Mass spectrometry pre-treatment apparatus and method

Abstract

The application relates to a mass spectrometry pretreatment device and method. In the mass spectrometry pretreatment device, a sample table module comprises a placement area, a conveying assembly which receives and conveys a sample tube placed at an emergency placement position when the sample tube is placed at the emergency placement position, and a control assembly which comprises a hooking mechanism, an information identifying mechanism, a clamping mechanism and a cap removing mechanism, the hooking mechanism is used for obtaining the sample tube from the conveying assembly, the information identifying mechanism is used for identifying information of the obtained sample tube, the clamping mechanism is used for clamping a tube body of the obtained sample tube, and the cap removing mechanism is used for removing a cap of the obtained sample tube; a pretreatment module comprises a conveying track assembly, a pipetting assembly, a reaction disc assembly which is used for performing magnetic bead pretreatment on a sample pipetted into a reaction cup, and a sample conveying assembly which is used for providing the mass spectrometry device with the sample subjected to the magnetic bead pretreatment. The mass spectrometry pretreatment device can realize different sample conveying modes.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of mass spectrometry detection technology, in particular to a mass spectrometry pretreatment device and method. BACKGROUND

[0002] Mass spectrometry technology has become a core means for trace substance detection due to its high sensitivity, high resolution and high throughput analysis capability, and is applied in the fields of life science, drug research and development, environmental monitoring and food safety. However, mass spectrometry analysis has very high requirements for the purity, concentration and ionization efficiency of samples. The wide application of mass spectrometry related detection technology is currently limited by complex biological sample matrixes. Interfering substances such as proteins, lipids and salts in these matrixes can significantly affect the sensitivity, specificity and instrument stability of detection, so sample pretreatment is a core link of mass spectrometry detection. As a key link connecting samples and mass spectrometers, pretreatment technology directly affects the accuracy, reproducibility and analysis efficiency of the final detection results.

[0003] Traditional pretreatment methods mainly include protein precipitation, liquid-liquid extraction and solid-phase extraction.

[0004] Protein precipitation is to precipitate proteins in samples by organic solvents or acids, and is mainly used for rapid deproteinization of biological samples such as blood and cell lysates. The advantages of protein precipitation are simple operation and compatibility with high-throughput use scenarios; the disadvantages are that only macromolecular proteins can be removed, small molecule interferents remain, and part of the target may be co-precipitated; high concentration of organic solvents need to be concentrated by nitrogen blowing, which increases the reaction steps.

[0005] Liquid-liquid extraction is based on the difference in distribution coefficient of target substances in two immiscible solvents for separation, and is mainly used for extraction of lipid-soluble compounds. The advantages of liquid-liquid extraction are low cost and simple operation, and it is suitable for concentration of large volume samples; but the disadvantages are also obvious, including large solvent consumption, large environmental pollution, low extraction efficiency for polar compounds, and possible introduction of emulsification problems which need to be treated by centrifugation or demulsifier.

[0006] Solid-phase extraction is to use adsorbents to selectively adsorb target substances, and to remove impurities by elution, and is mainly used for enrichment and purification of trace compounds in biological samples and environmental samples. The advantages of solid-phase extraction are good purification effect, which can remove >90% of matrix interference; flexible selection of adsorbents; suitable for concentration of low concentration samples; the disadvantages are complicated operation steps, extremely long time consumption, possible influence of batch-to-batch differences of adsorbents on reproducibility, and possible influence of high salt or high organic solvent eluent on mass spectrometry ion source, low overall throughput and poor consistency.

[0007] Emerging pretreatment technologies mainly include magnetic bead method, immunoaffinity extraction and online solid-phase extraction. Emerging mass spectrometry pretreatment technologies hope to get rid of the dependence on manual operation in traditional methods, and also hope to be high-throughput and intelligent. SUMMARY

[0008] Therefore, it is necessary to provide a mass spectrometry pretreatment device and method to solve at least one of the above problems.

[0009] In a first aspect, the present application provides a mass spectrometry pretreatment device for providing pretreated samples to a mass spectrometry device. The mass spectrometry pretreatment device comprises a sample stage module and a pretreatment module. The sample stage module comprises a placement area comprising a normal placement position and an emergency placement position, a conveying assembly configured to receive and convey a sample tube placed at the normal placement position, receive and convey a sample tube placed at the emergency placement position when the emergency placement position is placed with a sample tube, and a control assembly configured to control a sample tube to be transferred to the pretreatment module, the control assembly comprising a hooking mechanism, an information identification mechanism, a clamping mechanism, and a cap removing mechanism, the hooking mechanism being configured to obtain the sample tube from the conveying assembly, the information identification mechanism being configured to identify information of the obtained sample tube, the clamping mechanism being configured to clamp a tube body of the obtained sample tube, and the cap removing mechanism being configured to remove a cap of the obtained sample tube. The pretreatment module comprises a conveying track assembly comprising a normal sample inlet track and an emergency sample inlet track, the normal sample inlet track and the emergency sample inlet track being respectively connected to the hooking mechanism and being respectively configured to convey the controlled sample tube, a pipetting assembly configured to take liquid from the conveying track assembly and pipette the liquid, a reaction disc assembly configured to perform magnetic bead pretreatment on a sample pipetted into a reaction cup, and a sample conveying assembly configured to provide the sample subjected to the magnetic bead pretreatment to the mass spectrometry device.

