Medicine automatic processing and analysis detection method and system

Abstract

The invention provides a medicine automatic treatment and analysis detection method which comprises the following steps: an extraction step: conveying a sample container containing a sample into a shaking table of extraction equipment by transfer equipment, and carrying out oscillation incubation on the sample by a cold soaking method; in the preparation step, the transferring equipment conveys the sample subjected to oscillation incubation into at least one preparation equipment for preparation treatment; and an analysis step: transferring the prepared and treated sample to an analysis device by the transfer device for detection and analysis. The invention further provides a medicine automatic processing and analysis detection system. According to the invention, automation of the whole process of medicine treatment and analysis detection is realized.

Description

Technical Field

[0001] The present disclosure relates to the field of automation equipment technology, specifically to the field of pharmaceutical automation equipment technology, and more specifically to a pharmaceutical automation processing and analysis detection method and a pharmaceutical automation processing and analysis detection system. Background Art

[0002] At present, in the field of drug disposal, the processes of extraction, processing, detection, and analysis of sample components are mostly handled by a single module in conjunction with manual labor, and it is impossible to achieve automation of a single process or automation of the entire process. Summary of the invention

[0003] The present disclosure is completed in order to at least partially solve the technical problems existing in the prior art. The present disclosure provides a pharmaceutical automated processing and analysis detection system and method, which can realize full-process automation of a series of operations such as sample extraction, processing, detection and analysis.

[0004] According to one aspect of the present disclosure, there is provided a method for automated processing and analytical detection of medicines, comprising the following steps: an extraction step, in which a transport device sends a sample container containing a sample into a shaker of an extraction device to incubate the sample by shaking through a cold soak method; a preparation step, in which the transport device sends the sample after shaking through incubation into at least one preparation device for preparation; and an analysis step, in which the transport device transports the sample after preparation to an analysis device for detection and analysis.

[0005] In some embodiments, the extraction step includes: a loading step, in which a loading robot places the sample container containing the sample on a loading position; a visual recognition step, in which a visual recognition step is performed to identify whether the sample container is located in an appropriate storage position on the loading position; and a shaking incubation step, in which the loading robot grabs and carries the sample container to the shaker to perform the shaking incubation on the sample.

[0006] In some embodiments, the preparation step includes at least one of a dilution and reconstitution step, a centrifugal filtration step, a freeze-drying step, a centrifugal concentration step, a dry loading step, a medium-pressure preparation and separation step, and a high-pressure preparation and separation step.

[0007] In some embodiments, in the preparation step, at least one of the dilution and reconstitution step, the centrifugal filtration step, the freeze-drying step, the centrifugal concentration step, the dry loading step, the medium-pressure preparation and separation step, and the high-pressure preparation and separation step is performed once or multiple times.

[0008] In some embodiments, the dilution and reconstitution step is performed before the medium-pressure preparation and separation step; and the centrifugal concentration step is performed after the medium-pressure preparation and separation step.

[0009] In some embodiments, the dry loading step is performed before the medium-pressure preparative separation step.

[0010] In some embodiments, the dilution and reconstitution step is performed before the high pressure preparation and separation step; and the centrifugal concentration step is performed after the high pressure preparation and separation step.

[0011] In some embodiments, the lyophilization step is performed after the centrifugal concentration step.

[0012] In some embodiments, the dilution and reconstitution step is performed after the lyophilization step.

[0013] In some embodiments, the centrifugal filtration step is performed after the extraction step, and the analysis step is performed after the medium-pressure preparation and separation step and / or the high-pressure preparation and separation step.

[0014] In some embodiments, the preparation step includes a dilution and re-dissolution step, which includes: a liquid adding step, transferring the sample to a liquid adding module for liquid adding operation; a shaking step, after the liquid adding operation is completed, transferring the sample to a shaking module for ultrasonic shaking; a dissolution confirmation step, confirming that the sample is completely dissolved through a visual inspection module; and a merging step, merging the samples in multiple sample containers by at least one of pipetting and pouring.

[0015] In some embodiments, the dilution and reconstitution step further includes a centrifugation step, and the transport device moves the sample container into a centrifugation module for centrifugation as needed.

[0016] In some embodiments, the preparation step includes a centrifugal filtration step, which includes: a coarse filtration step, placing a clean coarse screen into a filtration module, and filtering the sample through the coarse screen for a coarse filtration operation, and then removing the coarse screen; a balancing step, weighing multiple samples that have undergone the coarse filtration operation, and if the weight difference between the multiple samples exceeds an allowable range, balancing the multiple samples through pipetting; a centrifugation step, moving the multiple samples that have completed balancing into a centrifugal device for a centrifugal operation; and a fine filtration step, placing a clean fine screen into a filtration module, and filtering the sample through the fine screen for a fine filtration operation, wherein the balancing step includes: a weighing step, weighing the multiple samples; and a pipetting step, moving a portion of the samples in a sample container containing more samples into another sample container.

[0017] In some embodiments, the preparation step includes a freeze-drying step, in which a sample container containing a sample is weighed, the weighed sample is sent to a freeze-drying device for freeze-drying, and the freeze-dried sample container is weighed.

[0018] In some embodiments, the preparation step includes a centrifugal concentration step, in which a plurality of sample containers are transferred to an adapter, and the adapter is loaded into a centrifugal concentration device for a centrifugal concentration operation, wherein the centrifugal concentration device includes an imbalance detection sensor, and when the imbalance detection sensor monitors that the weight difference between the plurality of sample containers in the adapter exceeds a predetermined threshold, the centrifugal concentration device automatically stops and balances the plurality of sample containers, and continues to start the centrifugal concentration device after balancing the plurality of sample containers.

[0019] In some embodiments, the preparation step includes a dry loading step, and the dry loading step includes: a powder adding step, placing a powder barrel and a rotary evaporation column filled with silica gel powder in a powder adding module, and the powder adding module adds silica gel powder to the rotary evaporation column; a rotary evaporation step, transferring the rotary evaporation column after powder addition to the rotary evaporation module, and the rotary evaporation module performs rotary evaporation on the rotary evaporation column; a powder scraping and rotating step, after the rotary evaporation column has been dried, transferring the rotary evaporation column to the powder scraping and rotating module, and replacing the powder scraping tool to scrape the powder on the rotary evaporation column.

[0020] In some embodiments, the dry loading step further includes: a judgment step, transferring the rotary evaporation column to a visual detection module, and the visual detection module analyzes the rotary evaporation column to judge the state of the sample in the rotary evaporation column.

[0021] In some embodiments, after the powder scraping and rotating step, the dry loading step further includes: a pouring step, replacing the pouring tool to pour the powder in the rotary evaporation column into the loading column; a powder shaking step, transferring the loading column to the powder shaking module for shaking the powder; and a powder adding step, transferring the powder barrel and the loading column to the powder adding module for powder adding.

[0022] In some embodiments, after the powder scraping and rotating step, the dry loading step further includes: a cleaning step of moving the powder scraping tool to a scraper cleaning module to clean the powder scraping tool.

[0023] In some embodiments, the preparation step includes a medium-pressure preparation and separation step, and the medium-pressure preparation and separation step includes: a preparation step, transferring the required materials through the transfer equipment; a preparation and separation step, transferring the required materials to a predetermined module through the transfer equipment, and in the case of dry loading, separating and purifying the components through a column packing module, a pump-valve module, a medium-pressure fraction collection module and a mobile phase buffer module; in the case of wet loading, separating and purifying the components through a column packing module, a sample addition and needle cleaning module, the pump-valve module, the medium-pressure fraction collection module and the mobile phase buffer module.

[0024] In some embodiments, in the preparation and separation step, in the case of dry sampling, the corresponding chromatographic column and the loading column are transported to the column packing module by the transfer equipment, the column packing module connects the chromatographic column and the loading column, and the predetermined mobile phase is extracted from the mobile phase buffer module through the pump-valve module and injected into the column packing module to elute the loading column and the chromatographic column. The eluted liquid is then introduced into the medium-pressure fraction collection module by the pump-valve module in the preparation and separation step to separate and purify the sample components.

[0025] In some embodiments, in the preparation and separation step, in the case of wet loading, the corresponding chromatographic column is transported to the column packing module by a transfer device, the column packing module is connected to the chromatographic column, and the tray containing the sample test tube is transferred to the sample loading and liquid addition and needle cleaning module by the transfer device, and the sample liquid in the test tube is introduced into the pump-valve module through the sample loading and liquid addition and needle cleaning module, the pump-valve module extracts a predetermined mobile phase from the mobile phase buffer module, mixes it with the sample liquid, and then injects it into the column packing module to elute the chromatographic column, and the eluted liquid is then introduced into the medium-pressure fraction collection module by the pump-valve module to separate and purify the sample components.

[0026] In some embodiments, the preparation step includes a high-pressure preparation and separation step, a high-pressure pre-filtration step, filtering the sample before high-pressure preparation and separation through a positive pressure filtration module or a screen filtration module; a high-pressure preparation step, sending the sample that has passed the high-pressure pre-filtration into the high-pressure preparation inlet and outlet sample module for high-pressure preparation and separation, a pump valve analysis module extracts the sample liquid from the high-pressure preparation inlet and outlet sample module, extracts a predetermined mobile phase from the mobile phase buffer and mixes it with the sample liquid, separates the components of the mixed liquid, and analyzes each component, and then exports the different components to the high-pressure preparation inlet and outlet sample module, and the high-pressure preparation inlet and outlet sample module collects the fractions condensed at different time periods or at different temperatures; and a pipetting step, transferring the sample from one sample container to other sample containers through a pipetting module for subsequent processing steps.

[0027] In some embodiments, the high-pressure preparation and separation step further comprises: in the case of the wet loading method, filtering the sample through a mesh filtration module, and then performing the medium-pressure preparation and separation step.

[0028] In some embodiments, in the analysis step, the treated sample is sent to an analysis device for detection and analysis to obtain the detection results of the sample, and the analysis step includes an LCMS analysis step and a cell analysis step. In the LCMS analysis step, the sample is sent to a mass spectrometer for LCMS analysis to obtain the detection results and upload a detection report, wherein a simpler analysis is performed on the sample by a first mass spectrometer and a complex sample analysis is performed by a second mass spectrometer; and in the cell analysis step, the cells added with the sample are incubated in a cell culture incubator and subjected to enzyme labeling detection by an enzyme labeling instrument and / or cell imaging analysis detection by a high-content imaging analysis module.

[0029] According to another aspect of the present disclosure, a pharmaceutical automated processing and analysis detection system is provided, comprising: an extraction device, which shakes and incubates a sample contained in a sample container by a shaker using a cold immersion method; a plurality of preparation devices, which perform preparation processing on the shaken and incubated samples; an analysis device, which detects and analyzes the prepared samples; and a transport device, which transports 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.

[0030] In some embodiments, material storage equipment is used to store consumables required in the process; and charging piles are used to charge devices that need to be charged.

[0031] In some embodiments, the material storage device includes a warehouse station, the warehouse station includes a warehouse station robot and one or more storage stacks, each of the one or more storage stacks includes multiple columns of storage racks, each column of storage racks has the same height and different numbers of storage layers are arranged according to the volume of the consumables placed; the materials are transported from the outside of the material storage device to the corresponding storage positions on the storage racks by AGV vehicles and warehouse station robots.

[0032] In some embodiments, the extraction device includes: a loading position, on which a sample container containing a sample is placed; a visual recognition module, which is used to identify whether the sample container is located in an appropriate storage position on the loading position; an extraction robot arm, which is used to grab and carry the sample container; and a shaker, which is used to shake and incubate the sample.

[0033] In some embodiments, the multiple preparation devices include a dilution and reconstitution device, which includes: a liquid adding module, which is used to add liquid to the sample container; a pipetting module, which is used to transfer at least a portion of the sample in one sample container to another sample container; an oscillation module, which is used to ultrasonically oscillate the sample container; a first visual inspection module, which is used to detect whether the sample in the sample container that has been ultrasonically oscillated is completely dissolved; and a centrifugation module, which is used to centrifuge the sample container that has been treated with ultrasonic oscillation when the sample container is a test tube.

[0034] In some embodiments, the multiple preparation devices include a centrifugal filtration device, which includes: a filtration module, which is used to perform a filtration operation on a sample to obtain a filtered sample; a centrifuge, which is used to centrifuge a sample container containing the filtered sample to separate the supernatant and the residue; a weighing and pipetting device, which performs a balancing operation on multiple sample containers; and a centrifugal filtration robot arm, which performs the filtration operation, the centrifugation operation, and the transfer operation required for the balancing operation by replacing different tools to assist in completing the filtration operation, the centrifugation operation, and the balancing operation.

[0035] In some embodiments, the multiple preparation equipment includes a freeze-drying equipment, which includes: a weighing module, which is used to weigh the sample container before and after the freeze-drying process; a freeze dryer, which is used to freeze-dry and concentrate the sample in the sample container; a labeler, which is used to label the sample container; and a freeze-drying robot arm, which transfers different types of sample containers between the weighing module, the freeze dryer and the labeler by replacing different grippers to assist in completing weighing operations, freeze-drying operations and labeling operations.

[0036] In some embodiments, the multiple preparation devices include a centrifugal concentration device, which includes: a centrifugal concentrator, which performs centrifugal concentration operations on samples in multiple sample containers, and the centrifugal concentrator has an imbalance detection sensor; a balancing weighing module, when the imbalance detection sensor detects that the weight difference of multiple sample containers exceeds a certain threshold, the balancing weighing module balances the samples in the multiple sample containers; and a centrifugal concentration robot arm, which transfers different types of grasped objects between the centrifugal concentrator and the balancing weighing module by replacing different jaws to assist in completing centrifugal concentration.

