Full-automatic mass spectrum sample pretreatment workstation

Abstract

The utility model discloses a full-automatic mass spectrum sample pretreatment workstation, which comprises a sample cup dividing module, a purification module and a transfer device, and the sample cup dividing module is positioned in a first chamber in a shell and can complete the cup dividing operation of a sample in a sample tube and the transfer of a product; the purification module and the transfer device are located in a second cavity in the machine shell, the purification module can separate and purify a target object in a sample to achieve first-time magnetic bead adsorption, and the transfer device is connected with the sample cup separation module and the purification module and can transfer the cup-separated sample into the purification module; meanwhile, the purified sample is transferred into the sample cup dividing module to be subjected to magnetic bead adsorption twice. The full-automatic mass spectrum sample pretreatment workstation adopts a three-stage magnetic separation technology to fully reduce residues of magnetic beads in a purified product, meets full-automatic pretreatment of a high-flux sample, enables an experimental process to be streamlined, standardized and normalized, reduces errors caused by manual operation, and improves the working efficiency of sample pretreatment.

Description

TECHNICAL FIELD

[0001] The utility model belongs to the field of biological medicine technology, more particularly to a full -automatic mass spectrum sample pretreatment workstation. BACKGROUND

[0002] Under the development trend of precision medicine, compared with traditional detection method, clinical mass spectrum is more and more widely used in life science basic research and clinical detection analysis with its high throughput, high sensitivity, high specificity, high precision and high efficiency. Mass spectrum is a kind of identification technology, its basic principle is to utilize electric field or magnetic field to ionize sample, and carry out detection record according to the different of ion mass-to-charge ratio and form spectrum, can obtain the information such as molecular weight, molecular formula, isotopic composition and molecular structure of sample through mass spectrum analysis, can carry out comprehensive qualitative identification and quantitative analysis to protein and metabolite in biological system, has developed into important weapon of proteome and metabolome research. At the same time, in clinical application, since mass spectrum technology can simultaneously and systematically accurately analyze hundreds of biomarkers in single detection, and can detect the biomarkers that traditional analysis technology cannot detect, these characteristics make mass spectrum technology obtain the wide application in clinical detection.

[0003] Before mass spectrometry detection, sample pretreatment is a very time-consuming, tedious and easy to introduce analysis error process, sample pretreatment plays a crucial role in the analysis of the sample, to some extent, the pretreatment determines the results of the analysis test. Its main purpose is to purify the sample, enrich the target component to be tested, reduce the matrix effect, improve the sensitivity, and also to protect the sample system and the chromatographic column, detector. The current sample purification methods include protein precipitation (Protein precipitation, PPT), liquid-liquid extraction (Liquid-liquid Extraction, LLE), solid phase supported liquid-liquid extraction (Sported Liquid Extraction, SLE), solid phase extraction (Solid-Phase Extraction, SPE) and magnetic bead method (Magnetic-SPE, MSPE) and so on, among which protein precipitation and liquid-liquid extraction are relatively traditional and mature methods, protein precipitation only removes proteins, endogenous impurities are not removed, long time detection may affect the service life of the chromatographic column and the instrument; LLE is difficult to realize automation and has low selectivity; solid phase supported liquid-liquid extraction SLE is an upgraded extraction method based on traditional liquid-liquid extraction LLE combined with the characteristics of solid phase extraction, which needs to increase additional pressure generating equipment or infrastructure, has high cost and certain environmental pollution problems; solid phase extraction SPE is a mature sample extraction method developed in the 1980s, which uses disposable filter core, increases the use cost, and needs to occupy a lot of time and resources to achieve the best analyte extraction.

[0004] The magnetic bead method has the advantages of simple operation steps, simplification of complex procedures, reduction of manual errors, more accurate results, higher recovery rate, better repeatability and the like, and is a technology with great development potential and wide application prospect in clinical application in recent years. For example, a kind of multifunctional modular sample pretreatment device for high-throughput mass spectrometry and its use method are disclosed in CN109613106B, which was authorized on December 12, 2023, and the sample pretreatment device includes an extraction module, a filtration module, a sample collection module and a device support. The extraction module, the filtration module and the sample collection module are all vertically arranged hollow column pipe structures with sealing covers. The extraction module and the upper filtration module are connected by a first horizontal hollow column pipe with a first plug, and the lower filtration module and the sample collection module are connected by a second horizontal hollow column pipe with a second plug. In the use process, the opening status of the plug needs to be paid attention to to control the flow of the sample, otherwise it will hinder the normal work of the next module. In addition, during the processing of different samples, impurities after the previous processing are easily left in the bending part of the hollow column pipe, which affects the accuracy of the final detection result. In addition, CN218823493U, which was authorized on April 7, 2023, discloses a protein mass spectrometry sample pretreatment device, wherein the base is connected with a reagent tank, a shaking device, a magnetic attraction device and an incubation device. During the whole sample processing process, the sample and the first reagent are transferred by using a pipette device, the second reagent is added, the magnetic beads are transferred, the first eluent is added, the second eluent is added, the third reagent is added, the supernatant is transferred, and the fourth reagent is added. As can be seen, the processing process involves adding different reagents and transferring multiple times, which is complicated and has the risk of reagent cross contamination. Moreover, the consumables for containing the sample are PCR plates, which can only process 8 samples at the same time, and the volume of the processed sample is limited, which is difficult to meet the processing needs of large-throughput samples.

[0005] The existing technology has the problems of complicated steps, limited sample processing throughput and low automation degree in the sample pretreatment process, and there is a problem that magnetic beads are left in the purified sample, which affects the safety of the mass spectrometry device and the accuracy of the results. Therefore, it is necessary to develop a pretreatment device with simple steps, shorter time consumption, reduced magnetic bead residue, suitable for large systems and various types of mass spectrometry samples. Invention content

[0006] In order to solve the above-mentioned problems existing in the prior art, the present application realizes the following technical solutions:

[0007] The utility model provides a kind of full-automatic mass spectrum sample pretreatment workstation, the full-automatic mass spectrum sample pretreatment workstation includes sample cup dividing module, transfer device and purification module, wherein, sample cup dividing module can complete the cup dividing operation of sample in sample tube, reagent transfer;Transfer device can transfer the sample after cup dividing to purification module to perform separation and purification, realize once magnetic bead adsorption by the cooperation of magnetic rod sleeve and magnetic bar, and transfer device can also transfer the product after purification to sample cup dividing module by magnetic attraction device, magnetic attraction piece carries out twice magnetic bead adsorption.

[0008] In an embodiment of the utility model, the sample cup dividing module includes a sample tube rack station, a product plate station, a reagent station, a sample tube transfer assembly, a switch cover assembly, a pipetting assembly, and a consumable placement station disposed on a workbench. The consumable placement station includes a deep-well plate turntable having a plurality of deep-well plate stations arranged in a circumferential direction. Each deep-well plate station is provided with a deep-well plate mounting seat, and a plurality of magnetic attraction devices are disposed on the deep-well plate mounting seat. A Tip head turntable is disposed at the center of the deep-well plate turntable, and N Tip head receiving stations are arranged on the Tip head turntable. The sample tube rack station can load a sample rack. The pipetting assembly includes at least one pipetting subunit. The pipetting assembly can take in at least one Tip head at a Tip head receiving station of the Tip head turntable and unload the Tip head after completing pipetting. The pipetting assembly can also transfer sample liquid in the sample tube to a deep-well plate in the deep-well plate station for sample liquid cup dividing and transfer reagents in the reagent station to the deep-well plate. The pipetting assembly can also transfer the product in the deep-well plate after completing the purification reaction in the purification module to a product plate in the product plate station. N is an integer greater than or equal to 1.

[0009] In an embodiment of the utility model, the sample rack is provided with a reagent bottle sleeve adapted to the sample rack. The reagent bottle sleeve includes an upper tube body and a lower tube body. The upper tube body has an open end provided with an inclined guide surface to facilitate the insertion of a reagent bottle into the sleeve. A plurality of grooves are disposed on the wall of the lower tube body.

[0010] In an embodiment of the utility model, the product plate station includes a base, a clamping portion, and a product plate. The clamping portion is disposed around the base. The product plate can hold the target object after purification. A plurality of magnetic attraction devices are uniformly arranged on the base.

[0011] In an embodiment of the utility model, the sample cup dividing module and the purification module are spliced through a connecting member. The connecting member includes a positioning seat, a positioning hook, and a positioning rod. The positioning seat and the positioning hook are respectively disposed across the sample cup dividing module and the purification module. The positioning rod is fixed to the positioning seat and can be clamped into the positioning hook.