[0010] By arranging the normal placement position, the emergency placement position, the normal sample inlet track, and the emergency sample inlet track, different sample conveying modes can be realized, and the sample tube placed at the emergency placement position can be processed by queuing. The automatic connection of the sample stage module and the pretreatment module is realized by the control assembly, and the pulsating work of the entire mass spectrometry pretreatment device is effectively arranged.

[0011] The mass spectrometry pretreatment device provided by the embodiments of the present application can achieve at least one of the following effects:

[0012] The magnetic bead method is used for pretreatment, and the method is compatible with solid-phase magnetic beads and immunomagnetic beads, and has good compatibility. The magnetic bead method can complete extraction in a short time, significantly shortening the experimental period. The selective adsorption mechanism of the magnetic bead method can obtain high-purity products, reducing the interference of subsequent experiments. The magnetic bead method does not require complex centrifugation or vacuum filtration steps, and only simple mixing, magnetic separation, and washing operations are required to complete extraction.

[0013] The magnetic bead method is suitable for various sample types such as blood, tissue, saliva, and environmental samples, and can adapt to different experimental needs.

[0014] The pre-treatment method is fully automated by taking advantage of the magnetic bead method, reduces manual errors and improves efficiency, adopts a pipeline operation mode to realize parallel processing of each process, and greatly improves the throughput of pre-treatment.

[0015] The pre-treatment module is compatible with multiple modes; the reaction cup is used as the processing unit at the front end, and one person's sample can be detected on the machine, realizing sample detection as soon as it comes, greatly reducing reagent waste; at the same time, the back end can be compatible with single-reaction-cup-to-96-well-plate sample loading function, making the mass spectrometry pre-treatment equipment have high compatibility;

[0016] The mass spectrometry pre-treatment equipment is configured with a high-capacity sample table module, supports online loading and unloading of sample baskets, uses a conveying assembly to intelligently grab sample racks, realizes emergency priority, intelligent insertion of quality control, and can cope with more complex use scenario requirements;

[0017] The maximum sample buffer capacity is 320 person samples, realizing 8-12 hours of unattended operation; in addition, it can also have a sample channel connected to a biochemical immune pipeline, and can seamlessly connect to a full-automatic detection pipeline.

[0018] In some embodiments, the conveying assembly includes a conveying vehicle movable in a first direction, along the travel of the conveying vehicle, an emergency placement position is arranged at one end, a control component is arranged at the other end, and a plurality of ordinary placement positions are arranged on both sides. Illustratively, the mass spectrometry pre-treatment equipment further includes a quality control placement position, and the quality control placement position and the emergency placement position are arranged on both sides of the conveying vehicle. Illustratively, the sample table module further includes an access interface, the access interface is arranged at intervals with the hooking mechanism, the access interface and the hooking mechanism can be connected through the conveying vehicle, and the access interface is used to connect to a biochemical immune pipeline.

[0019] In some embodiments, the mass spectrometry pre-treatment equipment further includes a sample rack, a sample basket, and a reversing turntable; the sample rack can carry a column of sample tubes, the sample basket is used to be placed in the ordinary placement position, the sample basket can carry a row of sample racks, and the sample basket is provided with an opening on the side facing the conveying vehicle; the conveying vehicle is provided with a telescopic part capable of collecting and sending out the sample rack in a second direction; the reversing turntable is arranged at intervals with the control component and can be connected to the conveying vehicle, and the reversing turntable is used to rotate and reverse the sample rack. Illustratively, the placement area can simultaneously carry 320 sample tubes placed in the ordinary placement position.

[0020] In some embodiments, the control assembly further comprises a pushing movement mechanism and a lifting mechanism, the pushing movement mechanism drives the hooking mechanism to move to correspond to the normal sample injection track and the emergency sample injection track respectively, and the lifting mechanism can drive the clamping mechanism to have a low position and a high position; the cap pulling mechanism is a rotary cap pulling mechanism, when the clamping mechanism is in the high position, the cap pulling mechanism can clamp the cap of the obtained sample tube. Exemplarily, the information identification mechanism comprises a first code scanning mechanism and a second code scanning mechanism, the first code scanning mechanism is used for scanning the obtained sample tube, and the second code scanning mechanism is used for scanning the sample tube clamped by the cap pulling mechanism.