[0037] In some embodiments, the multiple preparation devices include a dry loading device, which includes: a powder adding module, which is used to quantitatively add powder to the loading column and the rotary evaporation column; a rotary evaporation module, which is used to dry the sample in the rotary evaporation column; a powder scraping tool, which is used to scrape powder on the rotary evaporation column; a scraper cleaning module, which is used to clean and wipe the scraper of the scraper tool that performs the powder scraping operation; a powder flattening module, which is used to flatten the powder in the loading column; a switch cover and powder scraping rotation module, which are used to fix and rotate the columns when the rotary evaporation column and the loading column are opened and to fix and rotate the rotary evaporation column when the rotary evaporation column is scraped; and a second visual detection module, which is used to detect the state of the sample in the rotary evaporation column.

[0038] In some embodiments, the multiple preparation devices include a medium-pressure preparation and separation device, which includes: a column packing module, to which the chromatographic column and the loading column are transferred for column connection; a sample loading and liquid addition and needle cleaning module, which is used to perform sample loading and liquid addition and needle cleaning operations, and a sample container containing a sample is transferred to the sample loading and liquid addition and needle cleaning module; a medium-pressure fraction collection module, which is used to collect fractions condensed in different time periods or at different temperatures for subsequent analysis or use; a pump-valve module, which is used to perform related processing of pumping liquid and analysis; and a mobile phase buffer, which is used to cache the mobile phase required for placement processing; wherein the pump-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, respectively, to provide power for liquid transmission between the above modules.

[0039] In some embodiments, the plurality of preparation devices include a high-pressure preparation and separation device, and the high-pressure preparation and separation device includes a high-pressure preparation and separation station and a detection and filtration station.

[0040] In some embodiments, the detection and filtration station includes: a positive pressure filtration module, which is used for filtering before applying high pressure treatment to the sample; a mesh filtration module, which is used for filtering before applying high pressure treatment to the sample or before wet sampling of the sample; and a pipetting module, which is used to transfer the sample from one sample container to other sample containers for subsequent analysis procedures.

[0041] In some embodiments, the high-pressure preparation and separation station includes: a high-pressure preparation inlet and outlet sample module, which is used to perform high-pressure preparation separation on the sample that has passed through the positive pressure filtration module or the screen filtration module and transfer it to the pipetting module; a mobile phase buffer, which is used to import the sample in the high-pressure preparation inlet and outlet sample module, and import the predetermined mobile phase in the mobile phase buffer according to the imported sample, so that the sample is mixed with the predetermined mobile phase to obtain a second mixed liquid; and a pump-valve analysis module, which is used to perform related processing of pumping liquid and analysis, wherein the pump-valve analysis module separates the components of the second mixed liquid, analyzes each component, and then exports the different components to the high-pressure preparation inlet and outlet sample module for fraction collection.

[0042] In some embodiments, the analysis equipment includes an LCMS analysis device, which includes: a first mass spectrometer, which is used to perform simpler analysis on samples; a second mass spectrometer, which is used to perform complex sample analysis; a fraction collection module, which is used to receive fractions output after analysis by the first mass spectrometer or the second mass spectrometer or both; and an automatic sampler, which is used to automatically send samples into either the first mass spectrometer or the second mass spectrometer.

[0043] In some embodiments, the analysis equipment includes a cell analysis device, which includes: a pipetting workstation, which performs automatic precision pipetting operations on the well plate; a plate washer, which automatically cleans the well plate; a cell culture incubator, which provides a cell culture environment; a centrifuge, which is used to perform centrifugal operations on the well plate; an enzyme-labeled instrument, which is used to perform enzyme-labeled detection of targets on the well plate containing cultured cells; a labeling device, which is used to automatically label the well plate; and a high-content imaging analysis module, which performs cell imaging analysis on the cultured cells in the well plate.

[0044] In the pharmaceutical automated processing and analysis detection system and method provided by the present invention, the loading, temporary storage, handling and transfer of materials and consumables between extraction equipment, preparation equipment, analysis equipment, etc. are automated by adopting transfer equipment, thereby assisting in the full process automation of a series of operations such as sample extraction, processing, detection and analysis.

[0045] Other features and advantages of the present disclosure will be described in the following description, and partly become apparent from the description, or be understood by practicing the present disclosure. The purpose and other advantages of the present disclosure can be realized and obtained by the structures particularly pointed out in the description, claims and drawings. BRIEF DESCRIPTION OF THE DRAWINGS

[0046] The accompanying drawings are used to provide further understanding of the technical solution of the present disclosure and constitute a part of the specification. Together with the embodiments of the present disclosure, they are used to explain the technical solution of the present disclosure and do not constitute a limitation on the technical solution of the present disclosure.

[0047] Figure 1 A schematic block diagram of a pharmaceutical automated processing and analysis detection system according to an embodiment of the present disclosure is shown;

[0048] Figure 2 A top view showing the layout of a pharmaceutical automated processing and analysis detection system according to an embodiment of the present disclosure;

[0049] Figure 3 A perspective view of a warehouse station of a material storage device of a pharmaceutical automated processing and analysis detection system according to an embodiment of the present disclosure is shown;

[0050] Figure 4 A perspective view showing an extraction device of a pharmaceutical automated processing and analysis detection system according to an embodiment of the present disclosure;

[0051] Figure 5 A perspective view showing a dilution and reconstitution device of a pharmaceutical automated processing and analysis and detection system according to an embodiment of the present disclosure;

[0052] Figure 6a A perspective view showing a centrifugal filtration device of a pharmaceutical automated processing and analysis detection system according to an embodiment of the present disclosure;

[0053] Figure 6b A top view of a centrifugal filtration device of a pharmaceutical automated processing and analysis detection system according to an embodiment of the present disclosure is shown;

[0054] Figure 7a A perspective view showing a freeze-drying device of a pharmaceutical automated processing and analysis detection system according to an embodiment of the present disclosure;

[0055] Figure 7b A top view of a freeze-drying device of a pharmaceutical automated processing and analysis detection system according to an embodiment of the present disclosure is shown;

[0056] Figure 8 A perspective view showing a centrifugal concentration device of a pharmaceutical automated processing and analysis detection system according to an embodiment of the present disclosure;

[0057] Fig. 9 A perspective view showing a dry sample loading device of a pharmaceutical automated processing and analysis detection system according to an embodiment of the present disclosure;

[0058] Fig.10A perspective view showing a medium-pressure preparation and separation device of a pharmaceutical automated processing and analysis and detection system according to an embodiment of the present disclosure;

[0059] Fig.11 A top view of a high-pressure preparation and separation device of a pharmaceutical automated processing and analysis and detection system according to an embodiment of the present disclosure is shown;

[0060] Fig.12 A perspective view showing an LCMS analysis device of an analysis device of a pharmaceutical automated processing and analysis detection system according to an embodiment of the present disclosure;

[0061] Fig.13 A perspective view showing a cell analysis device of an analysis apparatus of a pharmaceutical automated processing and analysis detection system according to the present disclosure; and

[0062] Fig.14 A flow chart of a method for automated processing and analysis of medicines according to an embodiment of the present disclosure is shown. DETAILED DESCRIPTION

[0063] To make the purpose, technical solution and advantages of the embodiments of the present disclosure clearer, the specific implementation of the present disclosure is described in detail below in conjunction with the accompanying drawings. It should be understood that the specific implementation described here is only used to illustrate and explain the present disclosure, and is not used to limit the present disclosure.

[0064] For the convenience of description, in this specification, terms indicating directions such as "front", "rear", "up", "down", "left", "right", "horizontal" and "vertical" are used. These terms are used only to facilitate the indication of the relative positions of devices or components, and do not limit the installation or use orientation of the devices or components.

[0065] Figure 1 FIG. 1 is a schematic block diagram of a pharmaceutical automated processing and analysis detection system 1 according to an embodiment of the present disclosure. Figure 1 According to an embodiment of the present disclosure, the pharmaceutical automated processing and analysis detection system 1 includes: an extraction device 100, which shakes and incubates the sample contained in the sample container through a shaker; multiple preparation devices 110, which prepare and process the samples that have been shaken and incubated; an analysis device 120, which detects and analyzes the prepared samples; and a transport device 130, which transports the sample and the sample container within the extraction device 100, the multiple preparation devices 110 and the analysis device 120, and between the extraction device 100, the multiple preparation devices 110 and the analysis device 120.

[0066] The present 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 processes on medical samples: automated high-performance liquid chromatography-mass spectrometry detection and analysis of medical samples, automated high-performance liquid chromatography-mass spectrometry detection and analysis of medical samples, and automated detection and analysis of cell activity and toxicity of medical samples.

[0067] In some embodiments, the analysis equipment includes at least one of an equipment for automated high performance liquid chromatography-mass spectrometry detection and analysis of medical samples, an equipment for automated high performance liquid chromatography-mass spectrometry detection and analysis of medical samples, and an equipment for automated detection and analysis of cellular biological activity and toxicity of medical samples.

[0068] In some embodiments, the sample is a biological sample, a medical sample or a chemical sample. When the sample is a medical sample, it can be a Western medicine sample, a Chinese medicine sample, or other medicine samples with medicinal effects. For example, Chinese medicine samples include Chinese medicinal materials, Chinese medicine pieces, Chinese patent medicines, Chinese medicine semi-finished products, medicinal plants, etc.

[0069] The present invention realizes automation of each process and the entire process by adopting corresponding equipment to extract, handle and analyze samples, greatly improving the detection efficiency of samples and reducing labor costs.

[0070] Below, reference Figure 2 , further describing in detail the specific devices included in the pharmaceutical automated processing and analysis detection system 1 according to the embodiment of the present disclosure.

[0071] Figure 2 The top view of the layout of the pharmaceutical automated processing and analysis detection system 1 according to an embodiment of the present disclosure is exemplarily shown. The multiple preparation devices 110 of the pharmaceutical automated processing and analysis detection system 1 include: a dilution and reconstitution device 200, a centrifugal filtration device 300, a freeze-drying 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.

[0072] The analysis device 120 of the pharmaceutical automated processing and analysis detection system 1 includes an LCMS analysis device 900 and a cell analysis device 1000 .

[0073] The transport equipment 130 of the pharmaceutical automated processing and analysis and detection system 1 includes a robotic arm and an AGV (Automated Guided Vehicle). The robotic arm includes both the robotic arms between the various devices (e.g. Figure 2 The two robotic arms shown in the figure are AGV composite robotic arms), and also include robotic arms inside each device for performing various operations.

[0074] In addition, the pharmaceutical automated processing and analysis detection system 1 also includes: a material storage device 1100 for storing materials required in the process; and a charging pile 1200 for charging equipment that needs to be charged, such as the transfer equipment 130.

[0075] In some embodiments, Figure 2 The layout of the pharmaceutical automation processing and analysis detection system 1 is exemplarily shown, and the various devices of the pharmaceutical automation processing and analysis detection system 1 are basically arranged in two rows. The first row is sequentially provided with a cell analysis device 1000, a centrifugal filtration device 300, a charging pile 1200, an LCMS analysis device 900, an extraction device 100, a charging pile 1200 and a centrifugal concentration device 500; the second row is sequentially provided with a material storage device 1100, a high-pressure preparation and separation device 800, a medium-pressure preparation and separation device 700, a dry loading device 600, a dilution and re-dissolution device 200 and a freeze-drying device 400. In addition, two AGV composite robotic arms are exemplarily shown to shuttle between the various devices to carry the various items required. Those skilled in the art can also change the layout of the pharmaceutical automation processing and analysis detection system 1 and the number of each device as required.

[0076] Reference below Figures 3 to 11 , details of the pharmaceutical automated processing and analysis detection system 1 and its various devices according to an embodiment of the present disclosure are described in detail.

[0077] Each of the above-mentioned devices of the pharmaceutical automated processing and analysis detection system 1 is provided with an AGV interactive door and an AGV positioning QR code 12, which are used for material transportation between the AGV vehicle and the AGV exchange bin within the station.

[0078] In addition, each device is usually also equipped with: a corresponding AGV exchange warehouse or AGV interaction warehouse, which is used to transfer materials and consumables and other items delivered by external AGV vehicles; various temporary storage locations, which are used to temporarily store consumables or consumable trays, etc.; a switch cover module, which is used to open and close the cover of the sample container; and a tool library, which is used to store various corresponding tools.

[0079] Each device is usually also provided with various corresponding shelves to temporarily store or transfer corresponding items.

[0080] In each device of the present disclosure, a ground rail module is usually also provided, and the ground rail module can adopt a single-track design, a double-track design or any other suitable design. In some embodiments, the manipulator is arranged on the ground rail module, wherein the manipulator can move along the ground rail module. In some embodiments, the ground rail module includes only straight rails, or includes straight rails and curved rails, and the curved rails are used to change the direction of travel of the track, for example, when the ground rail module is L-shaped or other shapes that need to turn. In some embodiments, the manipulator has a component that matches the track on the ground rail module, so that the manipulator can move on the ground rail module, and can brake and fix when reaching the specified position of the ground rail module, so as to facilitate the improvement of the operational stability of the manipulator. In some embodiments, the robot 15 can be used for the transmission of materials and consumables and other items between various devices in the pharmaceutical automation processing and analysis and detection system. In some embodiments, the manipulator may include a mobile mechanism having at least one degree of freedom in one direction, specifically, a multi-degree-of-freedom manipulator (such as a four-axis manipulator, a six-axis manipulator, etc.), or an XYZ three-axis linear moving mechanism.

[0081] The samples mentioned in the present disclosure include various reagents such as medicaments, chemical agents, and especially Chinese medicines. In addition, in some embodiments, the sample containers mentioned in the present disclosure actually include shaking bottles, centrifuge bottles, and concentration bottles.

