A proteomic sample pre-treatment system and method of treatment

Abstract

The present specification discloses a proteomics sample pretreatment system and processing method, wherein the system comprises a machine frame, a moving crossbeam, a lifting column, a switching disc, a pipette, a gripper, a workbench, a test tube bracket, a magnetic separation module, a constant temperature oscillation module, a calibration assembly, a container accessory, an assisting assembly and a controller. The pipette and the gripper are moved to the operation position point of the designated work area of the workbench through the moving crossbeam and the lifting column. The work of the pipette or the gripper is activated through the switching disc, so as to realize the switching of liquid transfer and test tube transfer. The workbench is configured with the functional modules and the container accessories required for each step of the protein sample pretreatment. The controller can execute a specific processing method. Through the system and according to the processing method, the requirements for high efficiency and safety in proteomics detection can be met, automatic processing is realized, the intelligentization of protein sample processing is improved, and it is beneficial to be applied in the precision medical diagnosis of various diseases.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of medicine and biotechnology, in particular, to a proteomics sample pretreatment system and processing method. BACKGROUND

[0002] Blood tests are widely used in clinical detection and treatment. Proteins in blood samples are the most commonly used blood test markers, and protein detection is particularly important. With the continuous development, the demand for medical precision is growing, and the related research on proteomics to find blood protein markers for diseases is gradually deepening. However, in blood detection, high-abundance proteins can affect the detection of low-abundance proteins, and there is currently no efficient amplification method for effective proteins in samples, so protein samples are generally highly valuable and unique, and the complexity and low repeatability of sample pretreatment seriously restrict the development of proteomics.

[0003] The existing proteomics sample pretreatment method relies on manual operation. Even with a lot of training, manual operation will still bring many uncertainties, resulting in a decrease in the stability and reliability of the operation and affecting the accuracy of the detection results. The pipetting device can realize semi-automatic operation of proteomics sample pretreatment, but liquid transfer is only one link of sample pretreatment, and test tube transfer and sample enrichment cannot be standardized and automated. With the development of proteomics, the existing technology cannot meet the requirements of efficiency, accuracy and safety in the process of processing a large number of samples.

[0004] Therefore, there is an urgent need to invent an operation system that can automatically operate each step in the process of proteomics sample pretreatment, so as to facilitate precise medical diagnosis of various diseases. SUMMARY

[0005] The present application provides a proteomics sample pretreatment system and processing method to overcome at least one technical problem in the related art.

[0006] According to a first aspect of the embodiments of the present application, a proteomics sample pretreatment system is provided, comprising a body frame, a moving crossbeam, a lifting column, a switching disc, a pipette, a gripper, a workbench, a test tube holder, a magnetic separation module, a constant temperature oscillation module, a calibration assembly and a controller, wherein

[0007] The body frame is fixed with an external mounting surface.

[0008] The mobile crossbeam is fixed on the top of the machine body frame, and is used for moving the lifting column, switching disc, pipette and clamp on the mobile crossbeam to the position above the designated work area in the workbench, and comprises vertical fixed plates, vertical pulleys, vertical synchronous belts, vertical guide rails, vertical sliding blocks, vertical motors, transmission shafts, shaft couplings, first limit sensors, horizontal moving plates, horizontal guide rails, horizontal synchronous belts, horizontal pulleys, horizontal motors, horizontal sliding blocks and second limit sensors, wherein

[0009] The two vertical fixed plates are oppositely arranged and fixed on the two sides of the machine body frame, and each vertical fixed plate is internally provided with a vertical pulley, a vertical synchronous belt, a vertical guide rail and a vertical sliding block. The two sides are oppositely arranged, and a vertical motor is arranged at one end of one vertical fixed plate, which is connected with the vertical pulley of the other side through a transmission shaft and a shaft coupling. The vertical motor drives the vertical sliding block to slide on the vertical guide rail through the vertical pulley. A first limit sensor is arranged at the end of the vertical guide rail of the vertical fixed plate on one side of the vertical motor.

[0010] The horizontal moving plate slides on the vertical guide rail fixed on the vertical fixed plate, and the horizontal guide rail, the horizontal synchronous belt and the horizontal pulley are fixedly arranged on the horizontal moving plate. The horizontal sliding block is arranged on the horizontal guide rail and connected with the lifting column. The horizontal motor is arranged on one side of the horizontal guide rail. The horizontal motor drives the horizontal synchronous belt through the horizontal pulley, and then drives the horizontal sliding block to slide on the horizontal guide rail. A second limit sensor is arranged at one end of the horizontal guide rail.

[0011] The lifting column is vertically fixed on the mobile crossbeam and is used for changing the spatial height of the switching disc at the end of the lifting column, and comprises a primary push rod, a secondary push rod, a lifting motor, a screw shaft coupling, a primary screw rod, a primary sliding block, a primary gear, a secondary gear, a secondary sliding block, a secondary screw rod, a lifting frame and a third limit sensor, wherein

[0012] One end of the lifting frame is fixedly connected with the horizontal sliding block, and the other end is fixedly connected with the primary push rod. The lower end of the primary push rod is connected with the secondary push rod, and the secondary push rod is connected with the switching disc. The lifting motor is arranged in the lifting frame. The lifting motor is connected with the primary screw rod through the screw shaft coupling. The primary screw rod is provided with the primary sliding block. The primary gear is arranged at the end of the primary screw rod away from the lifting motor. The primary gear is engaged with the secondary gear. The secondary gear is arranged at one end of the secondary screw rod. The secondary screw rod is provided with the secondary sliding block. The primary screw rod is arranged in the primary push rod, and the secondary screw rod is arranged in the primary push rod. The third limit sensor is arranged at the end of the primary screw rod close to the lifting motor.

[0013] The switching disc is fixed at the end of the lifting column away from the mobile crossbeam and comprises a first mounting hole and a second mounting hole.

[0014] A pipette is fixed in the first mounting hole of the switching disc, and includes multiple pipetting channels for sucking and releasing liquid.

[0015] A gripper is fixed in the second mounting hole of the switching disc, and is used for clamping and releasing a test tube holder and batch transferring test tubes between various work areas.

[0016] A workbench is fixed at the bottom of the machine frame, and is used for carrying samples and performing sample pretreatment operations, and includes multiple work areas which are the smallest work units of sample pretreatment operations.

[0017] A test tube holder is located in a work area of the workbench, and includes a first number of test tube holes for carrying test tubes, and the first number is determined according to a preset sample throughput of the system.

[0018] A magnetic separation module is located in a first work area of the workbench, and is used for performing a magnetic bead separation operation, and includes multiple processing units and a module control unit, the processing unit includes a test tube hole and an iron core and a coil located around the hole, each processing unit is used to generate a controllable magnetic field for the reagent inside the test tube installed in the test tube hole, and the module control unit is used to control the processing unit and exchange data with the controller through the power supply and communication interface of the first work area.

[0019] A constant temperature shaking module is located in a second work area of the workbench, and is used for heating and shaking operation in the incubation link, and includes a temperature control unit, a shaking unit, a control unit and a test tube hole, the temperature control unit is used to heat the test tube installed in the corresponding test tube hole; the shaking unit is used to move the corresponding test tube in a preset direction quickly; the control unit is used to control the temperature control unit and the shaking unit and exchange data with the controller through the power supply and communication interface of the second work area.

[0020] A calibration assembly is used for calibrating the system, and includes a camera, a calibration block and a limit sensor, wherein

[0021] The camera is fixed to the lower part of the gripper, and when the gripper is located in the working angle gear position, the camera activates the working state to collect the image information directly below.

[0022] The calibration block is fixed at the gap between the work areas of the workbench, and includes standard scale information and position information, and the scale information and position information are used for camera acquisition.

