shaker door of the shaker 103 is automatically opened, the transfer device 130 removes the sample container from the loading position 101 and transfers it to the scanning device, the scanning device scans the label on the sample container for information identification and confirmation, the transfer device 130 places the confirmed sample container into the appropriate setting position inside the shaker; the shaker door is automatically closed, and the shaker 103 is turned on to shake and incubate the sample container based on the information obtained by the scanning device.

[0135] In some embodiments, preparation step S102 includes at least one of the following steps: dilution and reconstitution step, centrifugation and filtration step, freeze-drying step, centrifugation and concentration step, dry sample loading step, medium-pressure preparation and separation step, and high-pressure preparation and separation step.

[0136] In some embodiments, in preparation step S102, at least one of the following steps can be performed multiple times: dilution and reconstitution step, centrifugation and filtration step, freeze-drying step, centrifugation and concentration step, dry sample loading step, medium-pressure preparation and separation step, and high-pressure preparation and separation step.

[0137] In some embodiments, a dilution and reconstitution step is performed before the medium-pressure preparation and separation step, and a centrifugal concentration step is performed after the medium-pressure preparation and separation step; and a dilution and reconstitution step is performed before the high-pressure preparation and separation step, and a centrifugal concentration step is performed after the high-pressure preparation and separation step. A freeze-drying step is performed after the centrifugal concentration step.

[0138] In some embodiments, a dry loading step is performed before the medium-pressure preparative separation step. In some embodiments, a dilution and reconstitution step is performed after the lyophilization step. In some embodiments, a centrifugation and filtration step is performed after the extraction step, and an analytical step S104 is performed after the medium-pressure preparative separation step and / or the high-pressure preparative separation step.

[0139] In some embodiments, preparation step S102 may include a dilution and reconstitution step, which includes: a liquid addition step, in which the transfer device 130 transfers the sample to the liquid addition module 216 for liquid addition; a shaking step, in which the transfer device 130 transfers the sample to the shaking module 238 for ultrasonic shaking after the liquid addition is completed; a dissolution confirmation step, in which the transfer device 130 transfers the sample to the visual inspection module to confirm that the sample is completely dissolved; and a merging step, in which the samples in multiple sample containers are merged by at least one of pipetting and pouring. In some embodiments, if the sample container is a test tube, the dilution and reconstitution step further includes a centrifugation step, in which the transfer device 130 transfers the sample container to the centrifugation module for centrifugation before performing the merging step.

[0140] In some embodiments, preparation step S102 may include a centrifugal filtration step, which includes: a coarse filtration step, in which the transfer device 130 places a clean coarse sieve into the filtration module 316, and the filtration module 316 performs coarse filtration by suction filtration, passing the sample already poured into the filtration module 316 through the coarse sieve; then the transfer device 130 removes the coarse sieve; a balancing step, in which the transfer device 130 transfers the sample container to the weighing module 328 to weigh the multiple samples after coarse filtration; if the weight difference between the multiple samples exceeds the allowable range, the multiple samples are balanced by pipetting; a centrifugation step, in which the balanced multiple samples are transferred into a centrifuge for centrifugation; and a fine filtration step, in which the transfer device 130 places a clean fine sieve into the filtration module 316, and the filtration module 316 performs fine filtration by suction filtration, passing the sample already poured into the filtration module through the fine sieve. In some embodiments, the balancing step includes: a weighing step, in which multiple samples are weighed; and a pipetting step, in which a portion of the sample in a sample container containing more samples is transferred to another sample container.

[0141] In some embodiments, the automated pharmaceutical processing and analysis method further includes a centrifugation step, wherein the transfer device 130 transfers multiple balanced samples into a centrifuge for centrifugation.

[0142] In some embodiments, a judgment step is performed before centrifugation, and a determination is made based on the judgment result to determine whether to perform centrifugation. In the judgment step, if the sample is determined to have been pulverized based on the sample type, centrifugation is performed on the sample; if the sample is determined not to have been pulverized based on the sample type, centrifugation is not performed on the sample. Alternatively, in the judgment step, if the sample is determined not to be clear based on the sample state, centrifugation is not performed; if the sample is determined to be clear based on the sample state, centrifugation is performed.

