A high-speed mass spectrometry plate pretreatment system and its use method

Abstract

The present application relates to the technical field of mass spectrometry plate pretreatment, and provides a high-speed mass spectrometry plate pretreatment system and a method for use. The processing system includes a processing box; a sample position, which is arranged in the processing box and is used to place a test tube containing a sample to be tested; a reagent position, which is arranged in the processing box and is used to hold the reagents required during the experiment; a magnetic bead position, which is arranged in the processing box; a magnetic bead mixing module, which is arranged in the magnetic bead position and is used to mix the magnetic bead solution, including a placement box for placing the reagent bottle and a driving mechanism for driving the placement box to swing or vibrate; an incubation and shaking position, which is arranged in the processing box and is used to shake and mix the solution or reagent in the test tube and heat and incubate it during the experiment. The present application significantly reduces the time for waste liquid removal and magnetic bead mixing by using steel needles arranged in a matrix to replace the traditional TIP head, and combines it with a shaker-type magnetic bead shaking mechanism, thereby improving the overall processing efficiency.

Description

Technical Field

[0001] The present application relates to the technical field of mass spectrometry plate pretreatment, and in particular to a high-speed mass spectrometry plate pretreatment system and a method for using the same. Background Art

[0002] Mass spectrometry pretreatment methods have important applications in biomedical testing, drug analysis, and other fields, but their pretreatment steps are complex, typically involving multiple steps such as sample distribution, reagent distribution, waste liquid removal, and magnetic bead distribution. Traditional automated pretreatment equipment is mainly based on automatic pipetting workstations, relying on a robotic arm to drive the pipette to perform actions. These equipment suffer from problems such as long processing time, high cost, and poor stability. In particular, for the waste liquid removal step, traditional methods use a TIP tip. Since the TIP tip is a disposable consumable, this results in high consumable costs and long processing times, making it difficult to meet the needs of high-throughput testing. Therefore, further improvement is needed. Summary of the Invention

[0003] In order to solve the above problems, the present application provides a high-speed mass spectrometry plate pretreatment system and a method of use.

[0004] This application provides a high-speed mass spectrometry plate pretreatment system and method of use, which adopts the following technical solutions:

[0005] A high-speed mass spectrometry plate pretreatment system and a method of use, comprising:

[0006] Processing box;

[0007] A sample position is provided in the processing box and is used to place a test tube containing a sample to be tested;

[0008] Reagent position, set in the processing box, used to hold the reagents required during the experiment;

[0009] Magnetic bead position, set in the processing box;

[0010] The magnetic bead mixing module is arranged at the magnetic bead position to mix the magnetic bead solution, including a placement box for placing the reagent bottles and a driving mechanism for driving the placement box to swing or vibrate;

[0011] The incubation and shaking position is set in the processing box and is used to shake, mix, heat and incubate the solution or reagent in the test tube during the experiment;

[0012] The sample adding arm is arranged in the processing box and is provided with a pipette for adding various samples, reagents or magnetic bead solutions into the test tube, or for transferring various solutions after the reaction during the experiment;

[0013] The cleaning position is set in the processing box and is used to place test tubes that need to remove waste liquid;

[0014] The gripping arm is provided in the processing box and is used to drive the test tube to move back and forth between the cleaning position and the incubation and shaking position;

[0015] The magnetic attraction position is set in the processing box, and the bottom of the magnetic attraction position is equipped with a magnetic frame for magnetic attraction before the secondary transfer of the supernatant;

[0016] The cleaning module is arranged at the cleaning position to remove the waste liquid in the test tube located at the cleaning position, including a steel needle for sucking and removing the waste liquid, a mounting seat for installing the steel needle, a first driving component for driving the mounting seat to slide, a second driving component arranged on the mounting seat to drive the steel needle to extend into the test tube, a cleaning station for cleaning the outer surface of the steel needle and the built-in waste liquid, and a side suction magnetic component for magnetically attracting the magnetic beads in the test tube. There are a number of steel needles arranged in a matrix.

[0017] By adopting the above technical solution, traditional mass spectrometry pre-treatment equipment usually uses a TIP head to remove waste liquid in the waste liquid removal step, resulting in high consumables cost and long processing time. By adopting steel needles arranged in a matrix to replace the traditional TIP head, the waste liquid removal time is greatly shortened and the processing efficiency is significantly improved. And because the traditional TIP head can only be used once in the waste liquid removal step, resulting in high consumables cost, the use of steel needles to remove waste liquid and the use of lower-cost needle washing liquid instead of the TIP head reduce the use of consumables and reduce pre-treatment costs. And because the steel needles produced by modern and mature processing technology replace the TIP head to complete the waste liquid removal step, the consistency and stability of the waste liquid removal step are improved, and the reliability of the pre-treatment is improved.

[0018] In traditional experiments, in addition to the relatively time-consuming waste liquid removal mentioned above, the magnetic bead solution must also be mixed. Traditional magnetic bead solutions are usually pipetted multiple times. To further reduce processing time, a magnetic bead mixing module is provided to automatically shake the solution before aspirating the magnetic beads, ensuring that the magnetic bead solution is always mixed, eliminating the need for additional pipetting and mixing, significantly improving processing efficiency. Furthermore, since magnetic bead reconstitution solutions are mostly highly volatile organic solvents, the traditional method of pipetting in organic solvents for a long time can easily lead to solvent volatilization and shorten the equipment maintenance cycle. The provision of a mixing module reduces the possibility of the pipette being in contact with organic solvents for a long time, thereby extending the service life of the equipment.