[0023] The limit sensor includes a first limit stop, a second limit stop and a third limit stop, and is used to determine the initial position and the limit position of the moving cross beam and the lifting column.

[0024] The controller is fixedly arranged in the workbench and includes a central control unit, a motion control unit, an execution control unit, a function control unit, a communication unit and a power management unit, wherein

[0025] The central control unit is configured to coordinate operation of the units in the controller and to perform communication interaction and data storage.

[0026] The motion control unit is configured to control motors and sensors in the moving cross beam, the lifting column and the switching disc and to realize closed-loop motion control according to data returned by the sensors.

[0027] The execution control unit is configured to control motors and sensors in the pipettor and the gripper and to execute pipetting and transfer instructions issued by the central control unit.

[0028] The function control unit is configured to control each work area in the workbench and to execute separation, heating and oscillation instructions issued by the central control unit.

[0029] The communication unit is configured to process data interaction between the system and external devices.

[0030] The power management unit is configured to provide excitation for motors in the system.

[0031] Optionally, the switching disc includes a switching rack, a switching shaft, a mounting hole disc, a first mounting hole position, a second mounting hole position and a switching motor, wherein

[0032] The switching rack is connected to the end of the secondary push rod of the lifting column, one end of the switching shaft is fixedly connected to the switching rack, the other end of the switching shaft is fixedly connected to the mounting hole disc, the first mounting hole position and the second mounting hole position are arranged on the mounting hole disc, the switching motor is arranged in the switching rack, the switching motor drives the switching shaft to rotate, thereby driving the mounting hole disc to rotate, and the mounting hole position perpendicular to the workbench is switched.

[0033] Optionally, the pipettor includes a pipetting fixed point, a pipetting motor, a pipetting lead screw, a pipetting sliding block, a piston rod, a pipetting cavity, a push head, a suction head, a pipetting rack and a spring, wherein

[0034] The pipetting fixed point is fixedly connected to the first mounting hole position of the switching disc, the pipetting motor is connected to the pipetting lead screw, the pipetting lead screw is provided with the pipetting sliding block, the pipetting sliding block is fixedly connected to the second number of pipetting piston rods, the second number of pipetting piston rods are arranged vertically and parallel to each other, the upper end of each piston rod is provided with a spring, and the lower end is located in the pipetting cavity, the lower part of the pipetting cavity is connected to the second number of pipetting channels, the push head is arranged at the outlet of each pipetting channel, the suction head is arranged below the push head in the pipetting channel, the pipetting rack is fixedly connected to the pipetting fixed point and the pipetting cavity, and the second number is determined according to a preset sample throughput of the system.

[0035] Optionally, the gripper includes a gripping fixing point, a gripping frame, a gripping slide, a screw motor, a right slider, a left slider, a right gripper, and a left gripper, wherein...

[0036] The clamping fixing point is fixedly connected to the second mounting hole of the switching disk. The clamping frame connects the clamping fixing point and the clamping slide. The screw motor is located in the clamping slide. The output shaft of the screw motor is a bidirectional screw. The inner side of the right slider is fixedly connected to the right screw of the screw motor, and the outer side of the right slider is connected to the right jaw. The inner side of the left slider is fixedly connected to the left screw of the screw motor, and the outer side of the left slider is connected to the left jaw. When the screw motor rotates forward, the right slider moves to the left and the left slider moves to the right, and the jaw retracts. When the screw motor rotates in reverse, the right slider moves to the right and the left slider moves to the left, and the jaw opens.

[0037] Optionally, the test tube holder includes a rigid frame, a rubber block, a clamping opening, test tube holes, a skirt, and test tubes, wherein...

[0038] The test tube holder is composed of two I-shaped rigid frames on both sides and a rubber block in the middle. Each rigid frame is provided with a clamping port that cooperates with the gripper's claws. The rubber block is provided with a first number of test tube holes. Each test tube hole is provided with a skirt on the upper side. The test tube is inserted into the test tube hole through the skirt.

[0039] Optionally, the magnetic separation module includes a third number of processing units, the third number being determined based on the test tube size and a preset sample throughput of the system.

[0040] Optionally, the workbench includes a fourth number of work areas, each work area including a mounting slot, a power interface, and a communication interface, the fourth number being determined based on the system dimensions.

[0041] Optionally, the system further includes container accessories, which include an orifice plate, a suction head box, and a waste box, each fixed to the worktable by occupying a work area.

[0042] The well plate has a fifth number of wells for holding dispensed samples or reagents required for sample pretreatment. The fifth number is determined based on the test tube size and the preset system throughput. The pipette tip box has a sixth number of wells for holding pipette tips required for pipettes. The sixth number is determined based on the test tube size and the preset system throughput. The waste box is used to hold used pipette tips and excess reagents.

[0043] Optionally, the system further includes a collaboration component, which includes an outer frame, a connecting plate, a transition rail, and a transfer module, wherein...

[0044] An outer frame is fixed with the outer mounting surface, and vertical rails for mounting multiple devices at the top are provided; a transition rail is provided at the top of the outer frame and is used to connect the vertical rails of multiple systems; a connecting plate is provided on the vertical rails and is used to mount a moving cross beam; a transfer module is provided at the boundary of the worktable of multiple systems and includes a hole position of a test tube holder and is used for test tube exchange in the cooperation of multiple systems.

[0045] According to a second aspect of the embodiments of the present specification, a processing method based on a proteomics sample pretreatment system is provided, which is suitable for being executed on a controller of the proteomics sample pretreatment system, and includes the following steps:

[0046] Obtaining operation parameters of a sample to be processed, instantiating each functional module of a configuration work area according to the operation parameters, establishing an operation step of pretreatment corresponding to the sample to be processed according to the operation parameters, and generating an operation sequence according to the operation step.

[0047] According to the feedback data of the sensors in the system, the moving cross beam and the lifting column are moved to the position origin determined by the corresponding limit sensors, the switching disc is rotated to the angular position where the gripper is in the working state, the camera is activated to obtain the images of all work areas of the worktable, the system calibration is completed through the calibration assembly, and all operation points of the work area are identified.

[0048] According to the operation sequence, an execution action is started, which includes liquid transfer, test tube transfer, and function execution, wherein the action switching between the liquid transfer action and the test tube transfer action is achieved by rotating the switching disc, the position movement in the action execution is achieved by cooperation of the moving cross beam and the lifting column, the state changes of the system components, the functional modules, and the test tubes in the action execution are monitored and stored, the liquid transfer includes installing a suction head, sucking liquid, releasing liquid, and rejecting the suction head, the test tube transfer includes clamping a test tube holder, transferring the test tube holder, and placing the test tube holder, and the function execution includes magnetic bead separation, constant temperature heating, and shaking.

[0049] According to a preset early warning judgment condition, the execution of each action is checked, when the action meets the early warning judgment condition, an error alarm is triggered, and the action execution is paused.

[0050] Each component in the system is restored to the position origin, and the next action execution is prepared.

[0051] The beneficial effects of the embodiments of the present specification are as follows:

[0052] The embodiments of the present specification provide a proteomics sample pretreatment system and processing method. The system can realize high-precision spatial motion of the execution end through a moving cross beam and a lifting column, can realize seamless switching of liquid transfer and test tube transfer through a pipettor and a gripper, can cover processing operations of each link of sample pretreatment through a fully functional workbench that can be flexibly edited, and can adapt to high-throughput sample processing in large-scale industrialization of proteomics through a collaboration component that can be freely reorganized. The processing method based on the system has reliable precision calibration strategies and process execution monitoring, ensures the stability of the workstation during unmanned automatic processing, adapts to the experimental operation habits of localized users, and can effectively improve the intelligence, efficiency, accuracy and safety of each step in the proteomics sample pretreatment process, which is helpful for precise medical diagnosis of various diseases.