[0143] In some embodiments, preparation step S102 includes a freeze-drying step. In the freeze-drying step, the sample container containing the sample is weighed, the weighed sample is sent to a freeze dryer 422 for freeze-drying, and the freeze-dried sample container is weighed again. Based on the weighing result and the mass of the empty bottle, the initial mass and the mass of the freeze-dried product are calculated. Subsequent dissolution method parameters are obtained based on the initial mass and the mass of the freeze-dried product. The transfer device 130 uses a quick-change device to grasp the tray, concentration bottle, and test tubes. During weighing, the transfer device transfers the test tubes in the tray to a 0.01% weighing module for weighing, and transfers the concentration bottle in the tray to a 0.1% weighing module for weighing. In some embodiments, the freeze-drying step also includes labeling the sample container.

[0144] In some embodiments, preparation step S102 includes a centrifugal concentration step. In the centrifugal concentration step, the transfer device 130 transfers multiple sample containers to an adapter and loads the adapter into a centrifugal concentrator 510 for centrifugal concentration. In some embodiments, the centrifugal concentrator 510 includes an imbalance detection sensor. When the imbalance detection sensor detects that the weight difference between the multiple sample containers in the adapter exceeds a predetermined threshold, the centrifugal concentrator 510 automatically stops, and the transfer device 130 transfers the multiple sample containers to a balancing and weighing module for balancing. After balancing, the transfer device easily transfers the multiple sample containers back to the centrifugal concentrator, which automatically starts and continues the centrifugal concentration operation.

[0145] In some embodiments, preparation step S102 includes a dry sample loading step, which includes: a powder addition step, in which the transfer device 130 places a powder container containing silica powder and a rotary evaporation column into the powder addition module 612, and the powder addition module 612 adds silica powder to the rotary evaporation column; a rotary evaporation step, in which the transfer device 130 transfers the rotary evaporation column after adding powder to the rotary evaporation module 626, and the rotary evaporation module 626 performs rotary evaporation on the rotary evaporation column; and a powder scraping and rotating step, in which after the rotary evaporation column has been dried, the transfer device transfers the rotary evaporation column to the powder scraping and rotating module 624, and replaces the powder scraping tool to scrape powder from the rotary evaporation column. In some embodiments, the dry sample loading step further includes a judgment step, in which the transfer device 130 transfers the rotary evaporation column after rotary evaporation to the second visual inspection module 616, the second visual inspection module 616 analyzes the rotary evaporation column after rotary evaporation to determine whether the sample in the rotary evaporation column has been dried, and the rotary evaporation column after powder scraping is transferred to the second visual inspection module 616, the second visual inspection module 616 takes a picture of the rotary evaporation column after powder scraping for analysis to detect the state of the contents. In some embodiments, after the powder scraping and rotation step, the dry sample loading step further includes a cleaning step, in which the transfer device 130 moves the powder scraping tool to the scraper cleaning module 622 to clean the powder scraping tool. In some embodiments, after the powder scraping and rotating step, the dry sample loading step further includes: a pouring step, in which the transfer device 130 changes the pouring tool to pour the powder in the rotary evaporation column into the sample loading column; a shaking step, in which the transfer device 130 transfers the sample loading column to the powder shaking and leveling module 614 for shaking and leveling; and a powder addition step, in which the transfer device 130 transfers the powder bucket and the sample loading column to the powder addition module 612 for powder addition.