[0021] In some embodiments, the pretreatment module further comprises a loading module, the loading module comprises a feeding cabin, a waste cabin, a vertical pushing mechanism, a guide support, a horizontal pushing mechanism, a centering clamping mechanism and a receiving member, the feeding cabin and the waste cabin are arranged side by side, the vertical pushing mechanism is arranged on the feeding cabin, the guide support is arranged on the upper side of the vertical pushing mechanism and can be pushed away from the lower side, the horizontal pushing mechanism is arranged on the guide support, the centering clamping mechanism is arranged on the waste cabin and can clamp a pipette tip holder support frame, and the receiving member is arranged in the waste cabin.

[0022] In some embodiments, the pipetting assembly comprises a three-axis movement mechanism and a pipetting mechanism, the support legs of the three-axis movement mechanism are arranged on both sides of the reaction disc assembly along the extension direction of the conveying track assembly; the pipetting mechanism is fixed to the end of the three-axis movement mechanism, the pipetting mechanism comprises a driver, a pipette and a rejector, the driver is used to drive the pipette to suck and discharge liquid, and the rejector is used to reject the pipette tip installed on the pipette.

[0023] In some embodiments, the sample conveying assembly comprises a reaction cup conveying assembly and a 96-well plate placement position. The pretreatment module further comprises a reaction cup loading assembly and a cup taking and placing assembly. The reaction cup loading assembly comprises a hopper, a vertical pushing mechanism, a horizontal conveying mechanism and a rotary cup separating mechanism, the hopper has a limited selection type discharge port, the vertical pushing mechanism is used to push the reaction cup from the hopper to the limited selection type discharge port, and the horizontal conveying mechanism is used to convey the reaction cup from the limited selection type discharge port to the rotary cup separating mechanism; the hopper is located on the side of the reaction disc assembly away from the conveying track assembly, and the horizontal conveying mechanism extends to the conveying track assembly. The cup taking and placing assembly comprises a mechanical hand and a waste liquid suction needle, the mechanical hand is used to convey the reaction cup from the reaction cup loading assembly to the reaction disc assembly and to take down the discarded reaction cup from the reaction cup conveying assembly, and the waste liquid suction needle is used to suck waste liquid from the discarded reaction cup and to suck waste liquid from the reaction cup of the reaction disc assembly; the cup taking and placing assembly is arranged between the reaction disc assembly and the conveying track assembly. The 96-well plate placement position is arranged on the side of the reaction disc assembly away from the sample table module; the pipetting assembly is used to inject liquid into the 96-well plate at the 96-well plate placement position.

[0024] In some embodiments, the pre-processing module further comprises a reagent disc assembly, a reagent needle assembly, and a cleaning pool assembly. The reagent disc assembly comprises a third code scanning mechanism for scanning a reagent box in the reagent disc assembly; the reagent disc assembly is located between the reaction disc assembly and the sample stage module. The reagent needle assembly is used for transferring reagents from the reagent disc assembly to the reaction disc assembly; the reagent needle assembly comprises a lifting driving mechanism, a rotating driving mechanism, a spline shaft, a swing arm, and a reagent needle, the spline shaft is slidingly connected to the rotating driving mechanism and can be driven to rotate, the lifting driving mechanism is used for driving the spline shaft to slide, and the swing arm has two ends fixed to the spline shaft and the reagent needle, respectively. The reagent needle assembly is located between the reaction disc assembly and the reagent disc assembly. The cleaning pool assembly is used for cleaning the reagent needle.

[0025] In some embodiments, the reaction disc assembly comprises a first outer disc, a first inner disc, a first mixing assembly, a first magnetic suction assembly, and a washing assembly; the first outer disc and the first inner disc are used for limiting and adjusting the position of the corresponding reaction cup, the first mixing assembly is used for mixing the substances in the reaction cup, the first magnetic suction assembly is used for adsorbing the magnetic beads in the reaction cup, and the washing assembly is used for washing the magnetic beads and for pumping waste liquid.

[0026] In some embodiments, the pre-processing module further comprises a buffer disc assembly, the buffer disc assembly comprises a second outer disc, a second inner disc, a dilution assembly, a second mixing assembly, and a second magnetic suction assembly; the second outer disc and the second inner disc are used for limiting and adjusting the position of the corresponding reaction cup, the dilution assembly is used for diluting the substances in the reaction cup, the second mixing assembly is used for mixing the substances in the reaction cup, and the second magnetic suction assembly is used for adsorbing the magnetic beads in the reaction cup. Illustratively, the pipetting assembly is further used for transferring the sample from the reaction disc assembly to the buffer disc assembly, and the buffer disc assembly can accommodate a number of reaction cups greater than or equal to the number of reaction cups that the reaction disc assembly can accommodate.

