A sampling device and a pretreatment method for sample pretreatment

By designing a fully automated sample pretreatment device that integrates multiple components working together, the problem of low automation in sample pretreatment in existing technologies has been solved, and an efficient and stable automated sample processing flow has been achieved.

CN116430060BActive Publication Date: 2026-01-30HANGZHOU CALIBRA TECH CO LTD
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Patent Information

Application Number
CN202211459820.8
Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Filing Date
2022-08-15
Publication Date
2026-01-30
Estimated Expiration
2042-08-15

AI Technical Summary

Technical Problem

Current mass spectrometers have low levels of automation in sample pretreatment, requiring a lot of manual operation, especially in steps such as liquid-liquid extraction, protein precipitation, and SPE solid-phase extraction.

Method used

A fully automated sample pretreatment device was designed, comprising a frame assembly, a capping assembly, a blood collection tube gripping assembly, a pipette assembly, a platform assembly, a transport assembly, a sealing assembly, a magnetic solid phase extraction assembly, and a SPE positive pressure extraction assembly. The automated sample processing, including capping, sampling, sealing, and extraction, is achieved through the coordinated work of these components.

Benefits of technology

It achieves full automation of sample pretreatment, improves operational efficiency, reduces manual intervention, enhances equipment stability and reliability, simplifies mechanical structure, and improves the degree of automation in processing.

✦ Generated by Eureka AI based on patent content.

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Abstract

This invention provides a fully automated sample pretreatment device, comprising a frame assembly, a cap-opening assembly, a blood collection tube gripping assembly, a pipette assembly, a platform assembly, a transport assembly, a sealing assembly, a magnetic solid-phase extraction (SPE) assembly, a SPE positive pressure extraction (SPE) assembly, and a conveyor belt waste transport assembly. The conveyor belt waste transport assembly is located at the bottom of the frame assembly. From left to right, the cap-opening assembly, platform assembly, and magnetic solid-phase extraction (SPE) assembly are arranged sequentially in the middle of the frame assembly. The blood collection tube gripping assembly, pipette assembly, transport assembly, and sealing assembly are located at the top of the frame assembly. The magnetic solid-phase extraction (SPE) assembly and the SPE positive pressure extraction (SPE) assembly are detachable and interchangeable. This invention also provides a method for pretreatment using the above-mentioned device. This invention has a simple structure, reasonable design, and high stability, enabling fully automated sample pretreatment.
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Description

Technical Field

[0001] This invention relates to the field of medical devices, and more specifically, to a sampling device and a pretreatment method for sample pretreatment. Background Technology

[0002] Based on current market feedback, mass spectrometer sample pretreatment mainly relies on cupping, and most of it is still done manually with low automation. It mainly focuses on a single extraction method to address the problem of requiring a large amount of manual operation for methods such as liquid-liquid extraction, protein precipitation, and SPE solid-phase extraction.

[0003] Existing products from foreign brands such as Teco and Hamilton mainly focus on dispensing cups, lacking automatic cap opening at the front end and failing to integrate SPE positive pressure extraction and other functions. Domestic products are similar; their main function is liquid separation, and the degree of automation is low, requiring manual operation in the process. Therefore, there is an urgent need in the market for this type of automated sampling device. Summary of the Invention

[0004] This invention overcomes the shortcomings of the prior art and provides a high-throughput automated sampling device and pretreatment method for sample pretreatment.

[0005] The technical solution of the present invention is as follows:

[0006] A fully automated sample pretreatment device includes a frame assembly, a cap-opening assembly, a blood collection tube gripping assembly, a pipette assembly, a platform assembly, a conveying assembly, a sealing assembly, a magnetic solid-phase extraction assembly, a SPE positive pressure extraction assembly, and a conveyor belt waste transfer assembly. The conveyor belt waste transfer assembly is located at the bottom of the frame assembly. From left to right, the cap-opening assembly, platform assembly, and magnetic solid-phase extraction assembly are arranged sequentially in the middle of the frame assembly. The blood collection tube gripping assembly, pipette assembly, conveying assembly, and sealing assembly are located at the top of the frame assembly. The magnetic solid-phase extraction assembly and the SPE positive pressure extraction assembly are detachable and interchangeable.

[0007] The cap-opening assembly secures the blood collection tubes and, in conjunction with a partial blood collection tube gripping assembly, opens the blood collection tubes; the blood collection tube gripping assembly grips the blood collection tubes; the pipette assembly moves the corresponding sampled liquid; the transport assembly transports the liquid and sample; the sealing assembly seals the sampled liquid; the conveyor belt waste transport assembly includes a waste transport belt, a waste transport motor, and waste transport baffles; waste transport baffles are installed on both sides of the waste transport belt, and a waste transport motor is installed on one side of the waste transport baffle; a waste transport baffle is also installed at one end of the waste transport belt.

[0008] Furthermore, the sampling device consists of the cap opening assembly, the blood collection tube grasping assembly, and the pipette assembly. The blood collection tube grasping assembly is located on the left side of the pipette assembly, and the cap opening assembly is located below the pipette assembly.

[0009] The blood collection tube gripping assembly includes a blood collection tube gripper, a blood collection tube clamping block, a blood collection tube gripping guide rail, a blood collection tube screw motor, a blood collection tube stepper motor, and a blood collection tube timing belt. The blood collection tube stepper motor and the blood collection tube timing belt are fixed on the side of the pipette assembly near the blood collection tube gripping assembly and control the movement of other components of the blood collection tube gripping assembly in the direction set by the blood collection tube timing belt. The blood collection tube gripping guide rail is connected and fixed to the blood collection tube timing belt. The blood collection tube screw motor is fixed on the blood collection tube gripping guide rail, and the blood collection tube gripper is connected to the screw of the blood collection tube screw motor. The blood collection tube gripper controls the movement of the blood collection tube clamping block.

[0010] The cap opening assembly includes a cap opening support block, a cap opening stepper motor, a cap opening reverse screw, a cap opening timing belt, a cap opening clamping block, and a cap opening guide rail. The cap opening clamping block has cap opening support blocks at both ends, connected to the cap opening guide rail via the cap opening reverse screw. The cap opening reverse screws at both ends of the cap opening clamping block are connected via the cap opening timing belt. The cap opening reverse screw is connected to and controlled by the stepper motor. The cap opening clamping block uses two identical convex blocks, with the blood collection tube clamped between the longest sides of the two convex blocks.

[0011] The pipette assembly includes a pipette holder, a four-channel pipette, a pipetting equidistant conversion component, a pipetting guide rail, and a pipetting Y-axis guide rail. The pipetting equidistant conversion component is located on the side of the pipette holder away from the blood collection tube grasping component, and the pipetting guide rail is located on the side of the pipetting equidistant conversion component away from the blood collection tube grasping component. The four-channel pipette is mounted on the pipetting guide rail, and the pipetting Y-axis guide rail is mounted on the pipette holder, which drives the pipetting equidistant conversion component of the pipette assembly to move.

[0012] Furthermore, the blood collection tube clamping block adopts a symmetrical L-shaped clamping block, which is controlled by the blood collection tube gripper to move in opposite directions to form a clamping force; blood collection tube clamping balls are distributed on the blood collection tube clamping block.

[0013] Furthermore, an opening pressure spring and an opening pressure block are provided inside the convex block of the opening clamping block. The opening pressure spring is fixed inside the side furthest from the longest side of the convex block, and the opening pressure spring is connected to the opening pressure block.

[0014] Furthermore, an opening ball screw is provided inside the convex block of the opening clamping block. One end of the opening ball screw is fixed inside the side furthest from the longest side of the convex block, and the head of the opening ball screw protrudes outside the convex block.

[0015] Furthermore, the pipetting equidistant conversion assembly includes a pipetting equidistant conversion support, a pipette fixing block, two pipetting equidistant conversion lead screws, and a pipetting equidistant conversion motor;

[0016] The pipetting equidistant adjustment bracket is equipped with two pipetting equidistant adjustment screws, and four pipette fixing blocks are passed through the two pipetting equidistant adjustment screws. The two middle pipette fixing blocks are controlled by the same pipetting equidistant adjustment screw, and the two outer pipette fixing blocks are controlled by another pipetting equidistant adjustment screw. The two pipetting equidistant adjustment screws are connected to the pipetting equidistant adjustment motor via a conveyor belt. Pipetting guide rails are connected to the pipette fixing blocks.

[0017] The four modules within the four-channel pipette can move up and down independently, and the TIP tips of each module are spaced apart by the pipette fixing block of the pipetting equidistant conversion component moving on the pipetting guide rail.