[0019] Preferably, an elastic component is provided on the top of the steel needle.

[0020] By adopting the above technical solution and providing an elastic component, the device can completely touch the bottom during liquid aspiration, meeting the liquid residue requirements, and can also enhance the adaptability of the system, making it suitable for test tubes of different specifications and heights, thereby improving the versatility of the equipment.

[0021] Preferably, the inner diameter of the steel needle gradually increases toward the needle head, and a cross groove is provided at the needle head of the steel needle.

[0022] By adopting the above technical solution, the inner diameter of the steel needle gradually increases towards the needle tip, which can effectively reduce the possibility of large pieces of matter entering the steel needle and causing blockage.

[0023] Preferably, the cleaning station includes a cleaning pool, water spray pipes arranged on opposite side walls of the cleaning pool, and a water supply component for supplying water to the water spray pipes. The cleaning station is provided with an isolating component for dividing the pool into several cleaning areas, and the several cleaning areas are arranged in a matrix corresponding to the steel needles. The side walls of the isolating component are provided with water inlet holes, and four water inlet holes are arranged at intervals along the axis of the steel needle. The four water inlet holes are respectively arranged corresponding to the through grooves, and the bottom of the cleaning pool is provided with a drainage component for discharging water.

[0024] By employing this technical solution, the isolation elements within the cleaning tank divide the cleaning area into multiple cleaning zones, each corresponding to a corresponding steel needle. This ensures more even water distribution during the cleaning process, preventing interference between different steel needles. Four water inlet holes are spaced along the axis of the steel needles, corresponding one-to-one with the steel needles' grooves. This allows the cleaning fluid to precisely impact the grooves within the needles, effectively removing residue.

[0025] Preferably, the side wall of the steel needle is provided with a through groove connected to the cross groove, and the isolation member is provided as an isolation sleeve, and the inner diameter of the isolation sleeve gradually decreases in the direction away from the steel needle; the drainage member includes a drainage box with a cavity provided at the bottom of the cleaning pool, a piston plate slidably connected to the drainage box, a first driving member for driving the piston plate to slide, a first one-way valve fixedly penetrated through the top wall of the drainage box, a second one-way valve provided on the side wall of the drainage box, and a drainage pipe connected to the second one-way valve, the first one-way valve flows from the isolation sleeve to the drainage box, and the second one-way valve flows from the drainage box to the drainage pipe.

[0026] By adopting the above technical solution, a through groove is opened on the side wall of the steel needle, which further enhances the fluidity during the waste liquid absorption process, so that the waste liquid can be removed quickly and smoothly, thereby greatly shortening the waste liquid removal time.

[0027] The isolation element is designed as an isolation sleeve, with an inner diameter that gradually decreases away from the steel needle. This effectively guides waste liquid into the cleaning tank and reduces residual waste liquid. The piston plate, first and second one-way valves in the drainage element work together to allow waste liquid to flow smoothly from the isolation sleeve to the drainage box, and then from the drainage box to the drain pipe. This achieves efficient waste liquid discharge and reduces backflow or blockage. This design optimizes the waste liquid treatment process in the cleaning module and improves the stability and efficiency of equipment operation.

[0028] Preferably, a control component for controlling the horizontal positions of the four water inlet holes is further provided in the cleaning pool.

[0029] By employing this technical solution, the control assembly within the cleaning tank precisely adjusts the horizontal position of the four water inlet holes. This design allows the water inlet holes to better align with the steel needle's slots, allowing the cleaning fluid to be precisely sprayed onto specific areas of the needle, improving cleaning efficiency and effectiveness. Specifically, the control assembly flexibly adjusts the position of the water inlet holes to accommodate different needle sizes, reducing blind spots during cleaning and ensuring that the needle's outer surface and internal waste liquid are fully cleaned, extending the needle's service life and maintaining system stability.

[0030] Preferably, the control assembly includes a control ring coaxially sleeved on the outer peripheral wall of the isolation sleeve, a connecting rod arranged on the control ring, a control rod passing through several connecting rods, and a second driving member that drives the control rod to slide along the length direction of the cleaning tank. The control ring is fixedly sleeved on the isolation sleeve, and the control ring is arranged to avoid the water inlet hole. One end of the connecting rod is hinged to the control ring, and the other end of the connecting rod is provided with a through hole for the control rod to pass through. The through hole is arranged in a waist-shaped hole along the length direction of the connecting rod, and the control rod protrudes with a slider that slides along the length direction of the through hole.

[0031] By adopting this technical solution, the fixed fit between the control ring and the isolation sleeve provides a stable baseline for adjusting the position of the water inlet, improving the consistency of the cleaning process. The design of a second drive member driving the control rod to slide along the length of the cleaning tank utilizes the hinged structure of the connecting rod and the control rod, combined with the sliding movement of the slider within the waist-shaped hole, to flexibly adjust the position of the water inlet to meet different cleaning needs, improving cleaning efficiency and effectiveness.

[0032] Preferably, an air blowing assembly is further provided above the isolating member, and the air blowing assembly includes an air blowing sleeve coaxially sleeved on the steel needle, an air supply ring pipe coaxially sleeved outside the air blowing sleeve, and an air supply member connected to the air supply ring pipe. The outer peripheral wall of the sleeve is provided with four air blowing holes spaced apart along the axis of the steel needle, and the four air blowing holes are respectively provided corresponding to the through grooves, and the air holes are connected to the air supply ring pipe.