[0082] Generally, in the pharmaceutical field, high-throughput automated separation and detection systems are only for specific types of samples (such as blood, cells or swabs, etc.), so they are generally only compatible with a few types of consumables (such as blood collection tubes, microplates, etc.). The pharmaceutical automated processing and analysis detection system disclosed in the present invention needs to meet the automated extraction and separation of Chinese medicinal materials of different types and sizes, and needs to be able to perform automated operations on reagent bottles, reagent tubes, liquid phase vials, chromatographic columns, etc. of various specifications. Therefore, it is necessary to design and use modules and grippers that can automatically handle various types of solvents in order to achieve automated operations on multiple containers in a limited space.

[0083] Material storage equipment

[0084] First reference Figure 3 , describes an embodiment of a material storage device 1100 of a pharmaceutical automated processing and analysis detection system 1. The material storage device 1100 includes a warehouse station 1110, and the warehouse station 1110 includes a warehouse station robot arm 1120 and one or more storage stacks 1130. Each of the one or more storage stacks 1130 includes multiple columns of storage racks 1140. Each column of storage racks 1140 has the same height and is provided with different numbers of storage layers according to the volume of the consumables placed. The materials are transported from the outside of the material storage device 1100 to the corresponding storage positions on the storage racks 1140 by an AGV vehicle and a warehouse station robot arm 1120. Figure 2Two warehouse stations 1110 are shown in the figure as an example. The warehouse station 1110 can be a satellite warehouse, a transfer warehouse, a temporary storage warehouse, etc. Figure 3 The warehouse station 1110 includes a warehouse station robot 1120 for loading and unloading materials and one or more storage stacks 1130 ( Figure 3 Each storage stack 1130 includes a plurality of storage racks 1140 ( Figure 3 13 columns are shown by way of example in the figure), each column of storage racks 1140 has the same height, is designed to be easily disassembled, and can be set with different numbers of storage layers according to the volume of the materials placed. The materials are all placed on pallets, which are preferably standard pallets, and are placed in the corresponding positions of the storage stack 1130. The pallets are designed to facilitate loading and unloading of the robot arm and transportation by the AGV vehicle. The warehouse station 1110 is also provided with a material storage AGV exchange warehouse 1150. Before the processing begins, sufficient materials can be prepared by AGV vehicles or manually, the materials can be placed on the corresponding pallets, and the pallets containing the materials can be placed in the pallet storage positions corresponding to the single-column storage racks 1140.

[0085] The material storage device 1100 disclosed in the present invention realizes the automation of material loading and retrieval by using a warehouse station robot 1120 and an AGV vehicle to exchange materials at the material storage AGV exchange warehouse 1150, wherein the storage stack 1130 is designed to be easy to disassemble, and the pallet used to load materials is designed to be easy for the robot to grasp and carry, thereby helping to achieve automation.

[0086] Extraction equipment

[0087] Reference below Figure 4 , describes an embodiment of the extraction device 100 of the pharmaceutical automated processing and analysis detection system 1. The extraction device 100 uses a shaking table cold immersion method to shake and incubate the sample, and the extraction device 100 includes: a loading position 101, on which a sample container containing the sample is placed; a visual recognition module 106, which is used to identify whether the sample container is located in an appropriate storage position on the loading position 101; an extraction robot arm 104, which is used to grab and carry the sample container; and a shaker 103, which is used to shake and incubate the sample. The extraction device 100 also includes an extraction device AGV exchange bin 102 and a barcode scanner 105. The shaker 103 includes a plurality of shake bottle storage positions, each of which is provided with an automated fixture for fixing the shake bottle. The loading position 101 includes a plurality of shake bottle holes, and in some preferred embodiments, the number of shake bottle storage positions is the same as the number of shake bottle holes. In some embodiments, such as Figure 4As exemplarily shown in the figure, two loading positions are provided, but the number of loading positions can be changed as needed. Interactive doors are provided on both sides of the loading position. Personnel have the authority to open the interactive door, so that the interactive door can be opened manually, so that the shaking bottle can be directly placed in the corresponding shaking bottle hole position on the loading position before the processing begins. A QR code label is provided on the shaking bottle, and the label contains the material information and processing method corresponding to each shaking bottle. The barcode scanner 105 is used to scan the QR code label on the shaking bottle and read the relevant material information and / or processing method information. In Figure 4 In the figure, the visual recognition module 106 is exemplarily arranged directly above the two loading positions 101, respectively, for accurately identifying the storage information of the bottle shaking hole position after loading, and preventing the robot arm from grabbing empty space due to human factors.

[0088] At the beginning of the process, the shaker door is automatically opened, and the extraction robot arm 104 grabs the shake bottle from the loading position 101 and transfers it to the barcode scanner 105 for scanning and identification; the shake bottle after the scan information is confirmed is placed in the corresponding fixture hole in the shaker 103 until the extraction robot arm 104 takes and places the required shake bottles one by one according to the above process. The shaker door is automatically closed, the appropriate parameters are set for the shaker 103, and the shaking incubation is performed until the processing operation is completed. The shaker door is automatically opened again, and the extraction robot arm 104 takes the shake bottle out of the shaker 103 and places it in the extraction equipment AGV exchange bin 102, waiting to be transported by the AGV vehicle to the next equipment for subsequent processes.

[0089] The extraction device 100 disclosed in the present invention utilizes a shaking cold immersion method to incubate the sample by shaking to perform the extraction operation. This shaking cold immersion method can reduce energy consumption because it does not require heating. In addition, more than one solvent can be added to extract polar extracts and non-polar extracts respectively, thereby achieving standardization and improving extraction efficiency.

[0090] In addition, the extraction equipment 100 disclosed in the present invention realizes the automation of loading and handling by adopting the extraction robot arm 104 and the AGV vehicle, ensures the correct placement at the loading position 101 through the visual recognition module 106, and confirms the sample container information by using a scanner by setting a QR code label on the sample container, thereby realizing the full process automation of the shaking table extraction.

[0091] Dilution and reconstitution equipment

[0092] refer to Figure 5, introduces an embodiment of the dilution and reconstitution equipment 200 of the pharmaceutical automated processing and analysis detection system 1. Specifically, the dilution and reconstitution equipment 200 includes a dilution and reconstitution AGV exchange bin 210, a transfer storage position 212, a bottle shaking cover module 214, a liquid adding module 216, a pipetting module 218, a concentrate bottle cover module 220, a test tube centrifugal module 222, a dumping and merging position 224, a robot ground rail module 226, a dilution and reconstitution robot arm 236, a consumables long shelf 234, a consumables short shelf 235, an ultrasonic cleaning module 237, an oscillation module 238, a first visual inspection module 239 and a dilution and reconstitution tool library. The dilution and reconstitution tool library includes a tray handling tool 231, a concentrate bottle handling tool 232 and a test tube handling tool 233.

[0093] In the dilution and reconstitution device 200, the liquid adding module 216 is used to add liquid to the sample container. The pipetting module 218 is used to transfer at least a portion of the sample in a sample container (also called "consumables") to another sample container. The test tube centrifugal module 222 is used to centrifuge the sample container that has been treated with ultrasonic vibration when the sample container is a test tube. Because the amount of liquid in the test tube is relatively small, it is necessary to ensure that the liquid can be sucked as clean as possible during pipetting; therefore, the liquid on the wall of the test tube can be thrown to the bottom of the test tube by centrifugation to ensure that the liquid can be sucked clean during pipetting. The pouring and merging position 224 is used to merge the liquids in multiple concentration bottles by pouring. The ultrasonic cleaning module 237 is used to ultrasonically clean the sample container with residual samples. The oscillation module 238 is used to ultrasonically oscillate the sample container, which can be ultrasonic and oscillated at the same time, or can be ultrasonic and oscillated in any order. This oscillation operation is to accelerate the dissolution of the sample. The first visual inspection module 239 is used to detect whether the sample in the sample container that has been ultrasonically oscillated is completely dissolved.

[0094] In the preparation stage before processing, the external AGV transfers the tray / shaking bottle to the dilution and reconstitution AGV exchange bin 210, and the dilution and reconstitution robot arm 236 selects the corresponding transport tool (tray transport tool 231 or concentrate bottle transport tool 232) to transfer the tray (with test tubes / concentrate bottles on the tray) / shaking bottle on the dilution and reconstitution AGV exchange bin 210 to the transfer storage position 212, the consumables long shelf 234 or the consumables short shelf 235. After the required consumables are sent to the consumables long shelf 234 or the consumables short shelf 235, the dilution and reconstitution robot arm 236 selects the corresponding transport tool (test tube transport tool 233 or concentrate bottle transport tool 232) to transfer the test tube / concentrate bottle / shaking bottle to the shake bottle cover opening and closing module 214 or the concentrate bottle cover opening and closing module 220 for opening, and then the dilution and reconstitution robot arm 236 transfers the opened consumables to the liquid adding module 216 for liquid adding. After the addition is completed, the dilution and re-dissolution robot arm 236 transfers the shake bottle back to the transfer storage position 212, the consumables long shelf 234 or the consumables short shelf 235 at the appropriate time according to the needs, and transfers other consumables to the oscillation module 238. According to the processing requirements, you can choose to oscillate while ultrasonicating, or ultrasonicate first and then oscillate. After a certain period of ultrasonic oscillation, the dilution and re-dissolution robot arm 236 transports the consumables to the first visual inspection module 239, and the first visual inspection module 239 detects whether the sample in the consumables is completely dissolved. If the consumable used is a test tube, the dilution and re-dissolution robot arm 236 first transports the test tube to the test tube centrifugal module 222 for centrifugation. After the test tube is centrifuged for a certain period of time and speed, it is transferred to the pipetting module 218. The pipetting module 218 transfers the liquid in the test tube to the designated test tube / concentration bottle; if the consumable used is a concentration bottle, there is no need for centrifugation, and it is directly transferred to the pipetting module 218. The pipetting module 218 transfers the liquid in the concentration bottle to the designated test tube / concentration bottle. According to the processing requirements, when the amount of liquid in the test tube / concentration bottle is small, the liquid in multiple test tubes / concentration bottles can be merged through the pipetting module 218; and when the amount of liquid in the concentration bottle is large, the concentration bottle can be transferred to the pouring and merging position 224 first when merging, and the dilution and reconstitution robot arm 236 pours the concentration bottle to be merged into another designated concentration bottle by pouring, thereby improving the efficiency of liquid merging. After the test tube / concentration bottle completes the corresponding liquid addition, shaking, and merging operations, the dilution and reconstitution robot arm 236 transfers the test tube / concentration bottle to its corresponding shaking bottle switch cover module 214 or the concentration bottle switch cover module 220 for closing the cover. The closed test tube / concentration bottle is then sent back to the corresponding tray and stored in the consumables long shelf 234 or the consumables short shelf 235. When all samples are processed, the dilution and reconstitution robot arm 236 transfers all samples in turn to the dilution and reconstitution AGV exchange bin 210, and the external AGV vehicle then sends the samples on the dilution and reconstitution AGV exchange bin 210 to the corresponding process of the subsequent equipment to continue the processing operation.

[0095] The dilution and reconstitution equipment 200 disclosed in the present invention realizes the automation of loading, temporary storage, transportation and transfer of consumables between processing modules by adopting a dilution and reconstitution robot arm 236, an AGV vehicle and various transport tools, realizes the automation of opening and closing the covers of test tubes / concentration bottles / shaking bottles by adopting a cover opening and closing module, ensures the complete dissolution of samples in the consumables by the first visual inspection module 239, and realizes the automation of merging operations by the pipetting module 218 and the dilution and reconstitution robot arm 236, thereby realizing the automation of the entire process of dilution and reconstitution and ensuring the dissolution effect.

[0096] Centrifugal filtration equipment

[0097] refer to Figure 6a and Figure 6b , describes an embodiment of a centrifugal filtration device 300 of a pharmaceutical automated processing and analysis detection system 1. Specifically, the centrifugal filtration device 300 includes a centrifugal filtration AGV exchange bin 310, a shaking bottle temporary storage position 312, a centrifuge bottle / concentration bottle temporary storage position 313, a centrifugal filtration switch cover module 314, a filtration module 316, a loading shelf 318, a unloading shelf 320, a cleaning module 322, a centrifuge 324, a centrifugal filtration mechanical arm 326, a weighing module 328, a tray transfer unit 330 and a centrifugal filtration tool library 340. The centrifugal filtration tool library 340 includes a tray clamp, a concentration bottle clamp and a pipetting device 342, etc. In some embodiments, the pipetting device 340 is a 5ml pipette.

[0098] The filtering module 316 is used to filter the sample to obtain the filtered sample. The loading shelf 318 is used to store new screens. The unloading shelf 320 is used to store used screens. The centrifuge 324 is used to centrifuge the sample container containing the filtered sample to separate the supernatant and the residue. The weighing module 328 is used to weigh the multiple sample containers containing the filtered sample in sequence. The pipetting device 342 is used to transfer a part of the sample in the sample container containing more samples to another sample container. The weighing module 328 and the pipetting device 342 perform a balancing operation on the multiple sample containers. The centrifugal filtering mechanical arm 326 performs the transfer operation required for the filtering operation, the centrifugal operation and the balancing operation by replacing different tools to assist in completing the filtering operation, the centrifugal operation and the balancing operation. The cleaning module 322 is used to clean the sample container with the solid sample residue after filtering. The tray transfer unit 330 is used to transfer the tray inside the device. In addition, when the bottle is clamped with the concentrate bottle clamp and the sample in the bottle is poured onto the screen for filtration, fluid may drip, thereby contaminating the equipment; therefore, an anti-pollution design is provided on the concentrate bottle clamp to prevent the above-mentioned contamination of the fluid. In some embodiments, a layer of replaceable adhesive tape is attached to the bottle clamp. In this way, when pouring the fluid, the fluid remaining at the container mouth flows onto the adhesive tape and does not contaminate other mechanisms; when a fluid is filtered, the adhesive tape can be replaced manually or automatically; the adhesive tape can be, for example, Teflon adhesive tape or cloth-based adhesive tape.