[0027] Illustratively, the cup taking and placing assembly of the pre-processing module is used for transferring the reaction cup containing the sample from the buffer disc assembly to the reaction cup conveying assembly of the sample conveying assembly.

[0028] In a second aspect, the present application provides a mass spectrometry pre-treatment method based on the aforementioned mass spectrometry pre-treatment device. The mass spectrometry pre-treatment method comprises: transporting sample tubes to the control component, including: transporting the sample tube placed at the normal placement position to the control component; in response to the emergency placement position being placed with a sample tube, receiving the sample tube placed at the emergency placement position and inserting it before the sample tube placed at the normal placement position to be transported; controlling the sample tube to be transferred to the pre-treatment module, including: using the control component to identify the information of the obtained sample tube, the clamping mechanism of the control component clamping the tube body of the obtained sample tube, and the cover removal mechanism of the control component removing the cover of the obtained sample tube; transporting the controlled sample tube, including: using the normal sample inlet track to transport the controlled sample tube from the normal placement position; using the emergency sample inlet track to transport the controlled sample tube from the emergency placement position; taking and transferring liquid from the transport track component; performing magnetic bead pre-treatment on the sample transferred to the reaction cup; and providing the sample subjected to magnetic bead pre-treatment to the mass spectrometry device.

[0029] The mass spectrometry pre-treatment method provided by the embodiments of the present application uses the mass spectrometry pre-treatment device, and at least one of the effects of automation, high throughput, and strong compatibility can be achieved; and the overall performance of mass spectrometry analysis can be improved.

[0030] In some embodiments, the magnetic bead pre-treatment includes using immunomagnetic beads or solid-phase magnetic beads.

[0031] In some embodiments, the mass spectrometry pre-treatment method further comprises: transferring the sample from the reaction disc component to the cache disc component of the pre-treatment module; and using the take-and-place cup component of the pre-treatment module to transport the reaction cup containing the sample from the cache disc component to the reaction cup transport component of the sample transport component. For example, the sample is transferred from the cache disc component to the 96-well plate placed at the 96-well plate placement position of the sample transport component.

[0032] Exemplarily, the step of conveying the sample tube to the management and control assembly further comprises: in response to the sample tube being placed at the quality control placement position of the sample table module, inserting the sample tube placed at the quality control placement position of the sample table module before the sample tube placed at the ordinary placement position to be conveyed, and conveying to the management and control assembly; conveying the sample tube received from the biochemical immune pipeline at the access interface of the sample table module to the management and control assembly; and converting the sample tube arranged in reverse in front of the management and control assembly into forward arrangement by using the reversing turntable of the sample table module. The step of controlling the sample tube to be transferred to the forward processing module further comprises: horizontally scanning the obtained sample tube by using the first code scanning mechanism of the management and control assembly; clamping the sample tube by using the cap pulling mechanism of the management and control assembly and controlling the sample tube to rotate for one revolution, and scanning the sample tube controlled to rotate by using the second code scanning mechanism of the management and control assembly. The reaction cup loading assembly of the forward processing module is configured to be able to supply at least 1000 reaction cups, and the reagent disc assembly of the forward processing module is configured to be able to supply at least 3000 reagents, so that the unattended time of the mass spectrometry pre-processing method is greater than or equal to 8 hours. BRIEF DESCRIPTION OF DRAWINGS

[0033] Figure 1 schematic isometric view of a mass spectrometry pre-processing apparatus according to one or more embodiments;

[0034] Figure 2 schematic block diagram of a mass spectrometry system according to one or more embodiments;

[0035] Figure 3 schematic structural view of a sample table module according to one or more embodiments;

[0036] Figure 4 schematic structural view of a mass spectrometry pre-processing apparatus according to one or more embodiments;

[0037] Figure 5 schematic isometric view of Figure 4 enlarged view of area A in the middle;

[0038] Figure 6 schematic structural view of a management and control assembly according to one or more embodiments;

[0039] Figure 7 schematic structural view of a forward processing module according to one or more embodiments;

[0040] Figure 8 schematic isometric view of a forward processing module according to one or more embodiments;

[0041] Figure 9 schematic top view of a conveying track assembly according to one or more embodiments;

[0042] Figure 10 schematic structural view of a conveying track according to one or more embodiments;

[0043] Figure 11 A schematic side view of a pipetting assembly according to one or more embodiments;

[0044] Figure 12 A schematic isometric view of a pipetting assembly according to one or more embodiments;

[0045] Figure 13 A schematic front view of a pipetting mechanism according to one or more embodiments;

[0046] Figure 14 A schematic rear view of a pipetting mechanism according to one or more embodiments;

[0047] Figure 15 A schematic top view of a loading module according to one or more embodiments;