[0033] By adopting the above technical solution, the blowing sleeve and the air supply ring pipe cooperate to form a uniform and stable airflow, and blow air through the four blowing holes to the groove of the steel needle, thereby improving the removal effect of residues on the outer surface of the steel needle, reducing the possibility of cross contamination, and improving the accuracy and reliability of pretreatment.

[0034] Preferably, the outer surface of the steel needle is provided with an anti-corrosion coating.

[0035] By adopting the above technical solution, during the mass spectrometry pretreatment process, the magnetic bead reconstitution solution is often a highly volatile organic solvent, which can easily corrode the steel needle. Providing an anti-corrosion coating on the outer surface of the steel needle can effectively enhance the corrosion resistance of the steel needle and extend its service life.

[0036] A method for using a high-speed mass spectrometry plate pretreatment system, which can be used in positive and negative phase detection modes as required, wherein the positive phase detection mode includes the following steps:

[0037] S1, magnetic bead distribution, using the sample arm to sample the magnetic bead solution that has been mixed in the magnetic bead mixing module, and adding the sampled magnetic bead solution to the test tube in the incubation and shaking position for heating and shaking;

[0038] S2. Remove the waste liquid, shake it, and place the test tube in the cleaning position by using the gripping arm. Use the side suction magnetic component to adsorb the magnetic beads on the wall of the test tube. Then start the first drive component to move to the corresponding position, and start the second drive component to drive the steel needle into the test tube to absorb the waste liquid.

[0039] S3, sample distribution, after removal, the test tube is placed back to the incubation and shaking position by the grabbing arm, and the sample at the sample position is added to the test tube by the adding arm,

[0040] S4, reagent distribution, adding the reagent at the reagent position into the test tube through the sample adding arm, heating and shaking at the incubation shaking position to combine with the target substance;

[0041] S5, repeat the operation of S2;

[0042] S6. Dispense the eluent. After removal, place the test tube back to the incubation and shaking position using the gripping arm. Add the eluent from the reagent position to the test tube using the loading arm. Heat and shake the tube at the incubation and shaking position to remove loose non-target substances on the magnetic beads.

[0043] S7, repeat the operation of S2;

[0044] S8, dispensing the eluent, after removal, placing the test tube back to the incubation and shaking position by using the gripping arm, adding the eluent at the reagent position to the test tube by using the loading arm, heating and shaking at the incubation and shaking position to elute the target substance from the surface of the magnetic beads;

[0045] S9, pipetting, after shaking, the test tube is placed in the washing position by the gripping arm, the magnetic beads are adsorbed on the tube wall of the test tube by the side suction magnetic component, and then the liquid in the test tube is moved to the test tube at the magnetic suction position by the sample loading arm for static magnetic attraction;

[0046] S10, taking a sample, and then pipetting the liquid to the upper plate position through the sample loading arm for the next step;

[0047] The negative phase detection mode comprises the following steps:

[0048] S1. Sample and reagent distribution: The sample at the sample position and the reagent at the reagent position are added to the test tube at the incubation and shaking position by the sample adding arm, and the tube is heated and shaken at the incubation and shaking position to combine with the target substance;

[0049] S2. Pipetting. After shaking, the test tube is placed in the washing position by the gripping arm. The magnetic beads are adsorbed on the wall of the test tube by the side magnetic component. Then, the liquid in the test tube is moved to the test tube at the magnetic position by the sample loading arm for static magnetic attraction.

[0050] S3. Take a sample, and then pipette the liquid to the upper plate through the sample loading arm to proceed to the next step.

[0051] By adopting the above technical solution, in the normal phase detection mode, the magnetic bead solution is mixed and then added to the test tube for heating and shaking to ensure that the magnetic beads are fully dispersed and combined with the target substance, thereby improving the reaction efficiency and stability; in the waste liquid removal step, the steel needle is inserted into the test tube to absorb the waste liquid, which significantly shortens the waste liquid removal time and reduces the cost of consumables compared to the traditional TIP head method; the sample and reagent are added and shaken in sequence to improve the effect of full binding and separation of the target substance; and the addition of the eluent effectively removes non-target substances and improves the specificity of detection; the addition of the eluent achieves efficient elution of the target substance from the magnetic beads, ensuring the accuracy of the detection. In the negative phase detection mode, the sample and reagent are directly combined and then pipetted and magnetically absorbed, which simplifies the operation process and further improves the detection efficiency. The overall solution significantly shortens the pre-processing time, reduces the cost of consumables, improves the processing stability and detection reliability, and extends the service life of the equipment.

[0052] In summary, this application has the following beneficial effects:

[0053] 1. Significantly shortened processing time: By replacing the traditional TIP head with steel needles arranged in a matrix, combined with a shaker-type magnetic bead mixing mechanism, the time for waste liquid removal and magnetic bead mixing is significantly reduced, improving overall processing efficiency;

[0054] 2. Reduced consumables costs: Using needle wash solution to clean the steel needle instead of disposable TIP heads effectively reduces the use of consumables and reduces pre-processing costs;

[0055] 3. Improved processing stability: The steel needle adopts precision processing technology, combined with elastic components and special coating treatment, to ensure the consistency and stability of the waste liquid removal step, while reducing the fluctuation of mass spectrometry detection results caused by consumables errors. BRIEF DESCRIPTION OF THE DRAWINGS

[0056] Figure 1This is a schematic diagram of the overall structure of Example 1 of the present application;

[0057] Figure 2 is a schematic top view of the structure of Example 1 of the present application;

[0058] Figure 3 yes Figure 1 A partial enlarged schematic diagram of part A;