[0099] In the preparation stage before the experiment, the external AGV vehicle transfers the shake bottle / centrifuge bottle tray / concentration bottle tray to the centrifugal filtration AGV exchange bin 310, and the centrifugal filtration robot arm 326 selects the corresponding handling tool to transfer the shake bottle on the centrifugal filtration AGV exchange bin 310 to the shake bottle temporary storage position 312, and transfers the centrifuge bottle / concentration bottle tray to the centrifuge bottle / concentration bottle temporary storage position 313. The clean screen is placed on the loading shelf 318 manually or by a robot arm, and the tip head tray is placed in the tray transfer part 330. At the beginning of the experiment, the centrifugal filtration robot arm 326 uses different tools to move the shake bottle to the centrifugal filtration switch cover module 314 for opening, and then moves the centrifuge bottle tray from the centrifuge bottle / concentration bottle temporary storage position 313 to the tray transfer part 330, takes out the centrifuge bottle and sends it to the centrifugal filtration switch cover module 314 for opening, and after opening the cover, sends the centrifuge bottle to the liquid receiving position in the filtration module 316. Move the clean coarse screen from the loading shelf 318 to the filter module 316, move the shake bottle to the top of the filter module 316 for dumping, and complete the filtering action by vacuuming the top. After the filtering is completed, put the shake bottle back into the centrifugal filter switch cover module 314 for closing the cover, and then move it to the shake bottle temporary storage position 312. Move the used coarse screen to the unloading shelf 320. Move the centrifuge bottle to the centrifugal filter switch cover module 314 for closing the cover and then move it to the weighing module 328 for weighing. Repeat the above operation, gather multiple bottles of filtered centrifuge bottles and confirm that the weight difference between these centrifuge bottles is within the allowable range before putting them into the centrifuge 324 for centrifugation. If the weight difference exceeds the allowable range, move the centrifuge bottle to the centrifugal filter switch cover module 314 again for opening the cover, move the centrifuge bottle to the weighing module 328 and use the pipetting device 342 for balancing. After completing the balancing, move the centrifuge bottle to the centrifugal filter switch cover module 314, close the cover and then put it into the centrifuge 324. After centrifugation is completed, the centrifuge bottle is taken out and moved to the centrifugal filter switch cover module 314 to open the cover, and the concentration bottle is moved to the liquid receiving position in the filter module 316. A clean fine mesh is placed in the filter module 316, and then the centrifuge bottle is dumped to complete the filtering action. After the filtration is completed, the centrifuge bottle is moved to the centrifugal filter switch cover module 314, the cover is closed, and then returned to the tray transfer part 330. The used fine mesh is returned to its original position, and the concentration bottle is returned to the tray transfer part 330. Finally, the AGV vehicle is used to move the shaking bottle / centrifuge bottle tray / concentration bottle tray out of the equipment through the centrifugal filter AGV exchange bin 310.

[0100] In addition, it is not necessary to centrifuge the sample, and a judgment step is performed before the centrifugation operation. In some embodiments, in the judgment step, it is determined whether a centrifugation operation needs to be performed based on the sample type; if it is determined based on the sample type that the sample has been crushed, a centrifugation operation needs to be performed; if it is determined based on the sample type that the sample has not been crushed, only a filtering operation is performed without a centrifugation operation. That is, in some embodiments of the present disclosure, if the sample is a block-shaped, uncrushed block, a centrifugation operation is not performed; if the sample is a block-shaped, crushed powder, a centrifugation operation is performed. In some embodiments, whether a centrifugation operation needs to be performed can be determined based on the information recorded in the sample label, but other methods known in the art are also feasible. In some embodiments, whether a centrifugation operation needs to be performed can be determined by software based on rules.

[0101] In some embodiments, in the judgment step, whether a centrifugation operation needs to be performed is judged based on whether the sample is clear; if the sample is judged to be not clear, a centrifugation operation needs to be performed; if the sample is judged to be clear, a centrifugation operation is not performed. That is, in some embodiments of the present disclosure, if the sample is clarified after the filtration operation in the first step, a centrifugation operation is not required. The judgment can be made based on a visual analysis module, and the visual analysis module can use any suitable camera known in the art, and its specific structure and installation position are not limited, as long as the clarification state of the sample can be judged.

[0102] The centrifugal filtration equipment 300 disclosed in the present invention realizes the automation of loading, temporary storage, transportation and transfer of consumables between processing modules by adopting a centrifugal filtration robot arm 326, an AGV vehicle and various handling tools, realizes the automation of opening and closing the covers of test tubes / concentration bottles / shaking bottles by adopting a cover opening and closing module, and realizes automatic balancing operation without manual intervention by using a weighing module 328 and a pipetting device 342, thereby realizing the full process automation of a series of operations such as filtration, centrifugation, weighing and balancing in the centrifugal filtration treatment of samples.

[0103] Freeze drying equipment

[0104] The freeze-drying equipment 400 of the pharmaceutical automated processing and analysis and detection system 1 includes: a weighing module, which is used to weigh the sample container before and after the freeze-drying process; a freeze dryer 422, which is used to freeze-dry and concentrate the sample in the sample container; a labeler, which is used to label the sample container; and a freeze-drying robot 410, which transfers different types of sample containers between the weighing module, the freeze dryer and the labeler by replacing different grippers to assist in completing the weighing operation, the freeze-drying operation and the labeling operation.

[0105] refer to Figure 7a and Figure 7b , describes an embodiment of a freeze drying device 400 of a pharmaceutical automated processing and analysis detection system 1. The freeze drying device 400 includes a freeze drying robot arm 410, a ground rail 412, a freeze drying AGV exchange bin 414, a temporary test tube rack 416 in the station, a one percent weighing module 418, a one ten-thousandth weighing module 420, a freeze dryer 422, a label printing module 424, a labeling module 426, a manual loading 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 a tray clamp 442, a concentrate bottle clamp 444, and a test tube clamp 446.

[0106] The freeze-drying robot arm 410 moves back and forth on the ground rail 412, and a quick-change device is provided at its end. The quick-change device can be connected to the quick-change devices on the three end effectors, namely, the tray clamp 442, the concentrate bottle clamp 444, and the test tube clamp 446, placed in the freeze-drying tool library 440, to achieve quick change to match different work scenarios. The connection between the freeze-drying robot arm 410 and the tray clamp 442 can realize operations such as clamping the tray for transfer, pulling out and pushing in the drawer rack of the freeze dryer 422, etc. The connection between the freeze-drying robot arm 410 and the concentrate bottle clamp 444 can realize operations such as clamping the concentrate bottle from the tray to the one-hundredth weighing module 418 for weighing, clamping the concentrate bottle to the fully automatic labeling machine for labeling, etc. The connection between the freeze-drying robot arm 410 and the test tube clamp 446 can realize operations such as clamping the test tube from the tray to the one-ten-thousandth weighing module 420 for weighing, clamping the test tube to the labeling machine for labeling, etc.

[0107] The temporary test tube rack 416 is provided with a multi-layer tray storage position. The freeze-drying robot arm 410 grabs various sample containers from the freeze-drying AGV exchange bin 414, such as test tube, test tubes, 250 ml concentrate bottle trays, and transfer them to the temporary test tube rack 416.

[0108] When weighing, place the test tube (e.g. test tube, The test tube (e.g., 250 ml concentrate bottle) is transferred to the 1 / 10,000 weighing module 420 for weighing, and the concentrate bottle (e.g., 250 ml concentrate bottle) is transferred to the 1 / 10,000 weighing module 418 for weighing. In the 1 / 10,000 weighing module 418 and the 1 / 10,000 weighing module 420, the top cover door of the balance can be opened and closed automatically. When weighing is required, the top cover door of the balance is automatically opened, and after the material is placed on the balance, the top cover door of the balance is closed for weighing. After weighing is completed, the top cover door of the balance is automatically opened and the material is taken out, and then the top cover door of the balance is automatically closed. When weighing is not required, the top cover door of the balance is closed.

[0109] A drawer rack is provided in the freeze dryer 422, and the drawer rack is arranged in multiple layers and has multiple tray placement positions. The freeze dryer door is an automatic door. When the tray is placed in the freeze dryer 422, the freeze dryer door automatically opens, and the freeze drying robot arm 410 is connected to the tray clamp 442 to pull out the drawer rack of the freeze dryer 422 to the tray placement transfer position, and then the tray is clamped from the temporary test tube rack 416 and transferred to the drawer rack of the freeze dryer 422 to complete the tray transfer. Then, the drawer rack of the freeze dryer 422 is pushed to the freeze drying position. The freeze dryer door automatically closes, and the freeze dryer starts the freeze drying process.

[0110] The labeling machine is composed of a label printing module 424 and a rotary labeling module (also referred to as a "labeling module") 426. The label printing module 424 is used to print labels. The labeling scanner 434 is used to scan the labels of the labeled objects.

[0111] At the beginning of the experiment, the freeze-drying robot 410 transfers the tray that was transported by the AGV vehicle to the freeze-drying AGV exchange bin 414 in the previous link to the horizontal frame on the inner bottom side of the temporary test tube rack 416. The freeze-drying robot 410 switches the end clamp (concentration bottle clamp 444 or test tube clamp 446), grabs the corresponding test tube on the tray and labels it in the labeling machine, and then transports it to the weighing scanner 433 for scanning. After scanning, it is placed in the corresponding weighing module for weighing, and the weighed test tube is put back on the tray. The weighing results are automatically recorded by the software and matched with the barcode information of the test tube on the information system. After weighing all the test tubes on the tray, the hatch of the freeze dryer 422 is automatically opened. The freeze-drying robot 410 switches to the tray clamp 442, pulls out the pull-out rack inside the freeze dryer 422 through the tray clamp 442, and places the tray in the tray position corresponding to the pull-out rack to complete the tray transfer. Then, the tray clamp 442 pushes the drawer rack back to its original position. The hatch of the freeze dryer 422 is automatically closed. Appropriate parameters are set for the freeze dryer 422 to perform freeze drying and concentration operations. After the freeze drying process is completed, the hatch of the freeze dryer 422 is automatically opened, and the tray clamp 442 of the freeze drying mechanical arm 410 pulls out the drawer tray inside the freeze dryer 422, and transfers the tray to the horizontal rack on the inner side of the bottom of the temporary test tube rack 416. The freeze drying mechanical arm 410 switches the end clamp, grabs the test tube to the weighing scanner 433 for bar code scanning, and then transports it to the corresponding weighing module for weighing, and puts it back on the tray after weighing is completed. The weighing result after freeze drying is deducted from the empty bottle mass recorded in the information system to calculate the mass of the freeze-dried product. The freeze-dried product quality data and other information are calculated through regular formulas to obtain the method parameters for subsequent dissolution and record them in the information system. After the freeze-dried samples are weighed one by one, the freeze-dried robot arm 410 transfers the tray to the freeze-dried AGV exchange bin 414, and the AGV transfers it to the next process for subsequent processing. The freeze-dried AGV exchange bin 414 is provided with multiple tray storage positions, and the pins on the freeze-dried AGV exchange bin 414 are used to accurately position the tray.

[0112] The test tubes can be labeled at any appropriate time as needed. When labeling is required, the freeze-drying robot arm 410 is connected to the tray clamp 442 to clamp the tray that needs to be labeled from the temporary test tube rack 416 to the labeling transfer rack 430. The freeze-drying robot arm 410 switches to the test tube clamp 446, and the test tube clamp 446 clamps the test tube to the labeling position of the labeling machine to get close to the labeling module 426, so that the sixth axis of the freeze-drying robot arm 410 rotates parallel to the horizontal direction, thereby completing the test tube labeling. The freeze-drying robot arm 410 clamps the labeled test tube to the labeling scanner 434 for information binding. After labeling and scanning, put the test tube back into the labeling transfer rack 430 of the labeled test tube. The freeze-drying robot arm 410 clamps and transfers the tray to the freeze-drying AGV exchange bin 414, and the AGV vehicle clamps and transfers it to the next device. In some embodiments, manual loading can be supported so that the test tubes can be transferred to the manual loading rack 428 for the automatic labeling process of the test tubes. The system opens the side door opening permission, and the side door can be opened manually to load the tray loaded with the test tubes that need to be labeled into the manual loading rack 428. After the loading is completed, 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 bin 414, and the AGV vehicle is clamped and transferred to the next device; second, the tray is transferred to the manual loading rack 428 and unloaded manually.

[0113] The freeze-drying equipment 400 disclosed in the present invention realizes the automation of loading, temporary storage, transportation and transfer of consumables between processing modules by adopting a freeze-drying robot arm 410, an AGV vehicle and various handling tools, and realizes the automation of freeze-drying and labeling operations through a freeze dryer 422 and a labeler, thereby realizing the full process automation of freeze-drying treatment of samples.

[0114] Centrifugal Concentration Equipment

[0115] exist Figure 2 Two centrifugal concentration devices 500 are shown as an example in the top view.

[0116] refer to Figure 8 , describes an embodiment of a centrifugal concentration device 500 of a pharmaceutical automated processing and analysis detection system 1. The centrifugal concentration device 500 includes a centrifugal concentrator 510 (in Figure 8 5 are shown as examples), pallet racks 512 (in Figure 8 2 are shown as examples), a pallet transfer station 514, an adapter shelf 516, a weighing module 518, a liquid adding module 520, a centrifugal concentration AGV exchange bin 522, a centrifugal concentration robot arm 524, a ground rail module 526 and a centrifugal concentration tool library 530. The centrifugal concentration tool library 530 includes a pallet gripper, an adapter gripper and a bottle gripper.