[0048] Figure 16 This is a schematic isometric view of a loading module according to one or more embodiments;

[0049] Figure 17 This is a schematic structural diagram of a mass spectrometry pretreatment apparatus according to one or more embodiments;

[0050] Figure 18 for Figure 17 Enlarged view of point B in the middle;

[0051] Figure 19 A schematic structural diagram of a reaction disk assembly according to one or more embodiments;

[0052] Figure 20 This is a schematic diagram of the structure of a reaction disk assembly according to one or more embodiments;

[0053] Figure 21 A schematic isometric view of a reaction cup feeding assembly according to one or more embodiments;

[0054] Figure 22 This is a schematic diagram of the structure of a reaction cup feeding assembly according to one or more embodiments;

[0055] Figure 23 This is a schematic structural diagram of a cache disk component according to one or more embodiments;

[0056] Figure 24 This is a schematic diagram of the structure of a cache disk component according to one or more embodiments;

[0057] Figure 25 This is a schematic diagram of the structure of a reagent tray assembly according to one or more embodiments;

[0058] Figure 26schematic top view of a reagent disc assembly according to one or more embodiments;

[0059] Figure 27 schematic structural view of a reagent needle assembly according to one or more embodiments;

[0060] Figure 28 schematic structural view of a cup pick-and-place assembly according to one or more embodiments;

[0061] Figure 29 schematic flow chart of a mass spectrometry pre-treatment method according to one or more embodiments.

[0062] BRIEF DESCRIPTION OF DRAWINGS 1, general placement position; 2, emergency placement position; 3, transport vehicle; 4, hooking mechanism; 5, information identification mechanism; 6, clamping mechanism; 7, cap pulling mechanism; 8, general sample introduction track; 9, emergency sample introduction track; 10, quality control placement position; 11, access interface; 12, reversing turntable; 13, first waste box; 14, pushing movement mechanism; 15, lifting mechanism; 16, return track; 17, track conversion mechanism; 18, three-axis movement mechanism; 19, pipetting mechanism; 20, hopper; 201, selective discharge outlet; 21, vertical pushing mechanism; 22, horizontal conveying mechanism; 23, rotating cup separating mechanism; 24, robot arm; 25, waste liquid suction needle; 26, lifting driving mechanism; 27, rotating driving mechanism; 28, spline shaft; 29, swing arm; 30, reagent needle; 31, first outer disc; 32, first inner disc; 33, first mixing assembly; 34, first magnetic suction assembly; 35, elution assembly; 36, second outer disc; 37, second inner disc; 38, dilution assembly; 39, second mixing assembly; 40, second magnetic suction assembly; 41, reaction cup conveying assembly; 42, 96-well plate placement position; 43, second waste box; 44, refrigeration circulation assembly; 45, third outer disc; 46, third inner disc; 47, third mixing assembly; 48, refrigeration mechanism; 49, thermal insulation layer; 50, horizontal displacement driving mechanism; 51, vertical pick-and-place driving mechanism;

[0063] 101, first code scanning mechanism; 102, second code scanning mechanism; 103, feeding cabin; 104, waste cabin; 105, vertical pushing mechanism; 106, guide support; 107, horizontal pushing mechanism; 108, centering clamping mechanism; 109, receiving member; 110, supporting leg; 111, driver; 112, pipette; 113, ejector; 114, third code scanning mechanism; 115, first sensor; 116, waste cap delivery mechanism; 117, waste cap hopper; 118, waste liquid pump; 119, solvent bottle; 120, liquid path pump valve assembly; 121, liquid path switching assembly; 122, button indication assembly; 123, track mounting frame; 124, second sensor; 125, third sensor; 126, belt driving mechanism; 127, buffer assembly; 128, general sample positioning assembly; 129, emergency sample positioning assembly; 130, track switching driving mechanism; 131, track switching lever; 132, Y-axis transmission mechanism; 133, Y-axis driving mechanism; 134, X-axis transmission mechanism; 135, X-axis driving mechanism; 136, Z-axis lifting mechanism; 137, inclined support; 138, pipetting control board; 139, detection control board; 140, pipetting mounting seat; 141, first-stage reduction gear mechanism; 142, second-stage reduction gear mechanism; 143, third-stage reduction gear mechanism; 144, fourth sensor; 145, fifth sensor; 146, horizontal pushing driving mechanism; 147, clamping driving mechanism; 148, three-section push-pull rail; 149, magnet assembly; 150, drag chain; 151, elution liquid injection needle; 152, elution lifting mechanism; 153, elution water injection needle; 154, sixth sensor; 155, wiring transfer plate; 156, vertical pushing mechanism mounting seat; 157, crank slider mechanism; 158, vertical pushing driving assembly; 159, first-stage pushing plate; 160, second-stage pushing plate; 161, third-stage pushing plate; 162, seventh sensor; 163, buffer adjustment mechanism; 164, flat belt conveying assembly; 165, horizontal conveying driving assembly; 166, first cup pressing mechanism; 167, first inner disc driving mechanism; 168, second cup pressing mechanism; 169, second inner disc driving mechanism; 170, ninth sensor; 171, third inner disc driving mechanism; 172, mixing serrated plate; 173, fixed cover; 174, window cover; 175, liquid detection control board; 176, tenth sensor; 177, waste liquid vertical driving mechanism; 178, cup ejecting connecting rod; 179, input interface; 180, output interface;