[0012] In one embodiment of the utility model, another structure of the connecting member includes a mounting seat, a positioning column and a plurality of equidistant spacers, the mounting seat and the positioning column are oppositely arranged at the edges of different modules, an integrally-formed cross bar is further arranged on the mounting seat, the cross bar can be inserted into the insertion hole in the positioning column, and the plurality of equidistant spacers are arranged on both sides of the positioning column.

[0013] In one embodiment of the utility model, the connecting member further includes a locking component, the locking component includes a fixing seat, a draw hook and a bolt, one end of the draw hook is connected with the fixing seat through the bolt, the other end of the draw hook abuts against the back of one of the cup dividing module and the purification module, and the fixing seat is fixed on the back of the other module.

[0014] In one embodiment of the utility model, the transfer device is arranged above the deep hole plate stage of the purification module, the transfer device includes a fixed assembly and a movable assembly which linearly moves relative to the fixed assembly under the driving of a driving device, the fixed assembly includes a fixing frame and a fixing plate fixed on the fixing frame, and the driving device includes a first belt, a first driving wheel, a first driven wheel and a first driving mechanism; the movable assembly includes a telescopic arm, a second belt, a second driven wheel, a third driven wheel and a mechanical gripper assembly slidably installed on the telescopic arm; the fixed assembly further includes a first belt connecting piece, one end of the first belt connecting piece is fixedly connected with the first belt, and the other end of the first belt connecting piece is fixedly connected with the telescopic arm.

[0015] In one embodiment of the utility model, the movable assembly further includes a second belt connecting piece and a third belt connecting piece, one end of the second belt connecting piece is fixedly installed on the fixing plate, the other end of the second belt connecting piece is fixedly connected with the second belt; one end of the third belt connecting piece is fixedly connected with the second belt, and the other end of the third belt connecting piece is fixedly connected with the mechanical gripper assembly; under the driving of the first driving mechanism, the first belt connecting piece drives the telescopic arm to relatively move relative to the fixing plate, and at the same time, the second belt connecting piece drives the mechanical gripper assembly to slide relative to the telescopic arm through the second belt.

[0016] In an embodiment of the utility model, the purification module includes the support plate, first mounting plate, second mounting plate, purification lead screw and deep hole plate stage which are sequentially arranged from top to bottom, the purification lead screw is connected through the support plate, first mounting plate and second mounting plate, the deep hole plate stage can place the deep hole plate containing the sample to be purified, the deep hole plate stage is provided with heating device and deep hole plate stage transfer mechanism, the deep hole plate stage transfer mechanism can move the deep hole plate stage from the lower side of transfer device to the lower side of second mounting plate, a plurality of magnetic rods are installed on first mounting plate, a plurality of stirring sleeve connectors are installed on second mounting plate, the stirring sleeve connector can install stirring sleeve, the purification module further includes purification drive mechanism, the purification drive mechanism can drive first mounting plate and second mounting plate to reciprocate along the extension direction of purification lead screw, and can also drive the stirring sleeve installed on stirring sleeve connector to rotate, when the purification drive mechanism drives second mounting plate to run downward along the purification lead screw, second mounting plate realizes the installation of stirring sleeve, when the purification drive mechanism drives first mounting plate and second mounting plate to move up and down relative to the purification lead screw, the magnetic rod is inserted into the stirring sleeve to realize the transfer of target object in different hole positions in deep hole plate and the unloading of stirring sleeve.

[0017] Compared with the prior art, the utility model has the advantages that:

[0018] 1、The full-automatic mass spectrum sample pretreatment workstation can automatically complete sample identification, cover opening / closing, cup separation, sample tube recovery, deep hole plate transfer, target object purification and target object transfer, can realize automatic pretreatment of a large number of samples, makes experimental process flow, standardization and standardization, reduces error caused by manual operation, guarantees the accuracy, stability and traceability of mass spectrum detection result, and the full-automatic mass spectrum sample pretreatment workstation is compact in structure, high in space utilization and short in processing time.

[0019] 2、The full-automatic mass spectrum sample pretreatment workstation drives the transfer device with telescopic mechanical arm by the driving device, so that the mechanical gripper assembly can obtain double moving distance in limited space, the mechanical gripper assembly can realize horizontal and longitudinal movement on the telescopic arm, the transfer device can effectively connect the sample cup separation module and the purification module, realizes the transfer of the deep hole plate containing the sample to be purified to the purification module and the transfer of the deep hole plate containing the target object to the deep hole plate station after purification, the transfer device is compact in structure and low in manufacturing cost, further reduces the volume and cost of the full-automatic mass spectrum sample pretreatment workstation.

[0020] 3. The full-automatic mass spectrum sample pretreatment workstation provided by the utility model realizes the purification of target objects by adopting the magnetic bead method, realizes the first adsorption of magnetic beads in products by the cooperation of the magnetic bar and the stirring sleeve, then completes the second adsorption of residual magnetic beads in purified products by setting the deep hole plate base with a magnetic column, and finally realizes the third adsorption of residual magnetic beads in products by setting the product plate base with a magnetic suction element, so that the residual magnetic beads in the purified products are reduced in three stages, the accuracy of the final detection result is improved, and the risk of the blockage of the subsequent mass spectrum detection chromatographic column caused by the residual magnetic beads in the products is reduced.

[0021] The utility model will be further explained in detail in combination with the drawings and examples. DRAWINGS

[0022] Figure 1 is the overall structure schematic diagram of the full-automatic mass spectrum sample pretreatment workstation provided by the utility model;

[0023] Figure 2 is the three-dimensional structure schematic diagram of the full-automatic mass spectrum sample pretreatment workstation after the shell is removed provided by the utility model;

[0024] Figure 3 is the structure schematic diagram of the reagent bottle sleeve suitable for the sample holder in the full-automatic mass spectrum sample pretreatment workstation provided by the utility model;

[0025] Figure 4 is the structure schematic diagram of the sample tube transfer mechanical hand and the mechanical arm in the sample tube transfer assembly;

[0026] Figure 5 is Figure 4 the overhead structure schematic diagram of the conveying track assembly in the sample tube transfer assembly in

[0027] Figure 6 is the structure schematic diagram of the sample tube transfer assembly and the sample tube holder station cooperating to transfer the sample tube;

[0028] Figure 7 is the structure schematic diagram of the switch cover assembly in the full-automatic mass spectrum sample pretreatment workstation provided by the utility model;

[0029] Figure 8 is the structure schematic diagram of the pipette assembly in the full-automatic mass spectrum sample pretreatment workstation provided by the utility model;

[0030] Figure 9 is the overhead view of the workbench in the full-automatic mass spectrum sample pretreatment workstation provided by the utility model;

[0031] Figure 10 is the side view sectional schematic diagram of the workbench in the full-automatic mass spectrum sample pretreatment workstation provided by the utility model;

[0032] Figure 11 is a structural schematic view of a deep hole plate assembly in a full-automatic mass spectrum sample pretreatment workstation provided by the utility model;

[0033] Figure 12 is an enlarged structural schematic view of a part of a full-automatic mass spectrum sample pretreatment workstation provided by the utility model;

[0034] Figure 13 is a structural schematic view of a product plate station;

[0035] Figure 14 is a front structural schematic view of a transfer device in a full-automatic mass spectrum sample pretreatment workstation provided by the utility model;

[0036] Figure 15 is Figure 14 a back structural schematic view of the transfer device;

[0037] Figure 16 is Figure 14 an initial state structural schematic view of the transfer device;

[0038] Figure 17 is Figure 14 a structural schematic view of the transfer device in a movement process;

[0039] Figure 18 is a three-dimensional structural schematic view of a purification module;

[0040] Figure 19 is a structural schematic view of a base in the purification module;

[0041] Figure 20 is a structural schematic view of a first mounting plate in the purification module;

[0042] Figure 21 is a three-dimensional structural schematic view of a second mounting plate in the purification module;

[0043] Figure 22 is a side structural schematic view of the second mounting plate in the purification module;

[0044] Figure 23 is a structural schematic view of a connecting member in an embodiment of the utility model;

[0045] Figure 24 is a structural schematic view of a connecting member in another embodiment of the utility model;

[0046] Figure 25 is Figure 24 a structural schematic view of the connecting member in a use state;

[0047] Figure 26is a schematic view of the structure of the locking component;

[0048] Figure 27 is a schematic view of the structure of the locking component when locking from the back of the module;

[0049] Figure 28 is a schematic view of the working state of the transfer device picking up the deep-well plate from the deep-well plate station;

[0050] Figure 29 is a schematic view of the working state of the transfer device placing the deep-well plate on the deep-well plate loading platform.