[0059] Figure 4 Schematic diagram of the structure of the sample loading arm in Example 1 of the present application;

[0060] Figure 5 This is a schematic diagram of the structure of the gripping arm in Example 1 of the present application;

[0061] Figure 6 yes Figure 1 A partial enlarged schematic diagram of part B;

[0062] Figure 7 Schematic diagram of the cross-sectional structure of the steel needle in Example 2 of the present application;

[0063] Figure 8 Schematic diagram of the internal structure of the cleaning tank in Example 2 of the present application;

[0064] Figure 9 This is a schematic diagram of the structure of the control component in Example 2 of the present application;

[0065] Figure 10 This is another structural intention of the control component in Example 2 of the present application;

[0066] Figure 11 It is a structural schematic diagram of the blowing assembly in Example 3 of the present application.

[0067] Explanation of reference numerals: 1. Processing box; 11. Sample position; 12. Reagent position; 121. Reagent tank; 13. Magnetic bead position; 14. Magnetic bead mixing module; 141. Placement box; 142. Driving mechanism; 15. Incubation and shaking position; 16. Sample adding arm; 161. Pipette; 17. Cleaning position; 18. Grasping arm; 181. Grasping hand; 19. Magnetic position; 191. Magnetic stand; 2. Cleaning module; 3. Test tube rack; 4. Steel needle; 41. Cross groove; 42. Through groove; 5. Mounting seat; 6. First driving assembly; 7. Second driving assembly; 8. Cleaning station; 81. Cleaning tank; 811. Cleaning area; 8 2. Water spray pipe; 83. Water supply part; 84. Isolation part; 841. Isolation rod; 842. Isolation plate; 843. Isolation sleeve; 8431. Water inlet hole; 85. Drainage part; 851. Drain pipe; 852. Drain box; 853. Piston plate; 854. First drive part; 855. First one-way valve; 856. Second one-way valve; 86. Control assembly; 861. Control ring; 862. Connecting rod; 863. Control rod; 864. Incomplete gear; 865. Rack; 87. Blowing assembly; 871. Blowing sleeve; 8711. Blowing hole; 872. Gas ring pipe; 873. Gas transmission part. DETAILED DESCRIPTION

[0068] The following is combined with Figure 1-11 , further details of this application are given.

[0069] The embodiments of the present application disclose a high-speed mass spectrometry plate-type pretreatment system and a method of use.

[0070] Example 1

[0071] A high-speed mass spectrometry plate pretreatment system and its use method, referring to Figure 1 、 Figure 2 , including a processing box 1, a sample position 11 installed in the box, a reagent position 12, a magnetic bead position 13, a magnetic bead mixing module 14, an incubation and shaking position 15, a sample adding arm 16, a cleaning position 17, a grab arm 18, a magnetic suction position 19, a barcode scanner (not shown in the figure) and a cleaning module 2.

[0072] The processing box 1 is in the shape of a box with four sides closed. The processing box 1 can be made of transparent material, and a closed door (not shown in the figure) is installed on one side of the processing box 1 to facilitate the staff to open the closed door and place the test sample inside the processing box 1.

[0073] Among them, the sample position 11 is used to place test tubes containing samples to be tested. Specifically, a test tube rack 3 for placing test tubes is provided on the sample position 11. The test tube rack 3 is arranged in a rectangular shape, and the length direction of the test tube rack 3 is parallel to the width direction of the processing box 1; the reagent position 12 is used to hold the reagents required during the experiment. The reagent position 12 is provided with several reagent troughs 121 for placing reagents; and the magnetic bead position 13 is arranged between the sample position 11 and the reagent position 12.

[0074] Reference Figure 1 、 Figure 3 , wherein the magnetic bead mixing module 14 is arranged between the magnetic bead position 13 and the reagent position 12, and is used to mix the magnetic bead solution, including a placement box 141 for placing the reagent bottle and a driving mechanism 142 for driving the placement box 141 to swing or vibrate, wherein the placement box 141 is used to place the reagent bottle containing the magnetic bead solution, and can be made of stainless steel or corrosion-resistant plastic. The driving mechanism 142 can use a combination of a rotary motor with an eccentric wheel, or a linear motor with a spring, to drive the placement box 141 to swing or vibrate. The driving mechanism 142 can not only achieve rapid mixing of the magnetic bead solution, but also reduce the pipetting time. Since the driving mechanism 142 is a prior art, it will not be described in detail here.

[0075] Among them, the incubation and shaking position 15 is set on the side where the sample position 11 and the magnetic bead position 13 are close to each other. During the experiment, it is used to shake and mix the solution or reagent in the test tube and heat and incubate it. The incubation and shaking position 15 is also provided with a test tube rack 3 in a rectangular shape, and the length direction of the test tube rack 3 is parallel to the length direction of the processing box 1. The magnetic attraction position 19 is set on the side of the incubation and shaking position 15 away from the sample position 11 and close to the reagent position 12. The bottom of the magnetic attraction position 19 is adsorbed with a magnetic rack 191 for magnetic attraction before the secondary transfer of the supernatant. The magnetic attraction position 19 is also provided with a test tube rack 3 in a rectangular shape, and the length direction of the test tube rack 3 is parallel to the length direction of the processing box 1.

[0076] Among them, the sample adding arm 16 is provided with a pipette 161 for adding various samples, reagents or magnetic bead solutions into the test tube, or for transferring various solutions after the reaction during the experiment. In this embodiment, a number of pipettes 161 are arranged at intervals along the width direction of the processing box 1. For the flow direction of the supernatant subsequently absorbed by the pipette 161, corresponding pipelines are provided on the sample adding arm 16 for flow. Since it is a prior art, it will not be elaborated here.