[0053] The innovation points of the embodiments of the present specification include:

[0054] 1. In the present specification, the moving cross beam and the lifting column adopt a high-compactness design, which maximizes the use of the space within the machine frame. In the prior art, the waste of space within the machine frame is mainly because the movement in the vertical direction generally needs at least twice the stroke of itself to meet the extension and retraction of the push rod. In the present system, the lifting column adopts a two-stage lifting structure, the first stage is responsible for large-stroke height movement, and the second stage is responsible for small-stroke height fine adjustment, which reduces the space occupied by the initial stroke and also improves the efficiency of lifting movement, which is one of the innovation points of the embodiments of the present specification.

[0055] 2. In the present specification, the switching disc can realize quick switching of multiple actuators, which improves the execution efficiency of main actions in the pretreatment process. In the prior art, replacing different actuators requires re-installing the corresponding actuators to the actuator interface, or using special design to fix multiple actuators at the same time, which increases the volume occupation of the execution end and reduces the operation efficiency. In the present system, the switching disc can switch different actuators, which can realize switching of single-channel and multi-channel pipetting or switching of pipetting and clamping, thereby improving the efficiency of action execution, which is one of the innovation points of the embodiments of the present specification.

[0056] 3. In this specification, the editable workbench and the functional modules mounted on it can meet all the requirements of the sample pretreatment process, and the modular design also improves operational flexibility. In the prior art, the integration of functional modules themselves is not high, and the functional implementation is relatively weak. Therefore, more functional modules need to be installed to complete all the steps. Furthermore, since there is no unified interface for functional modules, there are problems with power supply and data interaction. In contrast, the workbench in this system covers the modules corresponding to each step required for proteomics pretreatment, and the execution of functional modules is optimized for the characteristics of pretreatment operations. For example, the magnetic separation module uses a controllable magnetic field to improve separation efficiency. Each functional module can be connected to the system controller and, in conjunction with the processing method, achieves more flexible and intelligent module configuration, which is one of the innovations of the embodiments in this specification.

[0057] 4. In this specification, the collaborative component supports the reconfiguration and splicing of multiple devices, enabling multi-machine collaboration and the construction of flexible pre-processing pipelines. In existing technologies, the splicability of equipment is poor; different specifications often require redesign and production, and direct collaboration and interaction among multiple devices are not supported, making it impossible to create a pipeline of a certain scale. In this embodiment of the invention, by designing transition components, connectors, and fasteners that support disassembly and assembly, the components of various specifications of equipment are unified, and reconfiguration and splicing are natively supported. The introduction of a transfer module to achieve multi-machine collaboration is one of the innovative points of this embodiment.

[0058] 5. In this specification, the workstation control method is optimized for proteomics preprocessing workflows, ensuring intuitive operation plan editing, accurate execution of actions, and reliable workflow operation. In existing technologies, operation plan editing is complex, lacks a systematic approach, and is poorly intuitive. Identification of working sites generally requires manual operation to the corresponding location for teaching. In this embodiment, functional parameter configuration uses description blocks and graph networks to construct functional modules and associate them with other functional blocks and related constraints. Plan editing employs a timeline and anchor point architecture, processing in layers according to workflow, steps, actions, and modules. Furthermore, visual calibration is used to locate the operating sites in each working area, reducing motion errors. This is one of the innovative aspects of this embodiment. Attached Figure Description

[0059] To more clearly illustrate the technical solutions in the embodiments or related technologies of this specification, the drawings used in the description of the embodiments or related technologies will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0060] Figure 1A structural schematic diagram of a proteomics sample pretreatment system provided by an embodiment of the present specification is shown in FIG. 1.

[0061] Figure 2 A structural schematic diagram of a moving beam of a proteomics sample pretreatment system provided by an embodiment of the present specification is shown in FIG. 2.

[0062] Figure 3 A structural schematic diagram of a lifting column and a switching disc of a proteomics sample pretreatment system provided by an embodiment of the present specification is shown in FIG. 3.

[0063] Figure 4 A structural schematic diagram of a pipettor of a proteomics sample pretreatment system provided by an embodiment of the present specification is shown in FIG. 4.

[0064] Figure 5 A structural schematic diagram of a gripper of a proteomics sample pretreatment system provided by an embodiment of the present specification is shown in FIG. 5.

[0065] Figure 6 A structural schematic diagram of a workbench of a proteomics sample pretreatment system provided by an embodiment of the present specification is shown in FIG. 6.

[0066] Figure 7 A structural schematic diagram of a test tube holder of a proteomics sample pretreatment system provided by an embodiment of the present specification is shown in FIG. 7.

[0067] Figure 8 A structural schematic diagram of a magnetic separation module of a proteomics sample pretreatment system provided by an embodiment of the present specification is shown in FIG. 8.

[0068] Figure 9 A structural schematic diagram of a constant temperature oscillation module of a proteomics sample pretreatment system provided by an embodiment of the present specification is shown in FIG. 9.

[0069] Figure 10 A structural schematic diagram of a collaborative component of a proteomics sample pretreatment system provided by an embodiment of the present specification is shown in FIG. 10.

[0070] Figure 11 A flowchart of a proteomics sample pretreatment method provided by an embodiment of the present specification is shown in FIG. 11. DETAILED DESCRIPTION

[0071] The technical solutions in the embodiments of the present specification will be described clearly and completely below with reference to the drawings in the embodiments of the present specification. Obviously, the described embodiments are only some of the embodiments of the present specification, but not all the embodiments. Based on the embodiments in the present specification, all other embodiments obtained by those skilled in the art without creative effort belong to the scope of protection of the present specification.

[0072] It should be noted that the terms "comprising" and "having," and any variations thereof, in the embodiments and drawings of this specification are intended to cover non-exclusive inclusion. For example, a process, method, system, product, or device that includes a series of steps or units is not limited to the steps or units listed, but may optionally include steps or units not listed, or may optionally include other steps or units inherent to these processes, methods, products, or devices.

[0073] This specification discloses a proteomics sample pretreatment system and method, which will be described in detail below.

[0074] Figure 1 This is a schematic diagram of the structure of a proteomics sample pretreatment system provided in one embodiment of this specification. Figure 1 As shown, a proteomics sample pretreatment system includes a frame 1, a moving crossbeam 2, a lifting column 3, a switching plate 4, a pipette 5, a clamp 6, a worktable 7, a test tube holder 8, a magnetic separation module 9, a constant temperature oscillation module 10, a calibration component 11, and a controller 12.

[0075] The main frame 1 is fixed to the external mounting surface.

[0076] The system frame includes an outer frame, protective partitions, and an operating port. The outer frame and protective partitions enclose a certain space capable of supporting all components within the system and are fixed to the external mounting surface. Simultaneously, they isolate the sample pretreatment work area from the external environment, preventing interference from external factors during sample processing. The operating port can be opened from the outside for inserting samples and adjusting the placement of the work area.

[0077] The movable crossbeam 2, fixed to the top of the machine frame 1, is used to move the lifting column 3, switching plate 4, pipette 5 and clamp on the crossbeam to a position above the designated work area in the worktable 6.

[0078] Figure 2 This is a schematic diagram of the moving crossbeam of a proteomics sample pretreatment system provided in one embodiment of this specification. Figure 2 As shown, the movable crossbeam 2 includes a vertical fixed plate 201, a vertical pulley 202, a vertical synchronous belt 203, a vertical guide rail 204, a vertical slider 205, a vertical motor 206, a transmission shaft 207, a coupling 208, a first limit sensor 209, a horizontal moving plate 210, a horizontal guide rail 211, a horizontal synchronous belt 212, a horizontal pulley 213, a horizontal motor 214, a horizontal slider 215, and a second limit sensor 216.