[0018] Furthermore, the conveying assembly includes a conveying bracket, a conveying gripper, a conveying clamping block, a conveying clamping guide rail, a conveying lead screw motor, a conveying stepper motor, and a conveying synchronous belt; the conveying stepper motor and the conveying synchronous belt are mounted on the conveying bracket and control the movement of other components of the conveying assembly in the direction of the conveying synchronous belt; the conveying clamping guide rail is connected and fixed to the conveying synchronous belt, the conveying lead screw motor is fixed on the conveying clamping guide rail, and the conveying gripper is connected to the lead screw of the conveying lead screw motor, which controls the movement of the conveying clamping block; wherein, the conveying clamping block is generally L-shaped;

[0019] The sealing assembly includes a sealing stepper motor, a sealing transverse guide rail, a sealing longitudinal guide rail, a sealing pressure column, a sealing vacuum circuit board, and a sealing pressure spring. The sealing assembly is located on the side of the transport bracket of the transport assembly away from the transport gripper. The sealing transverse guide rail is fixedly mounted on the transport bracket and controls the movement of other components of the sealing assembly in the direction of the sealing transverse guide rail. The sealing longitudinal guide rail is connected and fixedly mounted to the sealing transverse guide rail. The sealing stepper motor is fixed on the sealing longitudinal guide rail and controls the movement of the sealing pressure column, the sealing vacuum circuit board, and the sealing pressure spring. The sealing vacuum circuit board is located at the end of the sealing pressure column closest to the deep hole plate to be sealed, and the sealing pressure column passes through the sealing vacuum circuit board.

[0020] The other end of the sealing pressure column is fixed on the transport bracket and connected to one end of the sealing stepper motor, so that the sealing stepper motor controls the movement of the sealing pressure column. A sealing pressure spring is set between the sealing vacuum circuit board and the transport bracket.

[0021] The magnetic solid-phase extraction assembly includes a circular turntable, six evenly distributed processing stations, a magnetic frame, a sheath, a lead screw motor paired with the magnetic frame and sheath, a magnetic solid-phase extraction guide rail, and a magnetic solid-phase extraction support. The magnetic solid-phase extraction support houses the lead screw motor paired with the magnetic frame and sheath. The magnetic solid-phase extraction guide rail is positioned longitudinally within the support. The magnetic frame and sheath are mounted on the guide rail and move longitudinally. The magnetic frame matches the sheath, which can enclose all the magnetic rods on the magnetic frame. The circular turntable is controlled by an indexing plate, which is located below and connected to the turntable.

[0022] The SPE positive pressure extraction assembly includes a positive pressure extraction bracket, a positive pressure extraction longitudinal control cylinder, a positive pressure extraction longitudinal guide rail, a positive pressure extraction support rod, a positive pressure extraction pressure block, a positive pressure extraction cap, a positive pressure extraction transverse guide rail, a positive pressure extraction base plate, a positive pressure extraction lead screw motor, and a positive pressure extraction support plate.

[0023] A positive pressure extraction block is installed above the positive pressure extraction support, and the positive pressure extraction block is connected to the positive pressure extraction support via a positive pressure extraction support rod; a positive pressure extraction longitudinal control cylinder is installed inside the positive pressure extraction support, and the positive pressure extraction longitudinal control cylinder controls the positive pressure extraction block to move longitudinally;

[0024] It also includes a positive pressure extraction guide plate, and the two ends of the positive pressure extraction support rod are respectively connected and fixed to the positive pressure extraction guide plate and the positive pressure extraction block. The positive pressure extraction guide plate is also provided with a through hole for the positive pressure extraction guide rail to pass through. The positive pressure extraction guide plate is connected to the positive pressure extraction longitudinal control cylinder.

[0025] The positive pressure extraction transverse guide rail is set on the upper surface of the positive pressure extraction support, and is connected to and controlled by the positive pressure extraction lead screw motor; the positive pressure extraction lead screw motor is set on the positive pressure extraction support plate, which is located inside the positive pressure extraction support near the upper surface; a positive pressure extraction base plate is set on the positive pressure extraction transverse guide rail, and a perforated plate and an SPE plate are placed on the positive pressure extraction base plate;

[0026] The positive pressure extraction block is equipped with a positive pressure extraction silencer inside, and a positive pressure extraction sealing ring is provided at the contact position between the cover and the positive pressure extraction block. A positive pressure extraction silicone pad is provided at the bottom of the positive pressure extraction block, and an air inlet is provided at the center of the cover of the positive pressure extraction block to allow nitrogen to enter.

[0027] Furthermore, it also includes a cover plate, one end of which is connected to a cover plate motor and rotates under the control of the cover plate motor to block; the cover plate covers the entire magnetic frame.

[0028] Furthermore, it also includes a heating module, which is located below the circular turntable and at the position corresponding to the magnetic solid phase extraction support closest to the circular turntable.

[0029] The heating module is connected to the magnetic solid-phase extraction guide rail, and the heating module is connected to the oscillating motor, and the whole is controlled by the oscillating motor.

[0030] A fully automated sample pretreatment method, including the above-mentioned pretreatment equipment, specifically includes the following steps:

[0031] 101) Pretreatment steps: Place the corresponding sample and reagent solution on the platform assembly; and set up the magnetic solid phase extraction assembly or replace it with the SPE positive pressure extraction assembly as needed;

[0032] 102) Opening procedure: The sample collection tube is clamped by the blood collection tube gripping component and transferred to the opening component by the pipette component; then the opening component fixes the sample collection tube and removes the upper cap of the blood collection tube by moving the blood collection tube gripping component upward.

[0033] Specifically, the blood collection tube is moved from the blood collection tube gripping component to the cap opening component. The cap opening component clamps and fixes the lower part of the blood collection tube, while the blood collection tube gripping component no longer needs to clamp the blood collection tube. The blood collection tube gripper controls the blood collection tube clamping block to relax, but the blood collection tube is still placed on the blood collection tube clamping block. The blood collection tube screw motor controls its upward movement, thereby removing the upper cap of the blood collection tube and completing the cap opening.

[0034] 103) Sampling steps: The sample to be sampled is taken out from the blood collection tube fixed by the cap opening assembly using the pipette assembly, and then transferred into the corresponding deep well plate by the pipette assembly;

[0035] 104) Sealing step: The deep hole plate from step 103) is transported to the corresponding position by the transport assembly and sealed by the sealing assembly;

[0036] Specifically, the sealing film uses horizontal and vertical guide rails to achieve back-and-forth movement along the horizontal and vertical axes. The sealing film vacuum circuit board moves to above the required silicone diaphragm, then moves down to the upper surface of the diaphragm and adheres tightly to it. It continues to move downwards a certain distance, keeping the sealing spring compressed. At this point, the upper surface of the silicone diaphragm is tightly pressed against the sealing film vacuum circuit board, creating a vacuum under its suction. The silicone diaphragm is then lifted and moved directly above the deep hole plate. Under the action of the sealing film stepper motor, it moves downwards until the silicone diaphragm contacts the deep hole plate. The sealing film vacuum circuit board continues to move downwards, pressing the silicone diaphragm tightly under the force of the sealing spring. Simultaneously, as the sealing film pressure column moves downwards, the corresponding bosses on the silicone diaphragm and pressure column are stretched and their diameter reduced, thus pressing the silicone diaphragm into the deep hole plate.

[0037] 105) Sample processing steps: Install the corresponding magnetic solid phase extraction module or SPE positive pressure extraction module and perform the appropriate processing.

[0038] When using a magnetic solid-phase extraction (SPE) assembly, the reagent solution in the deep-well plate is added to the first of the six processing stations using a corresponding pipette. After each addition, the pipette is rotated at a certain angle until all six deep-well plates in the processing stations have been filled. A rotary table then rotates the first station directly below the magnetic frame. The sheath moves up and down under the action of a screw motor, ensuring thorough mixing of the reagent solution. After activation at the first station, the sheath moves downwards to the bottom of the deep-well plate, simultaneously controlling the magnetic frame to also move downwards to the bottom of the deep-well plate. At this point, the magnetic bead solution is adsorbed onto the outer edge of the sheath. Then, the sheath and magnetic frame begin to move upwards under the action of the screw motor. When removed from the deep-well plate, the cover plate rotates to the bottom of the magnetic frame to prevent solution outside the sheath from falling and contaminating other solutions.

[0039] The rotary table rotates again to the deep hole plate of the next processing station. The cover plate rotates back to the origin. The sheath and the magnetic frame move down to the bottom of the deep hole plate of the current processing station. The sheath remains stationary, and the magnetic frame moves up to the highest point. No further operation is performed afterward.

[0040] Then the sheath moves up and down to fully mix the reagent solution, and so on until the last deep hole plate of the six processing stations is completed.

[0041] The advantages of this invention are:

[0042] This invention achieves the following by having the cap opening component, the blood collection tube grasping component, and the pipette component work together: the pipette component and the blood collection tube grasping component move the blood collection tube from the sample placement position to the corresponding cap opening component; the cap opening component and the blood collection tube grasping component work together to open the cap; and the pipette component then removes the internal sample and places it into the corresponding reaction solution.