[0051] BRIEF DESCRIPTION OF THE DRAWINGS

[0052] 10 - sample dispensing module;

[0053] 11 - sample tube rack station, 1100 - sample rack turntable, 1101 - sample rack, 1102 - drive wheel, 1103 - sample rack drive motor, 1104 - rotating shaft, 1105 - sample tube, 1106 - reagent bottle sleeve, 11060 - upper tube body, 11061 - lower tube body, 11062 - observation port, 11063 - inclined guide surface, 11064 - annular groove;

[0054] 12 - deep-well plate station, 1200 - deep-well plate turntable, 1201 - second gear disc, 1202 - deep-well plate turntable drive motor, 1203 - first gear disc, 1204 - deep-well plate, 1205 - deep-well plate mounting seat, 1206 - connecting column, 12050 - magnetic attraction device;

[0055] 13 - Tip head receiving station, 1300 - Tip head turntable, 1301 - Tip head turntable drive motor, 1302 - Tip head belt, 1303 - Tip head pulley, 1304 - rotating mounting seat, 1305 - Tip gun head placement rack; 1306 - Tip head placement platform;

[0056] 14 - product plate station, 1400 - base, 1401 - magnetic attraction member, 1402 - clamping portion, 1403 - product plate;

[0057] 15 - reagent station;

[0058] 16 - sample tube transfer assembly, 1600 - sample tube transfer manipulator, 1601 - X-axis mechanical arm, 1602 - Y-axis mechanical arm, 1603 - clamping jaw, 1604 - conveying track assembly, 16041 - sample tube transfer pulley, 16042 - sample tube transfer belt, 16043 - conveying track, 16044 - clamping portion;

[0059] 17 - switch cover assembly, 1700 - support seat, 1701 - switch cover gripper bracket, 1702 - electric clamping jaw, 1703 - switch cover driving device;

[0060] 18 - pipetting assembly, 1800 - X-axis mechanical arm, 1801 - Y-axis mechanical arm, 1802 - dispensing device, 1803 - Tip mounting portion;

[0061] 19 - connecting member, 1901 - positioning seat, 1902 - positioning hook, 1903 - positioning rod; 1901' - mounting seat, 1902' - positioning column, 1903' - equidistant spacer, 1904' - locking part, 19040' - fixing seat, 19041' - pull hook, 19042' - bolt;

[0062] 20 - purification module, 201 - support plate, 2011 - first purification driving motor, 2012 - transmission wheel assembly; 202 - first mounting plate, 2021 - magnetic bar, 2022 - synchronous wheel, 2023 - second purification driving motor, 2024 - purification belt; 203 - second mounting plate, 2031 - rotary gear, 2032 - third purification driving motor, 2033 - screw connecting piece; 2034 - stirring sleeve connecting piece; 204 - deep well plate stage, 205 - base, 206 - purification lead screw, 207 - first purification pulley, 208 - second purification pulley, 209 - conveying belt, 210 - purification track;

[0063] 30 - transfer device, 301 - fixing frame, 302 - fixing plate, 303 - first driving mechanism, 304 - first driving wheel, 305 - first driven wheel, 306 - first belt, 307 - slide rail, 308 - first belt connecting piece, 309 - second belt connecting piece, 310 - third belt connecting piece, 311 - telescopic arm, 312 - second driven wheel, 313 - third driven wheel, 314 - second belt, 315 - mechanical gripper assembly, 3150 - second driving mechanism, 3151 - lead screw, 3152 - clamping jaw, 316 - transfer device slide; 317 - transfer device slider; 40 - Tip head recycling station. DETAILED DESCRIPTION

[0064] In order to further illustrate the technical means and effects taken by the utility model to achieve the predetermined utility model purposes and the effects, the following will be combined with the drawings and the specific embodiments to explain the scheme according to the utility model in detail.

[0065] The foregoing and other technical contents, features and effects of the present application can be clearly presented in the following detailed description of specific embodiments with reference to the accompanying drawings. Through the description of the specific embodiments, the technical means and effects taken by the present application to achieve the predetermined purpose can be more deeply and specifically understood. However, the accompanying drawings are provided for reference and illustration only, and are not intended to limit the technical solutions of the present application.

[0066] It should be noted that in this paper, relational terms such as first and second are used only to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply that there is any such actual relationship or order between these entities or operations. Moreover, the terms "include", "contain" or any other variant are intended to cover non-exclusive inclusion, so that the article or device including a series of elements not only includes those elements, but also includes other elements not explicitly listed. Without more limitations, the element defined by the sentence "including a" does not exclude the presence of other identical elements in the article or device including the element.

[0067] Please refer to Figure 1 and Figure 2 , Figure 1 is the overall structure schematic diagram of the full-automatic mass spectrum sample pretreatment work station provided by the present application, Figure 2It is the stereoscopic structure schematic drawing after the shell of the full-automatic mass spectrum sample pretreatment workstation is removed. The full-automatic mass spectrum sample pretreatment workstation, including sample cup dividing module 10, transfer device 30 and purification module 20, specifically, sample cup dividing module 10 can complete sample cup dividing operation and reagent transfer of sample in sample tube; transfer device 30 can transfer the sample after cup dividing to purification module 20 to perform separation and purification, and through the cooperation of magnetic rod sleeve and magnetic rod, one-time magnetic bead adsorption is realized; transfer device 30 can also transfer the purified product to sample cup dividing module 10 to perform two-time magnetic bead adsorption through magnetic attraction device and magnetic attraction piece. Specifically, the full-automatic mass spectrum sample pretreatment workstation, hereinafter referred to as workstation, sample cup dividing module 10 is located in the first chamber of the full-automatic mass spectrum sample pretreatment workstation, and purification module 20 and transfer device 30 are located in the second chamber in the full-automatic mass spectrum sample pretreatment workstation. Sample cup dividing module 10 can complete sample cup dividing operation and reagent transfer of sample in sample tube, and can also complete sample tube transfer, cover opening, cover closing and Tip head intake operation; transfer device 30 can connect sample cup dividing module 10 and purification module 20, transfer the sample after cup dividing to purification module 20 to separate and purify the target in the sample, and through the cooperation of magnetic rod sleeve and magnetic rod, first-time magnetic bead adsorption is realized; transfer device 30 can also transfer the purified product to sample cup dividing module 10, and sample cup dividing module 10 can sequentially perform second-time and third-time two-time magnetic bead adsorption on the purified product through magnetic attraction device and magnetic attraction piece. Optionally, the workstation further includes a shell 1, and the sample cup dividing module 10, the purification module 20 and the transfer device 30 are arranged in the shell.

[0068] Further, the sample cupping module 10 comprises a sample tube rack station 11 and a consumable placement station arranged on the workbench, the consumable placement station comprises a deep-well plate turntable 1200, a plurality of deep-well plate stations 12 are arranged in the circumferential direction of the deep-well plate turntable 1200, the deep-well plate station 12 is provided with a deep-well plate mounting seat 1205, a plurality of magnetic attraction devices 12050 are arranged on the deep-well plate mounting seat 1205, a Tip head turntable is arranged at the center of the deep-well plate turntable 1200, and N Tip head receiving stations 13 are arranged on the Tip head turntable, N is an integer greater than or equal to 1; the sample cupping module 10 further comprises a product plate station 14, a reagent station 15, a sample tube transfer assembly 16, a switch cover assembly 17 and a pipetting assembly 18, the sample tube rack station 11 can load a sample rack 1101, the pipetting assembly 18 comprises at least one pipetting subunit, the pipetting assembly 18 can suck at least one Tip head on one Tip head receiving station 13 of the Tip head turntable, and can unload the Tip head after completing pipetting, so as to transfer the sample liquid in the sample tube to the deep-well plate on the deep-well plate station 12 for sample liquid cupping, the pipetting assembly 18 can also transfer the reagent in the reagent station 15 to the deep-well plate, and the pipetting assembly 18 can also transfer the product in the deep-well plate which completes the purification reaction in the purification module 20 to the product plate in the product plate station 14. Specifically, the sample rack 1101 can place a smaller size reagent bottle and a plurality of conventional sample tubes containing samples to be processed, the deep-well plate station 12 comprises a deep-well plate base, a magnetic column is arranged on the deep-well plate base, a plurality of deep-well plates can be placed on the deep-well plate base to complete adsorption of residual magnetic beads in the purified product, a plurality of Tip heads are placed in the Tip head receiving station 13, and the reagent station 15 is used to place internal standard reagents required in the sample pretreatment process, such as IC reagent and PK reagent.The product plate station 14 is provided with a product plate base provided with a magnetic suction element, and the product plate base can receive a product plate capable of containing a target object after purification. The sample tube transfer assembly 16 can transfer the sample tube on the sample tube rack station 11 to the switch cover assembly 17, and the switch cover assembly 17 can realize the opening or closing operation of the sample tube. The pipetting assembly 18 can collect the sample liquid in the sample tube after opening and add it into the deep well plate 1204 on the deep well plate station 12 to realize sample cupping. The pipetting assembly 18 can replace the Tip head from the Tip head receiving station 13, and the pipetting assembly 18 can inject the reagent in the reagent station 15 into the sample in the deep well plate 1204. Then, the transfer device 30 sequentially transports the deep well plate 1204 containing the sample liquid and the reagent to the purification module 20 to complete the separation and purification of the target object. After the purification module 20 completes the purification process, the deep well plate 1204 containing the target object is output and sequentially transported to the deep well plate station 12 by the transfer device 30. The residual magnetic beads in the product are secondarily adsorbed by the plurality of magnetic suction devices on the deep well plate mounting base. The pipetting assembly 18 transfers the target object from the deep well plate 1204 to the product plate in the product plate station 14 to realize product collection and third magnetic bead adsorption by the magnetic suction element on the product plate base, thereby realizing the pretreatment process of the sample for mass spectrometric detection. In this process, after the pipetting assembly 18 completes the liquid collection in the sample tube, the switch cover assembly 17 performs the closing operation, and the sample tube transfer assembly 16 can transfer the sample tube back to the sample tube rack station 11 and continue to perform the transfer step of transferring the next sample tube to the switch cover assembly 17. The full-automatic mass spectrometric sample pretreatment work station provided in this embodiment simplifies the pretreatment steps of the mass spectrometric sample, maximally liberates the labor force, improves the sample processing timeliness, and ensures the safety in the sample pretreatment process and the accuracy of the detection result.