[0077] Among them, the cleaning position 17 is arranged on the side close to the sample position 11 and the incubation and shaking position 15, and is used to place test tubes that need to remove waste liquid. Specifically, a test tube rack 3 in a rectangular shape is also provided at the cleaning position 17, and the length direction of the test tube rack 3 is parallel to the length direction of the processing box 1.

[0078] Among them, the gripping arm 18 is provided with a gripper 181 for driving the test tube to move back and forth between the cleaning position 17 and the incubation and shaking position 15. In this embodiment, the gripping arm 18 is a three-axis mechanical gripping arm 18.

[0079] The barcode scanner, mounted on the sample loading arm 16, is used to scan sample barcodes for easy sample tracking and management. Specifically, it consists of a camera module and a decoding chip. The camera module captures the sample barcode image, while the decoding chip decodes the image and identifies the barcode information, ensuring accurate sample information. Since the barcode scanner is currently available, it will not be described in detail here.

[0080] Reference Figure 1 、 Figure 6 , wherein the cleaning module 2 is arranged at the cleaning position 17 to remove the waste liquid in the test tube located at the cleaning position 17, including a steel needle 4 for sucking the waste liquid for removal, a mounting seat 5 for mounting the steel needle 4, a first driving component 6 for driving the mounting seat 5 to slide, a second driving component 7 arranged on the mounting seat 5 to drive the steel needle 4 to extend into the test tube, a cleaning station 8 for cleaning the outer surface of the steel needle 4 and the built-in waste liquid, and a side suction magnetic component (not shown in the figure) for magnetically attracting the magnetic beads in the test tube.

[0081] Reference Figure 6 、 Figure 7 In this embodiment, a plurality of steel needles 4 are provided, and the plurality of steel needles 4 are arranged in a matrix, specifically in an 8×N (N≥2) matrix, specifically in an 8×2 matrix. For this, eight pipettes 161 are correspondingly provided on the sample adding arm 16 to perform pipetting-related actions. It should be noted that, in order to improve the removal effect of waste liquid, an elastic component is provided on the top of the steel needle 4. The elastic component can be a spring or a rubber pad to ensure that the liquid is completely bottomed out during aspiration to meet the liquid residue requirements. The inner diameter of the steel needle 4 gradually increases towards the needle tip, and a cross groove 41 is provided at the needle tip.

[0082] Furthermore, the surface of the steel needle 4 is provided with a coating, such as a polytetrafluoroethylene coating or a nickel-chromium alloy coating, to enhance corrosion resistance and service life. It should be noted that the coating can also be processed into a multi-layer composite coating, for example, including a bottom epoxy resin coating, an intermediate polytetrafluoroethylene coating, and a top nickel-chromium alloy coating, to further enhance corrosion resistance and service life.

[0083] Among them, the first drive component 6 can adopt a combination of a motor and a screw, or a combination of a cylinder and a slide rail, to drive the mounting seat 5 to slide, and the second drive component 7 can adopt an electric push rod or a hydraulic cylinder to drive the steel needle 4 into the test tube, which is specifically set according to needs.

[0084] Among them, the cleaning station 8 includes a cleaning pool 81, a water spray pipe 82, a water supply component 83, an isolation component 84 and a drainage component 85. In this embodiment, the cleaning pool 81 can be made of stainless steel, wherein the water spray pipe 82 is arranged along the opposite side walls of the cleaning pool 81 and can be set corresponding to the number of steel needles 4. Among them, the water supply component 83 can use a water pump to supply water to the cleaning pool 81 through an external water source or a water tank.

[0085] Among them, the isolation member 84 is used to divide the cleaning pool 81 into a number of cleaning areas 811. The cleaning areas 811 are arranged in a matrix corresponding to the steel needles 4. In this embodiment, the isolation member 84 specifically includes an isolation rod 841 parallel to the length of the cleaning pool 81 and an isolation plate 842 coaxially sleeved on the isolation rod 841. Eight isolation plates 842 are arranged at intervals along the length of the isolation rod 841. Together with the isolation rod 841, the cleaning pool 81 is divided into 8×2 cleaning areas 811. Each cleaning area 811 is for a steel needle 4 to be inserted for cleaning. The drainage member 85 can be a drain pipe 851 provided outside the cleaning pool 81 to pump a water pump provided on the drain pipe 851 to drain the waste liquid from the cleaning steel needles 4.

[0086] Among them, the side suction magnetic component uses a high-performance magnet to magnetically attract the magnetic beads in the test tube.

[0087] The embodiment of the present application is a high-speed mass spectrometry plate-type pretreatment system and its implementation principle: by adopting a matrix-arranged steel needle 4 to replace the traditional TIP head, the waste liquid removal time is greatly shortened and the processing efficiency is significantly improved. And because the traditional TIP head can only be used once in the waste liquid removal step, resulting in high consumables costs, the use of steel needles 4 to remove waste liquid and the use of lower-cost needle washing liquid to replace the TIP head reduce the use of consumables and reduce pretreatment costs. And because the steel needles 4 produced by the current modern and mature processing technology replace the TIP head to complete the waste liquid removal step, the consistency and stability of the waste liquid removal step are improved, and the reliability of the pretreatment is improved.