[0043] To improve the clamping force of the blood collection tube clamping block and prevent it from falling off, this invention employs symmetrically arranged L-shaped clamping blocks. These L-shaped blocks move in opposite directions under the control of the blood collection tube gripper, generating clamping force. Furthermore, the blood collection tube has a noticeable protrusion at the top, allowing it to rest on the L-shaped clamping blocks, thus better preventing detachment due to insufficient clamping. Clamping balls are also distributed on the blood collection tube clamping block, achieving better clamping through ball screws.

[0044] This invention moves the blood collection tube from the blood collection tube gripping component to the cap opening component. The cap opening component clamps and fixes the lower part of the blood collection tube, while the blood collection tube gripping component no longer needs to clamp the blood collection tube. The blood collection tube gripper controls the blood collection tube clamping block to relax, but the blood collection tube remains on the blood collection tube clamping block. The blood collection tube screw motor controls its upward movement, thereby removing the upper cap of the blood collection tube and completing the cap opening. This invention fully utilizes the blood collection tube gripping component to achieve dual functions and reduces the corresponding mechanical structure.

[0045] The pipetting equidistant adjustment component of the present invention achieves fine-tuning control of four pipette fixing blocks by cleverly setting two pipetting equidistant adjustment lead screws, which greatly reduces mechanical complexity, improves stability, and enables nutrient collection and pipetting operations in more complex environments.

[0046] In designing the automation of magnetic solid-phase extraction, this invention achieves the operation of six processing steps through the ingenious setting of a circular turntable, and uses a single processing tool, which greatly reduces mechanical complexity and improves stability.

[0047] This invention implements the process of adding reagent solutions from a 96-well plate to the first of six processing stations (activation station) using corresponding pipettes. After each addition, the pipette is rotated at a certain angle until all six 96-well plates at all processing stations have been filled. A rotary table then rotates the first station (activation station) directly below the magnetic frame. The sheath moves up and down under the action of a lead screw motor, ensuring thorough mixing of the reagent solutions. After activation at the first station, the sheath moves downwards to the bottom of the 96-well plate, simultaneously controlling the magnetic frame to also move downwards to the bottom of the 96-well plate. At this point, the magnetic bead solution is adsorbed onto the outer edge of the sheath. Then, the sheath and magnetic frame begin to move upwards under the action of a lead screw motor. When removed from the 96-well plate, the cover plate rotates to below the magnetic frame to prevent solution from falling onto the outside of the sheath and contaminating other solutions.

[0048] This invention provides a heating module located below a corresponding circular turntable. When the workstation requiring heating moves to this position, the heating module moves up and down to provide heating.

[0049] This invention utilizes transverse and longitudinal guide rails to achieve reciprocating motion along the horizontal and vertical axes. During this process, the sealing vacuum circuit board moves above the required silicone diaphragm, then moves down to the upper surface of the diaphragm and adheres tightly to it. It continues to move downwards a certain distance, keeping the sealing spring compressed. At this point, the upper surface of the silicone diaphragm is tightly pressed against the sealing vacuum circuit board, creating a vacuum under its suction. The silicone diaphragm is then lifted and moved directly above the 96mm deep hole plate. Driven by a sealing stepper motor, it moves downwards until the silicone diaphragm contacts the 96mm plate. The sealing vacuum circuit board continues to move downwards, pressing the silicone diaphragm firmly under the force of the sealing spring. Simultaneously, as the sealing pressure column moves downwards, the corresponding bosses on the silicone diaphragm and the sealing pressure column are stretched and their diameter reduced, making it easy to press into the 96mm deep hole plate.

[0050] This invention features a simple structure, reasonable design, high stability, fully automated sealing, and the ability to transfer the film to the next processing step. The sealing silicone used in this invention has protrusions at corresponding positions on the deep-hole plate, with the protrusion diameter larger than the hole diameter of the deep-hole plate to facilitate better sealing. Attached Figure Description

[0051] Figure 1 This is an overall schematic diagram of the SPE positive pressure extraction component of the present invention;

[0052] Figure 2 This is an overall schematic diagram of the magnetic solid-phase extraction component of the present invention;

[0053] Figure 3 This is a schematic diagram of the cover opening component of the present invention;

[0054] Figure 4 This is a cross-sectional view of the opening assembly of the present invention;

[0055] Figure 5 This is a schematic diagram of the opening assembly of the present invention from another angle;

[0056] Figure 6 This is a schematic diagram of the blood collection tube grasping assembly and pipette assembly of the present invention;

[0057] Figure 7 This is a partial cross-sectional view of the blood collection tube grasping component of the present invention;

[0058] Figure 8 This is a schematic diagram of the pipette assembly of the present invention;

[0059] Figure 9 This is a schematic diagram of the pipetting equidistant transformation component of the present invention.

[0060] Figure 10 This is a schematic diagram of the overall sealing assembly of the present invention;

[0061] Figure 11 This is a schematic diagram of the sealing film portion of the present invention;

[0062] Figure 12 This is a schematic diagram of the transport component of the present invention.

[0063] Figure 13 This is a schematic diagram of the overall magnetic solid-phase extraction assembly of the present invention;

[0064] Figure 14 This is a cross-sectional view of the magnetic solid-phase extraction component of the present invention;

[0065] Figure 15 This is a top view of the magnetic solid-phase extraction assembly of the present invention;

[0066] Figure 16 This is a schematic diagram of the conveyor belt waste transfer assembly of the present invention;

[0067] Figure 17 This is a schematic diagram of the SPE positive pressure extraction component of the present invention;

[0068] Figure 18 This is a cross-sectional view of the SPE positive pressure extraction component of the present invention.

[0069] The diagram shows: 1. Cap opening assembly; 2. Blood collection tube gripping assembly; 3. Pipette assembly; 4. Sealing assembly; 5. Transport assembly; 6. Magnetic solid phase extraction assembly; 7. Frame assembly; 8. Platform assembly; 10. SPE positive pressure extraction assembly; 11. Conveyor belt waste transfer assembly.

[0070] 1-1 opening support block, 1-2 opening stepper motor, 1-3 opening reverse screw, 1-4 opening timing belt, 1-5 opening clamping block, 1-6 opening guide rail, 1-7 opening pressure spring, 1-8 opening pressure block;

[0071] 2-1. Blood collection tube gripper; 2-2. Blood collection tube clamping block; 2-3. Blood collection tube gripping guide rail; 2-4. Blood collection tube lead screw motor; 2-5. Blood collection tube stepper motor; 2-6. Blood collection tube synchronous belt.

[0072] Pipette holder 3-1, four-channel pipette 3-2, pipetting equidistant conversion assembly 3-3, pipetting equidistant conversion bracket 3-31, pipette fixing block 3-32, two pipetting equidistant conversion lead screws 3-33, pipetting equidistant conversion motor 3-34, pipetting guide rail 3-4, pipetting Y-axis guide rail 3-5;

[0073] 4-1 sealing stepper motor, 4-2 sealing transverse guide rail, 4-3 sealing longitudinal guide rail, 4-4 sealing pressure column, 4-5 sealing vacuum circuit board, 4-6 sealing pressure spring, 4-7 silicone diaphragm;

[0074] 5-1. Handling gripper, 5-3. Handling clamping block, 5-4. Handling screw motor, 5-5. Handling stepper motor, 5-6. Handling synchronous belt, 5-7. Handling bracket;

[0075] 6-1 Circular turntable, 6-2 Machining station, 6-3 Sheath, 6-4 Lead screw motor, 6-5 Magnetic solid phase extraction guide rail, 6-6 Magnetic solid phase extraction support, 6-7 Cover plate, 6-8 Heating module, 6-9 Magnetic frame;

[0076] Positive pressure extraction support, positive pressure extraction longitudinal control cylinder 10-2, positive pressure extraction longitudinal guide rail 10-3, positive pressure extraction support rod 10-4, positive pressure extraction pressure block 10-5, positive pressure extraction cap 10-6, positive pressure extraction transverse guide rail 10-7, positive pressure extraction base plate 10-8, positive pressure extraction lead screw motor 10-9, positive pressure extraction support plate 10-10, positive pressure extraction silencer 10-11, positive pressure extraction sealing ring 10-12, positive pressure extraction silicone pad 10-13;

[0077] Waste conveyor belt 11-1, waste conveyor baffle 11-3. Detailed Implementation

[0078] The present invention will be further described below with reference to the accompanying drawings and specific embodiments. It should be understood that the specific embodiments described herein are only for explaining the present invention and are not intended to limit the present invention. Parts not explicitly described in this solution can be implemented using conventional technical means.