[0079] Two vertical fixing plates 201 are arranged opposite to each other and fixed to both sides of the machine frame 1. Each vertical fixing plate 201 has a vertical pulley 202, a vertical synchronous belt 203, a vertical guide rail 204 and a vertical slider 205 arranged on its inner side. The two sides are arranged opposite to each other. A vertical motor 206 is arranged at one end of one vertical fixing plate 201 and is connected to the vertical pulley 202 on the other side through a transmission shaft 207 and a coupling 208. The vertical motor 206 drives the vertical slider 205 to slide on the vertical guide rail 204 through the vertical pulley 202. A first limit sensor 209 is arranged at the end of the vertical guide rail 204 of the vertical fixing plate 201 on the side of the vertical motor 206.

[0080] The horizontal moving plate 210 slides on the vertical guide rail 204 fixed on the vertical fixed plate 201 via the vertical slider 205. The horizontal moving plate 210 is fixedly provided with a horizontal guide rail 211, a horizontal synchronous belt 212 and a horizontal pulley 213. A horizontal slider 215 is provided on the horizontal guide rail 211 and is connected to the lifting column 3 via the horizontal slider 215. The horizontal motor 214 is provided on one side of the horizontal guide rail 211. The horizontal motor 214 drives the horizontal synchronous belt 212 through the horizontal pulley 213, thereby driving the horizontal slider 215 to slide on the horizontal guide rail 211. A second limit sensor 216 is provided at one end of the horizontal guide rail 211.

[0081] Both the horizontal and vertical motors are equipped with motor encoders as displacement sensors to acquire the movement position in the horizontal and vertical directions. Vertical limit sensors are installed at both ends of the vertical guide rail, and horizontal limit sensors are installed at both ends of the horizontal guide rail, to determine the initial zero position and limit position of the slider on the guide rail, for calibration before movement and safety protection during movement.

[0082] The lifting column 3 is vertically fixed to the movable crossbeam 2 and is used to change the spatial height of the switching disk 4 located at the end of the lifting column 3.

[0083] Figure 3 This is a schematic diagram of the lifting column and switching disk of a proteomics sample pretreatment system provided in one embodiment of this specification. Figure 3 As shown, the lifting column 3 includes a primary push rod 301, a secondary push rod 302, a lifting motor 303, a lead screw coupling 304, a primary lead screw 305, a primary slider 306, a primary gear 307, a secondary gear 308, a secondary slider 309, a secondary lead screw 310, a lifting frame 311, and a third limit sensor 312.

[0084] The one end of the lifting frame 311 is fixedly connected with the horizontal sliding block 215, and the other end is fixedly connected with the first push rod 301. The lower end of the first push rod 301 is connected with the second push rod 302, the second push rod 302 is connected with the switching disc 4, the lifting motor 303 is arranged in the lifting frame 311, the lifting motor 303 is connected with the first lead screw 305 through the screw shaft coupler 304, the first lead screw 305 is provided with the first sliding block 306, the first lead screw 305 is provided with the first gear 307 at the end away from the lifting motor 311, the first gear 307 is engaged with the second gear 308, the second gear 308 is arranged at the one end of the second lead screw 310, the second lead screw 310 is provided with the second sliding block 309, the first lead screw 305 is arranged in the first push rod 301, the second lead screw 310 is arranged in the first push rod 301, and the third limit sensor 312 is arranged at the end of the first lead screw 310 close to the lifting motor 311.

[0085] The modulus of the second gear is consistent with the modulus of the first gear, but the number of teeth of the second gear is greater than the number of teeth of the first gear. The second lead screw is driven by the engagement of the first gear and the second gear to obtain the power of the lifting motor, and then drives the second sliding block to slide up and down in the sliding groove in the first push rod, thereby realizing the second lifting.

[0086] The lifting stroke of the first push rod is greater than the lifting stroke of the second push rod, and because the number of teeth of the first gear is less than the number of teeth of the second gear, the speed of the first lifting is faster than the speed of the second lifting.

[0087] The motor encoder is installed in the lifting motor as a displacement sensor for obtaining the lifting height. The limit sensor is located at the starting end of the first lead screw to determine the initial zero position and the limit position of the first sliding block on the first lead screw, which is used for calibration before movement and safety protection during movement.

[0088] The switching disc 4 is fixed to the end of the lifting column 3 away from the moving cross beam 2, and includes the first mounting hole position 404 and the second mounting hole position 405.

[0089] Figure 3 The structural schematic diagram of the lifting column and the switching disc of the proteomics sample pretreatment system provided in an embodiment of the present application is shown in FIG. 4. Figure 3 As shown in FIG. 4, the switching disc 4 includes a switching frame 401, a switching shaft 402, a mounting hole disc 403, a first mounting hole position 404, a second mounting hole position 405, and a switching motor 406.

[0090] The switching rack 401 is connected with the end of the secondary push rod 302 of the lifting column 3, one end of the switching shaft 402 is fixedly connected with the switching rack 401, the other end of the switching shaft 402 is fixedly connected with the mounting hole disc 403, the first mounting hole position 404 and the second mounting hole position 405 are arranged on the mounting hole disc 403, the switching motor 406 is arranged in the interior of the switching rack 401, the switching motor 406 drives the switching shaft 402 to rotate, and then drives the mounting hole disc 403 to rotate, and the mounting hole position of the mounting hole disc is switched to be located at different angle positions in sequence.

[0091] The switching motor is located in the interior of the switching rack and is fixedly connected with the switching rack. The upper end of the switching shaft is connected with the switching motor, the lower end is connected with the mounting hole disc, and the mounting hole disc can be rotated around the axis of the switching shaft under the driving of the switching motor, so that the mounting hole position on the mounting hole disc is sequentially located at different angle positions. The angle positions include a vertical angle position and an inclined angle position.

[0092] In the vertical angle position, the axis of the mounting hole is perpendicular to the workbench surface, so the actuator mounted in the mounting hole is also perpendicular to the workbench surface, and at this time, the actuator is in a working state.

[0093] In the inclined angle position, the axis of the mounting hole is at an angle with the workbench surface, so the actuator is kept at a large distance from the workbench surface and does not contact the workbench, and at this time, the actuator is in a non-working state.

[0094] The mounting hole can be mounted with pipettors of different channels and clamps of different sizes. In a common embodiment, the pipettor is mounted in the first mounting hole position, the clamp is mounted in the second mounting hole position, the switching shaft in the switching disc is rotated forward, the first mounting hole position is brought to the vertical angle position, at this time, the pipettor is in a working state and can perform a pipetting operation, and the switching shaft is reversely rotated, the second mounting hole position is brought to the vertical angle position, at this time, the clamp is in a working state and can perform a clamping operation.

[0095] The pipettor 5 is fixed in the first mounting hole position 404 in the switching disc 4 and includes a plurality of pipetting channels for sucking and releasing liquid.

[0096] Figure 4 The structural schematic diagram of the pipettor of the proteomics sample pretreatment system provided by an embodiment of the present application is shown in FIG. 5. Figure 4 As shown in FIG. 5, the pipettor 5 includes a pipetting fixing point 501, a pipetting motor 502, a pipetting lead screw 503, a pipetting sliding block 504, a piston rod 505, a pipetting cavity 506, a push head 507, a suction head 508, a pipetting rack 509, and a spring 510.

[0097] The pipetting fixing point 501 is matched and fixedly connected to the first mounting hole 404 of the switching disk 4. The pipetting motor 502 is connected to the pipetting screw 503. A pipetting slider 504 is provided on the pipetting screw 503. The pipetting slider 504 is fixedly connected to a second number of pipetting piston rods 505. The second number of pipetting piston rods 505 are arranged parallel to each other vertically. A spring 510 is provided at the upper end of each piston rod 505, and the lower end is located inside the pipetting chamber 506. The lower part of the pipetting chamber 506 is connected to a second number of pipetting channels. In each pipetting channel, a pusher 507 is provided at the outlet of the pipetting chamber 506. A pipette tip 508 is provided below the pusher 507 in the pipetting channel. The pipetting frame 509 is fixedly connected to the pipetting fixing point 501 and the pipetting chamber 506.