[0088] The present application also discloses a method for using a high-speed mass spectrometry plate pretreatment system, which can be used to perform positive and negative phase detection modes as required, wherein the positive phase detection mode includes the following steps:

[0089] S1, magnetic bead distribution, using the sample arm 16 to sample the magnetic bead solution that has been mixed in the magnetic bead mixing module 14, and adding the sampled magnetic bead solution to the test tube in the incubation and shaking position 15 for heating and shaking;

[0090] S2. Remove the waste liquid, shake it, and place the test tube in the cleaning position 17 by the gripping arm 18. Use the side suction magnetic component to adsorb the magnetic beads on the wall of the test tube. Then start the first drive component 6 to move to the corresponding position, and start the second drive component 7 to drive the steel needle 4 into the test tube to absorb the waste liquid.

[0091] S3, sample distribution, after removal, the test tube is placed back to the incubation and shaking position 15 by the gripping arm 18, and the sample at the sample position 11 is added to the test tube by the adding arm 16,

[0092] S4, reagent distribution, adding the reagent at the reagent position 12 to the test tube through the sample adding arm 16, heating and shaking at the incubation shaking position 15 to combine with the target substance;

[0093] S5, repeat the operation of S2;

[0094] S6. Dispense the eluent. After removal, place the test tube back to the incubation and shaking position 15 via the gripping arm 18. Add the eluent at the reagent position 12 to the test tube via the loading arm 16. Heat and shake at the incubation and shaking position 15 to remove loose non-target substances on the magnetic beads.

[0095] S7, repeat the operation of S2;

[0096] S8, dispensing the eluent, after removal, placing the test tube back to the incubation and shaking position 15 via the gripping arm 18, adding the eluent at the reagent position 12 to the test tube via the loading arm 16, heating and shaking at the incubation and shaking position 15, to elute the target substance from the surface of the magnetic beads;

[0097] S9, pipetting, after shaking, the test tube is placed in the washing position 17 by the gripping arm 18, the magnetic beads are adsorbed on the tube wall of the test tube by the side suction magnetic component, and then the liquid in the test tube is moved to the test tube at the magnetic suction position 19 by the sample adding arm 16 for static magnetic attraction;

[0098] S10, sampling, and then pipetting the liquid to the upper plate position through the sample loading arm 16 for the next step of operation;

[0099] The negative phase detection mode includes the following steps:

[0100] S1. Sample and reagent distribution: The sample at the sample position 11 and the reagent at the reagent position 12 are added to the test tube at the incubation and shaking position 15 by the sample adding arm 16, and heated and shaken at the incubation and shaking position 15 to combine with the target substance;

[0101] S2. Pipetting. After shaking, the test tube is placed in the washing position 17 by the gripping arm 18. The magnetic beads are adsorbed on the tube wall of the test tube by the side magnetic component. Then, the liquid in the test tube is moved to the test tube at the magnetic position 19 by the sample loading arm 16 for static magnetic attraction.

[0102] S3, sampling, and then the liquid is pipetted to the upper plate position through the sample adding arm 16 to perform the next step of the operation.

[0103] The system's flexibility and applicability are enhanced by the combination of positive and negative phase detection modes, meeting diverse experimental requirements. The positive phase mode is suitable for experiments requiring multiple washes and separations, while the negative phase mode is ideal for simple sample and reagent binding experiments. This design significantly enhances the automation and detection efficiency of the pretreatment system.

[0104] Example 2

[0105] Reference Figure 8 The difference from Example 1 is that, in this embodiment, the side wall of the steel needle 4 is provided with a through groove 42 connected to the cross groove 41. This design can reduce the possibility of large pieces of matter being blocked in the steel needle 4, and is also convenient for cleaning.

[0106] Among them, the isolation member 84 adopts an isolation sleeve 843, the inner diameter of which gradually decreases in the direction away from the steel needle 4, and the side wall of the isolation sleeve 843 is provided with a water inlet hole 8431. There are four water inlet holes 8431 spaced apart along the axis of the steel needle 4, and the four water inlet holes 8431 are respectively arranged corresponding to the through groove 42.

[0107] In this embodiment, the drain member 85 specifically includes a drain box 852 having a cavity, a piston plate 853 slidably connected to the drain box 852, a first driving member 854 for driving the piston plate 853 to slide, a first one-way valve 855 fixedly installed on the top wall of the drain box 852, a second one-way valve 856 installed on the side wall of the drain box 852, and a drain pipe 851 connected to the second one-way valve 856. The drain box 852 can be provided with a partition at the bottom of the cleaning tank 81 to separate the drain box 852 having a cavity. The first driving member 854 can be a cylinder or an electric push rod. The first one-way valve 855 is fixedly installed on the partition and flows from the isolation sleeve 843 to the drain box 852. The second one-way valve 856 is fixedly installed on the side wall of the drain box 852 and flows from the drain box 852 to the drain pipe 851.

[0108] Reference Figure 8 、 Figure 9Referring to the figure, a control assembly 86 for controlling the horizontal position of four water inlet holes 8431 is also provided within the cleaning tank 81. This control assembly 86 may specifically include a control ring 861 coaxially sleeved on the outer circumferential wall of the isolation sleeve 843, a connecting rod 862 mounted on the control ring 861, a control rod 863 extending through several connecting rods 862, and a second drive member (not shown) that drives the control rods 863 to slide along the length of the cleaning tank 81. The lower end of the isolation sleeve 843 is rotatably connected to the partition plate. The control ring 861 is fixedly mounted on the isolation sleeve 843, avoiding the water inlet holes 8431. One end of the connecting rod 862 is hingedly connected to the control ring 861. The other end of the connecting rod 862 has a through-hole for the control rod 863 to pass through. The through-hole is arranged in a waist-shaped pattern along the length of the connecting rod. The control rod 863 has a protruding slider that slides along the length of the through-hole. The second drive member may be provided at the same time as the first drive member 854.