[0069] Further, the common sample rack on the market cannot meet the demand of independent placement of small-size reagent bottles. Therefore, the sample rack 1101 in the sample cupping module 10 provided in this embodiment is provided with a reagent bottle sleeve 1106 matched with the sample rack. As shown in Figure 3 The reagent bottle sleeve 1106 includes an upper tube body 11060 and a lower tube body 11061. The upper tube body 11060 has an open end, and a side wall of the upper tube body 11060 is provided with an observation opening 11062. The open end is provided with an inclined guide surface 11063 to facilitate the insertion of the reagent bottle into the sleeve. The observation opening 11062 facilitates the exposure of the identification code on the reagent bottle. The lower tube body 11061 is provided with a plurality of grooves 11064 on the tube wall to facilitate the clamping of the reagent bottle sleeve 1106 in the sample rack. Preferably, the grooves 11064 are annular grooves.

[0070] Further, please refer to Figure 4 and Figure 5 , Figure 4is a structural schematic diagram of a sample tube transfer mechanical hand and a mechanical arm in a sample tube transfer assembly, Figure 5 is Figure 4 is a top view structural schematic diagram of a conveying track assembly in a sample tube transfer assembly. The sample tube transfer assembly 16 comprises a sample tube transfer mechanical hand 1600 and a mechanical arm, the mechanical arm comprising an X-axis mechanical arm and a Y-axis mechanical arm extending in perpendicular directions, specifically, the Y-axis mechanical arm extends in a first direction and the X-axis mechanical arm extends in a second direction perpendicular to the first direction. The sample tube transfer mechanical hand 1600 can be driven to move along the Y-axis mechanical arm and the Y-axis mechanical arm can be driven to slide along the X-axis mechanical arm, thereby realizing the movement of the sample tube transfer mechanical hand 1600 in a two-dimensional space. The sample tube transfer mechanical hand 1600 is provided with a gripper 1603 capable of grabbing a sample tube 1105 on the sample tube rack station 11. The sample tube transfer mechanical hand 1600 is also provided with a gripper control mechanism capable of controlling the movement of the gripper 1603 in a third direction, the third direction being perpendicular to the extending directions of the Y-axis mechanical arm and the X-axis mechanical arm, respectively. Specifically, the lower end of the sample tube transfer mechanical hand 1600 is provided with a gripper for clamping the sample tube 1105. Each gripper is provided with a gripper 1603. Preferably, each gripper is provided with four grippers 1603. The distance between the grippers 1603 can be adjusted by an external control mechanism to adapt to sample tubes of different diameters. The mechanical arm comprises a Y-axis mechanical arm 1602 and an X-axis mechanical arm 1601. Specifically, the front-to-back direction is defined as the X-axis direction, the left-to-right direction is defined as the Y-axis direction, and the up-to-down direction is defined as the Z-axis direction. The sample tube transfer mechanical hand 1600 is in sliding connection with the Y-axis mechanical arm 1602, and the Y-axis mechanical arm 1602 is in sliding connection with the X-axis mechanical arm 1601 through a sliding block. Meanwhile, the sample tube transfer mechanical hand 1600 is internally provided with a gripper control mechanism (not shown in the figure) for moving the gripper 1603 in the third direction, which is the Z-axis direction perpendicular to the X-axis direction and the Y-axis direction, thereby realizing the movement of the sample tube transfer mechanical hand 1600 in a three-dimensional space and flexibly grabbing the sample tube 1105 on the sample tube rack station 11.

[0071] The sample tube transfer assembly 16 further comprises a conveying track assembly 1604 cooperating with the sample tube transfer mechanical hand 1600. The conveying track assembly 1604 is arranged on a workbench below the sample tube transfer mechanical hand 1600. The conveying track assembly 1604 comprises conveying units. Each conveying unit comprises a clamping part 16044 for clamping a sample tube, a conveying track 16043, a belt pulley driving mechanism, and a sample tube transfer belt pulley 16041 around which a sample tube transfer belt 16042 is arranged. The clamping part 16044 is slidably arranged on the conveying track 16043. The conveying track 16043 extends towards the direction in which the switch cover assembly 17 is located. The clamping part 16044 is fixedly connected with the sample tube transfer belt 16042. As Figure 6As shown, when the sample tube transfer robot 1600 places the sample tube 1105 on the clamping part 16044, the clamping part 16044 shrinks inward to clamp the sample tube 1105, and then the belt wheel driving mechanism drives the sample tube transfer belt wheel 16041 to drive the sample tube transfer belt 16042 to move the clamping part 16044 to the lower side of the opening and closing cover assembly 17 and cooperate with the opening and closing cover assembly 17 to complete the opening and closing cover operation of the sample tube. In the embodiment, the conveying track assembly 1604 is provided with four clamping parts 16044, which can clamp four sample tubes at a time, and each two clamping parts 16044 form a conveying unit, that is, the conveying track assembly 1604 includes two conveying units, and the moving speed of the two conveying units can be controlled by an external control mechanism, thereby improving the use efficiency of the conveying track assembly.

[0072] Preferably, the conveying track 16043 further extends to the lower area of the pipetting assembly 18, that is, the extension direction of the conveying track 16043 passes through the moving area of the opening and closing cover assembly 17 and the pipetting assembly 18, so that the pipetting assembly 18 can conveniently suck the sample in the sample tube.

[0073] Preferably, a code scanner is installed on the side wall of the sample cup dividing module 10, which can identify the information of the sample tube 1105 and the sample rack 1101. After the sample tube transfer robot 1600 grabs the sample tube, it stops in front of the code scanner and rotates a circle, and cooperates with the code scanner to scan the sample information.

[0074] Please refer to Figure 7 , Figure 7 is the structural schematic diagram of the opening and closing cover assembly in the full-automatic mass spectrum sample pretreatment workstation. The opening and closing cover assembly 17 comprises a supporting seat 1700, the supporting seat 1700 is provided with an opening and closing cover gripper support 1701, the opening and closing cover gripper support 1701 is provided with an electric clamp jaw 1702, and the opening and closing cover assembly 17 further comprises an opening and closing cover driving device 1703. Specifically, the supporting seat 1700 is provided with two opening and closing cover gripper supports 1701, and can simultaneously clamp two sample tubes for automatic opening and closing cover. The opening and closing cover gripper support 1701 can be driven to move in the Y-axis direction and the Z-axis direction. Preferably, the opening and closing cover driving device 1703 comprises two driving motors which work independently, and drives the electric clamp jaw 1702 to rotate forward and reverse, so as to realize the opening and closing cover operation of the sample tube.