[0064] 1000, mass spectrometry pre-treatment device; 1100, sample table module; 1101, placement area; 1102, conveying assembly; 1103, control assembly; 1104, sample basket; 1105, sample table frame; 1106, first control element; 1200, pre-treatment module; 1201, conveying track assembly; 1202, pipetting assembly; 1203, reaction disc assembly; 1204, sample conveying assembly; 1205, loading module; 1206, reaction cup loading assembly; 1207, cup taking and placing assembly; 1208, reagent disc assembly; 1209, reagent needle assembly; 1210, cleaning pool assembly; 1211, buffer disc assembly; 1212, pre-treatment frame; 1213, second control element;

[0065] 2000, mass spectrometry device; 3000, biochemical immunological pipeline; 4000, sample holder; 5000, sample tube; 6000, reaction cup. DETAILED DESCRIPTION

[0066] In order to make the above objectives, features and advantages of the present application more apparent, specific embodiments of the present application will be described in detail below with reference to the accompanying drawings. In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present application. It will be apparent, however, to one skilled in the art that the present application can be practiced in a variety of ways beyond the specific embodiments described herein without departing from the spirit of the present application, and it is therefore intended that the present application not be limited to the described embodiments.

[0067] In the description of the present application, it should be understood that the terms "center", "longitudinal", "lateral", "length", "width", "thickness", "upper", "lower", "front", "back", "left", "right", "vertical", "vertical", "horizontal", "top", "bottom", "inner", "outer", "clockwise", "counterclockwise", "axial", "radial", "circumferential" and the like indicate the orientation or positional relationship based on the orientation or positional relationship shown in the drawings, and are only for the purpose of facilitating the description of the present application and simplifying the description, and therefore cannot be understood as indicating or implying that the device or element referred to must have a particular orientation, be constructed and operated in a particular orientation, and therefore cannot be understood as limiting the present application.

[0068] In the present application, unless otherwise explicitly specified and limited, the first feature is "on" or "under" the second feature, which can be direct contact between the first and second features, or indirect contact between the first and second features through an intermediate medium. Moreover, the first feature "above", "above" and "above" the second feature can be directly above or obliquely above the first feature, or simply indicate that the horizontal height of the first feature is higher than that of the second feature. The first feature "below", "below" and "below" the second feature can be directly below or obliquely below the first feature, or simply indicate that the horizontal height of the first feature is less than that of the second feature.

[0069] In addition, the terms "first", "second", "third", etc. are only used for descriptive purposes and cannot be understood as indicating or implying relative importance or implying the number of the technical features indicated. Therefore, the features defined as "first", "second" can explicitly or implicitly include at least one of the features. For example, the first outer disc can also be referred to as the second outer disc, and the second outer disc can also be referred to as the first outer disc. In the description of the present application, the meaning of "a plurality of" is at least two, for example, two, three, etc., unless otherwise explicitly specified and limited.

[0070] In the present application, unless otherwise explicitly specified and limited, the terms "connected", "connected" and the like should be understood in a broad sense, for example, it can be fixedly connected, or it can be detachably connected, or it can be integrated; it can be flexibly connected, or it can be rigidly connected in at least one direction; it can be mechanically connected, or it can be electrically connected; it can be directly connected, or it can be indirectly connected through an intermediate medium, or it can be directly connected while an intermediate medium exists, or it can be the internal communication of two elements or the interaction relationship between two elements, unless otherwise explicitly limited. The terms "installation", "arrangement", "fixation" and the like can be understood as connection in a broad sense. For those skilled in the art, the specific meaning of the above terms in the present application can be understood according to the specific circumstances.

[0071] The current conventional mass spectrometry pretreatment techniques mainly include solid phase extraction, liquid-liquid extraction, protein precipitation and ultrafiltration, etc. These pretreatment methods have their own advantages, but also have their own obvious limitations. The above traditional mass spectrometry pretreatment techniques usually include sample enrichment, separation, derivatization and ionization pre-lead steps, which have the following technical bottlenecks: high operation complexity: relying on manual operation, easy to introduce human error, difficult to realize high-throughput analysis; low time efficiency: solid phase extraction, liquid-liquid extraction and other steps take a long time, which is difficult to meet the demand of rapid detection; limited sensitivity: interference in complex matrix can easily suppress the signal of the target; insufficient compatibility: some pretreatment methods have poor compatibility with emerging mass spectrometry technologies.