[0146] In some embodiments, preparation step S102 includes a medium-pressure preparation and separation step, which includes: a preparation step, transferring the required materials via a transfer device; and a preparation and separation step, transferring the required materials to a predetermined module via a transfer device. In the case of dry loading, the corresponding chromatographic column and loading column are transported to the column packing module 716 via the transfer device 130. The column packing module 716 connects the chromatographic column and the loading column. A predetermined mobile phase is drawn from the mobile phase buffer module 724 via the pump valve module 720 and injected into the column packing module 716 for elution of the loading column and the chromatographic column. The eluted liquid is then introduced into the medium-pressure fraction collection via the pump valve module 720 in the preparation and separation step. Module 722 performs sample component separation and purification. In the case of wet loading, the corresponding chromatographic column is transported to the column packing module 716 via the transfer device 130. The column packing module 716 is connected to the chromatographic column. The tray containing the sample tube is transferred to the sample loading and needle cleaning module 718 via the transfer device 130. The sample liquid in the test tube is introduced into the pump valve module 720 via the sample loading and needle cleaning module 718. The pump valve module 720 extracts a predetermined mobile phase from the mobile phase buffer module 724, mixes it with the sample liquid, and injects it into the column packing module 716 for column elution. The eluted liquid is then introduced into the medium-pressure fraction collection module 722 via the pump valve module 720 for sample component separation and purification.

[0147] In some embodiments, preparation step S102 includes a high-pressure preparation separation step, a high-pressure pre-filtration step, where the transfer device 130 sends the sample before high-pressure preparation separation to a positive pressure filtration module 858 for filtration; in the high-pressure preparation step, the transfer device 130 sends the sample after high-pressure pre-filtration to a high-pressure preparation sample inlet / outlet module 810 for high-pressure preparation separation, the pump valve analysis module 812 extracts sample liquid from the high-pressure preparation sample inlet / outlet module 810, extracts a predetermined mobile phase from the mobile phase buffer 814 and mixes it with the sample liquid, separates the components of the mixture, analyzes each component, and then exports the different components to the high-pressure preparation sample inlet / outlet module 810, where the high-pressure preparation sample inlet / outlet module 810 collects the fractions condensed at different time periods or temperatures; and a pipetting step, where the pipetting module 862 transfers the sample from one sample container to other sample containers for subsequent processing.

[0148] In some embodiments, the high-pressure preparation and separation step further includes: in the case of wet sample loading, transferring the sample into the sieve filtration module 860 via the transfer device 130 to filter the sample, and then performing the medium-pressure preparation and separation step.

[0149] In some embodiments, in analysis step S104, the transport device 130 delivers the treated sample to the analysis device for detection and analysis to obtain the sample detection results. In some embodiments, analysis step S104 includes an LCMS analysis step and a cell analysis step. In the LCMS analysis step, the transport device 130 delivers the sample to a mass spectrometer for LCMS analysis to obtain detection results and upload a detection report; in the cell analysis step, the transport device 130 delivers cells with added samples to a cell culture incubator for incubation, and performs enzyme labeling detection using an enzyme-linked immunosorbent assay (ELISA) reader 1016 and / or cell imaging analysis detection using a high-content imaging analysis module 1026. In some embodiments, the LCMS analysis step includes: performing a simpler analysis of the sample using a first mass spectrometer 912; and performing a complex sample analysis using a second mass spectrometer 914.

[0150] Those skilled in the art will understand that the preparation step S102 in the pharmaceutical automated processing and analysis detection method of this disclosure may actually include a dilution and reconstitution step, a centrifugation and filtration step, a lyophilization step, a centrifugation and concentration step, a dry sample loading step, a medium-pressure preparation and separation step, and a high-pressure preparation and separation step, while the analysis step S104 may include an LCMS analysis step and a cell analysis step; those skilled in the art will also understand that at least some of these steps may be selected as needed and performed in any suitable order.

[0151] In some embodiments, a dilution and reconstitution step is performed before the medium-pressure preparation and separation step, and a centrifugal concentration step is performed after the medium-pressure preparation and separation step; and a dilution and reconstitution step is performed before the high-pressure preparation and separation step, and a centrifugal concentration step is performed after the high-pressure preparation and separation step. A freeze-drying step is performed after the centrifugal concentration step.

[0152] In some embodiments, a dry loading step is performed before the medium-pressure preparative separation step. In some embodiments, a dilution and reconstitution step is performed after the lyophilization step. In some embodiments, a centrifugation and filtration step is performed after the extraction step, and an analytical step S104 is performed after the medium-pressure preparative separation step and / or the high-pressure preparative separation step.