[0075] Please refer to Figure 8 , Figure 8It is the structural schematic view of the pipetting assembly in the full-automatic mass spectrum sample pretreatment workstation provided by the utility model, the pipetting assembly 18 includes X axis mechanical arm 1800, Y axis mechanical arm 1801, dispensing device 1802 and Tip installation part 1803, Tip installation part 1803 is arranged on dispensing device 1802, in the embodiment, the number of Tip installation part 1803 is two and is independent of each other, and the spacing can be adjusted;In order to facilitate obtaining larger movement range, dispensing device 1802 is slidingly installed on Y axis mechanical arm 1801, Y axis mechanical arm is slidingly installed on X axis mechanical arm 1800, and Tip control assembly for driving Tip installation part 1803 to move in Z axis direction is also included on dispensing device 1802, and dispensing device 1802 adopts the ADP pipettor widely used in market, can ensure the pipetting precision each time, thereby realizing the smooth and accurate suction and transfer of sample and reagent.

[0076] Please refer to Figure 9 And Figure 10 , Figure 9 It is the top view of the workbench in the full-automatic mass spectrum sample pretreatment workstation provided by the utility model, Figure 10 It is the side view sectional schematic view of the workbench in the full-automatic mass spectrum sample pretreatment workstation provided by the utility model. Preferably, deep hole plate turntable 1200 and Tip head turntable 1300 are located on the same horizontal plane, and the central axes of the two turntables substantially coincide, sample tube rack station 11 is provided with sample rack turntable 1100, thereby reducing the space occupancy of each component in the workstation and improving the compatibility inside the workstation. Sample tube rack station 11 also includes sample rack driving motor 1103 and driving wheel 1102, sample rack 1101 is detachably installed on sample rack turntable 1100, a plurality of sample tubes containing reagent samples are placed on sample rack 1101, sample rack 1101 is the sample rack commonly used in the prior art and can accommodate 96 sample tubes, and the sample tube includes but is not limited to sample test tube, blood collection tube and centrifugal test tube. Sample rack turntable 1100 is fixedly connected with driving wheel 1102, preferably, sample rack turntable 1100 is fixedly connected with driving wheel 1102 through pivot 1104. Driving wheel 1102 is connected with the output end of sample rack driving motor 1103 through a belt. The central position of sample rack 1101 substantially coincides with the center position of sample rack turntable 1100, so that after sample rack turntable 1100 rotates 180°, the arrangement range of sample tube coincides with the movement path range of sample tube transfer mechanical hand 1600, facilitating the smooth grabbing of sample tube transfer assembly 16.

[0077] Please refer to Figure 11 And Figure 12 , Figure 11 It is the structural schematic view of the deep hole plate assembly in the full-automatic mass spectrum sample pretreatment workstation provided by the utility model, Figure 12is a partial amplification structure schematic view of the full-automatic mass spectrum sample pretreatment workstation provided by the utility model. A plurality of deep hole plate mounting seats 1205 for placing deep hole plates 1204 are evenly arranged on the deep hole plate turntable 1200 in the circumferential direction, specifically, the number of deep hole plates 1204 arranged for the processing amount of 96 human samples is 6, and the specific specification of the deep hole plate 1204 is the common 96-hole deep hole plate in the field, and a single hole can accommodate 1.5-1.7ml of liquid reagent. In order to facilitate the adsorption of magnetic beads remaining in the eluent, a plurality of magnetic attraction devices 12050 are arranged on each deep hole plate mounting seat 1205, and in the embodiment, the magnetic attraction device 12050 is a magnetic column, the cross section of the magnetic column is in close contact with the outer wall of the hole of the deep hole plate 1204, and specifically, in order to reduce the production cost, the magnetic column is arranged at the hole outer wall of the elution hole of the deep hole plate 1204. Preferably, the deep hole plate turntable 1200 and the tip head turntable 1300 have independent driving structures, so that the two turntables can rotate independently, the deep hole plate turntable 1200 is driven by the meshing gear pair transmission driven by the deep hole plate turntable driving motor 1202, and the meshing gear pair is configured with low gear number and high gear number. Specifically, the driving structure of the deep hole plate turntable 1200 comprises a deep hole plate turntable driving motor 1202, a first toothed disc 1203, a second toothed disc 1201 and a connecting column 1206, the output end of the deep hole plate turntable driving motor 1202 is connected with the first toothed disc 1203, the first toothed disc 1203 and the second toothed disc 1201 are engaged, the second toothed disc 1201 is arranged below the deep hole plate turntable 1200 and is fixedly connected with the deep hole plate turntable 1200 through the connecting column 1206, under the driving of the deep hole plate turntable driving motor 1202, the first toothed disc 1203 drives the second toothed disc 1201 to rotate, and the second toothed disc 1201 drives the deep hole plate turntable 1200 to rotate.

[0078] Further, the deep hole plate 1204 is a 96-hole deep hole plate, and the side wall of the deep hole plate is provided with a groove capable of cooperating with a mechanical gripper.

[0079] Please continue to refer to Figure 9 and Figure 10The Tip head rotating disc 1300 is driven by the Tip head rotating disc driving motor 1301 through a belt drive. Specifically, the driving structure of the Tip head rotating disc 1300 includes the Tip head rotating disc driving motor 1301, a Tip head pulley 1303, a Tip head belt 1302, a rotating mounting seat 1304, and a Tip gun head placing rack 1305. The center of the Tip head rotating disc 1300 substantially coincides with the center of the deep well plate rotating disc 1200. The Tip gun head placing rack 1305 is fixedly arranged on the Tip head rotating disc 1300 and can place a plurality of Tip heads. In addition, a row of Tip head placing tables 1306 is additionally arranged at the edge of the Tip head placing rack 1305 to avoid affecting the normal operation of the pipetting assembly 18 due to insufficient Tip heads. The Tip head pulley 1303 is connected to the output end of the driving motor 1301 through the Tip head belt 1302. A rotating shaft is arranged between the Tip head pulley 1303 and the rotating mounting seat 1304. The Tip head rotating disc 1300 is fixedly arranged on the rotating mounting seat 1304. In this embodiment, the Tip head rotating disc 1300 rotates by 180° or the deep well plate rotating disc 1200 rotates by 180°, so that the arrangement range of the Tip heads on the Tip gun head placing rack 1305 and the arrangement range of the deep well plate 1204 substantially coincide with the movement path range of the pipetting assembly 18. The Tip head rotating disc 1300 and the deep well plate rotating disc 1200 are controlled by different driving motors and independently operate.

[0080] The workbench is also provided with a Tip head recycling station 40. After the pipetting assembly 18 performs a pipetting operation, the Tip heads are unloaded to the Tip head recycling station 40 to obtain new Tip heads.

[0081] Please refer to Figure 12 and Figure 13 , Figure 13 is a structural schematic view of the product plate station. The product plate station 14 includes a base 1400, clamping portions 1402, and a product plate 1403. The clamping portions 1402 are arranged around the base 1400. Preferably, the clamping portions 1402 are symmetrically arranged at the four corners of the base 1400. The product plate 1403 can be used to hold the target substance after purification. A plurality of magnetic members are uniformly arranged on the base. Each magnetic member is in close contact with the outer wall of four holes of the product plate. Preferably, each magnetic member is in close contact with the outer wall of four holes of the product plate.

[0082] Preferably, the product plate is a 96-hole shallow well plate. Each hole can hold 250-700 μl of liquid reagent. In order to facilitate the aggregation of the target substance at the bottom of the hole of the product plate, magnetic members 1401 are uniformly arranged on the base. Each magnetic member 1401 is in close contact with the outer wall of four holes of the product plate to further reduce the residual magnetic beads in the product after purification.

[0083] Please refer toFigure 14 and Figure 15 , Figure 14 is the front structure schematic view of the transfer device in the full-automatic mass spectrum sample pretreatment workstation provided by the utility model, Figure 15 is Figure 14 The back structure schematic view of the transfer device. The transfer device 30 is arranged above the deep well plate stage 204 of the purification module 20, the transfer device 30 comprises a fixed assembly and a movable assembly linearly moving relative to the fixed assembly under the driving of a driving device, the fixed assembly comprises a fixed frame 301 and a fixed plate 302 fixed on the fixed frame 301, and the driving device comprises a first belt 306, a first driving wheel 304, a first driven wheel 305 and a first driving mechanism 303. Specifically, the first driving mechanism 303 and the first driving wheel 304 are installed on the fixed plate 302, one end of the first driving mechanism 303 is fixedly connected with the first driving wheel 304, the output end of the first driving mechanism 303 is connected with the first driving wheel 304, and the first driving wheel 304 is connected with the first driven wheel 305 through the first belt 306. The movable assembly comprises a telescopic arm 311, a second belt 314, a second driven wheel 312, a third driven wheel 313, a mechanical gripper assembly 315 slidingly installed on the telescopic arm 311, and the telescopic arm 311 is slidingly connected with the fixed plate 302. Specifically, the telescopic arm 311 is also provided with a slide 316 horizontally, the mechanical gripper assembly 315 is slidingly arranged in the slide 316, the telescopic arm 311 is slidingly connected with the slide rail 307 provided horizontally on the fixed plate 302 through the sliding block 317, the second driven wheel 312 and the third driven wheel 313 are arranged at two ends of the telescopic arm 311 respectively, the third driven wheel 313 is fixedly installed on the telescopic arm 311, and the second belt 314 is wound between the second driven wheel 312 and the third driven wheel 313. The fixed assembly further comprises a first belt connecting piece 308, one end of the first belt connecting piece 308 is fixedly connected with the first belt 306, and the other end of the first belt connecting piece 308 is fixedly connected with the telescopic arm 311.