[0117] The centrifugal concentrator 510 performs centrifugal concentration operations on samples in multiple sample containers, and the centrifugal concentrator 510 has an imbalance detection sensor. The pallet rack 512 is arranged in multiple layers, for example, 5 layers, etc., for temporary storage of pallets during processing. The weighing module 518 and the liquid adding module 520 constitute a balancing weighing module of the centrifugal concentration device 500. When the imbalance detection sensor detects that the weight difference of multiple sample containers exceeds a certain threshold, the balancing weighing module balances the samples in the multiple sample containers. Centrifugal concentration robot arm 524, the centrifugal concentration robot arm 524 transfers different types of grasped objects between the centrifugal concentrator 510 and the balancing weighing module by replacing different grippers to assist in completing centrifugal concentration. Adapters include, for example, 250ml concentration bottle adapters, Test tube adapter and Test tube adapter.

[0118] At the beginning of the experiment, the centrifugal concentration robot arm 524 cooperates with the pallet gripper to transfer the pallet from the centrifugal concentration AGV exchange bin 522 to the pallet rack 512, and at the same time transfers the corresponding adapter to the pallet rack 512. The end of the centrifugal concentration robot arm 524 switches to the bottle gripper, and the bottle gripper transfers the bottle in the pallet to the adapter. The end of the centrifugal concentration robot arm 524 switches to the adapter gripper, and the adapter gripper places the adapter into the centrifugal concentrator 510. The centrifugal concentrator 510 is equipped with an automatic door. When centrifugal concentration is required, the centrifugal concentrator 510 automatically opens the door. After the centrifugal concentration robot arm 524 places the adapter, the centrifugal concentrator 510 automatically closes the door. Set appropriate centrifugal concentration parameters and start processing. The centrifugal concentrator 510 has an imbalance detection sensor. When the imbalance detection sensor detects that the weight difference of the bottle in the adapter reaches a certain threshold, the centrifugal concentrator 510 automatically stops and opens the door. The centrifugal concentration robot arm 524 takes out the adapter and transfers it to the weighing module 518 for weighing. According to the weighing result, the bottle in the adapter is added with liquid through the liquid adding module 520 for balancing. After balancing, the adapter is placed in the centrifugal concentrator 510 for further concentration. After concentration, the centrifugal concentrating robot arm 524 takes out the adapter and places it on the pallet rack 512. The bottle gripper is switched at the end of the centrifugal concentrating robot arm 524, and after the bottle is transferred to the pallet, the centrifugal concentrating robot arm 524 switches the pallet gripper to transfer the pallet to the centrifugal concentrating AGV exchange bin 522.

[0119] The centrifugal concentration device 500 disclosed in the present invention realizes the automation of loading, temporary storage, transportation and transfer of consumables between processing modules by adopting a centrifugal concentration robot arm 524, an AGV vehicle and various handling tools, and realizes the automation of centrifugal concentration and automatic balancing operations through a centrifugal concentrator 510, a weighing module 518 and a liquid adding module 520, thereby realizing the full process automation of centrifugal concentration of samples.

[0120] Dry loading equipment

[0121] See also Fig. 9 According to an embodiment of the present disclosure, the dry loading device 600 includes a loading robot arm 610, a powder adding module 612, a powder leveling module 614, a second visual inspection module 616, a docking track 618, a loading rack module 620, a scraper cleaning module 622, a switch cover and a powder scraping rotating module 624, a rotary evaporation module 626, and a loading tool library 630. The loading tool library 630 includes a handling tool, a pouring tool, and a powder scraping tool. The loading rack module 620 includes a powder barrel rack 642, a funnel rack 644, a rotary evaporation column rack 646, and a loading column rack 648.

[0122] The powder adding module 612 is used for quantitatively adding powder to the sample loading column and the rotary evaporation column. The rotary evaporation module 626 is used for rotary drying the sample in the rotary evaporation column. The powder scraping tool is used for scraping powder on the rotary evaporation column. The scraper cleaning module 622 is used for cleaning and wiping the scraper of the scraping tool that performs the powder scraping operation. The powder leveling module 614 is used for leveling the powder in the sample loading column. The switch cover and powder scraping rotation module 624 is used for fixing and rotating the column when opening the cover of the rotary evaporation column and the sample loading column, and fixing and rotating the rotary evaporation column when performing the powder scraping operation on the rotary evaporation column. The second visual detection module 616 is used to detect the state of the sample in the rotary evaporation column.

[0123] The loading robot arm 610 is used to quickly connect with various tools (such as handling tools, pouring tools, powder scraping tools, etc.) in the tool library to perform corresponding operations. The second visual detection module 616 detects the state of the sample in the rotary evaporation column, for example, including detecting whether the sample in the rotary evaporation column is dried, detecting whether the powder in the rotary evaporation column is scraped clean, etc. The second visual detection module 616 can use any suitable equipment to collect images. In some embodiments, a CCD visual module can be used to collect images of the rotary evaporation column. The docking track 618 is used for the loading robot arm 610 to move. The loading rack module 620 is used for the external AGV vehicle to interact with the device for materials and consumables, that is, the powder barrel tray, the funnel tray, the rotary evaporation column tray, the loading column tray, etc. can be interacted. The switch cover and the powder scraping rotation module 624 are used in conjunction with the handling tool when the rotary evaporation column and the loading column are opened and closed, and are used in conjunction with the powder scraping tool when the rotary evaporation column is scraped. The loading tool library 630 is used to temporarily store various tools such as carrying tools, pouring tools, and powder scraping tools; the carrying tools are used to carry various containers, such as loading columns, rotary evaporation columns, powder barrels, funnels, etc., the pouring tools are used to carry various containers and pour powder, and the powder scraping tools are used to scrape powder samples from the side walls and bottom of the rotary evaporation column.

[0124] Before the process starts, the materials (powder barrel, funnel, rotary evaporation column, loading column) and the like required by the loading rack module 620 are manually placed in the corresponding positions on the loading rack module 620, wherein the rotary evaporation column can also be derived from the product after the dilution and re-dissolution equipment 200 is merged. The loading robot arm 610 switches the handling tool to place the powder barrel and rotary evaporation column filled with silica gel powder in the powder adding module 612, and the powder adding module 612 quantitatively adds silica gel powder to the rotary evaporation column. The loading robot arm 610 transfers the rotary evaporation column after powder addition to the rotary evaporation module 626, and the rotary evaporation module 626 performs rotary evaporation on the rotary evaporation column. The loading robot arm 610 transfers the rotary evaporation column after rotary evaporation to the second visual inspection module 616, and the second visual inspection module 616 takes photos and analyzes it to determine whether the sample in the rotary evaporation column has been dried. After determining that the rotary evaporation column has been dried, the sample loading robot 610 transfers the rotary evaporation column to the switch cover and the powder scraping rotating module 624, and replaces the powder scraping tool to scrape the rotary evaporation column. After the powder scraping is completed, the sample loading robot 610 moves the powder scraping tool to the scraper cleaning module 622 to clean the powder scraping tool. The sample loading robot 610 switches the transport tool to transfer the rotary evaporation column after the powder is scraped to the second visual inspection module 616 again, and the second visual inspection module 616 takes a photo and analyzes it to detect the state of the contents (mixed sample silica gel). The sample loading robot 610 transfers the sample loading column to the switch cover and the powder scraping rotating module 624 to open the cover. The sample loading robot 610 places the funnel at the opening of the sample loading column, changes to the pouring tool to pour the powder in the rotary evaporation column into the sample loading column, and then switches back to the transport tool to put the funnel back into the loading rack module 620. The loading robot 610 transfers the loading column to the powder shaking module 614 for shaking the powder, transfers the powder barrel and the loading column to the powder adding module 612 for powder loading, and transfers the loaded loading column after powder loading to the switch cover and the powder scraping and rotating module 624 for closing the cover; the AGV transfers the loading column to the next device (e.g., medium-pressure preparation and separation equipment). In some embodiments, quartz sand is added when loading powder. The quartz sand mainly plays two roles: one is to flatten the surface of the sample mixed with silica gel after drying (so that it can contact with the reagent at the same time when the components are separated later); the other is to reduce the excess space in the loading column; quartz sand is an inert substance and will not react with the sample or reagent, nor will it dissolve. However, quartz sand is just an example, and other materials can also be added as needed.

[0125] The dry loading device disclosed in the present invention realizes the automation of consumables loading, temporary storage, transportation and transfer between processing modules by adopting a loading robot arm 610, an AGV vehicle and various handling tools, and realizes the automation of loading, detection, cleaning and opening and closing cover operations through the powder adding module 612, the second visual inspection module 616, the powder leveling module 614, the scraper cleaning module 622, the opening and closing cover and the powder scraping rotation module 624 and the rotary evaporation module 626, thereby realizing the full process automation of dry loading of samples.

[0126] Medium pressure preparation and separation equipment

[0127] See also Fig.10 The medium-pressure preparation and separation device 700 according to the embodiment of the present disclosure includes a medium-pressure preparation and separation exchange chamber 710, a medium-pressure preparation and separation mechanical arm 712, a ground rail module 714, a column packing module 716, a sample loading and liquid addition and needle cleaning module 718, and a pump valve module 720 ( Fig.10 2 are shown in the figure), medium pressure fraction collection module 722 ( Fig.10 2 are shown in the figure), mobile phase buffer module 724, transfer buffer position 726 ( Fig.10 3 are shown by way of example), a cleaning column module 728, an upper plug placement module 730 and an end clamp 732.

[0128] In the column packing module 716, the chromatographic column and the loading column are transferred here for column connection. The loading liquid addition and needle cleaning module 718 is used to perform the loading liquid addition and needle cleaning operations, and the sample container containing the sample is transferred to the loading liquid addition and needle cleaning module 718. The medium-pressure fraction collection module 722 is used to be compatible with a variety of different trays, cache different containers, and is used to collect fractions condensed at different time periods or different temperatures for subsequent analysis or use. The pump valve module 720 is used to perform related processing of pumping liquid and analysis. The mobile phase buffer module 724 is used to cache the mobile phase required for the experimental process. The mobile phase buffer module 724 can include multiple mobile phase storage boxes, and the mobile phases in different storage boxes can be different. The pump valve module 720 is connected to the loading liquid addition and needle cleaning module 718, the column packing module 716, the medium-pressure fraction collection module 722, and the mobile phase buffer module 724 through pipelines, respectively, to provide power for liquid transmission between the above modules. The cleaning column module 728 is arranged on one side of the column packing module 716, and is used for caching and placing multiple cleaning columns; the cleaning column module 728 can be regarded as a placement seat, and the placement seat can place multiple cleaning columns, for example, four, and the cleaning columns are used in conjunction with the column packing module 716. When the column packing module 716 needs to clean the pipeline or clean the chromatographic column / loading column, the medium-pressure preparation and separation robot arm 712 takes out the cleaning column from the placement seat and installs the cleaning column in the column packing module 716 to realize the cleaning of the pipeline or chromatographic column / loading column of the column packing module 716. In addition, the cleaning column can also be used as a connecting pipeline when the chromatographic column / loading column is separately loaded and eluted. The upper plug placement module 730 is used to cache and place the upper plugs of various chromatographic columns and loading columns.

[0129] Before the process starts, the external AGV vehicle transfers the tray carrying the empty test tubes to the medium-pressure preparation and separation exchange chamber 710, and the medium-pressure preparation and separation robot arm 712 and the ground rail module 714 transport the tray carrying the empty test tubes on the medium-pressure preparation and separation exchange chamber 710 through the end clamp 732 of the medium-pressure preparation and separation robot arm 712 and transfer it to the transfer cache position 726. After the process starts, the medium-pressure preparation and separation robot arm 712 and the ground rail module 714 transport the corresponding chromatographic column and the loading column to the column loading module 716. In some embodiments, after the column is connected, the medium-pressure preparation and separation robot arm 712 and the ground rail module 714 transport the tray carrying the empty test tubes on the transfer cache position 726 to the medium-pressure fraction collection module 722 through the end clamp 732 of the medium-pressure preparation and separation robot arm 712 to complete the preparation work. The external AGV vehicle transfers the tray of the test tubes containing the samples to the medium-pressure preparation and separation exchange chamber 710, and the medium-pressure preparation and separation robot arm 712 and the ground rail module 714 transport the tray of the test tubes containing the samples on the medium-pressure preparation and separation exchange chamber 710 through the end clamp 732 of the medium-pressure preparation and separation robot arm 712 and transfer it to the sample loading and liquid addition and needle cleaning module 718. Then, the medium-pressure preparation and separation robot arm 712 and the ground rail module 714 transport the tray of the empty test tubes on the transfer buffer position 726 through the end clamp 732 of the medium-pressure preparation and separation robot arm 712 and transfer it to the medium-pressure fraction collection module 722, thereby achieving separation and purification of sample components through the medium-pressure preparation and separation equipment 700.

[0130] The medium-pressure preparative separation equipment disclosed in the present invention realizes the automation of consumable loading, temporary storage, transportation and transfer between processing modules by adopting a medium-pressure preparative separation robot arm 712, an AGV vehicle and various handling tools, and realizes the automation of medium-pressure preparative separation, purification and collection operations through a column loading module 716, a sample loading and liquid addition and needle cleaning module 718, a pump valve module 720, a medium-pressure fraction collection module 722, a mobile phase buffer module 724 and a cleaning column module 728.

[0131] High pressure preparation and separation equipment

[0132] See also Fig.11 According to an embodiment of the present disclosure, the high-pressure preparation and separation device 800 includes a high-pressure preparation and separation station 820 and a detection and filtration station 850. The high-pressure preparation and separation station 820 includes a high-pressure preparation inlet and outlet sample module 810, a corresponding pump valve analysis module 812 and a mobile phase buffer 814. The detection and filtration station 850 includes a detection and filtration mechanical arm 852, a detection and filtration AGV exchange bin 854, a main shelf 856, a positive pressure filtration module 858, a screen filtration module 860, a pipetting module 862 (for example, a 1 ml pipetting module) and a cache rack 864.