[0098] The second number is determined based on the preset sample throughput of the system, and can be selected as four, eight, or ninety-six, etc.

[0099] The pipetting fixation point is installed in the mounting hole in the switching panel, providing both a fixing point and electrical contacts. The pipetting motor drives the pipetting screw to rotate, thus moving the pipetting slider up and down. The pipetting slider is fixed to four piston rods, which in turn move the piston rods up and down. The end of the piston rod is located inside the pipetting chamber, changing its volume to allow liquid to be drawn into or released from the chamber. The pusher is located at the liquid outlet of the pipetting chamber and can be pushed a certain distance by the piston rod, disengaging the tip from the liquid outlet. The tip is installed at the liquid outlet to receive the aspirated liquid. The pipetting frame connects the pipetting fixation point and the pipetting chamber. A spring is located at the upper end of the piston rod. When the piston rod is pushed to its lowest point by the pipetting slider, the spring is compressed to its limit position and springs back when the pipetting slider reverses its movement, ensuring the piston rod is always under pressure.

[0100] The clamp 6 is fixed in the second mounting hole 405 in the switching disk 4 and is used to clamp and release the test tube holder 8 and to transfer test tubes in batches between various work areas 701.

[0101] Figure 5 This is a schematic diagram of the gripper of a proteomics sample pretreatment system provided in one embodiment of this specification. Figure 5 As shown, the gripper 6 includes a gripping fixing point 601, a gripping frame 602, a gripping slide 603, a screw motor 604, a right slider 605, a left slider 606, a right gripper 607, and a left gripper 608.

[0102] The clamping fixed point 601 is fixedly connected with the second mounting hole 405 of the switching disc 4. The clamping rack 602 is connected with the clamping fixed point 601 and the clamping sliding groove 603. The screw motor 604 is located in the clamping sliding groove 603. The motor output shaft of the screw motor 604 is a bidirectional screw. The inner side of the right sliding block 605 is fixedly connected with the right screw of the screw motor 604. The outer side of the right sliding block 605 is connected with the right clamping jaw 607. The inner side of the left sliding block 606 is fixedly connected with the left screw of the screw motor 604. The outer side of the left sliding block 606 is connected with the left clamping jaw 608. When the screw motor 604 rotates in the forward direction, the right sliding block 605 moves to the left, the left sliding block 606 moves to the right, and the clamping jaw is retracted. When the screw motor 604 rotates in the reverse direction, the right sliding block 605 moves to the right, the left sliding block 606 moves to the left, and the clamping jaw is opened.

[0103] The clamping fixed point is mounted in the mounting hole in the switching disc and has a fixed point and an electrical contact point.

[0104] The workbench 7 is fixed to the bottom of the machine body frame 1 and is used to carry samples and perform sample pretreatment operations. The workbench 7 includes a plurality of work areas 701, which are the smallest work units for sample pretreatment operations.

[0105] Figure 6 The structural diagram of the workbench of the proteomics sample pretreatment system provided in an embodiment of the present specification is shown in FIG. 7. As shown in FIG. 7, the workbench 7 includes a fourth number of work areas 701. The work areas include mounting card slots, power interfaces, and communication interfaces. The fourth number is determined according to the size of the system. Figure 6

[0106] The number of work areas is determined by the size of the device. Commonly used configurations include 9 work areas, 12 work areas, and 18 work areas.

[0107] The work areas are on the workbench surface 702. Containers, accessories 13, magnetic separation modules 9, and constant-temperature oscillation modules 10 can be loaded through the mounting card slots arranged around the workbench surface 702. Energy and data interaction between the modules and the system can be achieved through the reserved power interfaces 703 and communication interfaces 704.

[0108] In specific embodiments, the system further includes container accessories 13. The container accessories include a hole plate 1301, a suction head box 1302, and a waste box 1303, which are respectively fixed to the workbench 7 in the form of occupying one work area 701.

[0109] ​The well plate 1301 has a fifth number of well sites for accommodating the sample after dispensing or reagents required for sample pretreatment, the fifth number is determined according to the size of the test tube and the preset sample processing flux of the system; the tip box 1302 has a sixth number of well sites for accommodating the tips required by the pipettor, the sixth number is determined according to the size of the test tube and the preset sample processing flux of the system; the waste box 1303 is used to accommodate the used tips and excess reagents.

[0110] The fifth number and the sixth number can be 96.

[0111] The test tube holder 8 is located in the working area 701 of the workbench 7, and includes a first number of test tube well sites 804 for carrying test tubes, the first number being determined according to the preset sample processing flux of the system.

[0112] The number of test tube well sites is determined by the system flux, and common well site numbers include 4, 8, and 96.

[0113] Figure 7 The structural schematic diagram of the test tube holder of the proteomics sample pretreatment system provided by an embodiment of the present specification is shown in FIG. 8. Figure 7 As shown in FIG. 8, the test tube holder 8 includes a rigid skeleton 801, a rubber block 802, a clamping opening 803, a test tube well site 804, a skirt 805, and a test tube 806, wherein

[0114] The test tube holder 8 is fixedly connected by two H-shaped rigid skeletons 801 on both sides and a rubber block 802 in the middle, each rigid skeleton 801 is provided with a clamping opening 803 matched with the clamping jaw of the clamp 6, the rubber block 802 is provided with a first number of test tube well sites 804, the upper side of each test tube well site 804 is provided with a skirt 805, and the test tube 806 is clamped into the test tube well site 804 through the skirt 805.

[0115] The test tube holder is composed of an inner rigid skeleton and a middle outer rubber block, both sides have clamping openings designed for the clamping jaw in the clamp, the skirt of the test tube can be clamped into the test tube well site, and the rubber block deforms under the action of the clamping force on both sides, thereby clamping and fastening the test tube, so that the test tube is not easy to fall off.

[0116] The magnetic separation module 9 is located in the first working area of the workbench 7, and is used for performing magnetic bead separation operation.

[0117] Figure 8 The structural schematic diagram of the magnetic separation module of the proteomics sample pretreatment system provided by an embodiment of the present specification is shown in FIG. 9. Figure 8As shown, the magnetic separation module 9 includes a plurality of processing units 901 and a module control unit 902, the processing unit 901 includes a test tube hole 903 and an iron core 904 and a coil 905 located around the hole, each processing unit 901 is used to generate a controllable magnetic field for the internal reagent of the test tube installed in the test tube hole 903, and the module control unit 902 is used to control the processing unit 901 and interact with the controller through the power supply and communication interface of the first working area.

[0118] Specifically, the magnetic separation module includes a third number of processing units 901, and the third number is determined according to the size of the test tube and the preset sample flux of the system processing.

[0119] The commonly used configuration forms of the magnetic separation module include 8 processing units, 12 processing units, 96 processing units, etc.

[0120] The constant temperature shaking module 10 is located in the second working area of the workbench 7, and is used for heating and shaking operation in the incubation link.

[0121] Figure 9 The structure diagram of the constant temperature shaking module of the proteomics sample pretreatment system provided by an embodiment of the present application is shown in the figure. Figure 9 As shown, the constant temperature shaking module 10 includes a temperature control unit 1001, a shaking unit 1002, a control unit 1003 and a test tube hole 1004, the temperature control unit 1001 is used to heat the test tube installed in the corresponding test tube hole 1004; the shaking unit 1002 is used to move the corresponding test tube in a predetermined direction; the control unit 1003 is used to control the temperature control unit 1001 and the shaking unit 1002 and interact with the controller through the power supply and communication interface of the second working area.