[0153] The following describes a possible execution sequence as an example. First, extraction step S100 is performed using a shaker for extraction; then, centrifugation filtration, centrifugal concentration and / or lyophilization, dilution and reconstitution (and merging in this step), and a first medium-pressure preparation separation are performed sequentially. One part of the separated sample is analyzed by LCMS to obtain results, while the other part is sequentially analyzed by centrifugation concentration, lyophilization, dilution and reconstitution, and a second medium-pressure preparation separation; the sample separated by the second medium-pressure preparation separation is again divided into two parts for LCMS analysis to obtain results and sequentially analyzed by centrifugation concentration, lyophilization, and dilution and reconstitution; the diluted and reconstituted sample is then subjected to high-pressure preparation separation, and the separated sample is again divided into two parts for LCMS analysis to obtain results and sequentially analyzed by centrifugation concentration, lyophilization, and dilution and reconstitution.

[0154] The pharmaceutical automated processing and analysis detection system and method disclosed herein automates the loading, temporary storage, handling, and transfer of materials and consumables between processing modules by employing corresponding robotic arms, AGVs, and various handling tools, thereby assisting in the full-process automation of a series of operations such as sample extraction, processing, detection, and analysis.

[0155] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of this disclosure, and are not intended to limit them. Although this disclosure has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features therein. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of this disclosure.

Claims

1. An automated pharmaceutical processing and analysis method, characterized in that, The automated pharmaceutical processing and analysis method includes the following steps: In the extraction step, the transfer device sends the sample container containing the sample into the loading position of the extraction device. The visual recognition module set directly above the loading position identifies whether the sample container is in the appropriate storage position on the loading position. The transfer device places the sample container in the corresponding setting position in the shaker of the extraction device to incubate the sample by shaking using the cold soaking method. In the preparation step, the transfer device delivers the sample, which has been incubated by shaking, into at least one preparation device for preparation processing; as well as In the analysis step, the transfer device transfers the prepared sample to the analysis device for detection and analysis.

2. The automated pharmaceutical processing and analysis method according to claim 1, characterized in that, The AGV of the transfer equipment transfers various materials, including the sample and the sample container, between the extraction equipment, the at least one preparation equipment, and the analysis equipment. The robotic arm of the transfer device will send the material transferred from the AGV vehicle to the AGV exchange bin into the corresponding device in the extraction device, the at least one preparation device and the analysis device, perform material transfer in the corresponding device, and take the material out of the corresponding device and transfer it into the AGV exchange bin for transfer by the AGV vehicle. The robotic arm transfers different materials by selecting the appropriate tools.

3. The automated pharmaceutical processing and analysis method according to claim 1, characterized in that, In the extraction step, the shaking table door of the shaking table opens automatically, the transfer device takes the sample container from the loading position and transfers it to the scanning device, the scanning device scans the label on the sample container for information identification and confirmation, and the transfer device places the confirmed sample container into the appropriate setting position inside the shaking table. The shaker door is automatically closed, and the shaker is turned on to incubate the sample container by shaking based on the information obtained from the scanning device.

4. The automated pharmaceutical processing and analysis method according to claim 1, characterized in that, The preparation steps include a dilution and reconstitution step, which includes: In the liquid addition step, the transfer device transfers the sample to the liquid addition module for liquid addition. In the oscillation step, after the liquid addition operation is completed, the transfer device transfers the sample to the oscillation module for ultrasonic oscillation; In the dissolution confirmation step, the transfer device transfers the sample to a visual inspection module to confirm that the sample is completely dissolved; and The merging step involves combining samples from multiple sample containers using at least one of pipetting and pouring methods.

5. The automated pharmaceutical processing and analysis method according to claim 4, characterized in that, If the sample container is a test tube, the dilution and reconstitution step further includes a centrifugation step, in which the transfer device moves the sample container into the centrifugation module for centrifugation, and then performs the merging step.