[0133] The detection and filtration robot 852 is used to carry various pallets and consumables inside the high-pressure preparation and separation equipment 800. The detection and filtration AGV exchange bin 854 is used to transfer pallets delivered by external AGV vehicles. The main shelf 856 is used to store pallets delivered by external AGV vehicles. The positive pressure filtration module 858 is used for filtering before applying high pressure treatment to the sample, and is used to filter a small amount of sample liquid, such as a sample liquid contained in a filter column. The screen filtration module 860 is used for filtering before applying high pressure treatment to the sample, and is used to filter a large amount of sample liquid, such as a sample liquid contained in a solvent bottle; in addition, the screen 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 analysis processes. The cache rack 864 is used to temporarily store funnel trays and concentration bottle trays for screen filtration.

[0134] In the preparation stage before processing, the external AGV transfers the tray to the detection and filtration AGV exchange bin 854, and the detection and filtration robot 852 moves the tray to the main shelf 856. When the sample begins to be filtered before high pressure, when a small amount of sample liquid is filtered, the detection and filtration robot 852 transfers the test tube tray and the filter column tray from the main shelf 856 to the positive pressure filtration module 858 for filtration. The detection and filtration robot 852 automatically clamps the filter column. The sample liquid to be filtered is placed in the filter column, which is provided with a blocking mechanism, such as a plug, to prevent the liquid from leaking out in advance. The detection and filtration robot 852 removes the plug, pierces the filter head and inserts the Tip head at the filter head outlet. If the sample amount is small (for example, 0-2ml), puncture and filter the sample into a liquid phase vial; if the sample amount is large (for example, 2-30ml), filter it into a test tube. When filtering a large amount of sample liquid, the detection and filtration robot 852 transfers the concentration bottle tray and the filter funnel tray from the main shelf 856 to the cache rack 864. The detection and filtration robot 852 takes an empty concentration bottle and a filter funnel and places them in the corresponding position in the mesh filtration module 860, and takes a concentration bottle containing a sample and places it in the corresponding position in the mesh filtration module 860; the sample is poured into the filter funnel, and the sealing pressure plate of the mesh filtration module 860 is automatically pressed down to pressurize the funnel to complete the filtration. When a batch of high-pressure fractions is collected, the detection and filtration robot 852 pulls out the fraction drawer, puts the test tube tray in the corresponding position in the transfer module 862, and the transfer module 862 inserts the Tip head, draws the sample from the fraction test tube, and transfers the sample to the liquid phase vial for subsequent operation.

[0135] The high-pressure sample preparation inlet and outlet module 810 is used to perform high-pressure preparation separation on the sample. During the processing, after filtering in the positive pressure filtration module 858 or the screen filtration module 860, the sample is transferred to the high-pressure sample preparation inlet and outlet module 810, and then the sample processed in the high-pressure sample preparation inlet and outlet module 810 is transferred to the above-mentioned pipetting module 862. The pump valve analysis module 812 is connected to the high-pressure sample preparation inlet and outlet module 810 through a pipeline not shown in the figure and is used for related processing of pumping liquid and analysis. In some embodiments, two high-pressure sample preparation inlet and outlet modules 810 are provided, and two pump valve analysis modules 812 (such as Fig.11 ). The mobile phase buffer 814 is also connected to the pump-valve analysis module 812 through a pipeline not shown in the figure, and is used to introduce the sample in the high-pressure sample preparation module 810 through the pipeline, that is, a group of sample injections in the high-pressure sample preparation module 810, and then introduce the predetermined mobile phase in the mobile phase buffer 814 according to the introduced sample, so that the sample is mixed with the predetermined mobile phase. The function of the mobile phase buffer 814 disclosed in the present invention is to store a large capacity of mobile phase liquid; the mobile phase buffer 814 can be regarded as a box structure, and a flip door is provided on the outer shell of the box, and a large capacity barrel (for example, 30L) filled with mobile phase is placed inside. When the liquid in the barrel is insufficient, the flip door is manually opened, and the barrel inside is taken out to add liquid. The barrel inside is connected to the pump-valve analysis module 812 through a pipeline via a through hole on the outer shell of the box; in the prior art, the structure capacity of the mobile phase buffer is relatively small, and frequent manual liquid addition is required. The pump valve analysis module 812 separates the components of the mixed liquid and analyzes each component, and then guides the different components through pipelines to the high-pressure preparation input and output sample module 810 for fraction collection, that is, the multiple groups of fractions in the above-mentioned high-pressure preparation input and output sample module 810 are collected.

[0136] When the sample begins to be filtered before wet medium pressure, the detection and filtration robot 852 transfers the concentration bottle tray and the filter funnel tray from the main shelf 856 to the cache rack 864, and the detection and filtration robot 852 takes an empty concentration bottle and a filter funnel and places them in the corresponding position in the mesh filtration module 860, and takes a concentration bottle containing a sample and places it in the corresponding position in the mesh filtration module 860; the sample is poured into the filter funnel, and the sealing plate of the mesh filtration module 860 is automatically pressed down to pressurize the funnel to complete the filtration. The detection and filtration robot 852 puts the filter funnel and the concentration bottle back to the corresponding tray, and puts the tray back to the main shelf 856. The sample that has been filtered before wet medium pressure can be transferred to the medium pressure preparation and separation equipment 700 for wet medium pressure treatment.

[0137] The high-pressure preparation and separation equipment disclosed in the present invention realizes the automation of consumables loading, temporary storage, transportation and transfer between processing modules by adopting a detection and filtration robot arm 852, an AGV vehicle and various handling tools, and realizes the automation of high-pressure preparation separation, purification, collection and filtration operations through a high-pressure preparation and separation station 820 and a detection and filtration station 850.

[0138] Analytical equipment

[0139] LCMS analysis device

[0140] See also Fig.12 According to the LCMS analysis device 900 of the analysis equipment disclosed in the present invention, different mass spectrometers are used to implement LCMS analysis from different aspects, which includes a robot arm and ground rail module 910, a first mass spectrometer 912, a second mass spectrometer 914, an LCMS analysis AGV exchange bin 916, and a temporary storage shelf 918 ( Fig.12 3 are shown in the figure), fraction collection module 920 and automatic sample injector 922 ( Fig.12 2 are shown as examples in FIG.

[0141] The first mass spectrometer 912 is used to perform simpler analysis such as molecular weight analysis on the sample. The second mass spectrometer 914 is used to perform complex sample analysis such as molecular structure analysis. For example, in some preferred embodiments, the first mass spectrometer 912 can be a single-rod mass spectrometer, and the second mass spectrometer 914 can be a QOTF mass spectrometer so that the device can independently perform HPLC and QTOF analysis, but the first mass spectrometer 912 and the second mass spectrometer 914 can select any of various mass spectrometers known in the art such as quadrupole mass spectrometer, ion trap mass spectrometer, time-of-flight mass spectrometer and magnetic mass spectrometer as needed. By using different first mass spectrometers 912 and second mass spectrometers 914, different analyses can be performed independently on the sample at the same time, thereby shortening the time consumption of the entire processing and improving the efficiency of the separation and analysis processing. The fraction collection module 920 is used to receive the fractions output after LCMS analysis. The automatic sampler 922 is used to automatically send the sample to any one of the first mass spectrometer 912 and the second mass spectrometer 914.

[0142] Before the process begins, the AGV places the trays to be tested and the trays to be collected for fractions in the LCMS analysis AGV exchange bin 916. The robot arm and the ground rail module 910 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 test requirements, thereby directly obtaining the test results and uploading the test report. On the other hand, the fractions output after LCMS analysis are received by the corresponding fraction collection module 920, and then transported to the LCMS analysis AGV exchange bin 916 by the robot arm and the ground rail module 910, and transported to the next process by the AGV.

[0143] The LCMS analysis device 900 disclosed in the present invention realizes the automation of loading, temporary storage, transportation and transfer of consumables between processing modules by adopting a robotic arm and a ground rail module 910, an AGV vehicle and various transport tools, and realizes the automation of operations such as LCMS analysis by a first mass spectrometer 912, a second mass spectrometer 914, a fraction collection module 920 and an automatic sampler 922, and can simultaneously perform different LCMS analyses on samples as needed.

[0144] Cell analysis device

[0145] See also Fig.13 According to the analysis equipment disclosed herein, the cell analysis device 1000 includes a pipetting workstation 1010, a plate washer 1012, an analysis centrifuge 1014, an ELISA instrument 1016, a labeling device 1018, an AGV interactive rack 1020, a storage stack 1022, a cell culture incubator 1024, a high-content imaging analysis module 1026, and a robotic arm and floor rail module 1028.

[0146] The pipetting workstation 1010 performs automatic precision pipetting operations on the well plate. The plate washer 1012 automatically cleans the well plate. The analytical centrifuge 1014 is used for centrifugation operations. Generally, the centrifuge 1014 performs centrifugation operations on up to 2 well plates at a time; in some embodiments, the centrifuge 1014 is used to centrifuge the liquid in the well plate. The microplate reader 1016 is used for enzyme label detection; generally, the microplate reader can be used for enzyme-linked immunosorbent assay (ELISA), and can be used for cell target detection in the present disclosure. The labeling device 1018 can automatically label the well plate, for example, automatically labeling on four sides. The AGV interactive rack 1020 can be used to realize the interaction between the cell analysis device 1000 and various parts of the entire pharmaceutical automated processing and analysis detection system. The periphery of the cell analysis device 1000 is reserved with a manual door for manual maintenance. The storage stack section 1022 is used to store consumables and well plates for cell culture detection. In some embodiments, 9 columns and 16 layers of standard well plate storage positions are provided. The cell culture box 1024 provides a cell culture environment for cell culture. The high-content imaging analysis module 1026 can be used for cell imaging analysis detection; in some embodiments, the high-content imaging analysis module 1026 can be used for cell phenotype detection and cell target detection. The robotic arm and ground rail module 1028 is used to transfer and connect various functional modules in series.

[0147] In some embodiments, such an analysis and detection process can be performed. In the cell analysis device 1000, cells or samples and cells are added to the well plate as needed, and the well plate is transferred to the cell culture box 1024 for culture and incubation through the robotic arm and the ground rail module 1028. After the incubation is completed, the incubated cells are transferred to the plate washer 1012 for washing. Next, a portion of the cells are transferred to the high-content imaging analysis module 1026 for imaging detection; another portion of the cells is transferred to the cell culture box 1024, the color development solution is added and transferred to the microplate reader 1016 for microplate detection. In this way, a portion of cells can be used for high-content and microplate reader analysis at the same time.

[0148] In the cell analysis device 1000 of the present invention, the loading, temporary storage, transportation and transfer of consumables between processing modules are automated by replacing manual operations with a robotic arm and a ground rail module 1028, an AGV vehicle and various transport tools, and automatic cell analysis is achieved through a plate washer 1012, an analytical centrifuge 1014, an ELISA instrument 1016, a labeling device 1018, a cell culture box 1024 and a high-content imaging analysis module 1026.

[0149] In addition, the present disclosure also provides a method for automated processing and analysis of medicines.

[0150] See also Fig.14According to an embodiment of the present disclosure, the method for automated processing and analysis of medicines includes the following steps: an extraction step S100, in which the transport device sends the sample container containing the sample into the shaker 103 of the extraction device, and incubates the sample by shaking through a cold soaking method; a preparation step S102, in which the transport device sends the sample after shaking and incubation into at least one preparation device for preparation; and an analysis step S104, in which the transport device transports the sample after preparation to the analysis device for detection and analysis.

[0151] The present 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 processes on medical samples: automated high-performance liquid chromatography-mass spectrometry detection and analysis of medical samples, automated detection and analysis of medical samples by high-performance liquid chromatography-mass spectrometry, and automated detection and analysis of cellular biological activity and toxicity of medical samples.

[0152] In some embodiments, the analysis equipment includes at least one of an equipment for automated high performance liquid chromatography-mass spectrometry detection and analysis of medical samples, an equipment for automated high performance liquid chromatography-mass spectrometry detection and analysis of medical samples, and an equipment for automated detection and analysis of cell activity and toxicity of medical samples.

[0153] In some embodiments, the extraction step S100 includes: a loading step, in which a loading robot places a sample container containing a sample on the loading position 101; a visual recognition step, in which a visual recognition step is performed to identify whether the sample container is located in an appropriate storage position on the loading position 101; and a shaking incubation step, in which the loading robot grabs and moves the sample container to the shaker 103 for shaking incubation of the sample.

[0154] In some embodiments, the preparation step S102 includes at least one of a dilution and reconstitution step, a centrifugal filtration step, a freeze-drying step, a centrifugal concentration step, a dry loading step, a medium-pressure preparation and separation step, and a high-pressure preparation and separation step.

[0155] In some embodiments, in the preparation step S102, at least one of the dilution and reconstitution step, the centrifugal filtration step, the freeze-drying step, the centrifugal concentration step, the dry loading step, the medium-pressure preparation and separation step, and the high-pressure preparation and separation step can be performed multiple times.

[0156] In some embodiments, the dilution and reconstitution step is performed before the medium-pressure preparation and separation step, and the centrifugal concentration step is performed after the medium-pressure preparation and separation step; and the dilution and reconstitution step is performed before the high-pressure preparation and separation step, and the centrifugal concentration step is performed after the high-pressure preparation and separation step. The freeze-drying step is performed after the centrifugal concentration step.

[0157] In some embodiments, the dry loading step is performed before the medium pressure preparation and separation step. In some embodiments, the dilution and reconstitution step is performed after the freeze drying step. In some embodiments, the centrifugal filtration step is performed after the extraction step, and the analysis step S104 is performed after the medium pressure preparation and separation step and / or the high pressure preparation and separation step.