[0084] Further, the mechanical gripper assembly 315 comprises a clamping jaw 3152, a second driving mechanism 3150 and a lead screw 3151, the output end of the second driving mechanism 3150 is provided with the lead screw 3151, the clamping jaw 3152 is movably connected with the lead screw 3151, and the clamping jaw 3152 can move longitudinally relative to the telescopic arm 311 under the driving of the second driving mechanism 3150.

[0085] Preferably, as Figure 16As shown, the movable assembly further comprises a second belt connecting member 309 and a third belt connecting member 310. One end of the second belt connecting member 309 is fixedly installed on the fixed plate 302, and the other end of the second belt connecting member 309 is fixedly connected with the second belt 314. One end of the third belt connecting member 310 is fixedly connected with the second belt 314, and the other end of the third belt connecting member 310 is fixedly connected with the mechanical gripper assembly 315. Under the driving of the first driving mechanism 303, the first belt connecting member 308 drives the telescopic arm 311 to produce relative movement with respect to the fixed plate 302, and at the same time, the second belt connecting member 309 drives the mechanical gripper assembly 315 to slide with respect to the telescopic arm 311 through the second belt 314. Specifically, when the transfer device is in the initial state, the telescopic arm 311 and the fixed plate 302 do not move relative to each other, thereby saving space in the workstation. When the first driving mechanism 303 is positively rotated, the first driving wheel 304 rotates to drive the first belt 306 to slide around the first driven wheel 305, and as shown, the first belt connecting member 308 drives the telescopic arm 311 to move away from the first driving wheel 304 under the driving of the first belt 306, i.e., the telescopic arm 311 is driven to extend horizontally to the left along the slide rail 307. At the same time, as the telescopic arm 311 extends to the left, the second belt connecting member 309 drives the second belt 314 to slide around the second driven wheel 312 and the third driven wheel 313, and in turn, the second belt 314 drives the mechanical gripper assembly 315 to produce relative movement along the slide 316, so that the mechanical gripper assembly 315 increases the travel distance by one time. When the first driving mechanism 303 is reversely rotated, the telescopic arm 311 moves in the opposite direction, and the telescopic arm 311 can be driven to slide horizontally to the right along the slide rail 307 to the top end of the slide rail 307. Figure 17

[0086] Please refer to Figure 18 and Figure 19 , Figure 18 is a schematic view of the structure of the purification module, Figure 19 ​is a structural schematic view of the base of the purification module. The purification module 20 uses a magnetic bead method to purify the target in the sample, and the purification module 20 includes a support plate 201, a first mounting plate 202, a second mounting plate 203 and a deep well plate stage 204 arranged in sequence from top to bottom, and the purification module 20 further includes a purification lead screw 206 and a purification driving mechanism. The purification lead screw 206 penetrates through the support plate 201, the first mounting plate 202 and the second mounting plate 203, and the deep well plate stage 204 can place a deep well plate containing a sample to be purified. The deep well plate stage 204 is provided with a heating device to meet the heating needs in the purification process of different types of samples. The deep well plate stage 204 is also provided with a deep well plate stage transfer mechanism, which can move the deep well plate stage 204 from below the transfer device 30 to below the second mounting plate 203. A plurality of magnetic rods are installed on the first mounting plate 202, and a plurality of stirring sleeve connectors are installed on the second mounting plate 203. The stirring sleeve connectors can install stirring sleeves, and the purification driving mechanism can drive the first mounting plate 202 and the second mounting plate 203 to reciprocate along the extension direction of the purification lead screw 206, and also drive the stirring sleeves installed on the stirring sleeve connectors to rotate. When the purification driving mechanism drives the second mounting plate 203 to run downward along the purification lead screw 206, the second mounting plate 203 realizes the installation of the stirring sleeve. When the purification driving mechanism drives the first mounting plate 202 and the second mounting plate 203 to move up and down relative to each other along the purification lead screw 206, the magnetic rods penetrate into the stirring sleeves to realize the transfer of the target in different hole positions in the deep well plate and the unloading of the stirring sleeves.

[0087] Preferably, the deep well plate stage transfer mechanism is arranged below the deep well plate stage 204, and the deep well plate stage transfer mechanism includes a base 205, a purification track 210, a first purification pulley 207, a second purification pulley 208, a transmission belt 209 wound between the first purification pulley 207 and the second purification pulley 208, and a driving assembly (not shown in the figure). The purification track 210 is arranged on the base 205, the deep well plate stage 204 is slidingly arranged on the purification track 210, and the deep well plate stage 204 is fixed to one end of the transmission belt 209. The transmission belt 209 is consistent with the extension direction of the purification track 210. When the first purification pulley 207 and the second purification pulley 208 are driven to rotate by the driving assembly, the deep well plate stage 204 slides along the extension direction of the purification track 210, so as to move the deep well plate from below the transfer device 30 to below the second mounting plate 203. In the present embodiment, 3*3 groups of deep well plate placing grooves are arranged on the deep well plate stage 204, which are compatible with various 1.0ml specification deep well plates, realize the purification treatment of 96 flux samples, and the heating device is arranged at the bottom of the deep well plate stage 204.

[0088] The purification driving mechanism comprises a support plate driving mechanism arranged on the support plate 201, a first mounting plate driving mechanism arranged on the first mounting plate 202, and a second mounting plate driving mechanism arranged on the second mounting plate 203.

[0089] Further, the support plate 201 is arranged with a support plate driving mechanism, which comprises a first purification driving motor 2011 and a transmission wheel assembly 2012. The first purification driving motor 2011 is in transmission connection with the transmission wheel assembly 2012, and the purification lead screw 206 is in transmission connection with the transmission wheel assembly 2012. When the first purification driving motor 2011 drives the transmission wheel assembly 2012, the purification lead screw 206 is driven.

[0090] Please refer to Figure 20 , Figure 20 is a structural diagram of the first mounting plate in the purification module. The first mounting plate 202 is arranged with a plurality of magnetic rods 2021, and is further arranged with a first mounting plate driving mechanism. The first mounting plate driving mechanism is arranged with a second purification driving motor 2023, two synchronous wheels 2022, and a purification belt 2024. The purification belt 2024 is arranged between the two synchronous wheels 2022, the synchronous wheels 2022 are in rotational connection with the purification lead screw 206, and the synchronous wheels 2022 are indirectly connected with the output end of the second purification driving motor 2023 through the belt. When the second purification driving motor 2023 drives the synchronous wheels 2022 to transmit, the purification lead screw 206 is driven to transmit, and the first mounting plate 202 moves longitudinally along the purification lead screw 206, thereby driving the plurality of magnetic rods 2021 to move longitudinally along the purification lead screw 206.