[0072] The emerging mass spectrometry pretreatment techniques mainly include magnetic bead method, immunoprecipitation and online solid phase extraction. Mass spectrometry pretreatment techniques are evolving from traditional methods relying on manual operation to automation, high-throughput and intelligentization. And it is expected that the development of mass spectrometry pretreatment techniques can improve the detection efficiency and accuracy, provide the basis for precision medicine and point-of-care testing (POCT), with the rapid development and breakthrough of mass spectrometry pretreatment techniques, mass spectrometry technology will play a more extensive role in clinical testing.

[0073] Reference Figure 1 , Figure 1A mass spectrometry pre-treatment device in an embodiment of the present application is shown. The mass spectrometry pre-treatment device 1000 can be used to provide a pre-treated sample to a mass spectrometry device 2000. In an exemplary embodiment, the mass spectrometry pre-treatment device 1000 comprises a sample stage module 1100 and a pre-treatment module 1200. Figure 2 As shown, Figure 2 A mass spectrometry system in an embodiment of the present application is shown. The mass spectrometry pre-treatment device 1000 can be used to provide a pre-treated sample to a mass spectrometry device 2000. In an exemplary embodiment, the mass spectrometry pre-treatment device 1000 comprises a sample stage module 1100 and a pre-treatment module 1200.

[0074] The sample rack 4000 and the sample tube 5000 can be considered as external devices delivered by the mass spectrometry pre-treatment device 1000, and the sample tube 5000 is used to hold a substance to be analyzed. The mass spectrometry pre-treatment device 1000 can also comprise the sample rack 4000, which can carry, for example, a column of sample tubes 5000. The sample stage module 1100 and the pre-treatment module 1200 respectively position the sample tube 5000 through the sample rack 4000.

[0075] For the convenience of description, a spatial rectangular coordinate system XYZ is established. The X-axis direction can be referred to as the first direction, the Y-axis direction can be referred to as the second direction, and the Z-axis direction can be referred to as the third direction. The sample stage module 1100 and the pre-treatment module 1200 can be arranged along the Y-axis direction.

[0076] Referring to Figure 3 The sample stage module 1100 can comprise a placement area 1101 and a conveying assembly 1102. The placement area 1101 is used to place the sample tube 5000 and can be provided with a plurality of sensors capable of identifying whether the sample tube 5000 is placed. The conveying assembly 1102 is used to receive the sample tube 5000 of the placement area 1101, specifically, can be to receive the sample rack 4000.

[0077] The sample stage module 1100 can further comprise a sample stage frame 1105 and a first control element 1106. The placement area 1101 and the conveying assembly 1102 can be respectively arranged on the sample stage frame 1105. The first control element 1106 can be arranged in the sample stage frame 1105. The first control element 1106 can comprise a switching power supply, a control PLC and various electrical elements, electrically connected to the placement area 1101 and the conveying assembly 1102, for realizing the automatic control and logic implementation of the sample stage module 1100. The control unit of the mass spectrometry pre-treatment device 1000 can be centrally arranged or distributed.

[0078] The placement area 1101 comprises a normal placement position 1 and an emergency placement position 2, and different placement positions can be respectively provided with sensors. The conveying assembly 1102 is used to receive and transport the sample tube 5000 placed at the normal placement position 1. When the emergency placement position 2 is placed with the sample tube 5000, the conveying assembly 1102 cuts in front of the normal placement position 1, and first receives and transports the sample tube 5000 placed at the emergency placement position 2.

[0079] The mass spectrometry pre-treatment device 1000 can further include a sample basket 1104. The sample basket 1104 is used for placement in the common placement position 1, and the sample basket 1104 can carry, for example, a row of sample racks 4000 arranged along the X-axis direction, and the sample rack 4000 can have a column of sample tubes 5000 arranged along the Y-axis direction. The sample basket 1104 can include a basket body and a rotatable handle that can be laid down for easy taking and placing. The basket body can be provided with eight sample rack limiting grooves, and each sample rack 4000 can hold five sample tubes 5000, and 40 sample tubes 5000 can be transferred at a time. The emergency placement position 2 can only hold one sample rack 4000. The placement area 1101 can simultaneously carry 320 sample tubes 5000 placed in the common placement position 1.