[0109] For the control component 86, it is also possible to Figure 10 As shown, it may specifically include an incomplete gear 864 coaxially sleeved outside the isolation sleeve 843, a rack 865 meshing with the outer ring gear, and a third driving member (not shown in the figure) driving the rack 865 to move along the length direction of the cleaning tank 81. The third driving member is arranged with the second driving member.

[0110] Example 3

[0111] Reference Figure 11 , the difference from Example 1 is that, in this embodiment, an air blowing assembly 87 is provided above the isolation piece 84, and the air blowing assembly 87 includes an air blowing sleeve 871 for being coaxially sleeved on the steel needle 4, an air supply ring pipe 872 coaxially sleeved outside the air blowing sleeve 871, and an air supply member 873 connected to the air supply ring pipe 872. The outer wall of the air blowing sleeve 871 is provided with four air blowing holes 8711 spaced apart along the axis of the steel needle 4. The lower end of the air blowing sleeve 871 is fixedly connected to the top of the isolation sleeve 843 and is coaxially arranged.

[0112] It should be noted that the blowing direction of the air holes 8711 is inclined downward, and the four air holes 8711 are respectively provided corresponding to the through slots 42. The air holes 8711 are connected to the air supply ring pipe 872. After the steel needle 4 completes the absorption of waste liquid, it returns to the cleaning station 8 for cleaning. At this time, the air supply component 873 introduces high-pressure gas into the air supply ring pipe 872, and the gas is ejected at high speed through the air holes 8711 to sweep the outer surface and residual waste liquid inside the steel needle 4. At the same time, the water flow from the water spray pipe 82 is used to further improve the cleaning effect. When the steel needle 4 is separated from the isolation sleeve 843, some cleaning liquid remaining on the steel needle 4 is blown off, which has a certain drying effect.

[0113] The above are all preferred embodiments of the present application, and are not intended to limit the scope of protection of the present application. Therefore, any equivalent changes made based on the structure, shape, and principle of the present application should be included in the scope of protection of the present application.

Claims

1. A high-speed mass spectrometry plate pretreatment system, characterized in that: include: Processing box (1); A sample position (11) is provided in the processing box (1) and is used to place a test tube containing a sample to be tested; A reagent position (12) is provided in the processing box (1) and is used to hold reagents required during the experiment; A magnetic bead position (13) is disposed in the processing box (1); A magnetic bead mixing module (14) is provided at the magnetic bead position (13) for mixing the magnetic bead solution, and includes a placement box (141) for placing the reagent bottle and a driving mechanism (142) for driving the placement box (141) to swing or vibrate; An incubation shaking position (15) is provided in the processing box (1) and is used to shake, mix, heat and incubate the solution or reagent in the test tube during the experiment; A sample adding arm (16) is provided in the processing box (1) and is provided with a pipette (161) for adding various samples, reagents or magnetic bead solutions into the test tube, or for transferring various solutions after reaction during the experiment; A cleaning position (17) is provided in the processing box (1) and is used for placing test tubes that need to remove waste liquid; A gripping arm (18) is disposed in the processing box (1) and is used to drive the test tube to move back and forth between the cleaning position (17) and the incubation and shaking position (15); A magnetic attraction position (19) is provided in the processing box (1), and a magnetic frame (191) is provided at the bottom thereof for magnetic attraction before the secondary transfer of the supernatant; A cleaning module (2) is provided at the cleaning position (17) for removing waste liquid in a test tube located at the cleaning position (17), comprising a steel needle (4) for absorbing and removing the waste liquid, a mounting seat (5) for mounting the steel needle (4), a first driving assembly (6) for driving the mounting seat (5) to slide, a second driving assembly (7) provided on the mounting seat (5) for driving the steel needle (4) to extend into the test tube, a cleaning station (8) for cleaning the outer surface of the steel needle (4) and the waste liquid therein, and a side-attraction magnetic assembly for magnetically attracting magnetic beads in the test tube, wherein a plurality of the steel needles (4) are provided, and the plurality of the steel needles (4) are arranged in a matrix. The inner diameter of the steel needle (4) gradually increases toward the needle head. A cross groove (41) is provided at the needle head of the steel needle (4). A through groove (42) communicating with the cross groove (41) is provided on the side wall of the steel needle (4). The cleaning station (8) includes a cleaning pool (81), a water spray pipe (82) provided on opposite side walls of the cleaning pool (81), and a water supply member (83) for supplying water to the water spray pipe (82). The cleaning station (8) is provided with an isolating member (84) for dividing the pool into a plurality of cleaning areas (811). The plurality of cleaning areas (811) are arranged in a matrix corresponding to the steel needles (4). The side wall of the isolating member (84) is provided with water inlet holes (8431). Four water inlet holes (8431) are provided at intervals along the axis of the steel needles (4). The four water inlet holes (8431) are provided corresponding to the through grooves (42). The bottom of the cleaning pool (81) is provided with a drainage member (85) for discharging water. The isolating member (84) is provided for an isolating sleeve (843), and the inner diameter of the isolating sleeve (843) gradually decreases in the direction away from the steel needle (4); the drainage member (85) comprises a drainage box (852) with a cavity provided at the bottom of the cleaning tank (81), a piston plate (853) slidably connected to the drainage box (852), a first driving member (854) for driving the piston plate (853) to slide, a first one-way valve (855) fixedly provided on the top wall of the drainage box (852), and a device A second one-way valve (856) is disposed on a side wall of the drainage box (852) and a drainage pipe (851) connected to the second one-way valve (856); the first one-way valve (855) flows from the isolation sleeve (843) to the drainage box (852), and the second one-way valve (856) flows from the drainage box (852) to the drainage pipe (851); a partition is provided at the bottom of the cleaning tank (81) to separate the drainage box (852) having a cavity, and the lower end of the isolation sleeve (843) is rotatably connected to the partition; The cleaning tank (81) is further provided with a control assembly (86) for controlling the horizontal positions of the four water inlet holes (8431); the control assembly (86) comprises a control ring (861) coaxially sleeved on the outer peripheral wall of the isolation sleeve (843), a connecting rod (862) provided on the control ring (861), a control rod (863) passing through the plurality of connecting rods (862), and a second driving member for driving the control rod (863) to slide along the length direction of the cleaning tank (81). The control ring (861) is fixedly sleeved on the isolation sleeve (843), and the control ring (861) is arranged to avoid the water inlet hole (8431). One end of the connecting rod (862) is hinged to the control ring (861), and the other end of the connecting rod (862) is provided with a through hole for the control rod (863) to pass through. The through hole is arranged in a waist-shaped hole along the length direction of the connecting rod (862), and the control rod (863) protrudes with a slider that slides along the length direction of the through hole.