[0079] The following is an explanation of any terms that may be involved:

[0080] like Figures 1 to 18 As shown, a fully automated sample pretreatment device includes a frame assembly 7, a cap-opening assembly 1, a blood collection tube gripping assembly 2, a pipette assembly 3, a platform assembly 8, a transport assembly 5, a sealing assembly 4, a magnetic solid-phase extraction assembly 6, a SPE positive pressure extraction assembly 10, and a conveyor belt waste transfer assembly 11. The conveyor belt waste transfer assembly 11 is located at the bottom of the frame assembly 7. The cap-opening assembly 1, the platform assembly 8, and the magnetic solid-phase extraction assembly 6 are arranged sequentially from left to right in the middle of the frame assembly 7. The blood collection tube gripping assembly 2, the pipette assembly 3, the transport assembly 5, and the sealing assembly 4 are located at the top of the frame assembly 7. The magnetic solid-phase extraction assembly 6 and the SPE positive pressure extraction assembly 10 are detachable and interchangeable components.

[0081] The cap-opening assembly 1 secures the blood collection tubes and, in conjunction with the partial blood collection tube gripping assembly 2, opens the blood collection tubes; the blood collection tube gripping assembly 2 grips the blood collection tubes; the pipette assembly 3 moves the corresponding sampled liquid; the transport assembly 5 transports the liquid and sample; the sealing assembly 4 seals the sampled liquid; the conveyor belt waste transport assembly 11 includes a waste transport belt 11-1, a waste transport motor, and a waste transport baffle 11-3; the waste transport belt 11-1 has waste transport baffles 11-3 on both sides, and a waste transport motor is installed on one side of the waste transport baffle 11-3; a waste transport baffle 11-3 is also installed at one end of the waste transport belt 11-1. The conveyor belt waste transport assembly 11 includes a waste transport belt 11-1, a waste transport motor, and a waste transport baffle 11-3; the waste transport belt 11-1 has waste transport baffles 11-3 on both sides, and a waste transport motor is installed on one side of the waste transport baffle 11-3. A waste conveying baffle 11-3 is also installed at one end of the waste conveying belt 11-1.

[0082] Specifically, the sampling device includes a cap-opening assembly 1, a blood collection tube gripping assembly 2, and a pipette assembly 3. The blood collection tube gripping assembly 2 is located to the left of the pipette assembly 3, and the cap-opening assembly 1 is located below the pipette assembly 3. The cap-opening assembly 1, the blood collection tube gripping assembly 2, and the pipette assembly 3 work together to move the blood collection tube from the sample placement position to the corresponding cap-opening assembly 1 using the pipette assembly 3 and the blood collection tube gripping assembly 2. The cap is then opened using the cap-opening assembly 1 and the blood collection tube gripping assembly 2, and the internal sample is removed by the pipette assembly 3 and placed into the corresponding reaction solution.

[0083] Specifically, the blood collection tube gripping assembly 2 includes a blood collection tube gripper 2-1, a blood collection tube clamping block 2-2, a blood collection tube gripping guide rail 2-3, a blood collection tube screw motor 2-4, a blood collection tube stepper motor 2-5, and a blood collection tube synchronization belt 2-6. The blood collection tube stepper motor 2-5 and the blood collection tube synchronization belt 2-6 are fixed to the side of the pipette assembly 3 near the blood collection tube gripping assembly 2, and control the movement of other components of the blood collection tube gripping assembly 2 in the direction of the blood collection tube synchronization belt 2-6. The blood collection tube gripping guide rail 2-3 is connected and fixed to the blood collection tube synchronization belt 2-6. The blood collection tube screw motor 2-4 is fixed to the blood collection tube gripping guide rail 2-3, and the blood collection tube gripper 2-1 is connected to the screw of the blood collection tube screw motor 2-4. The blood collection tube gripper 2-1 controls the movement of the blood collection tube clamping block. That is, the blood collection tube gripper 2-1 controls the blood collection tube clamping block 2-2 to clamp and grab blood collection tubes from the sample holder each time, typically grabbing eight at a time. The blood collection tube stepper motor 2-5 controls the blood collection tube synchronous belt 2-6, which moves the connected blood collection tube gripping guide rail 2-3 laterally. The blood collection tube screw motor 2-4 controls the blood collection tube gripper 2-1 to move longitudinally on the blood collection tube gripping guide rail 2-3, and then the pipette assembly 3 drives the entire blood collection tube gripping assembly 2 to move horizontally, thereby moving the blood collection tube onto the cap opening assembly 1.

[0084] To improve the clamping force of the blood collection tube clamping blocks and prevent them from falling off, the clamping blocks are designed with symmetrical L-shaped cross-sections. These L-shaped blocks move in opposite directions under the control of the blood collection tube gripper 2-1, generating clamping force. Because the upper part of the blood collection tube has a noticeable protrusion, it can rest on the L-shaped clamping blocks, further preventing detachment due to insufficient clamping. As a preferred solution, blood collection tube clamping balls can be distributed on the clamping blocks, achieving better clamping through ball screws. Ideally, the ball screws should be positioned directly below the noticeable protrusion of the blood collection tube.

[0085] The cap-opening assembly 1 includes a cap-opening support block 1-1, a cap-opening stepper motor 1-2, a cap-opening reverse screw 1-3, a cap-opening timing belt 1-4, a cap-opening clamping block 1-5, and a cap-opening guide rail 1-6. The cap-opening clamping block 1-5 has cap-opening support blocks 1-1 at both ends, connected to the cap-opening guide rail 1-6 via the cap-opening reverse screw 1-3. The cap-opening reverse screws 1-3 at both ends of the cap-opening clamping block 1-5 are connected via the cap-opening timing belt 1-4. The cap-opening reverse screw 1-3 is connected to and controlled by the stepper motor. The cap-opening clamping block 1-5 uses two identical convex blocks, with the longest side of the two convex blocks clamping the blood collection tube. That is, this cap-opening assembly 1 effectively clamps the blood collection tube, controlling the clamping movement of the cap-opening clamping block 1-5 by controlling the rotation of the cap-opening reverse screw 1-3 through the cap-opening stepper motor 1-2. The actual opening of the blood collection tube is achieved by the slow upward movement of the blood collection tube gripping component 2. Specifically, the blood collection tube is moved from the gripping component 2 onto the opening component 1, where the lower part of the tube is clamped and fixed. The gripping component 2 no longer needs to clamp the tube; the gripper 2-1 releases the clamping block, but the tube remains on the clamping block. The tube is then moved upward by the lead screw motor 2-4, thus removing the upper cap and completing the opening. This fully utilizes the gripping component 2 to achieve dual functions while reducing the need for additional mechanical structures.

[0086] Preferably, an opening pressure spring 1-7 and an opening pressure block 1-8 are installed inside the convex block of the opening clamping block 1-5. The opening pressure spring 1-7 is fixed on the side furthest from the longest side of the convex block, and is connected to the opening pressure block 1-8. Specifically, the opening pressure block 1-8 has some arc-shaped grooves to better restrict the blood collection tubes, and the opening pressure spring 1-7 pushes the opening pressure block 1-8 to achieve secondary clamping on top of the original clamping force. Raised points or rubber parts can be distributed at corresponding positions on the opening pressure block 1-8 to increase friction. Alternatively, an opening ball screw can be installed inside the convex block of the opening clamping block 1-5. One end of the opening ball screw is fixed on the side furthest from the longest side of the convex block, with the head of the screw protruding outside the convex block. The opening ball screw further enhances clamping.

[0087] The pipette assembly 3 includes a pipette holder 3-1, a four-channel pipette 3-2, a pipetting equidistant conversion component 3-3, a pipetting guide rail 3-4, and a pipetting Y-axis guide rail 3-5. The pipetting equidistant conversion component 3-3 is located on the side of the pipette holder 3-1 away from the blood collection tube grasping component 2. The pipetting guide rail 3-4 is located on the side of the pipetting equidistant conversion component 3-3 away from the blood collection tube grasping component 2. The four-channel pipette 3-2 is mounted on the pipetting guide rail 3-4, and the pipetting Y-axis guide rail 3-5 is mounted on the pipette holder 3-1, which drives the pipetting equidistant conversion component 3-3 of the pipette assembly 3 to move. Specifically, the movement of the four-channel pipette 3-2, the pipetting equidistant adjustment module 3-3, and the pipetting guide 3-4 along the Y-axis is controlled by a corresponding motor (not specified herein). The movement of the four-channel pipette 3-2 along the longitudinal axis is controlled by the pipetting guide 3-4 (which naturally has a corresponding motor control, not detailed in existing technology). The pipetting equidistant adjustment module 3-3 can control the four-channel pipette 3-2 for localized fine-tuning along the Y-axis. Each module of the four-channel pipette 3-2 can move independently up and down, with intervals between the tips of each module, allowing for adjustments on the pipetting guide 3-4 via the pipetting equidistant adjustment module, with a adjustment range between 18 and 36 mm. Structurally, the pipette fixing block 3-32 of the pipetting equidistant adjustment module moves along the pipetting guide 3-4 through the intervals between the tips of each module.

[0088] Specifically, the pipetting equidistant conversion assembly 3-3 includes a pipetting equidistant conversion bracket 3-31, a pipette fixing block 3-32, two pipetting equidistant conversion lead screws 3-33, and a pipetting equidistant conversion motor 3-34.