6. The automated pharmaceutical processing and analysis method according to claim 1, characterized in that, The preparation step includes a centrifugal filtration step, which includes: In the coarse filtration step, the transfer device places a clean coarse sieve into the filtration module. The filtration module uses suction filtration to pass the sample that has been poured into the filtration module through the coarse sieve for coarse filtration. Then, the transfer device removes the coarse sieve. In the balancing step, the transfer device transfers the sample container to the weighing module to weigh the multiple samples that have undergone the coarse filtration operation. If the weight difference between the multiple samples exceeds the allowable range, the multiple samples are balanced by pipetting. The centrifugation step involves transferring the balanced samples into a centrifuge apparatus for centrifugation; and In the fine filtration step, the transfer device places a clean fine sieve into the filtration module, and the filtration module uses suction filtration to pass the sample, which has been poured into the filtration module, through the fine sieve for fine filtration. The balancing step includes: a weighing step, which weighs the plurality of samples; and a pipetting step, which transfers a portion of the sample from a sample container containing a larger number of samples into another sample container.

7. The automated pharmaceutical processing and analysis method according to claim 1, characterized in that, The preparation steps include a freeze-drying step, in which the sample container containing the sample is weighed, the weighed sample is sent to a freeze-drying device for freeze-drying, and the freeze-dried sample container is weighed again. Based on the weighing results and the mass of the empty bottle, the initial mass and the mass of the freeze-dried product are calculated. Based on the initial mass and the mass of the freeze-dried product, the subsequent dissolution method parameters are obtained. The transfer device uses a quick-change device to grab the tray, concentration bottle and test tube. During weighing, the transfer device transfers the test tube in the tray to a 0.01% weighing module for weighing, and transfers the concentration bottle in the tray to a 0.1% weighing module for weighing.

8. The automated pharmaceutical processing and analysis method according to claim 1, characterized in that, The preparation steps include a centrifugal concentration step, in which the transfer device transfers multiple sample containers into an adapter and the adapter is inserted into the centrifugal concentration apparatus for centrifugal concentration. The centrifugal concentration device includes an imbalance detection sensor. When the imbalance detection sensor detects that the weight difference between the plurality of sample containers in the adapter exceeds a predetermined threshold, the centrifugal concentration device automatically stops. The transfer device transfers the plurality of sample containers to the balancing and weighing module for balancing. After balancing between the plurality of sample containers, the transfer device easily transfers the plurality of samples back to the centrifugal concentration device. The centrifugal concentration device automatically starts and continues the centrifugal concentration operation.

9. The automated pharmaceutical processing and analysis method according to claim 1, characterized in that, The preparation steps include a dry sample loading step, which includes: In the powder addition step, the transfer device places a powder bucket containing silica powder and a rotary evaporation column into the powder addition module, and the powder addition module adds silica powder to the rotary evaporation column. In the rotary evaporation step, the transfer device transfers the powdered rotary evaporation column to the rotary evaporation module, where the rotary evaporation module performs rotary evaporation on the column; and In the powder scraping and rotating step, after the rotary evaporator column has been dried, the transfer device transfers the rotary evaporator column to the powder scraping and rotating module, and replaces the powder scraping tool to scrape powder off the rotary evaporator column.

10. The automated pharmaceutical processing and analysis method according to claim 9, characterized in that, The dry sample loading step further includes a judgment step, in which the transfer device transfers the rotary evaporation column to the visual inspection module, and the visual inspection module analyzes the rotary evaporation column to determine the state of the sample in the rotary evaporation column.

11. The automated pharmaceutical processing and analysis method according to claim 9, characterized in that, Following the powder-scraping and rotating step, the dry sample loading step further includes: In the pouring step, the transfer device replaces the pouring tool to pour the powder in the rotary evaporation column into the sample loading column; In the powder shaking step, the transfer device transfers the sample column to the powder shaking and leveling module for powder shaking. In the powder loading step, the transfer device transfers the powder container and the sample loading column to the powder loading module for powder loading; and The cleaning step involves moving the powder scraping tool to the scraper cleaning module for cleaning.