[0122] The calibration assembly 11 is used for calibrating the system, including a camera 111, a calibration block 112 and a limit sensor 113, wherein

[0123] The camera 111 is fixed to the lower part of the gripper 6, when the gripper 6 is located in the working angle gear position, the camera 111 activates the working state, which is used to collect the image information directly below.

[0124] The calibration block 112 is fixed to the gap between the working areas 701 in the workbench 7, including standard scale information and position information, and the scale information and position information are used for the camera 111 to collect.

[0125] The limit sensor 113 includes a first limit 209, a second limit 216 and a third limit 312, which is used to determine the initial position and the limit position of the moving cross beam 2 and the lifting column 3.

[0126] The controller 12, fixedly installed inside the workbench, includes a central control unit 1201, a motion control unit 1202, an execution control unit 1203, a function control unit 1204, a communication unit 1205, and a power management unit 1206.

[0127] The central control unit 1201 is used to coordinate the operation of each unit in the controller 7, as well as to perform communication and data storage.

[0128] The motion control unit 1202 is used to control the motors and sensors in the moving beam 2, lifting column 3, and switching plate 4, and to realize closed-loop motion control based on the data returned by the sensors.

[0129] The execution control unit 1203 is used to control the motors and sensors in the pipette 5 and the clamp 6, and to execute the pipetting and transfer instructions issued by the central control unit.

[0130] The function control unit 1204 is used to control each working area 701 in the workbench 7 and to execute the separation, heating and vibration commands issued by the central control unit 1201.

[0131] The communication unit 1205 is used to handle data interaction between the system and external devices.

[0132] The power management unit 1206 is used to provide excitation for the motors in the system.

[0133] Figure 10 This is a schematic diagram of the structure of the collaborative components of a proteomics sample pretreatment system provided in one embodiment of this specification. Figure 10 As shown, the system also includes a collaboration component 14, which includes an outer frame 1401, a connecting plate 1402, a transition rail 1403, and a transfer module 1404.

[0134] The outer frame 1401 is fixed to the outer mounting surface, and the top is equipped with vertical guide rails 204 for multiple devices; the transition guide rail 1403 is set on the top of the outer frame 1401 and is used to connect the vertical guide rails 204 of multiple systems; the connecting plate 1402 is set on the vertical guide rail 204 and is used to install the moving crossbeam 2; the transfer module 1404 is set at the boundary of the workbench 7 of multiple systems, including the hole position of the test tube holder 8, and is used for the exchange of test tubes in multi-system collaboration.

[0135] The outer frame replaces the original body frame of each stand-alone device and is used to fix multiple devices to form a combined whole. The connecting plate is used to connect the cross beams between multiple devices and corresponds to the vertical guide rails of each device. The transition guide rail is used to connect the vertical guide rails of multiple devices so that they have integrity and continuity in the combined whole. The transfer module is used to realize the exchange of test tubes in the cooperation of multiple devices and includes holes for test tube holders to store the test tube holders.

[0136] In a specific embodiment, the first workstation and the second workstation are replaced by removing the independent outer frame part in the body frame and replacing it with a combined outer frame, and placing a transfer module at the boundary of the workbench of the two workstations to realize multi-machine cooperation. The first workstation and the second workstation are systems in the embodiments of the present specification.

[0137] In another specific embodiment, the third workstation and the workstation without lifting columns are replaced by replacing the combined outer frame, and the vertical guide rails on both sides are respectively equipped with connecting plates and transition guide rails. The third workstation's executor can expand the working range to the working range of the two workstations, realizing the reorganization of the workstations. The third workstation is a system in the embodiments of the present specification.

[0138] Figure 11 The flowchart of the proteomics sample pretreatment method provided by an embodiment of the present specification is shown in FIG. 1. As shown in FIG. 1, a processing method based on a proteomics sample pretreatment system is suitable for being executed on a controller of a proteomics sample pretreatment system, and includes the following steps. Figure 11

[0139] S110, obtaining operation parameters of a sample to be processed, instantiating each functional module of the configuration work area according to the operation parameters, establishing an operation step of pretreatment corresponding to the sample to be processed according to the operation parameters, and generating an operation sequence according to the operation step.

[0140] The modules loaded in each work area are instantiated, the types, specifications, types and specifications of the objects operated, and the intermediate parameters required for the implementation of the functional modules are configured. Each module is encapsulated into a functional block through a structured description language, the topological relationship between each functional block is indexed through a graph structure, and a data flow channel is formed.

[0141] An operation sequence required for a pretreatment task is established, including a time sequence axis, anchor points, and branches. The time sequence axis connects all the steps required for a task in series, and the system executes the steps in order from the starting segment of the time sequence axis to the termination segment to complete a task. The anchor points are located on the time sequence axis, each step can include one or more anchor points, each anchor point can assign an action, and each action is associated with one or more modules. Branches are generated by anchor points and are used to realize conditional judgment and loop jumping.

[0142] ​S120, according to the backhaul data of the sensors in the system, moving the moving cross beam and the lifting column to the position origin determined by the limit sensors, rotating the switching disc to the angle position where the gripper is in the working state, activating the camera to obtain the images of all working areas of the workbench, completing system calibration through the calibration assembly, and identifying all operation points in the working area.

[0143] To improve the accuracy of motion control and avoid the accumulation of errors, four steps are performed: resetting the motion axis, calibrating the plane position point, calibrating the height, and identifying the working area.

[0144] Resetting the motion axis involves moving the moving cross beam and the lifting column to the position origin determined by the limit sensors, rotating the switching disc to the angle position where the gripper is in the working state, and activating the camera.

[0145] Calibrating the plane position point involves moving the moving cross beam to the center of the camera, recording the current displacement sensor value, and comparing it with the installation position of the calibration block to complete the plane position correction.

[0146] Calibrating the height involves moving the lifting column to the specified pixel block of the calibration block after calibrating the plane position point, converting the actual height based on the camera parameters and the actual size of the calibration block, and comparing it with the displacement sensor value to complete the height correction.

[0147] After completing the calibration of all calibration blocks, the global working area image is obtained, and all operation points in the working area that have been configured are identified.

[0148] S130, according to the operation sequence, the execution action is started, which includes liquid transfer, test tube transfer, and function execution. The action switching between liquid transfer and test tube transfer is achieved by rotating the switching disc, the position movement in action execution is achieved by moving the cross beam and the lifting column, the state changes of system components, function modules, and test tubes during action execution are monitored and stored, the liquid transfer includes installing the suction head, sucking the liquid, releasing the liquid, and rejecting the suction head, the test tube transfer includes clamping the test tube holder, transferring the test tube holder, and placing the test tube holder, the function execution includes magnetic bead separation, constant temperature heating, and shaking.

[0149] The processing flow obtained by the execution flow editing step includes magnetic bead cleaning, protein enrichment, enzyme digestion of protein, etc., and the actions include installing the suction head, sucking the liquid, releasing the liquid, rejecting the suction head, test tube transfer, magnetic bead separation, constant temperature heating, and shaking. All state changes generated during the flow execution are monitored and stored by the workstation, the correctness of each operation is checked according to the preset warning judgment condition, and error alarm is triggered if necessary to pause the execution of the flow.

[0150] S140, according to the preset early warning judgment condition, check the execution of each action, when the action meets the early warning judgment condition, trigger the error alarm, suspend the action execution.

[0151] S150, restore each component in the system to the position origin, prepare for the next action execution.

[0152] In one specific embodiment, the operator specifies reagents including magnetic beads, buffer, protease, serum sample, specifies containers including well plate, pipette tip box, waste box, and specifies modules including magnetic separation module, constant temperature oscillation module.

[0153] The process steps include four sub-steps, namely magnetic bead cleaning, protein enrichment, repeated sub-steps, and enzymatic protein.