2. A high-speed mass spectrometry plate-type pretreatment system according to claim 1, characterized in that: An elastic component is provided on the top of the steel needle (4).

3. The high-speed mass spectrometry plate-type pretreatment system according to claim 1, characterized in that: A blowing assembly (87) is further provided above the isolation member (84), the blowing assembly (87) comprising a blowing sleeve (871) coaxially sleeved on the steel needle (4), an air supply ring tube (872) coaxially sleeved outside the blowing sleeve (871), and an air supply member (873) connected to the air supply ring tube (872). The outer peripheral wall of the sleeve is provided with four blowing holes (8711) spaced apart along the axis of the steel needle (4). The four blowing holes (8711) are respectively provided corresponding to the through grooves (42), and the blowing holes (8711) are connected to the air supply ring tube (872).

4. The high-speed mass spectrometry plate-type pretreatment system according to claim 1, characterized in that: The outer surface of the steel needle (4) is provided with an anti-corrosion coating.

5. A method for using a high-speed mass spectrometry plate-type pretreatment system, applied to a high-speed mass spectrometry plate-type pretreatment system according to any one of claims 1 to 4, to perform positive and negative phase detection modes as required, wherein the positive phase detection mode comprises the following steps: S1, magnetic bead distribution, sampling the magnetic bead solution that has been mixed at the magnetic bead mixing module (14) through the sample adding arm (16), and adding the sampled magnetic bead solution to the test tube at the incubation and shaking position (15) for heating and shaking; S2. Take out the waste liquid, shake it, and place the test tube in the cleaning position (17) by the grab arm (18). Use the side suction magnetic component to adsorb the magnetic beads on the wall of the test tube. Then start the first drive component (6) to move to the corresponding position, and start the second drive component (7) to drive the steel needle (4) into the test tube to absorb the waste liquid. S3, sample distribution, after removal, the test tube is placed back to the incubation and shaking position (15) through the grab arm (18), and the sample at the sample position (11) is added to the test tube through the sample adding arm (16). S4, reagent distribution, adding the reagent at the reagent position (12) into the test tube through the sample adding arm (16), heating and shaking at the incubation shaking position (15) to combine with the target substance; S5, repeat the operation of S2; S6, dispensing the eluent, after removal, placing the test tube back to the incubation and shaking position (15) through the grasping arm (18), adding the eluent at the reagent position (12) to the test tube through the sample adding arm (16), heating and shaking at the incubation and shaking position (15) to remove loose non-target substances on the magnetic beads; S7, repeat the operation of S2; S8, dispensing the eluent, after removal, placing the test tube back to the incubation and shaking position (15) through the grasping arm (18), adding the eluent at the reagent position (12) to the test tube through the sample adding arm (16), heating and shaking at the incubation and shaking position (15) to elute the target substance from the surface of the magnetic beads; S9, pipetting, after shaking, the test tube is placed in the washing position (17) by the grasping arm (18), the magnetic beads are adsorbed on the tube wall of the test tube by the side suction magnetic component, and then the liquid in the test tube is moved to the test tube at the magnetic suction position (19) by the sample adding arm (16) for static magnetic suction; S10, taking a sample, and then pipetting the liquid to the upper plate position through the sample loading arm (16) for the next step of operation; The negative phase detection mode comprises the following steps: S1, sample and reagent distribution, the sample at the sample position (11) and the reagent at the reagent position (12) are added to the test tube at the incubation and shaking position (15) by the sample adding arm (16), and heated and shaken at the incubation and shaking position (15) to combine with the target substance; S2, pipetting, after shaking, the test tube is placed in the washing position (17) by the grasping arm (18), the magnetic beads are adsorbed on the tube wall of the test tube by the side suction magnetic component, and then the liquid in the test tube is moved to the test tube at the magnetic suction position (19) by the sample adding arm (16) for static magnetic suction; S3, sampling, and then pipetting the liquid to the upper plate position through the sample loading arm (16) to carry out the next step of the operation.

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