[0091] Please refer to Figure 21 and Figure 22 , Figure 21 is a three-dimensional structural diagram of the second mounting plate in the purification module, Figure 22is a side view structural schematic diagram of the second mounting plate in the purification module. The second mounting plate 203 is provided with a stirring sleeve connector 2034 and a second mounting plate driving mechanism, and the second mounting plate driving mechanism is provided with a third purification driving motor 2032 and a plurality of mutually meshing rotating gears 2031. The lower end of the rotating gear 2031 is fixedly connected with the stirring sleeve connector 2034, and the stirring sleeve connector 2034 is used for mounting the stirring sleeve, and the third purification driving motor 2032 drives the mutually meshing rotating gears 2031 to rotate, thereby driving the rotation of the stirring sleeve, so as to realize the mixing of the sample and reagent in the deep well plate. The interior of the rotating gear 2031 is hollow and corresponds to the number and position of the magnetic bar 2021, so that the magnetic bar 2021 can pass through the rotating gear 2031 and enter the interior of the stirring sleeve. The stirring sleeve and the magnetic bar 2021 cooperate with each other to realize the adsorption of the magnetic beads in the deep well plate outside the stirring sleeve and the unloading of the stirring sleeve. The second mounting plate 203 is also provided with a lead screw connector 2033, and the purification lead screw 206 is connected with the lead screw connector 2033, so that the second mounting plate 203 is rotationally connected with the purification lead screw 206. Therefore, when the first purification driving motor 2011 is driven, the purification lead screw 206 drives the second mounting plate 203 to move longitudinally, thereby realizing the clamping of the stirring sleeve, the third purification driving motor 2032 drives the mutually meshing rotating gears 2031 to rotate, thereby driving the rotation of the stirring sleeve, so as to realize the mixing of the sample and reagent in the deep well plate. At the same time, the second purification driving motor 2023 drives the synchronous wheel 2022 to rotate, thereby driving the first mounting plate 202 to move longitudinally along the purification lead screw 206. The relative rotation speed of the purification lead screw 206 and the synchronous wheel 2022 is adjusted, the first mounting plate 202 and the second mounting plate 203 move up and down relative to each other along the purification lead screw 206, so that the magnetic bar 2021 extends into the interior of the stirring sleeve to realize the transfer of the target object in the lysis hole, the washing hole and the elution hole in the deep well plate, the separation of the target object and the magnetic beads in the elution hole, and the unloading of the stirring sleeve.

[0092] In an embodiment of the present application, in order to facilitate the installation of the sample cup dividing module 10 and the purification module 20, a connecting member 19 is arranged on the workbench between the sample cup dividing module 10 and the purification module 20, that is, the sample cup dividing module 10 and the purification module 20 are spliced through the connecting member 19, as shown in Figure 23As shown, the connecting member 19 includes a positioning seat 1901, a positioning hook 1902 and a positioning rod 1903, the positioning seat 1901 and the positioning hook 1902 are respectively arranged on the sample cup dividing module 10 and the purification module 20, the positioning rod 1903 is fixed on the positioning seat 1901 and can be clamped into the positioning hook 1902. Specifically, the positioning seat 1901 is arranged on the right side of the deep well plate turntable 1200, the positioning hook 1902 is arranged on the base 205, and the positioning hook 1902 is symmetrically arranged with the positioning seat 1901, the positioning rod 1903 is clamped into the positioning hook 1902, so that the front and back of the sample cup dividing module 10 and the purification module 20 are limited.

[0093] In another embodiment of the present application, as shown in the drawings, Figure 24 Another structure of the connecting member 19 can also limit the different sample modules, which includes a mounting seat 1901', a positioning column 1902' and a plurality of equidistant spacers 1903'. The mounting seat 1901' and the positioning column 1902' are arranged opposite to the edges of different modules. The mounting seat 1901' is further provided with an integrally formed crossbar which can be inserted into the insertion hole in the positioning column 1902' to limit the front and back of different modules. The plurality of equidistant spacers 1903' are arranged on both sides of the positioning column 1902', and each equidistant spacer 1903' is arranged on the edge of the module where the positioning column 1902' is located, so that the spacing between different sample modules is equal. Further, the connecting member 19 further includes a locking component 1904', which is detachably fixed to the back of the module to lock different modules in the horizontal direction. Specifically, as shown in the drawings, Figure 25 The mounting seat 1901' is fixedly installed on the right side of the deep well plate turntable 1200, and the positioning column 1902' is fixedly installed on the edge of the base 205 and opposite to the mounting seat 1901'. The mounting seat 1901' is further provided with an integrally formed crossbar which can be inserted into the insertion hole in the positioning column 1902', thereby limiting the front and back of the sample cup dividing module 10 and the purification module 20.

[0094] Please refer to Figure 26 , Figure 26 is a structural diagram of the locking component. The locking component 1904' includes a fixing seat 19040', a pull hook 19041' and a bolt 19042'. One end of the pull hook 19041' is connected to the fixing seat 19040' through the bolt 19042', and the other end of the pull hook 19041' abuts against the back of one of the cup dividing module 10 and the purification module 20. The fixing seat 19040' is fixed to the back of the other one of the cup dividing module 10 and the purification module 20. Specifically, as shown in the drawings, Figure 27As shown, the fixing seat 19040' is fixedly installed on the back of the base 205, one end of the pull hook 19041' abuts against the convex rib on the back of the sample cup dividing module workbench, the locking component 1904' can reduce the spacing between the sample cup dividing module 10 and the purification module 20, and a structure same equidistant spacer 1903' is respectively installed at the edge of the base 205 close to the workbench, so that the workbench and the base 205 can be ensured to be on the same straight line, and the spacing between the workbench and the base 205 is ensured to be equidistant during the assembly and locking of the sample cup dividing module 10 and the purification module 20.

[0095] Further, the purification module can select a full-automatic nucleic acid extractor instrument according to actual purification project needs or different purification fluxes.

[0096] The full-automatic mass spectrum sample pretreatment device provided by the embodiment can complete 96 sample cover opening, cup dividing (dispensing), and target purification within 55 min, is short in time consumption, and is high in processing efficiency. The working process of the utility model is described below:

[0097] Step 1, consumable and reagent preparation;

[0098] Load the sample tube and sample holder, load the corresponding types and specifications of reagents and the corresponding number of pipetting consumables such as Tip gun heads, deep-well plates pre-packaged with purification reagents, stirring sleeves and the like, close the cabin door of the machine shell, and start the control program.

[0099] Step 2, the transfer device transfers the sample tube to the lower part of the pipetting assembly for pipetting;

[0100] The sample tube transfer assembly 16 follows the mechanical arm to grab the sample tube on the sample rack at the sample rack station 11, stops in front of the code scanner and rotates a circle, cooperates with the code scanner to scan the sample information, realizes the uploading of the sample information, and then the sample tube transfer assembly 16 places the sample tube in the conveying track assembly 1604 in turn, the clamping part 16044 clamps the sample tube, the sample tube is conveyed to the lower side of the cap opening and closing assembly 17 through the conveying track 16043, and the clamping part 16044 and the cap opening and closing assembly 17 cooperate to complete the opening of the sample tube. Then the conveying track assembly 1604 continues to convey the opened sample tube to the lower side of the pipetting assembly 18, the pipetting assembly 18 completes the suction of the sample in the sample tube and the reagent at the reagent station and injects into the deep well plate 1204, and then the cap opening and closing assembly 17 completes the closing operation of the sample tube. The sample tube transfer assembly 16 places the sample tube that has completed the dispensing operation back to the original position of the sample rack, and the dispensing operation of 96 samples is realized in this way. In this process, the pipetting assembly 18 changes the tip gun head once for each time of pipetting. In addition, the sample rack turntable 1100, the deep well plate turntable 1200 and the tip head turntable 1300 can rotate according to the dispensing situation of the sample in the sample tube and the use situation of the tip head under the control program, and complete the suction and transfer of all samples on the sample rack.

[0101] Step 3, the transfer device transfers the deep well plate containing the sample to be purified to the purification module for the first time of magnetic bead adsorption;

[0102] Please refer to Figure 28 and Figure 29 , Figure 28 is a working state schematic diagram of the transfer device grabbing the deep well plate from the deep well plate station, Figure 29 is a working state schematic diagram of the transfer device placing the deep well plate on the deep well plate loading platform. The transfer device 30 transfers the deep well plate containing the sample to be purified to the purification module 20 through the mechanical gripper assembly 315, and after cracking, multiple washing and elution, the magnetic rod 2021 and the stirring sleeve in the purification module 20 cooperatively realize the first separation of the magnetic beads in the purified product.

[0103] Step 4, the transfer device transfers the deep well plate containing the target object to the deep well plate mounting seat and the product plate in turn for two times of magnetic bead adsorption.

[0104] The transfer device 30 transfers the deep-well plate containing the target object to the mounting seat of the deep-well plate carousel 1200 at this time, and since the magnetic attraction device 12050 is arranged on the deep-well plate mounting seat 1205, the second adsorption of the magnetic beads in the product is realized, so as to avoid the residual magnetic beads in the product.

[0105] Therefore, the device provided by the utility model realizes full-process automation, can efficiently and quickly purify large system samples, reduces the interference of human factors, improves the processing efficiency, and reduces the residual magnetic beads in the product.

[0106] The full-automatic mass spectrum sample pretreatment workstation provided in the embodiment can automatically complete sample identification, cover opening / closing, cup separation, sample tube recovery, deep-well plate transfer, target object purification, and target object transfer, can realize automatic pretreatment of a large number of samples, makes the experimental process flow, standardized, and normalized, reduces errors caused by human operation, and guarantees the accuracy, stability, and traceability of the mass spectrum detection result.