[0154] During the process execution, in the sub-step of magnetic bead cleaning, the switching disc of the system switches the pipette to the working state, the moving cross beam and the lifting column touch the tip box with the tip of the pipette, and the tip is loaded into the pipette by moving down, and then the moving cross beam and the lifting column touch the well plate containing the buffer with the tip of the pipette, the pipette sucks the buffer and transfers it to the test tube in the test tube rack fixed on the magnetic separation module, the magnetic separation module starts the magnetic separation mixing mode, controls the magnetic beads to suspend and mix for 5 seconds, and then switches to the magnetic separation ring wall distribution mode to make the magnetic beads distribute on the wall of the tube, and at the same time, the moving cross beam and the lifting column of the system move the remaining buffer in the pipette tip and the tip to the waste box.

[0155] In the sub-step of protein enrichment in the process execution, the moving cross beam and the lifting column of the system touch the tip box with the tip of the pipette, load the tip into the pipette by moving down, and then move the moving cross beam and the lifting column to move the pipette to the well plate containing the serum sample, the pipette sucks the serum sample and transfers it to the test tube in the test tube rack fixed on the magnetic separation module, and then moves the tip to the waste box, repeats the pipette operation in the previous step to suck the buffer into the test tube, and moves the remaining liquid and the tip to the waste box. The magnetic separation module starts the magnetic separation mixing mode to keep the magnetic beads rotating at a low speed for 10 minutes, and then switches to the magnetic separation ring wall distribution mode to make the magnetic beads distribute on the wall of the tube, and completes the step.

[0156] In the sub-step of enzymatic hydrolysis of protein in the process execution, the moving cross beam and the lifting column touch the tip of the pipette to the tip box, and the tip is loaded into the pipette by moving the moving cross beam and the lifting column downward, and then the pipette is moved to the well plate containing protease by moving the moving cross beam and the lifting column again, the pipette sucks the serum sample and transfers it into the test tube in the test tube rack fixed on the magnetic separation module, and then the tip is transferred to the waste box, the magnetic separation module starts the magnetic separation mixing mode, and the magnetic beads are kept rotating at a low speed for 10 seconds, and after the end, the switching disc switches the gripper to the working state, clamps the test tube rack fixed on the magnetic separation module to the constant temperature shaking module, and starts the incubation function of the constant temperature shaking module, and continues for 4 hours, and then clamps the test tube rack and places it on the magnetic separation module again, the magnetic separation module starts the ring wall distribution mode, and the magnetic beads are distributed on the wall of the tube, the switching disc switches the pipette to the working state, goes to the tip and adsorbs a new tip, and then goes to the magnetic separation module to suck the enzymolysis product in the test tube in the test tube rack and transfers it to the well plate for elution, and the pipette rejects the tip, and the step is completed.

[0157] In the device reset step, all process procedures are ended, the moving cross beam, the lifting column and the switching disc are reset to the initial position, and the operator is prompted to take out the processed sample.

[0158] In summary, the proteomic sample pretreatment system and the processing method provided by the embodiments of the present application can effectively improve the intelligentization of each step in the proteomic sample pretreatment process, meet the high efficiency, accuracy and safety requirements of high-throughput sample pretreatment, accelerate the development of the field of proteomic technology, and make a creative technical contribution to the precise medical diagnosis of various diseases.

[0159] Those skilled in the art can understand that the drawings are only schematic diagrams of an embodiment, and the modules or processes in the drawings are not necessarily necessary for implementing the present application.

[0160] Those skilled in the art can understand that the modules in the device in the embodiments can be distributed in the device in the embodiments as described in the embodiments, or can be located in one or more devices different from the embodiments. The modules in the above embodiments can be combined into one module, or can be further split into multiple sub-modules.

[0161] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present application, and not to limit them; although the present application has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that they can still modify the technical solutions recorded in the foregoing embodiments, or make equivalent replacement for part of the technical features; and these modifications or replacements do not make the essence of the corresponding technical solutions deviate from the spirit and scope of the technical solutions of the embodiments of the present application.

Claims

1. A proteomics sample pretreatment system, characterized in that, The system includes a frame, moving crossbeam, lifting column, switching plate, pipettes, grippers, worktable, test tube holders, magnetic separation module, constant temperature oscillation module, calibration components, and controller. The frame is fixed to the external mounting surface; A movable crossbeam, fixed to the top of the machine frame, is used to move the lifting column, switching plate, pipette, and gripper on the crossbeam to a position above the designated working area on the worktable. It includes a vertical fixed plate, vertical pulley, vertical synchronous belt, vertical guide rail, vertical slider, vertical motor, drive shaft, coupling, first limit sensor, horizontal moving plate, horizontal guide rail, horizontal synchronous belt, horizontal pulley, horizontal motor, horizontal slider, and second limit sensor. Two vertical fixing plates are arranged opposite each other and fixed to both sides of the machine frame. Each vertical fixing plate has a vertical pulley, a vertical synchronous belt, a vertical guide rail and a vertical slider on its inner side. The two sides are arranged opposite each other. A vertical motor is set at one end of one vertical fixing plate and is connected to the vertical pulley on the other side through a transmission shaft and a coupling. The vertical motor drives the vertical slider to slide on the vertical guide rail through the vertical pulley. A first limit sensor is set at the end of the vertical guide rail of the vertical fixing plate on the side of the vertical motor. The horizontal moving plate slides on a vertical guide rail fixed to a vertical fixed plate via a vertical slider. A horizontal guide rail, a horizontal synchronous belt, and a horizontal pulley are fixedly installed on the horizontal moving plate. A horizontal slider is installed on the horizontal guide rail and connected to a lifting column via the horizontal slider. A horizontal motor is installed on one side of the horizontal guide rail and drives the horizontal synchronous belt through the horizontal pulley, thereby driving the horizontal slider to slide on the horizontal guide rail. A second limit sensor is installed at one end of the horizontal guide rail. The lifting column, vertically fixed to the moving crossbeam, is used to change the spatial height of the switching plate located at the end of the lifting column. It includes a primary push rod, a secondary push rod, a lifting motor, a lead screw coupling, a primary lead screw, a primary slider, a primary gear, a secondary gear, a secondary slider, a secondary lead screw, a lifting frame, and a third limit sensor. One end of the lifting frame is fixedly connected to a horizontal slider, and the other end is fixedly connected to a first-stage push rod. The lower end of the first-stage push rod is connected to a second-stage push rod, which is connected to a switching disc. The lifting motor is located inside the lifting frame and is connected to the first-stage lead screw via a lead screw coupling. A first-stage slider is located on the first-stage lead screw. A first-stage gear is located at the end of the first-stage lead screw away from the lifting motor. The first-stage gear meshes with the second-stage gear. The second-stage gear is located at one end of the second-stage lead screw. A second-stage slider is located on the second-stage lead screw. The first-stage lead screw is located inside the first-stage push rod, and the second-stage lead screw is located inside the first-stage push rod. A third limit sensor is located at the end of the first-stage lead screw near the lifting motor. The switching plate is fixed to the end of the lifting column away from the moving crossbeam, and includes a first mounting hole and a second mounting hole. A pipette, fixed in the first mounting hole in the switching disk, includes multiple pipetting channels for aspirating and dispensing liquids; The clamp, fixed in the second mounting hole in the switching plate, is used to clamp and release the test tube holder and to transfer test tubes in batches between various work areas. The worktable, fixed to the bottom of the machine frame, is used to support samples and perform sample pretreatment operations. It includes multiple work areas, each of which is the smallest working unit for sample pretreatment operations. A test tube holder, located in the working area of ​​the workbench, includes a first number of test tube holes for holding test tubes, the first number being determined according to the preset sample throughput of the system. The magnetic separation module, located in the first working area of ​​the workbench, is used for magnetic bead separation. It includes multiple processing units and a module control unit. Each processing unit includes test tube holes and iron cores and coils located around the holes. Each processing unit is used to generate a controllable magnetic field for the reagent inside the test tube installed in the test tube hole. The module control unit is used to control the processing units and to interact with the controller through the power and communication interfaces of the first working area. The constant temperature oscillation module, located in the second working area of ​​the workbench, is used for heating and oscillation operations during the incubation process. It includes a temperature control unit, an oscillation unit, a control unit, and test tube wells. The temperature control unit is used to heat the test tubes installed in the corresponding wells. The oscillation unit is used to move the corresponding test tubes rapidly in a preset direction. The control unit is used to control the temperature control unit and the oscillation unit and to interact with the controller through the power and communication interfaces of the second working area. The calibration components, used for system calibration, include a camera, calibration block, and limit sensor. The camera is fixed to the lower part of the clamp. When the clamp is in the working angle position, the camera is activated to collect image information directly below. The calibration block is fixed in the gap between the working areas in the workbench and includes standard dimensional information and position information, which are used for camera acquisition. The limit sensor includes a first limiter, a second limiter, and a third limiter, used to determine the initial and extreme positions of the moving crossbeam and the lifting column. The controller, fixedly installed inside the workbench, includes a central control unit, a motion control unit, an execution control unit, a function control unit, a communication unit, and a power management unit. The central control unit is used to coordinate the operation of each unit in the controller, as well as to perform communication and data storage. The motion control unit is used to control the motors and sensors in the moving crossbeam, lifting column, and switching panel, and to realize closed-loop motion control based on the data returned by the sensors. The execution control unit is used to control the motors and sensors in the pipette and holder, and to execute the pipetting and transfer instructions issued by the central control unit; The functional control unit is used to control each working area in the workbench and to execute the separation, heating, and vibration commands issued by the central control unit. The communication unit is used to handle data interaction between the system and external devices; The power management unit is used to provide excitation for the motors in the system.