[0089] Two pipetting equidistant adjustment screws 3-33 are installed on the pipetting equidistant adjustment bracket 3-31, and four pipette fixing blocks 3-32 pass through the two pipetting equidistant adjustment screws 3-33. The two middle pipette fixing blocks 3-32 are controlled by the same pipetting equidistant adjustment screw, and the two outer pipette fixing blocks 3-32 are controlled by another pipetting equidistant adjustment screw. To confirm the position of the pipette fixing blocks 3-32, sensors can be installed at corresponding positions for limit movement.

[0090] Two pipetting equidistant lead screws 3-33 are connected to a pipetting equidistant motor 3-34 via a conveyor belt. A pipetting guide rail 3-4 is connected to the pipetting fixing block 3-32. By cleverly designing two pipetting equidistant lead screws 3-33, the pipetting equidistant assembly 3-3 achieves fine-tuning control of the four pipetting fixing blocks 3-32, greatly reducing mechanical complexity, improving stability, and enabling sampling and pipetting operations in more complex environments.

[0091] The sealing assembly 4 includes a sealing stepper motor 4-1, a sealing transverse guide rail 4-2, a sealing longitudinal guide rail 4-3, a sealing pressure column 4-4, a sealing vacuum circuit board 4-5, and a sealing pressure spring 4-6. The sealing assembly 4 is positioned on the side of the transport bracket 5-7 of the transport assembly 5 away from the transport gripper 5-1. The sealing transverse guide rail 4-2 is fixedly mounted on the transport bracket 5-7 and controls the movement of other components of the sealing assembly 4 in the direction of the sealing transverse guide rail 4-2. The sealing longitudinal guide rail 4-3 is connected and fixed to the sealing transverse guide rail 4-2. The sealing stepper motor 4-1 is fixed on the sealing longitudinal guide rail 4-3 and controls the movement of the sealing pressure column 4-4, the sealing vacuum circuit board 4-5, and the sealing pressure spring 4-6. In this design, a sealing vacuum circuit board 4-5 is installed at one end of the sealing pressure column 4-4 near the deep hole plate to be sealed, and the sealing pressure column 4-4 penetrates through the sealing vacuum circuit board 4-5. Under the control of the sealing stepper motor 4-1, the sealing pressure column 4-4 can extend beyond the sealing vacuum circuit board 4-5.

[0092] Specifically, the sealing film is moved laterally and longitudinally via the sealing film transverse guide rail 4-2, the sealing film longitudinal guide rail 4-3, and their corresponding motors (not shown in the figure), which in turn move the sealing film stepper motor 4-1, the sealing film pressure column 4-4, the sealing film vacuum circuit board 4-5, and the sealing film pressure spring 4-6. The sealing film stepper motor 4-1 further controls the longitudinal movement of the sealing film pressure column 4-4, the sealing film vacuum circuit board 4-5, and the sealing film pressure spring 4-6 to achieve the sealing process for the deep hole plate that needs to be sealed.

[0093] Specifically, the other end of the sealing pressure column 4-4 is fixed to the transport bracket 5-7 and connected to one end of the sealing stepper motor 4-1, so that the sealing stepper motor 4-1 controls the movement of the sealing pressure column 4-4, that is, the silicone mold is sealed on the deep hole plate mainly by pushing the sealing pressure column 4-4. Preferably, a sealing pressure spring 4-6 is set between the sealing vacuum circuit plate 4-5 and the transport bracket 5-7, so as to increase the force of pressing down the sealing pressure column 4-4.

[0094] In essence, the entire system achieves back-and-forth movement along the horizontal and vertical axes via the transverse guide rail 4-2 and the longitudinal guide rail 4-3. During this time, the sealing vacuum air circuit plate 4-5 moves above the required silicone diaphragm 4-7, then moves down to the upper surface of the silicone diaphragm 4-7 and adheres tightly to it. It continues to move downwards a certain distance, keeping the sealing spring compressed. At this point, the upper surface of the silicone diaphragm 4-7 is tightly pressed against the sealing vacuum air circuit plate 4-5, forming a vacuum under the suction of the sealing vacuum air circuit plate 4-5. The silicone diaphragm 4-7 is lifted and moved to directly above the 96-hole plate. Under the action of the sealing stepper motor 4-1, it moves downwards until the silicone diaphragm 4-7 contacts the 96-hole plate. As it continues to move downwards, the sealing vacuum circuit plate 4-5 presses the silicone diaphragm 4-7 firmly under the force of the sealing spring. Simultaneously, as the sealing pressure column 4-4 moves downwards, the corresponding bosses on the silicone diaphragm 4-7 and the sealing pressure column 4-4 are stretched, reducing their diameter, thus easily pressing them into the 96-hole plate. Preferably, the sealing silicone is provided with bosses at the corresponding positions on the deep hole plate, and the diameter of the bosses is larger than the diameter of the holes in the deep hole plate.

[0095] The conveying assembly 5 includes a conveying bracket 5-7, a conveying gripper 5-1, a conveying clamping block, a conveying clamping guide rail 5-3, a conveying lead screw motor 5-4, a conveying stepper motor 5-5, and a conveying timing belt 5-6. The conveying stepper motor 5-5 and the conveying timing belt 5-6 are mounted on the conveying bracket 5-7 and control the movement of other components of the conveying assembly 5 in the direction of the conveying timing belt 5-6. The conveying clamping guide rail 5-3 is connected and fixed to the conveying timing belt 5-6. The conveying lead screw motor 5-4 is fixed to the conveying clamping guide rail 5-3, and the conveying gripper 5-1 is connected to the lead screw of the conveying lead screw motor 5-4. The conveying gripper 5-1 controls the movement of the conveying clamping block. The conveying clamping block is generally L-shaped for better conveying of the deep hole plate.

[0096] The magnetic solid-phase extraction assembly 6 includes a circular turntable 6-1, six evenly distributed processing stations 6-2, a magnetic frame 6-9, a sheath 6-3, a lead screw motor 6-4 paired with the magnetic frame 6-9 and the sheath 6-3, a magnetic solid-phase extraction guide rail 6-5, and a magnetic solid-phase extraction support 6-6. The magnetic solid-phase extraction support 6-6 houses the lead screw motor 6-4 paired with the magnetic frame 6-9 and the sheath 6-3. The magnetic solid-phase extraction guide rail 6-5 is positioned in the longitudinal direction of the magnetic solid-phase extraction support 6-6. The magnetic frame 6-9 and the sheath 6-3 are mounted on the magnetic solid-phase extraction guide rail 6-5 and move longitudinally. The magnetic frame 6-9 matches the sheath 6-3, and the sheath 6-3 can cover all the magnetic rods on the magnetic frame 6-9. The magnetic rod 6-9 and the sheath 6-3 are moved up and down on the magnetic solid-phase extraction guide rail 6-5 by a lead screw motor 6-4 paired with them. Six processing stations 6-2 evenly distributed on the circular turntable 6-1 are rotated by corresponding motors. This allows for the magnetic solid-phase extraction operation to be performed after the corresponding reagent solution is loaded into the corresponding processing station 6-2 via other devices, and then the magnetic rod and sheath 6-3 are operated. The six evenly distributed processing stations 6-2 are divided into activation processing station 6-2, equilibration processing station 6-2, sample loading processing station 6-2, first elution processing station 6-2, second elution processing station 6-2, and elution processing station 6-2. Reagent solutions are added in this order each time, and the magnetic solid-phase extraction operation is also performed according to this station sequence.

[0097] Specifically, the circular turntable 6-1 is controlled by an indexing plate, which is located below and connected to the circular turntable 6-1. Using the indexing plate allows for precise control of the rotation angle of the circular turntable 6-1, reducing the need for additional high-precision instruments and thus minimizing costs.

[0098] It also includes a cover plate 6-7, one end of which is connected to a cover plate 6-7 motor and rotates under the control of the cover plate 6-7 motor to block the flow of liquid. Furthermore, the cover plate 6-7 can cover the entire magnetic frame 6-9 to prevent external solution from falling into the protective sleeve 6-3. The overall structure has an obtuse angle, designed to completely cover the magnetic frame 6-9.

[0099] It also includes a heating module 6-8, which is positioned below the circular turntable 6-1 and at the workstation closest to the magnetic solid-phase extraction support 6-6. The heating module 6-8 can also be connected to the magnetic solid-phase extraction guide rail 6-5. The heating module 6-8 is connected to an oscillating motor and is controlled by the oscillating motor. Alternatively, the oscillating motor can also be directly installed inside the magnetic solid-phase extraction support 6-6.