[0158] In some embodiments, the preparation step S102 may include a dilution and re-dissolution step, which includes: a liquid addition step, in which the sample is transferred to the liquid addition module 216 for liquid addition operation; an oscillation step, in which after the liquid addition operation is completed, the sample is transferred to the oscillation module 238 for ultrasonic oscillation; a dissolution confirmation step, in which the sample is confirmed to be completely dissolved by the visual inspection module 239; 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, the dilution and re-dissolution step also includes a centrifugation step, in which the transport device moves the sample container into the centrifugation module 222 for centrifugation as needed.

[0159] In some embodiments, the preparation step S102 may include a centrifugal filtration step, which includes: a coarse filtration step, in which a clean coarse screen is placed in the filtration module 316, and the sample is filtered through the coarse screen for coarse filtration, and then the coarse screen is removed; a balancing step, in which a plurality of samples that have undergone coarse filtration are weighed, and if the weight difference between the plurality of samples exceeds the allowable range, a balancing operation is performed on the plurality of samples by pipetting; a centrifugal step, in which the plurality of samples that have completed balancing are moved into a centrifugal device for centrifugal operation; and a fine filtration step, in which a clean fine screen is placed in the filtration module 316, and the sample is filtered through the fine screen for fine filtration. In some embodiments, the balancing step includes: a weighing step, in which a plurality of samples are weighed; and a pipetting step, in which a portion of the samples in a sample container containing more samples are moved into another sample container.

[0160] In some embodiments, the 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 the freeze dryer 422 for freeze drying, and the freeze-dried sample container is weighed. In some embodiments, the freeze-drying step also includes labeling the sample container.

[0161] In some embodiments, the preparation step S102 includes a centrifugal concentration step. In the centrifugal concentration step, multiple sample containers are transferred to an adapter, and the adapter is loaded 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 balances the multiple sample containers. After balancing the multiple sample containers, the centrifugal concentrator 510 is started again.

[0162] In some embodiments, the preparation step S102 includes a dry loading step, which includes: a powder adding step, placing the powder barrel and the rotary evaporation column containing silica gel powder in the powder adding module 612, and the powder adding module 612 adds silica gel powder to the rotary evaporation column; a rotary evaporation step, transferring 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, after the rotary evaporation column has been dried, transferring the rotary evaporation column to the powder scraping and rotating module 624, and replacing the powder scraping tool to scrape the powder on the rotary evaporation column. In some embodiments, the dry loading step also includes: a judgment step, transferring the rotary evaporation column after rotary evaporation to the second visual detection module 616, and the second visual detection module 616 analyzes the rotary evaporation column after rotary evaporation to determine whether the sample in the rotary evaporation column is dried, and transferring the rotary evaporation column after scraping powder to the second visual detection module 616, and the second visual detection module 616 takes photos and analyzes the rotary evaporation column after scraping powder to detect the state of the contents. In some embodiments, after the powder scraping and rotating step, the dry loading step further includes: a cleaning step, moving 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 loading step further includes: a pouring step, replacing the pouring tool to pour the powder in the rotary evaporation column into the loading column; a powder shaking step, transferring the loading column to the powder shaking module 614 for powder shaking; and a powder loading step, transferring the powder barrel and the loading column to the powder adding module 612 for powder loading.

[0163] In some embodiments, the preparation step S102 includes a medium-pressure preparation and separation step, which includes: a preparation step, transferring the required materials through a transfer device; and a preparation and separation step, transferring the required materials to a predetermined module through a transfer device. In the case of dry loading, the components are separated and purified through the column packing module 716, the pump-valve module 720, the medium-pressure fraction collection module 722 and the mobile phase buffer module 724; in the case of wet loading, the components are separated and purified through the column packing module 716, the sample addition and needle cleaning module 718, the pump-valve module 720, the medium-pressure fraction collection module 722 and the mobile phase buffer module 724.

[0164] In some embodiments, in the preparation and separation step, in the case of dry sampling, the corresponding chromatographic column and the loading column are transported to the column packing module 716 by a transfer device. The column packing module 716 connects the chromatographic column and the loading column. The predetermined mobile phase is extracted from the mobile phase buffer module 724 through the pump-valve module 720 and injected into the column packing module 716 to elute the loading column and the chromatographic column. The eluted liquid is then introduced into the medium-pressure fraction collection module 722 by the pump-valve module 720 in the preparation and separation step to separate and purify the sample components.

[0165] In some embodiments, in the preparation and separation step, in the case of wet loading, the corresponding chromatographic column is transported to the column packing module 716 by a transport device, the column packing module 716 is connected to the chromatographic column, and the tray containing the sample test tube is transferred to the sample loading and liquid addition and needle cleaning module 718 by the transport device. The sample liquid in the test tube is introduced into the pump-valve module 720 through the sample loading and liquid addition 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 then injects it into the column packing module 716 to elute the chromatographic column. The eluted liquid is then introduced into the medium-pressure fraction collection module 722 by the pump-valve module 720 to separate and purify the sample components.

[0166] In some embodiments, the preparation step S102 includes a high-pressure preparation and separation step, a high-pressure pre-filtration step, in which the sample before the high-pressure preparation and separation is filtered by the positive pressure filtration module 858; a high-pressure preparation step, in which the sample that has been filtered before the high-pressure preparation is sent to the high-pressure preparation inlet and outlet sample module 810 for high-pressure preparation and separation, and the pump valve analysis module 812 extracts the sample liquid from the high-pressure preparation inlet and outlet sample 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 mixed liquid, and analyzes each component, and then exports the different components to the high-pressure preparation inlet and outlet sample module 810, and the high-pressure preparation inlet and outlet sample module 810 collects the fractions condensed at different time periods or different temperatures; and a pipetting step, in which the sample is transferred from one sample container to other sample containers through the pipetting module 862 for subsequent processing steps.

[0167] In some embodiments, the high-pressure preparation and separation step further includes: in the case of wet loading, filtering the sample through the mesh filtration module 860, and then performing the medium-pressure preparation and separation step.

[0168] In some embodiments, in the analysis step S104, the treated sample is sent to the analysis equipment for detection and analysis to obtain the detection result of the sample. In some embodiments, the analysis step S104 includes an LCMS analysis step and a cell analysis step. In the LCMS analysis step, the sample is sent to the mass spectrometer for LCMS analysis to obtain the detection result and upload the detection report; in the cell analysis step, the enzyme label detection is performed by the microplate reader 1016 and the cell imaging analysis detection is performed by the high content imaging analysis module 1026. In some embodiments, the LCMS analysis step includes: performing a simpler analysis on the sample by the first mass spectrometer 912; and performing complex sample analysis by the second mass spectrometer 914.

[0169] Those skilled in the art can understand that the preparation step S102 in the pharmaceutical automated processing and analysis detection method disclosed in the present invention can actually include a dilution and reconstitution step, a centrifugal filtration step, a freeze-drying step, a centrifugal concentration step, a dry loading step, a medium-pressure preparation and separation step, and a high-pressure preparation and separation step, and the analysis step S104 can include an LCMS analysis step and a cell analysis step; those skilled in the art can also understand that at least some of these steps can be selected as needed to be performed in any suitable order.

[0170] The following is an example of a possible execution sequence. First, perform extraction step S100 to perform shaking extraction; then perform centrifugal filtration, centrifugal concentration and / or freeze-drying, dilution and re-dissolution (and merge in this step) and the first medium-pressure preparative separation in sequence, and one part of the separated sample is subjected to LCMS analysis to obtain results while the other part is subjected to centrifugal concentration, freeze-drying, dilution and re-dissolution and the second medium-pressure preparative separation in sequence; the sample separated by the second medium-pressure preparative separation is divided into two parts again to perform LCMS analysis to obtain results and centrifugal concentration, freeze-drying and dilution and re-dissolution in sequence; the diluted and re-dissolved part of the sample is subjected to high-pressure preparative separation, and then the separated sample is divided into two parts again to perform LCMS analysis to obtain results and centrifugal concentration, freeze-drying and dilution and re-dissolution in sequence.

[0171] In the pharmaceutical automated processing and analysis detection system and method provided in the present invention, the automation of loading, temporary storage, transportation and transfer of materials and consumables between processing modules is realized by adopting corresponding robotic arms, AGV vehicles and various handling tools, thereby assisting in the full process automation of a series of operations such as sample extraction, disposal, detection and analysis.

[0172] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present disclosure, rather than to limit them. Although the present disclosure has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or replace some or all of the technical features therein by equivalents. However, these modifications or replacements do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present disclosure.

Claims

1. A method for automated processing and analysis of medicines, characterized in that: The automated processing of medical samples comprises the following steps: In the extraction step, the transport device transports the sample container containing the sample into the shaker of the extraction device, and shakes and incubates the sample by cold immersion method; The preparation step, wherein the transport device sends the sample after shaking incubation to at least one preparation device for preparation processing; as well as In the analysis step, the transport device transports the prepared sample to the analysis device for detection and analysis.

2. The method for automated processing and analysis of medicines according to claim 1, characterized in that: The extraction step comprises: A loading step, in which a loading robot arm places the sample container containing the sample on a loading position; a visual recognition step of recognizing whether the sample container is located at a proper storage position on the loading station; and In the shaking and incubation step, the loading robot grabs and carries the sample container to the shaking table to perform the shaking and incubation on the sample.

3. The method for automated processing and analysis of medicines according to claim 1, characterized in that: The preparation steps include at least one of a dilution and reconstitution step, a centrifugal filtration step, a freeze-drying step, a centrifugal concentration step, a dry loading step, a medium-pressure preparation and separation step, and a high-pressure preparation and separation step.

4. The method for automated processing and analysis of medicines according to claim 3, characterized in that: In the preparation steps, at least one of the dilution and reconstitution step, the centrifugal filtration step, the freeze-drying step, the centrifugal concentration step, the dry loading step, the medium-pressure preparation and separation step, and the high-pressure preparation and separation step is performed once or multiple times.

5. The method for automated processing and analysis of medicines according to claim 3, characterized in that: The dilution and re-dissolution step is performed before the medium-pressure preparation and separation step; as well as The centrifugal concentration step is performed after the medium-pressure preparative separation step.

6. The method for automated processing and analysis of medicines according to claim 3, characterized in that: The dry loading step is performed before the medium-pressure preparative separation step.

7. The method for automated processing and analysis of medicines according to claim 3, characterized in that: performing the dilution and reconstitution step before the high pressure preparation and separation step; and The centrifugal concentration step is performed after the high pressure preparative separation step.

8. The method for automated processing and analysis of medicines according to claim 3, characterized in that: The lyophilization step is performed after the centrifugal concentration step.

9. The method for automated processing and analysis of medicines according to claim 3, characterized in that: The dilution and reconstitution step is performed after the lyophilization step.

10. The method for automated processing and analysis of medicines according to claim 3, characterized in that: The centrifugal filtration step is performed after the extraction step, and the analysis step is performed after the medium-pressure preparation and separation step and / or the high-pressure preparation and separation step.

11. The method for automated processing and analysis of medicines according to claim 1, characterized in that: The preparation step includes a dilution and re-dissolution step, and the dilution and re-dissolution step includes: Liquid adding step, transferring the sample to the liquid adding module for liquid adding operation; A shaking step, after the liquid adding operation is completed, transferring the sample to a shaking module for ultrasonic shaking; a dissolution confirmation step, confirming that the sample is completely dissolved by a visual inspection module; and The merging step is to merge the samples in the plurality of sample containers by at least one of pipetting and pouring.

12. The method for automated processing and analysis of medicines according to claim 11, characterized in that: The dilution and reconstitution step also includes a centrifugation step, and the transport device moves the sample container into a centrifugation module for centrifugation as needed.

13. The method for automated processing and analysis of medicines according to claim 1, characterized in that: The preparation step includes a centrifugal filtration step, and the centrifugal filtration step includes: A coarse filtration step, placing a clean coarse screen into a filtration module, and filtering the sample through the coarse screen for coarse filtration, and then removing the coarse screen; a balancing step, weighing the multiple samples after the coarse filtration operation, and if the weight difference between the multiple samples exceeds the allowable range, balancing the multiple samples by pipetting operation; a centrifugation step, transferring the balanced samples into a centrifugal device for centrifugation; and In the fine filtration step, a clean fine mesh is placed in the filtration module, and the sample is filtered through the fine mesh to perform a fine filtration operation. The balancing step includes: a weighing step of weighing the multiple samples; and a pipetting step of transferring a portion of the samples in a sample container containing more samples into another sample container.

14. The method for automated processing and analysis of medicines according to claim 1, characterized in that: The preparation step includes a freeze-drying step, in which a sample container containing a sample is weighed, the weighed sample is sent to a freeze-drying device for freeze-drying, and the freeze-dried sample container is weighed.

15. The method for automated processing and analysis of medicines according to claim 1, characterized in that: The preparation step includes a centrifugal concentration step, in which a plurality of sample containers are transferred to an adapter, and the adapter is placed in a centrifugal concentration device for centrifugal concentration operation. Wherein, the centrifugal concentrator includes an imbalance detection sensor. When the imbalance detection sensor monitors that the weight difference between the multiple sample containers in the adapter exceeds a predetermined threshold, the centrifugal concentrator automatically stops and balances the multiple sample containers. After balancing the multiple sample containers, the centrifugal concentrator continues to start.

16. The method for automated processing and analysis of medicines according to claim 1, characterized in that: The preparation step includes a dry loading step, and the dry loading step includes: A powder adding step, placing a powder barrel containing silica gel powder and a rotary evaporation column in a powder adding module, wherein the powder adding module adds silica gel powder to the rotary evaporation column; A rotary evaporation step, transferring the powdered rotary evaporation column to a rotary evaporation module, wherein the rotary evaporation module performs rotary evaporation on the rotary evaporation column; and The powder scraping and rotating step is to transfer the rotary evaporation column to a powder scraping and rotating module after the rotary evaporation column has been dried, and replace the powder scraping tool to scrape the powder on the rotary evaporation column.