2. The system according to claim 1, characterized in that, The switching plate includes a switching frame, a switching shaft, a mounting plate, a first mounting hole, a second mounting hole, and a switching motor. The switching frame is connected to the end of the secondary push rod of the lifting column. One end of the switching shaft is fixedly connected to the switching frame, and the other end of the switching shaft is fixedly connected to the mounting plate. The mounting plate is provided with a first mounting hole and a second mounting hole. The switching motor is located inside the switching frame. The switching motor drives the switching shaft to rotate, which in turn drives the mounting plate to rotate, switching the mounting hole perpendicular to the worktable.

3. The system according to claim 1, characterized in that, The pipette includes a pipetting point, a pipetting motor, a pipetting screw, a pipetting slider, a piston rod, a pipetting chamber, a pusher, a pipette tip, a pipetting frame, and a spring. The pipetting fixation point mates with and is fixedly connected to the first mounting hole of the switching disk. The pipetting motor is connected to the pipetting screw, which is equipped with a pipetting slider. The pipetting slider is fixedly connected to a second number of pipetting piston rods. The second number of pipetting piston rods are arranged parallel to each other vertically. Each piston rod has a spring at its upper end and its lower end located inside the pipetting chamber. The lower part of the pipetting chamber is connected to a second number of pipetting channels. In each pipetting channel, a pusher is provided at the outlet of the pipetting chamber, and a pipette tip is located below the pusher in the pipetting channel. The pipetting frame is fixedly connected to the pipetting fixation point and the pipetting chamber. The second number is determined according to the preset sample throughput of the system.

4. The system according to claim 1, characterized in that, The gripper includes a clamping fixing point, a clamping frame, a clamping slide, a screw motor, a right slider, a left slider, a right gripper, and a left gripper. The clamping fixing point is fixedly connected to the second mounting hole of the switching disk. The clamping frame connects the clamping fixing point and the clamping slide. The screw motor is located in the clamping slide. The motor output shaft of the screw motor is a bidirectional screw. The inner side of the right slider is fixedly connected to the right screw of the screw motor. The outer side of the right slider is connected to the right jaw. The inner side of the left slider is fixedly connected to the left screw of the screw motor. The outer side of the left slider is connected to the left jaw. When the screw motor rotates in the forward direction, the right slider moves to the left and the left slider moves to the right, causing the grippers to retract; when the screw motor rotates in the reverse direction, the right slider moves to the right and the left slider moves to the left, causing the grippers to open.

5. The system according to claim 1, characterized in that, The test tube holder includes a rigid frame, a rubber block, a clamping opening, test tube holes, a skirt, and test tubes. The test tube holder is composed of two I-shaped rigid frames on both sides and a rubber block in the middle. Each rigid frame is provided with a clamping port that cooperates with the gripper's claws. The rubber block is provided with a first number of test tube holes. Each test tube hole is provided with a skirt on the upper side. The test tube is inserted into the test tube hole through the skirt.

6. The system according to claim 1, characterized in that, The magnetic separation module includes a third number of processing units, the third number being determined based on the test tube size and the preset sample throughput of the system.

7. The system according to claim 1, characterized in that, The workbench includes a fourth number of work areas, each work area including a mounting slot, a power interface, and a communication interface, the fourth number being determined based on the system dimensions.

8. The system according to claim 1, characterized in that, The system also includes container accessories, which consist of an orifice plate, a suction head box, and a waste box, each fixed to the worktable by occupying a work area. The well plate has a fifth number of wells for accommodating dispensed samples or reagents required for sample pretreatment. The fifth number is determined based on the test tube size and the preset system throughput for sample processing. The pipette tip box has a sixth number of holes for storing pipette tips required for pipettes. The sixth number is determined based on the test tube size and the preset system sample processing throughput. The waste container is used to hold used pipette tips and excess reagents.

9. The system according to claim 1, characterized in that, The system also includes a collaboration component, which comprises an outer frame, a connecting plate, a transition rail, and a transfer module. The outer frame is fixed to the outer mounting surface, and the top has vertical guide rails for mounting multiple devices; Transition rails, located at the top of the outer frame, are used to connect vertical rails of multiple systems; A connecting plate, mounted on the vertical guide rail, is used to install the movable crossbeam; The transfer module, located at the boundary between the workbenches of multiple systems, includes holes for test tube holders and is used for exchanging test tubes during multi-system collaboration.

10. A processing method based on a proteomics sample pretreatment system, characterized in that, Suitable for execution on the controller of a proteomics sample pretreatment system, including: Obtain the operation parameters of the sample to be processed, configure each functional module of the work area by instantiating the operation parameters, establish the pre-processing operation steps corresponding to the sample to be processed according to the operation parameters, and generate an operation sequence according to the operation steps. Based on the data returned by the sensors in the system, the moving beam and the lifting column are moved to the position origin determined by the corresponding limit sensor. The switching disk is rotated to the angle position where the gripper is in working condition. The camera is activated to acquire images of all working areas of the worktable. The system is calibrated through the calibration component, and all operation points in the working area are identified. The operation sequence is initiated and executed, including liquid transfer, test tube transport, and function execution. The liquid transfer and test tube transport actions are switched by rotating a switching disk. The positional movement during the execution of the actions is achieved by the cooperation of a moving beam and a lifting column. The status changes of system components, functional modules, and test tubes during the execution of the actions are monitored and stored. The liquid transfer includes installing pipette tips, drawing liquid, releasing liquid, and removing pipette tips. The test tube transport includes clamping test tube holders, transferring test tube holders, and placing test tube holders. The function execution includes magnetic bead separation, constant temperature heating, and shaking. Based on the preset warning judgment conditions, check the execution of each action. When an action meets the warning judgment conditions, trigger an error alarm and suspend the execution of the action. The system restores each component to its original position, preparing for the next action.

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