[0100] During magnetic solid-phase extraction, the reagent solution in the 96-well plate is added to the first station (activation station 6-2) of the six processing stations 6-2 using a corresponding pipette. After each addition, the plate is rotated at a certain angle until all the 96-well plates in the six processing stations 6-2 have been filled. Then, the circular turntable 6-1 rotates the first station (activation station 6-2) directly below the magnetic frame 6-9. The sheath 6-3 moves up and down under the action of the lead screw motor 6-4, ensuring thorough mixing of the reagent solution. After activation at the first station, the sheath 6-3 moves downward to the bottom of the 96-well plate, and at the same time, the magnetic frame 6-9 also moves downward to the bottom of the 96-well plate. At this time, the magnetic bead solution is adsorbed on the outside of the sheath 6-3. Then, the sheath 6-3 and the magnetic frame 6-9 begin to move upward under the action of the lead screw motor 6-4. When they are removed from the 96-well plate, the cover plate 6-7 rotates to the bottom of the magnetic frame 6-9 to prevent the solution outside the sheath 6-3 from falling and contaminating other solutions.

[0101] The circular turntable 6-1 rotates again to the 96 deep hole plate of the next processing station 6-2. The cover plate 6-7 rotates back to the origin. The sheath 6-3 and the magnetic frame 6-9 move down to the bottom of the 96 deep hole plate of the current processing station 6-2. The sheath 6-3 remains stationary, and the magnetic frame 6-9 moves up to the highest point. No further operation will be performed afterward.

[0102] Then the sheath 6-3 moves up and down to fully mix the reagent solution, and so on until the last 96 deep hole plate of the six processing stations 6-2 is completed.

[0103] Because there is a heating module 6-8 below the corresponding circular turntable 6-1, when the workstation requiring heating moves to this position, the heating module 6-8 can be moved up and down to perform heating. That is, when heating is needed, the heating module is moved upwards until it is in close contact with the bottom of the 96mm deep hole plate, and then moved downwards after heating is completed. This will not affect the rotation of the circular turntable 6-1. Naturally, it is easier to set up a corresponding up-and-down moving structure at the position corresponding to the magnetic frame 6-9 (not shown in the figure).

[0104] When SPE positive pressure extraction is used, the specific SPE positive pressure extraction assembly 10 includes a positive pressure extraction support, a positive pressure extraction longitudinal control cylinder 10-2, a positive pressure extraction longitudinal guide rail 10-3, a positive pressure extraction support rod 10-4, a positive pressure extraction pressure block 10-5, a positive pressure extraction cap 10-6, a positive pressure extraction transverse guide rail 10-7, a positive pressure extraction base plate 10-8, a positive pressure extraction lead screw motor 10-9, and a positive pressure extraction support plate 10-10.

[0105] A positive pressure extraction block 10-5 is installed above the positive pressure extraction support, and the positive pressure extraction block 10-5 is connected to the positive pressure extraction support via a positive pressure extraction support rod 10-4; a positive pressure extraction longitudinal control cylinder 10-2 is installed inside the positive pressure extraction support, and the positive pressure extraction longitudinal control cylinder 10-2 controls the positive pressure extraction block 10-5 to move longitudinally.

[0106] It also includes a positive pressure extraction guide plate. The two ends of the positive pressure extraction support rod 10-4 are respectively connected and fixed to the positive pressure extraction guide plate and the positive pressure extraction block 10-5. The positive pressure extraction guide plate is also provided with a through hole for the positive pressure extraction guide rail to pass through. The positive pressure extraction guide plate is connected to the positive pressure extraction longitudinal control cylinder 10-2.

[0107] A positive pressure extraction transverse guide rail 10-7 is set on the upper surface of the positive pressure extraction support, and is connected to and controlled by the positive pressure extraction lead screw motor 10-9; the positive pressure extraction lead screw motor 10-9 is set on the positive pressure extraction support plate 10-10, which is located inside the positive pressure extraction support near the upper surface; a positive pressure extraction base plate 10-8 is set on the positive pressure extraction transverse guide rail 10-7, and a perforated plate and an SPE plate are placed on the positive pressure extraction base plate 10-8;

[0108] The positive pressure extraction block 10-5 is equipped with a positive pressure extraction silencer 10-11 inside, and a positive pressure extraction sealing ring 10-12 is provided at the contact position between the cover of the positive pressure extraction block 10-5 and the positive pressure extraction block 10-5. A positive pressure extraction silicone pad 10-13 is provided at the bottom of the positive pressure extraction block 10-5, and an air inlet is provided at the center of the cover of the positive pressure extraction block 10-5 for nitrogen to enter.

[0109] A fully automated sample pretreatment method includes the following steps:

[0110] 101) Pretreatment steps: Place the corresponding sample and reagent solution on the platform component 8; and set the magnetic solid phase extraction component 6 or replace it with the SPE positive pressure extraction component 10 as needed;

[0111] 102) Opening procedure: The sample collection tube is clamped by the blood collection tube gripping component 2 and transferred to the opening component 1 by the pipette component 3; then the opening component 1 fixes the sample collection tube and removes the upper cap of the blood collection tube by moving the blood collection tube gripping component 2 upward.

[0112] Specifically, the blood collection tube is moved from the blood collection tube gripping component 2 to the cap opening component 1. The cap opening component 1 clamps and fixes the lower part of the blood collection tube, while the blood collection tube gripping component 2 no longer needs to clamp the blood collection tube. The blood collection tube gripper controls the blood collection tube clamping block to relax, but the blood collection tube is still placed on the blood collection tube clamping block. The blood collection tube screw motor controls its upward movement, thereby removing the upper cap of the blood collection tube and completing the cap opening.

[0113] 103) Sampling steps: The sample to be sampled is taken out from the blood collection tube fixed by the capping assembly 1 through the pipette assembly 3 and transferred into the corresponding deep well plate by the pipette assembly 3;

[0114] 104) Sealing step: The deep hole plate from step 103) is transported to the corresponding position by the transport assembly 5 and sealed by the sealing assembly 4;

[0115] Specifically, the sealing film uses horizontal and vertical guide rails to achieve back-and-forth movement along the horizontal and vertical axes. The sealing film vacuum circuit board moves to above the required silicone diaphragm, then moves down to the upper surface of the diaphragm and adheres tightly to it. It continues to move downwards a certain distance, keeping the sealing spring compressed. At this point, the upper surface of the silicone diaphragm is tightly pressed against the sealing film vacuum circuit board, creating a vacuum under its suction. The silicone diaphragm is then lifted and moved directly above the deep hole plate. Under the action of the sealing film stepper motor, it moves downwards until the silicone diaphragm contacts the deep hole plate. The sealing film vacuum circuit board continues to move downwards, pressing the silicone diaphragm tightly under the force of the sealing spring. Simultaneously, as the sealing film pressure column moves downwards, the corresponding bosses on the silicone diaphragm and pressure column are stretched and their diameter reduced, thus pressing the silicone diaphragm into the deep hole plate.

[0116] 105) Sample processing steps: Install the corresponding module magnetic solid phase extraction component 6 or SPE positive pressure extraction component 10, and perform the corresponding processing.

[0117] When using the magnetic solid-phase extraction component 6, the reagent solution in the deep well plate is added to the first of the six processing stations using a corresponding pipette. After each addition, the pipette is rotated at a certain angle until all the deep well plates at the six processing stations have been filled. Then, a circular turntable rotates the first station directly below the magnetic frame. The sheath moves up and down under the action of a screw motor, ensuring thorough mixing of the reagent solution. After activation at the first station, the sheath moves down to the bottom of the deep well plate, and the magnetic frame also moves down to the bottom of the deep well plate. At this point, the magnetic bead solution is adsorbed around the sheath. Then, the sheath and magnetic frame begin to move up under the action of the screw motor. When they are removed from the deep well plate, the cover plate rotates to the bottom of the magnetic frame to prevent the solution outside the sheath from falling and contaminating other solutions.

[0118] The rotary table rotates again to the deep hole plate of the next processing station. The cover plate rotates back to the origin. The sheath and the magnetic frame move down to the bottom of the deep hole plate of the current processing station. The sheath remains stationary, and the magnetic frame moves up to the highest point. No further operation is performed afterward.

[0119] Then the sheath moves up and down to fully mix the reagent solution, and so on until the last deep hole plate of the six processing stations is completed.