12. The automated pharmaceutical processing and analysis method according to claim 1, characterized in that, The preparation steps include a medium-pressure preparation and separation step, which includes: Preparation steps, including transferring the required materials using the aforementioned transfer equipment; and In the preparation and separation step, the required materials are transferred to a predetermined module via the transfer device. Under dry loading conditions, the corresponding chromatographic column and sample loading column are transported to the column packing module via the transfer device. The column packing module connects the chromatographic column and the sample loading column. A predetermined mobile phase is drawn from the mobile phase buffer module via a pump valve module and injected into the column packing module for elution of the sample loading column and the chromatographic column. The eluted liquid is then introduced into a medium-pressure fraction collection module via the pump valve module for the separation and purification of sample components. Under wet loading conditions, the... The transport device moves the corresponding chromatographic column to the column packing module, which is connected to the chromatographic column. The transport device transfers the tray containing the sample tube to the sample loading and needle cleaning module. The sample liquid in the sample tube is introduced into the pump valve module through the sample loading and needle cleaning module. The pump valve module draws a predetermined mobile phase from the mobile phase buffer module, mixes it with the sample liquid, and injects it into the column packing module for column elution. The eluted liquid is then introduced into the medium-pressure fraction collection module through the pump valve module for the separation and purification of sample components.

13. The automated pharmaceutical processing and analysis method according to claim 12, characterized in that, The preparation steps include a high-pressure preparation and separation step. In the high-pressure pre-filtration step, the transfer device delivers the sample before high-pressure preparation and separation into a positive-pressure filtration module or a screen filtration module for filtration; and In the high-pressure preparation step, the transfer device sends the sample that has passed the high-pressure pre-filtration into the high-pressure preparation sample inlet / outlet module for high-pressure preparation separation. The pump valve analysis module extracts the sample liquid from the high-pressure preparation sample inlet / outlet module, extracts a predetermined mobile phase from the mobile phase buffer and mixes it with the sample liquid, separates the components of the mixture, analyzes each component, and then exports the different components to the high-pressure preparation sample inlet / outlet module. The high-pressure preparation sample inlet / outlet module collects the fractions condensed at different time periods or at different temperatures. as well as The pipetting step involves transferring samples from one sample container to another using a pipetting module for subsequent processing.

14. The automated pharmaceutical processing and analysis method according to claim 13, characterized in that, The high-pressure preparation and separation step further includes: in the case of wet sample loading, the sample is transferred into the sieve filtration module through the transfer device to filter the sample, and then the medium-pressure preparation and separation step is performed.

15. The automated pharmaceutical processing and analysis method according to claim 1, characterized in that, In the analytical step, the transport device delivers the treated sample into the analytical device for detection and analysis to obtain the test results of the sample. The analytical steps include at least one of LCMS analysis and cell analysis. In the LCMS analysis step, the transport device delivers the sample to a mass spectrometer for LCMS analysis to obtain detection results and upload a detection report. The first mass spectrometer performs simpler analysis of the sample, while the second mass spectrometer performs analysis of more complex samples. In the cell analysis step, the transport device delivers cells containing the sample into a cell culture incubator for incubation, and performs enzyme labeling detection using an ELISA reader and / or cell imaging analysis using a high-content imaging analysis module.

16. A pharmaceutical automated processing and analysis detection system, characterized in that, The automated pharmaceutical processing, analysis, and testing system includes: An extraction device, wherein the extraction device uses a shaker to incubate a sample contained in a sample container by cold immersion. Multiple preparation devices are used to prepare samples that have undergone shaking incubation. Analytical equipment, said analytical equipment for detecting and analyzing prepared samples; and A transport device for transporting the sample and the sample container within the extraction device, the preparation device, and the analysis device, and between the extraction device, the preparation device, and the analysis device. When the sample container is sent into the extraction device for extraction, the sample container is sent to the loading position of the extraction device. The visual recognition module of the extraction device, which is set directly above the loading position, identifies whether the sample container is in an appropriate storage position on the loading position. The transfer device then transfers the sample container to the corresponding set position in the shaker of the extraction device for the shaking incubation.