[0107] The full-automatic mass spectrum sample pretreatment workstation provided in the embodiment is provided with the transfer device with the telescopic mechanical arm driven by the driving device, so that the mechanical gripper assembly can obtain double moving distance in limited space, and the mechanical gripper assembly can realize horizontal and longitudinal movement on the telescopic arm, the transfer device can effectively connect the sample cup separation module and the purification module, realizes the transfer of the deep-well plate containing the sample to be purified to the purification module and the transfer of the deep-well plate containing the target object to the deep-well plate station after purification, the transfer device is compact in structure and low in manufacturing cost, and further reduces the volume and cost of the full-automatic mass spectrum sample pretreatment workstation.

[0108] The full-automatic mass spectrum sample pretreatment workstation provided in the embodiment adopts the magnetic bead method to realize the purification of the target object, realizes the first adsorption of the magnetic beads in the product through the cooperation of the magnetic rod and the stirring sleeve, then realizes the second adsorption of the residual magnetic beads in the purified product through the deep-well plate base provided with the magnetic column, and finally realizes the third adsorption of the residual magnetic beads in the product through the product plate base provided with the magnetic attraction piece, so that the three-stage magnetic attraction reduces the residual magnetic beads in the purified product, improves the accuracy of the final detection result, and reduces the risk of clogging of the chromatographic column in subsequent mass spectrum detection caused by the residual magnetic beads in the product.

[0109] The above is further detailed description of the utility model in combination with specific preferred embodiments, and cannot be deemed as limitation of the specific implementation of the utility model to these descriptions. For ordinary skilled persons in the technical field to which the utility model belongs, without departing from the concept of the utility model, a number of simple deductions or substitutions can be made, and all of them shall be deemed as belonging to the protection scope of the utility model.

Claims

1. A fully automated mass spectrometry sample pre-treatment station, characterized in that, The device comprises a sample cupping module (10), a transfer device (30) and a purification module (20), wherein, The sample cupping module (10) can complete the sample cupping operation and reagent transfer in the sample tube; the transfer device (30) can transfer the sample after cupping to the purification module (20) to perform separation and purification, and realize one-time magnetic bead adsorption through the cooperation of the magnetic rod sleeve and the magnetic rod; the transfer device (30) can also transfer the purified product to the sample cupping module (10) to perform two-time magnetic bead adsorption through the magnetic attraction device and the magnetic attraction element.

2. The fully automated mass spectrometry sample preparation station according to claim 1, characterized in that, The sample cupping module (10) comprises a sample tube rack station (11), a product plate station (14), a reagent station (15), a sample tube transfer assembly (16), a cap opening and closing assembly (17), a pipetting assembly (18) and a consumable placement station arranged on a workbench, wherein the consumable placement station comprises a deep well plate turntable, a plurality of deep well plate stations (12) are arranged in the circumferential direction of the deep well plate turntable, the deep well plate station (12) is provided with a deep well plate mounting seat, and a plurality of magnetic attraction devices are arranged on the deep well plate mounting seat; a Tip head turntable is arranged at the center of the deep well plate turntable, N Tip head receiving stations (13) are arranged on the Tip head turntable, the sample tube rack station (11) can load a sample rack, the pipetting assembly (18) comprises at least one pipetting subunit, the pipetting assembly (18) can take at least one Tip head on one Tip head receiving station (13) of the Tip head turntable and unload the Tip head after completing pipetting, transfer the sample liquid in the sample tube to the deep well plate in the deep well plate station (12) to perform sample liquid cupping, and transfer the reagent in the reagent station (15) to the deep well plate, and the pipetting assembly (18) can also transfer the product in the deep well plate after completing the purification reaction in the purification module (20) to the product plate in the product plate station (14), and N is an integer greater than or equal to 1.

3. The fully automated mass spectrometry sample-pre-treatment station according to claim 2, characterized in that, The sample rack is provided with a reagent bottle sleeve matched with the sample rack, the reagent bottle sleeve comprises an upper tube body and a lower tube body, the upper tube body has an open end, the open end is provided with an inclined guide surface to facilitate the insertion of the reagent bottle into the sleeve, and a plurality of grooves are arranged on the wall of the lower tube body.

4. The fully automated mass spectrometry sample preparation station according to claim 2, characterized in that, The product plate station (14) comprises a base, a clamping part and a product plate, the clamping part is arranged around the base, the product plate can contain the target object after purification, and a plurality of magnetic attraction elements are uniformly arranged on the base.

5. The fully automated mass spectrometry sample preparation station according to claim 1, characterized in that, The sample cupping module (10) and the purification module (20) are spliced through a connecting member (19), the connecting member (19) comprises a positioning seat, a positioning hook and a positioning rod, the positioning seat and the positioning hook are respectively arranged on the sample cupping module (10) and the purification module (20), and the positioning rod is fixed on the positioning seat and can be clamped into the positioning hook.

6. The fully automated mass spectrometry sample pretreatment station according to claim 5, characterized in that, Another structure of the connecting member (19) comprises a mounting seat, a positioning column and a plurality of equidistant spacers, the mounting seat and the positioning column are arranged opposite to the edges of different modules, an integral transverse rod is further arranged on the mounting seat, the transverse rod can be inserted into the insertion hole in the positioning column, and the plurality of equidistant spacers are arranged on both sides of the positioning column.

7. The fully automated mass spectrometry sample-pre-treatment station according to claim 6, characterized in that, The connecting member (19) further comprises a locking component, which comprises a fixing seat, a draw hook and a bolt, one end of the draw hook is connected with the fixing seat through the bolt, and the other end of the draw hook abuts against the back of one of the cup dividing module (10) and the purification module (20), and the fixing seat is fixed on the back of the other module.

8. The fully automated mass spectrometry sample preparation station according to claim 1, characterized in that, The transfer device (30) is arranged above the deep well plate stage of the purification module (20), and the transfer device (30) comprises a fixed assembly and a movable assembly which moves linearly relative to the fixed assembly under the driving of a driving device, the fixed assembly comprises a fixing frame and a fixed plate fixed on the fixing frame, and the driving device comprises a first belt, a first driving wheel, a first driven wheel and a first driving mechanism; the movable assembly comprises a telescopic arm, a second belt, a second driven wheel, a third driven wheel and a mechanical gripper assembly slidably mounted on the telescopic arm; the fixed assembly further comprises a first belt connecting piece, one end of which is fixedly connected with the first belt, and the other end of which is fixedly connected with the telescopic arm.

9. The fully automated mass spectrometry sample-pre-treatment station according to claim 8, characterized in that, The movable assembly further comprises a second belt connecting piece and a third belt connecting piece, one end of the second belt connecting piece is fixedly mounted on the fixed plate, and the other end of the second belt connecting piece is fixedly connected with the second belt; one end of the third belt connecting piece is fixedly connected with the second belt, and the other end of the third belt connecting piece is fixedly connected with the mechanical gripper assembly; under the driving of the first driving mechanism, the first belt connecting piece drives the telescopic arm to move relatively to the fixed plate, and at the same time, the second belt connecting piece drives the mechanical gripper assembly to slide relative to the telescopic arm through the second belt.

10. The fully automated mass spectrometry sample preparation station according to claim 1, characterized in that, The purification module (20) comprises a support plate, a first mounting plate, a second mounting plate, a purification lead screw and a deep well plate stage arranged in sequence from top to bottom, the purification lead screw penetrates through the support plate, the first mounting plate and the second mounting plate, the deep well plate stage can place a deep well plate containing a sample to be purified, the deep well plate stage is provided with a heating device and a deep well plate stage transfer mechanism, the deep well plate stage transfer mechanism can move the deep well plate stage from below the transfer device (30) to below the second mounting plate, a plurality of magnetic rods are mounted on the first mounting plate, a plurality of stirring sleeve connecting pieces are mounted on the second mounting plate, the stirring sleeve connecting pieces can install stirring sleeves, the purification module (20) further comprises a purification driving mechanism, the purification driving mechanism can drive the first mounting plate and the second mounting plate to reciprocate along the extension direction of the purification lead screw, and can also drive the stirring sleeves mounted on the stirring sleeve connecting pieces to rotate, when the purification driving mechanism drives the second mounting plate to run downward along the purification lead screw, the second mounting plate realizes the installation of the stirring sleeves, and when the purification driving mechanism drives the first mounting plate and the second mounting plate to move relatively up and down along the purification lead screw, the magnetic rods penetrate into the stirring sleeves to realize the transfer of the target objects in different hole positions in the deep well plate and the unloading of the stirring sleeves.

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