17. The method for automated processing and analysis of medicines according to claim 16, characterized in that: The dry loading step further includes: a judgment step, transferring the rotary evaporation column to a visual detection module, wherein the visual detection module analyzes the rotary evaporation column to judge the state of the sample in the rotary evaporation column.

18. The method for automated processing and analysis of medicines according to claim 16, characterized in that: After the powder scraping and rotating step, the dry loading step further comprises: A pouring step, replacing a pouring tool to pour the powder in the rotary evaporation column into the loading column; a powder shaking step, transferring the sample loading column to a powder shaking module for powder shaking; and The powder material loading step is to transfer the powder barrel and the loading column to the powder loading module for powder material loading.

19. The method for automated processing and analysis of medicines according to claim 18, characterized in that: After the powder scraping and rotating step, the dry loading step further comprises: The cleaning step is to move the powder scraping tool to a scraper cleaning module to clean the powder scraping tool.

20. The method for automated processing and analysis of medicines according to claim 1, characterized in that: The preparation step includes a medium-pressure preparation and separation step, and the medium-pressure preparation and separation step includes: a preparation step, transferring the required materials through the transfer equipment; and The preparation and separation step is to transfer the required materials to the predetermined module through the transfer equipment. In the case of dry sampling, the components are separated and purified through the column packing module, the pump-valve module, the medium-pressure fraction collection module and the mobile phase buffer module; in the case of wet sampling, the components are separated and purified through the column packing module, the sample addition and needle cleaning module, the pump-valve module, the medium-pressure fraction collection module and the mobile phase buffer module.

21. The method for automated processing and analysis of medicines according to claim 20, characterized in that: In the preparation and separation step, in the case of dry sampling, the corresponding chromatographic column and the loading column are transported to the column packing module by the transfer equipment, the column packing module is connected to the chromatographic column and the loading column, and the predetermined mobile phase is extracted from the mobile phase buffer module through the pump-valve module and injected into the column packing module to elute the loading column and the chromatographic column. The eluted liquid is then introduced into the medium-pressure fraction collection module by the pump-valve module in the preparation and separation step to separate and purify the sample components.

22. The method for automated processing and analysis of medicines according to claim 20, characterized in that: In the preparation and separation step, in the case of wet sampling, the corresponding chromatographic column is transported to the column packing module by the transport equipment, the column packing module is connected to the chromatographic column, and the tray containing the sample tube is transferred to the sample loading and liquid addition and needle cleaning module by the transport equipment. The sample liquid in the test tube is introduced into the pump-valve module through the sample loading and liquid addition and needle cleaning module. The pump-valve module extracts a predetermined mobile phase from the mobile phase buffer module and mixes it with the sample liquid and then injects it into the column packing module to elute the chromatographic column. The eluted liquid is then introduced into the fraction collection module by the pump-valve module to separate and purify the sample components.

23. The method for automated processing and analysis of medicines according to claim 20, characterized in that: The preparation step includes a high pressure preparation separation step, A high-pressure pre-filtration step, filtering the sample before high-pressure preparation and separation through a positive pressure filtration module or a screen filtration module; The high-pressure preparation step is to send the sample that has been filtered before high pressure into the high-pressure preparation inlet and outlet sample module for high-pressure preparation separation, the pump valve analysis module extracts the sample liquid from the high-pressure preparation inlet and outlet sample module, extracts a predetermined mobile phase from the mobile phase buffer and mixes it with the sample liquid, separates the components of the mixed liquid, and analyzes each component, and then guides the different components to the high-pressure preparation inlet and outlet sample module, and the high-pressure preparation inlet and outlet sample module collects the fractions condensed at different time periods or different temperatures; as well as The pipetting step is to transfer the sample from one sample container to other sample containers through the pipetting module for subsequent processing.

24. The method for automated processing and analysis of medicines according to claim 23, characterized in that: The high-pressure preparation and separation step further comprises: in the case of the wet loading method, filtering the sample through a mesh filtration module, and then performing the medium-pressure preparation and separation step.

25. The method for automated processing and analysis of medicines according to claim 1, characterized in that: In the analysis step, the treated sample is sent to an analysis device for detection and analysis to obtain the test result of the sample. The analysis step includes an LCMS analysis step and a cell analysis step, In the LCMS analysis step, the sample is sent to a mass spectrometer for LCMS analysis to obtain a test result and upload a test report, wherein a simpler analysis of the sample is performed by a first mass spectrometer and a complex sample analysis is performed by a second mass spectrometer; and In the cell analysis step, the cells added with the sample are incubated in a cell culture incubator and subjected to enzyme labeling detection by an ELISA reader and / or cell imaging analysis detection by a high-content imaging analysis module.

26. A pharmaceutical automated processing and analysis detection system, characterized in that: The pharmaceutical automated processing and analysis detection system comprises: An extraction device, wherein the extraction device shakes and incubates the sample contained in the sample container by a cold immersion method through a shaker; A plurality of preparation devices, wherein the plurality of preparation devices perform preparation processing on the samples after shaking incubation; An analysis device for detecting and analyzing the prepared sample; and A transport device is provided for transporting samples and sample containers within and between the extraction device, the preparation device and the analysis device.

27. The pharmaceutical automated processing and analysis detection system according to claim 26, characterized in that: The pharmaceutical automated processing and analysis detection system also includes: Material storage equipment to hold the consumables needed in the process; and Charging pile, used to charge devices that need to be charged.

28. The pharmaceutical automated processing and analysis detection system according to claim 27, characterized in that: The material storage equipment includes a warehouse station, The warehouse station includes a warehouse station robot and one or more storage stacks, Each of the one or more storage stacks includes a plurality of columns of storage racks, each column of storage racks has the same height and is provided with different numbers of storage layers according to the volume of the consumables placed; The materials are transported from the outside of the material storage device to the corresponding storage position on the storage rack through the AGV vehicle and the warehouse station robot arm.

29. The pharmaceutical automated processing and analysis detection system according to claim 26, characterized in that: The extraction device comprises: Loading position, the sample container containing the sample is placed on the loading position; A visual recognition module, the visual recognition module is used to identify whether the sample container is located at a proper storage position on the loading position; An extraction robot arm, the extraction robot arm is used to grab and carry the sample container; and A shaker is used for shaking and incubating the sample.

30. The pharmaceutical automated processing and analysis detection system according to claim 26, characterized in that: The multiple preparation equipment includes a dilution and re-dissolution equipment, and the dilution and re-dissolution equipment includes: A liquid adding module, the liquid adding module is used to add liquid to the sample container; A pipetting module, the pipetting module is used to transfer at least a portion of a sample in a sample container to another sample container; An oscillation module, the oscillation module is used to perform ultrasonic oscillation on the sample container; A first visual inspection module, the first visual inspection module is used to detect whether the sample in the sample container after ultrasonic vibration is completely dissolved; and A centrifugal module, when the sample container is a test tube, the centrifugal module is used to perform a centrifugal operation on the sample container that has been treated with ultrasonic vibration.

31. The pharmaceutical automated processing and analysis detection system according to claim 26, characterized in that: The plurality of preparation devices include a centrifugal filtration device, wherein the centrifugal filtration device includes: A filtering module, wherein the filtering module is used to perform a filtering operation on the sample to obtain a filtered sample; a centrifuge, the centrifuge being used to centrifuge the sample container containing the filtered sample to separate the supernatant and the residue; a weighing and pipetting device that performs a balancing operation on a plurality of sample containers; and A centrifugal filtering robot arm performs the transfer operations required for the filtering operation, the centrifugal operation and the balancing operation by replacing different tools to assist in completing the filtering operation, the centrifugal operation and the balancing operation.

32. The pharmaceutical automated processing and analysis detection system according to claim 26, characterized in that: The plurality of preparation equipment includes a freeze-drying equipment, and the freeze-drying equipment includes: A weighing module, the weighing module is used to weigh the sample container before and after freeze-drying; A freeze dryer, the freeze dryer is used to freeze-dry and concentrate the sample in the sample container; A labeling machine, the labeling machine is used to label the sample container; and The freeze-drying robot arm transfers different types of sample containers between the weighing module, the freeze dryer and the labeling machine by replacing different grippers to assist in completing weighing operations, freeze-drying operations and labeling operations.

33. The pharmaceutical automated processing and analysis detection system according to claim 26, characterized in that: The plurality of preparation devices include a centrifugal concentration device, wherein the centrifugal concentration device includes: A centrifugal concentrator, which performs centrifugal concentration operations on samples in a plurality of sample containers, and has an imbalance detection sensor; a balancing weighing module, which balances the samples in the multiple sample containers when the imbalance detection sensor detects that the weight difference of the multiple sample containers exceeds a certain threshold; and A centrifugal concentration robot arm transfers different types of grasped objects between the centrifugal concentrator and the balancing weighing module by replacing different grippers to assist in completing centrifugal concentration.

34. The pharmaceutical automated processing and analysis detection system according to claim 26, characterized in that: The plurality of preparation devices include a dry method sample loading device, and the dry method sample loading device includes: A powder adding module, which is used to quantitatively add powder to the sample loading column and the rotary evaporation column; A rotary evaporation module, the rotary evaporation module is used to spin dry the sample in the rotary evaporation column; A powder scraping tool, which is used to scrape powder from the rotary evaporation column; A scraper cleaning module, the scraper cleaning module is used to clean and wipe the scraper of the powder scraping tool performing the powder scraping operation; A powder leveling module, the powder leveling module is used to level the powder in the sample loading column; A switch cover and a powder scraping and rotating module, wherein the switch cover and the powder scraping and rotating module are used to fix and rotate the rotary evaporation column and the sample loading column when the covers are opened, and to fix and rotate the rotary evaporation column when the powder scraping operation is performed on the rotary evaporation column; and The second visual detection module is used to detect the state of the sample in the rotary evaporation column.

35. The pharmaceutical automated processing and analysis detection system according to claim 26, characterized in that: The plurality of preparation equipments include a medium-pressure preparation and separation equipment, and the medium-pressure preparation and separation equipment includes: a column packing module, to which the chromatographic column and the loading column are transferred for column connection; A sample loading, liquid adding and needle cleaning module, which is used to perform sample loading, liquid adding and needle cleaning operations, and a sample container containing a sample is transferred to the sample loading, liquid adding and needle cleaning module; A medium-pressure fraction collection module, which is used to collect fractions condensed at different time periods or temperatures for subsequent analysis or use; A pump-valve module, which is used to perform related processing of pumping liquid and analysis; and A mobile phase buffer, the mobile phase buffer is used to cache the mobile phase required for processing; The pump-valve module is connected to the sample loading and needle cleaning module, the column packing module, the medium-pressure fraction collection module, and the mobile phase buffer module through pipelines, respectively, to provide power for liquid transmission between the above modules.

36. The pharmaceutical automated processing and analysis detection system according to claim 26, characterized in that: The multiple preparation equipments include high-pressure preparation and separation equipment, and the high-pressure preparation and separation equipment includes a high-pressure preparation and separation station and a detection and filtration station.

37. The pharmaceutical automated processing and analysis detection system according to claim 36, characterized in that: The detection and filtration station comprises: A positive pressure filtration module, which is used for filtering before applying high pressure treatment to the sample; A mesh filtration module, the mesh filtration module is used for filtering before applying high pressure treatment to the sample or before wet loading the sample; and A pipetting module is used to transfer samples from one sample container to other sample containers for subsequent analysis procedures.

38. The pharmaceutical automated processing and analysis detection system according to claim 37, characterized in that: The high pressure preparation and separation station comprises: A high-pressure sample preparation inlet and outlet module, which is used to perform high-pressure preparation separation on the sample that has passed through the positive pressure filtration module or the mesh filtration module and transfer it to the pipetting module; A mobile phase buffer, the mobile phase buffer is used to introduce the sample in the high pressure sample preparation inlet and outlet module, and introduce a predetermined mobile phase in the mobile phase buffer according to the introduced sample, so that the sample and the predetermined mobile phase are mixed to obtain a second mixed solution; and A pump-valve analysis module, which is used for performing related processing of pumping liquid and analysis, wherein the pump-valve analysis module separates the components of the second mixed liquid, analyzes each component, and then exports the different components to the high-pressure preparation input and output sample module for fraction collection.

39. The pharmaceutical automated processing and analysis detection system according to claim 26, characterized in that: The analytical equipment comprises an LCMS analytical device, and the LCMS analytical device comprises: a first mass spectrometer for performing a simpler analysis of the sample; a second mass spectrometer, the second mass spectrometer being used to perform complex sample analysis; a fraction collection module, the fraction collection module being used to receive the fractions output after being analyzed by the first mass spectrometer or the second mass spectrometer or both; and An automatic sample injector, the automatic sample injector is used to automatically send a sample into any one of the first mass spectrometer and the second mass spectrometer.

40. The pharmaceutical automated processing and analysis detection system according to claim 26, characterized in that: The analysis equipment comprises a cell analysis device, and the cell analysis device comprises: A pipetting workstation, which performs automatic precision pipetting operations on the well plate; A plate washer, which automatically cleans the well plate; A cell culture box, which provides a cell culture environment; A centrifuge, the centrifuge is used to perform a centrifugal operation on the orifice plate; An enzyme-labeling instrument, which is used to perform enzyme-labeling detection of targets on the well plate containing the cultured cells; a labeling device, the labeling device being used to automatically label the orifice plate; and A high-content imaging analysis module is used to perform cell imaging analysis on the cultured cells in the well plate.

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