[0120] The above description is only a preferred embodiment of the present invention. It should be noted that those skilled in the art can make several improvements and modifications without departing from the concept of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A fully automated sample preparation apparatus, characterized by: The rack assembly, the cap opening assembly, the blood collection tube grabbing assembly, the pipette assembly, the platform assembly, the carrying assembly, the film sealing assembly, the magnetic solid phase extraction assembly, the SPE positive pressure extraction assembly and the conveyor waste transmission assembly are arranged in sequence from left to right; the conveyor waste transmission assembly is arranged at the bottom of the rack assembly; the cap opening assembly, the platform assembly and the magnetic solid phase extraction assembly are arranged in sequence from left to right in the middle of the rack assembly; the blood collection tube grabbing assembly, the pipette assembly, the carrying assembly and the film sealing assembly are arranged at the upper part of the rack assembly; the magnetic solid phase extraction assembly and the SPE positive pressure extraction assembly are detachable and replaceable components; The cap opening assembly fixes the blood collection tube and opens the cap of the blood collection tube in combination with the blood collection tube grabbing assembly; the blood collection tube grabbing assembly grabs the blood collection tube; the pipette assembly moves the corresponding sampling liquid; the carrying assembly carries the liquid and the sample; the film sealing assembly seals the sampling liquid; the conveyor waste transmission assembly comprises a conveyor waste belt, a conveyor waste motor and a conveyor waste baffle; the conveyor waste belt is provided with the conveyor waste baffles on both sides, and the conveyor waste motor is arranged on one side of the conveyor waste baffles; one end of the conveyor waste belt is also provided with a conveyor waste baffle; The magnetic solid phase extraction assembly comprises a circular turntable, six uniformly distributed processing stations, a magnetic frame, a sheath, a lead screw motor matched with the magnetic frame and the sheath, a magnetic solid phase extraction guide rail and a magnetic solid phase extraction support; the lead screw motor matched with the magnetic frame and the sheath is arranged in the magnetic solid phase extraction support; the magnetic solid phase extraction guide rail is arranged in the longitudinal direction of the magnetic solid phase extraction support; the magnetic frame and the sheath are arranged on the magnetic solid phase extraction guide rail and move in the longitudinal direction; the magnetic frame is matched with the sheath, and the sheath can cover all the magnetic rods on the magnetic frame; the circular turntable is controlled by a protractor disc arranged below the circular turntable and connected with the circular turntable; The cap opening assembly, the blood collection tube grabbing assembly and the pipette assembly form a sampling device; the blood collection tube grabbing assembly is arranged on the left side of the pipette assembly; the cap opening assembly is arranged below the pipette assembly; The blood collection tube grabbing assembly comprises a blood collection tube gripper, a blood collection tube clamping block, a blood collection tube grabbing guide rail, a blood collection tube lead screw motor, a blood collection tube stepping motor and a blood collection tube synchronous belt; the blood collection tube stepping motor and the blood collection tube synchronous belt are fixed on one side of the pipette assembly close to the blood collection tube grabbing assembly, and control the movement of other components of the blood collection tube grabbing assembly in the arrangement direction of the blood collection tube synchronous belt; the blood collection tube grabbing guide rail is fixedly connected with the blood collection tube synchronous belt; the blood collection tube lead screw motor is fixed on the blood collection tube grabbing guide rail, and the lead screw of the blood collection tube lead screw motor is connected with the blood collection tube gripper; the blood collection tube gripper controls the movement of the blood collection tube clamping block; The cap opening assembly comprises a cap opening support block, a cap opening stepping motor, a cap opening reverse lead screw, a cap opening synchronous belt, a cap opening clamping block and a cap opening guide rail; the cap opening clamping block is provided with the cap opening support blocks at both ends and is connected through the cap opening reverse lead screw and the cap opening guide rail; the cap opening reverse lead screws at both ends of the cap opening clamping block are connected through the cap opening synchronous belt; the cap opening reverse lead screw is connected with the stepping motor and is controlled by the stepping motor; the cap opening clamping block adopts two identical convex blocks, and the longest sides of the two convex blocks clamp the blood collection tube. The pipette assembly comprises a pipette support, a four-channel pipette, a pipette equidistance conversion assembly, a pipette guide rail and a pipette Y-axis guide rail; the pipette equidistance conversion assembly is arranged on the side of the pipette support away from the blood collection tube grabbing assembly, the pipette guide rail is arranged on the side of the pipette equidistance conversion assembly away from the blood collection tube grabbing assembly, the four-channel pipette is arranged on the pipette guide rail, and the pipette Y-axis guide rail is arranged on the pipette support to drive the pipette equidistance conversion assembly of the pipette assembly to move.

2. A fully automated sample preparation apparatus, characterized by: The device comprises a rack assembly, an uncapping assembly, a blood collection tube grabbing assembly, a pipette assembly, a platform assembly, a carrying assembly, a film sealing assembly, a magnetic solid-phase extraction assembly, an SPE positive pressure extraction assembly and a conveyor belt waste conveying assembly; the bottom of the rack assembly is provided with the conveyor belt waste conveying assembly, the middle of the rack assembly is sequentially provided from left to right with the uncapping assembly, the platform assembly and the magnetic solid-phase extraction assembly, and the upper part of the rack assembly is provided with the blood collection tube grabbing assembly, the pipette assembly, the carrying assembly and the film sealing assembly; the magnetic solid-phase extraction assembly and the SPE positive pressure extraction assembly are detachable and replaceable assemblies; The uncapping assembly realizes the fixation of the blood collection tube and the uncapping of the blood collection tube in combination with the blood collection tube grabbing assembly; the blood collection tube grabbing assembly realizes the grabbing of the blood collection tube; the pipette assembly realizes the displacement of the corresponding sampling liquid; the carrying assembly realizes the carrying of the liquid and the sample; the film sealing assembly realizes the film sealing of the sampling liquid; the conveyor belt waste conveying assembly comprises a conveying waste belt, a conveying waste motor and a conveying waste baffle; the conveying waste belt is provided with the conveying waste baffles on both sides, and the conveying waste motor is arranged on one side of the conveying waste baffles; one end of the conveying waste belt is also provided with a conveying waste baffle; The SPE positive pressure extraction assembly comprises a positive pressure extraction support, a positive pressure extraction longitudinal control cylinder, a positive pressure extraction longitudinal guide rail, a positive pressure extraction support rod, a positive pressure extraction pressing block, a positive pressure extraction cover, a positive pressure extraction transverse guide rail, a positive pressure extraction bottom plate, a positive pressure extraction screw rod motor and a positive pressure extraction support plate; The positive pressure extraction pressing block is arranged above the positive pressure extraction support and is connected to the positive pressure extraction support through the positive pressure extraction support rod; the positive pressure extraction longitudinal control cylinder is arranged in the positive pressure extraction support, and the positive pressure extraction longitudinal control cylinder controls the movement of the positive pressure extraction pressing block in the longitudinal direction; The positive pressure extraction guiding plate is further arranged, and the two ends of the positive pressure extraction support rod are respectively connected to the positive pressure extraction guiding plate and the positive pressure extraction pressing block; the positive pressure extraction guiding plate is further provided with a through hole for the positive pressure extraction guide rail to pass through, and the positive pressure extraction guiding plate is connected to the positive pressure extraction longitudinal control cylinder; The positive pressure extraction transverse guide rail is arranged on the upper surface of the positive pressure extraction support, is connected to the positive pressure extraction screw rod motor and is controlled by the positive pressure extraction screw rod motor; the positive pressure extraction screw rod motor is arranged on the positive pressure extraction support plate, and the positive pressure extraction support plate is arranged at a position close to the upper surface in the positive pressure extraction support; the positive pressure extraction bottom plate is arranged on the positive pressure extraction transverse guide rail, and the hole plate and the SPE plate are placed on the positive pressure extraction bottom plate; The positive pressure extraction briquet is internally provided with a positive pressure extraction silencer, a positive pressure extraction sealing ring is arranged at the contact position of the cover of the positive pressure extraction briquet and the positive pressure extraction briquet, a positive pressure extraction silica gel pad is arranged at the bottom of the positive pressure extraction briquet, and an air inlet hole is arranged at the central position of the cover of the positive pressure extraction briquet for the nitrogen gas to enter. The uncapping assembly, the blood collection tube grabbing assembly and the pipette assembly form a sampling device, the blood collection tube grabbing assembly is arranged on the left side of the pipette assembly, and the uncapping assembly is arranged below the pipette assembly. The blood collection tube grabbing assembly comprises a blood collection tube gripper, a blood collection tube clamping block, a blood collection tube grabbing guide rail, a blood collection tube screw rod motor, a blood collection tube stepping motor and a blood collection tube synchronous belt; the blood collection tube stepping motor and the blood collection tube synchronous belt are fixed on one side of the pipette assembly close to the blood collection tube grabbing assembly, and control the movement of other components of the blood collection tube grabbing assembly in the arrangement direction of the blood collection tube synchronous belt; the blood collection tube grabbing guide rail is fixedly connected with the blood collection tube synchronous belt, the blood collection tube screw rod motor is fixed on the blood collection tube grabbing guide rail, and a screw rod of the blood collection tube screw rod motor is connected with the blood collection tube gripper, so that the blood collection tube gripper controls the movement of the blood collection tube clamping block; The uncapping assembly comprises an uncapping support block, an uncapping stepping motor, an uncapping reverse screw rod, an uncapping synchronous belt, an uncapping clamping block and an uncapping guide rail; the uncapping clamping block is provided with uncapping support blocks at both ends and is connected through the uncapping reverse screw rod and the uncapping guide rail; the uncapping reverse screw rod at both ends of the uncapping clamping block is connected through the uncapping synchronous belt; the uncapping reverse screw rod is connected with the stepping motor and is controlled thereby; wherein the uncapping clamping block adopts two identical convex blocks, and the longest sides of the two convex blocks clamp the blood collection tube; The pipette assembly comprises a pipette support, a four-channel pipette, a pipette equidistance conversion assembly, a pipette guide rail and a pipette Y-axis guide rail; the pipette equidistance conversion assembly is arranged on the side of the pipette support away from the blood collection tube grabbing assembly, the pipette guide rail is arranged on the side of the pipette equidistance conversion assembly away from the blood collection tube grabbing assembly, the four-channel pipette is arranged on the pipette guide rail, and the pipette Y-axis guide rail is arranged on the pipette support to drive the pipette equidistance conversion assembly of the pipette assembly to move.