17. The automated pharmaceutical processing and analysis system according to claim 16, characterized in that, The transfer equipment includes AGV vehicles and robotic arms. The AGV transports various materials, including the sample and the sample container, between the extraction equipment, the multiple preparation equipment, and the analysis equipment. The robotic arm delivers the material transferred from the AGV vehicle to the AGV exchange bin into the corresponding device among the extraction device, the plurality of preparation devices and the analysis device, performs material transfer in the corresponding device, and removes the material from the corresponding device and transfers it into the AGV exchange bin for transfer by the AGV vehicle. The robotic arm transfers different materials by selecting the appropriate tools.

18. The automated pharmaceutical processing and analysis system according to claim 16, characterized in that, The extraction device also includes a scanning device, which scans the label on the sample container that is taken out and transferred from the loading position by the transfer device for information identification and confirmation.

19. The automated pharmaceutical processing and analysis system according to claim 16, characterized in that, The automated pharmaceutical processing, analysis, and testing system also includes: Material storage equipment is used to store consumables required in the process. The material storage equipment includes a storage station, which includes a storage station robotic arm and one or more storage stacks. Each of the one or more storage stacks includes multiple rows of storage racks, each row of storage racks having the same height and a different number of storage layers depending on the volume of the consumables placed thereon; The robotic arm at the warehouse station is used to move the consumables to the corresponding storage location on the storage rack.

20. The automated pharmaceutical processing and analysis system according to claim 16, characterized in that, The plurality of preparation devices includes a dilution and reconstitution device, which includes: A liquid addition module, which is used to add liquid to the sample container; A pipetting module for transferring at least a portion of a sample from one sample container to another sample container; An oscillation module is used to perform ultrasonic oscillation on the sample container; A first visual inspection module is used to detect whether the sample in the sample container, after ultrasonic vibration, has completely dissolved; and The centrifugation module is used to centrifuge the sample container after it has been subjected to ultrasonic vibration when the sample container is a test tube.

21. The automated pharmaceutical processing and analysis system according to claim 16, characterized in that, The plurality of preparation devices includes a centrifugal filtration device, which includes: A filtration module is used to perform filtration operations on a sample, including at least one of coarse filtration and fine filtration, to obtain a filtered sample. A centrifuge for centrifuging a sample container holding the filtered sample to separate the supernatant and residue; and A weighing and pipetting device for balancing multiple sample containers; The transfer equipment, by changing different tools, performs the transfer operations required for the filtration, centrifugation, and balancing operations to assist in completing these operations.

22. The automated pharmaceutical processing and analysis system according to claim 16, characterized in that, The plurality of preparation devices includes a freeze-drying device, which includes: A weighing module for weighing the sample container before and after freeze-drying; A freeze dryer, used for freeze-drying and concentrating a sample in the sample container; and A labeling machine, used for labeling the sample containers; The transfer device uses a quick-change device to replace different grippers to transfer different types of sample containers between the weighing module, the freeze dryer, and the labeling machine to assist in completing the weighing, freeze-drying, and labeling operations.

23. The pharmaceutical automated processing and analysis detection system according to claim 16, characterized in that, The plurality of preparation devices includes a centrifugal concentration device, which includes: A centrifugal concentrator, which performs centrifugal concentration operations on samples in multiple sample containers, and which has an imbalance detection sensor; and The balancing and weighing module balances the samples in the multiple sample containers when the imbalance detection sensor detects that the weight difference between multiple sample containers exceeds a predetermined threshold. The transfer device uses a quick-change device to replace different grippers to transfer different types of objects between the centrifugal concentrator and the balancing and weighing module to assist in completing the centrifugal concentration.

24. The automated pharmaceutical processing and analysis system according to claim 16, characterized in that, The plurality of preparation devices includes a dry sample loading device, which includes: A powder addition module, which is used to quantitatively add powder to the sample loading column and the rotary evaporation column; A rotary evaporation module, used to evaporate the sample in the rotary evaporation column; A powder scraping tool, used for scraping powder from the rotary evaporator column; A scraper cleaning module is used to clean and wipe the scraper of the powder scraping tool that performs the powder scraping operation; A powder leveling module is used to level the powder in the sample loading column. A switch cover and a powder scraping rotation module are used to fix and rotate the column when opening the rotary evaporation column and the sample loading column, and to fix and rotate the rotary evaporation column when performing powder scraping operations; and The second visual inspection module is used to detect the state of the sample inside the rotary evaporation column.

25. The automated pharmaceutical processing and analysis system according to claim 16, characterized in that, The plurality of preparation devices includes a medium-pressure preparation and separation device, which includes: The column packing module is used to connect the chromatographic column and the sample loading column; The sample loading and liquid addition and needle cleaning module is used to perform sample loading and liquid addition and needle cleaning operations on the sample container containing the transferred sample. A medium-pressure fraction collection module is used to collect fractions condensed at different time periods or temperatures for subsequent analysis or use. Pump valve module, the pump valve module being used for pumping fluid and related analytical processing; and A mobile phase buffer module, which is used to buffer and store the mobile phase required for processing; The pump and valve module is connected to the sample loading and liquid addition and needle cleaning module, the column packing module, the medium-pressure fraction collection module, and the mobile phase buffer module through pipelines, providing power for liquid transfer between the above modules.

26. The automated pharmaceutical processing and analysis system according to claim 16, characterized in that, The plurality of preparation equipment includes a high-pressure preparation and separation device, which includes a high-pressure preparation and separation station and a detection and filtration station.

27. The automated pharmaceutical processing and analysis system according to claim 26, characterized in that, The detection and filtration station includes: A positive pressure filtration module is used to filter samples before high pressure treatment is applied; A sieve filtering module, used for filtering samples prior to either high-pressure treatment or wet loading treatment; and A pipetting module for transferring samples from one sample container to other sample containers for subsequent analytical procedures.

28. The automated pharmaceutical processing and analysis system according to claim 27, characterized in that, The high-pressure preparation and separation station includes: A high-pressure preparation sample inlet / outlet module is used to perform high-pressure preparation and separation of the sample that has passed through one of the positive pressure filtration module and the sieve filtration module, and then transfer it to the pipetting module. A mobile phase buffer is used to introduce the sample from the high-pressure preparation sample inlet / outlet module, and to introduce a predetermined mobile phase into the mobile phase buffer according to the introduced sample, thereby mixing the sample with the predetermined mobile phase to obtain a second mixture; and The pump valve analysis module is used to perform pumping fluid and related analysis. The pump valve analysis module separates the components of the second mixture, analyzes each component, and then exports the different components to the high-pressure preparation sample inlet / outlet module for fraction collection.

29. The automated pharmaceutical processing and analysis system according to claim 16, characterized in that, The analysis equipment includes an LCMS analysis device, which comprises: The first mass spectrometer is used to perform simpler analyses on the sample. A second mass spectrometer is used to perform complex sample analysis; A fraction collection module, wherein the fraction collection module is used to receive fractions output from analysis by at least one of the first mass spectrometer and the second mass spectrometer; and An autosampler for automatically feeding a sample into either the first mass spectrometer or the second mass spectrometer.

30. The automated pharmaceutical processing and analysis system according to claim 16, characterized in that, The analytical device includes a cell analysis apparatus, which comprises: A pipetting workstation that performs automated and precise pipetting operations on well plates used to hold cells; A plate washing machine that automatically cleans the perforated plate; Cell culture incubator, which provides a cell culture environment; A centrifuge, the centrifuge being used to centrifuge the orifice plate; An enzyme-linked immunosorbent assay (ELISA) reader, used to perform enzyme-linked immunosorbent assay (ELISA) detection on well plates containing cultured cells; Labeling device, the labeling device being used for automatically labeling the perforated plate; and A high-content imaging analysis module is provided for performing cell imaging analysis on cultured cells in the well plate.

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