3. The fully automated sample preparation device according to claim 1 or 2, characterized in that The blood collection tube clamping block adopts symmetrically arranged L-shaped clamping blocks in cross section, the L-shaped clamping blocks are controlled by the blood collection tube gripper to move oppositely to form a clamping force, and blood collection tube clamping balls are arranged on the blood collection tube clamping block.

4. The fully automated sample preparation device according to claim 1 or 2, characterized in that: The convex block of the uncapping clamping block is internally provided with an uncapping pressure spring and an uncapping pressure block, the uncapping pressure spring is fixed in the side away from the longest side of the convex block, and the uncapping pressure spring is connected with the uncapping pressure block.

5. The fully automated sample preparation device according to claim 1 or 2, characterized in that: The convex block of the uncapping clamping block is internally provided with an uncapping ball screw, one end of the uncapping ball screw is fixed in the side away from the longest side of the convex block, and the head of the uncapping ball screw is exposed outside the convex block.

6. The fully automated sample preparation device according to claim 1 or 2, characterized in that: The pipette equidistance conversion assembly comprises a pipette equidistance conversion support, a pipette fixing block, two pipette equidistance conversion screw rods and a pipette equidistance conversion motor. The two pipette equidistant conversion lead screws are arranged on the pipette equidistant conversion support, and four pipette fixing blocks are arranged on the two pipette equidistant conversion lead screws. The two pipette fixing blocks in the middle are controlled by the same pipette equidistant conversion lead screw, and the two pipette fixing blocks on the outside are controlled by the other pipette equidistant conversion lead screw. The two pipette equidistant conversion lead screws are connected with the pipette equidistant conversion motor through the transmission belt, and the pipette fixing blocks are connected with the pipette guide rail. The four modules in the four-channel pipette can be moved up and down independently, and the intervals between the TIP heads of each module are moved on the pipette guide rail through the pipette fixing blocks of the pipette equidistant conversion assembly.

7. The fully automated sample preparation device according to claim 1 or 2, characterized in that: The carrying assembly comprises a carrying support, a carrying gripper, a carrying clamping block, a carrying clamping guide rail, a carrying screw motor, a carrying stepping motor and a carrying synchronous belt. The carrying stepping motor, the carrying synchronous belt and other components of the carrying assembly are arranged on the carrying support and are controlled to move in the direction in which the carrying synchronous belt is arranged. The carrying clamping guide rail is fixedly connected with the carrying synchronous belt, the carrying screw motor is fixed on the carrying clamping guide rail, and the carrying gripper is connected with the screw of the carrying screw motor. The carrying gripper controls the movement of the carrying clamping block. The carrying clamping block is in the shape of L as a whole. The film sealing assembly comprises a film sealing stepping motor, a film sealing transverse guide rail, a film sealing longitudinal guide rail, a film sealing pressing column, a film sealing vacuum air path plate and a film sealing pressure spring. The film sealing assembly is arranged on the side of the carrying support of the carrying assembly away from the carrying gripper. The film sealing transverse guide rail is fixedly arranged on the carrying support and controls the movement of other components of the film sealing assembly in the direction in which the film sealing transverse guide rail is arranged. The film sealing longitudinal guide rail is fixedly connected with the film sealing transverse guide rail. The film sealing stepping motor is fixed on the film sealing longitudinal guide rail and controls the movement of the film sealing pressing column, the film sealing vacuum air path plate and the film sealing pressure spring. The film sealing pressing column is arranged on the side close to the deep hole plate to be sealed. The film sealing pressing column penetrates through the film sealing vacuum air path plate. The other end of the film sealing pressing column is fixed on the carrying support and is connected with one end of the film sealing stepping motor, so that the film sealing stepping motor controls the movement of the film sealing pressing column. The film sealing pressure spring is arranged between the film sealing vacuum air path plate and the carrying support.

8. The fully automated sample preparation device according to claim 1 or 2, characterized in that: The cover plate is connected with the cover plate motor at one end and is controlled to rotate and shield by the cover plate motor. The cover plate covers the entire magnetic force frame.

9. The fully automated sample preparation device according to claim 1 or 2, characterized in that: The heating module is arranged below the circular turntable and corresponds to the position of the work station closest to the magnetic solid phase extraction support. The heating module is connected with the magnetic solid phase extraction guide rail. The heating module is connected with the oscillation motor and is controlled as a whole.

10. A fully automated sample pre-treatment method, characterized by: The specific operation of the pretreatment device comprises the following steps: 101) Pretreatment step: placing the corresponding treatment sample and the corresponding reagent solution on the platform assembly; and setting the magnetic solid phase extraction assembly or replacing it with an SPE positive pressure extraction assembly as needed; 102) Cover opening step: clamping the sample blood collection tube by the blood collection tube grabbing assembly, and transferring it to the cover opening assembly by the pipette assembly; then fixing the sample blood collection tube by the cover opening assembly, and removing the upper cover of the sample blood collection tube by cooperating with the upward movement of the blood collection tube grabbing assembly; Specifically, the blood collection tube is moved from the blood collection tube grabbing assembly to the cap opening assembly, the cap opening assembly clamps and fixes the lower part of the blood collection tube, and the blood collection tube grabbing assembly does not need to clamp the blood collection tube at this time, the blood collection tube clamping block is released by the blood collection tube grabbing hand, but the blood collection tube is still clamped on the blood collection tube clamping block, and the blood collection tube is moved upward by the blood collection tube lead screw motor, so as to remove the upper cap of the blood collection tube, and the cap opening is completed. 103) Sampling step: the sample in the blood collection tube fixed by the cap opening assembly is taken out by the pipette assembly, and is moved into the corresponding deep well plate by the pipette assembly. 104) Membrane sealing step: the deep well plate of step 103) is carried to the corresponding position by the carrying assembly, and is sealed by the membrane sealing assembly. Specifically, the membrane sealing transverse guide rail and the membrane sealing longitudinal guide rail are used to realize the back and forth movement in the horizontal axis and the vertical axis directions; at this time, the membrane sealing vacuum air path plate moves to the position above the silica gel film, then moves downward to the upper surface of the silica gel film and tightly adheres to the upper surface, continues to move downward by a certain distance to keep the membrane sealing spring in the compressed state, at this time, the upper surface of the silica gel film is tightly adhered to the membrane sealing vacuum air path plate, and a vacuum is formed under the action of the suction force of the membrane sealing vacuum air path plate, the silica gel film is sucked up, then moves to the position directly above the deep well plate, moves downward to the position where the silica gel film contacts with the deep well plate under the action of the membrane sealing stepping motor, continues to move downward, the silica gel film is tightly pressed under the action of the membrane sealing spring, at the same time, the silica gel film and the corresponding position boss of the membrane sealing pressure column are elongated and the diameter is reduced, so as to be pressed into the deep well plate; 105) Sample processing step: install the corresponding module magnetic solid phase extraction assembly or SPE positive pressure extraction assembly for processing, and the corresponding processing can be performed; When the magnetic solid phase extraction assembly is selected, the reagent solution in the deep well plate is added to the first working position of the six processing working positions by the corresponding pipette, and is turned by a certain angle after each addition, until the reagent solution in the deep well plate of the six processing working positions is added completely, then the first working position is turned to the position directly below the magnetic holder by the circular turntable, and the sheath moves up and down under the action of the lead screw motor, so that the reagent solution is mixed sufficiently; After the activation in the first working position is completed, the sheath moves downward to the bottom of the deep well plate, and the magnetic holder also moves downward to the bottom of the deep well plate at the same time, at this time, the magnetic bead solution is adsorbed on the periphery of the sheath, at this time, the sheath and the magnetic holder start to move upward under the action of the lead screw motor, when the deep well plate is moved out, the cover plate is turned to the position below the magnetic holder, so as to prevent the solution outside the sheath from falling and contaminating other solutions; The circular turntable is turned again to the deep well plate of the next processing working position, the cover plate is turned back to the original position, the sheath and the magnetic holder move downward to the bottom of the deep well plate of the processing working position at this moment, the sheath is stationary, the magnetic holder moves to the highest point, and the next operation is not performed. Then the sheath moves up and down to mix the reagent solution sufficiently, and the same is repeated until the last deep well plate of the six processing working positions is completed.

Citation Information

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