[0080] Exemplarily, the conveying assembly 1102 can include a track arranged along the X-axis direction and a conveying vehicle 3. The conveying vehicle 3 is movable along the X-axis direction. The conveying vehicle 3 can include clamping grooves along the Y-axis direction and telescopic portions, and the telescopic portions can hook the sample rack 4000 from the bottom, for example, including a telescopic rod and a lifting hook arranged on the telescopic rod and liftable along the Z-axis direction, so as to push and pull the sample rack 4000 along the Y-axis direction. The sample rack 4000 in the sample basket 1104 or the emergency placement position 2 can be moved into the clamping groove or moved in the opposite direction. In order to facilitate the sliding of the sample rack 4000, the side of the sample basket 1104 facing the conveying vehicle 3 is provided with an opening. Exemplarily, the conveying vehicle 3 can include two clamping grooves and two telescopic portions, and the pushing and pulling of the two sample racks 4000 can be performed synchronously or alternately.

[0081] The placement area 1101 can be provided with sensors for each placement position, and can be respectively provided with a plurality of indicator lights, which can effectively monitor whether the sample basket 1104 is present at the current position, and display the current state of the current sample basket 1104, for example, whether the sample extraction has been performed.

[0082] Along the stroke of the conveying vehicle 3, a plurality of common placement positions 1 are arranged on the side. A plurality of common placement positions 1 can be arranged on both sides of the track, for example, four on each side. The sample tubes 5000 are usually attached with labels in a neat and uniform manner, so the labels of the sample tubes 5000 received by the conveying vehicle 3 from different sides face in opposite directions. The conveying assembly 1102 of the sample table module 1100 can further include a reversing turntable 12, which can be connected to the conveying vehicle 3 and used for rotating and reversing the sample rack 4000, which helps to ensure that the label positions of the sample tubes 5000 sent out by the conveying vehicle 3 are basically the same.

[0083] Reference Figure 4 、 Figure 5 and Figure 6The sample table module 1100 can include a control component 1103 for controlling the sample tube 5000 to be transferred to the front-end processing module 1200. The control component 1103 includes a hooking mechanism 4 for obtaining the sample tube 5000 from the transport vehicle 3 of the transport component 1102 and can be used for delivery.

[0084] The transport vehicle 3 has a stroke along the X-axis direction, the first end is arranged with the emergency placement position 2, and the second end is arranged with the control component 1103. The reversing turntable 12 can be arranged at the second end and spaced apart from the control component 1103. The placement area 1101 of the mass spectrometry front-end processing device 1000 also includes a quality control placement position 10 arranged on both sides of the transport vehicle 3 with the emergency placement position 2. The sample table module 1100 can also include an access interface 11 arranged spaced apart from the hooking mechanism 4, and the access interface 11 and the hooking mechanism 4 can be docked through the transport vehicle 3. It can also be considered that the transport component 1102 includes the access interface 11. The layout of the sample table module 1100 is compact, the automatic action positions are concentrated near the control component 1103, and the manual operation positions are extended far away, avoiding the influence of manual operation on automatic action, and also keeping the operator away from the action mechanism. The sample table module 1100 occupies a small area and is suitable for cooperating with external modules.

[0085] Reference Figure 3 The access interface 11 is used to dock the biochemical immunology pipeline 3000. The mass spectrometry front-end processing device 1000 realizes access to the full-automatic detection pipeline, for example, can realize seamless connection with the biochemical immunology pipeline. The sample rack 4000 sent by the biochemical immunology pipeline 3000 can be sent to the control component 1103; when the subsequent congestion occurs, the sample rack 4000 can also be sent to the general placement position 1. The priority of the transport component 1102 to transport the sample tube 5000 to the control component 1103 can be the highest in the emergency placement position 2, and then in turn for the quality control placement position 10, the general placement position 1, and the access interface 11; it can also be adjusted according to actual needs, for example, quality control according to period. The emergency placement position 2 is provided with a sensor to identify the presence or absence, which can automatically identify and give priority to the queue, realize the function of emergency priority and immediate measurement. The quality control placement position 10 can also be provided with a sensor to identify the presence or absence, which can realize the function of intelligent insertion of quality control in testing according to needs, greatly ensuring the reliability and stability of the mass spectrometry front-end processing device 1000 and its detection results.

[0086] Reference Figure 5The access interface 11 can include an input interface 179 and an output interface 180. The input interface 179 can receive the sample tube 5000 or the sample tube 5000 carried by the sample rack 4000 from the biochemical immune pipeline 3000, and the output interface 180 can return the sample tube 5000 sampled by the mass spectrometry pretreatment device 1000 to the biochemical immune pipeline 3000, which helps to realize the fully automatic flow processing. Along the X-axis direction, the output interface 180 is located on the side away from the placement area 1101 of the input interface 179. The reversing turntable 12 can be located between the input interface 179 and the output interface 180, and the reversing turntable 12 cooperates with the access interface 11 to construct a compact layout. The output interface 180 has a relatively loose docking space. The switching stroke of the transport vehicle 3 is short, and the action time is less.

[0087] Reference Figure 4 And Figure 5 The control component 1103 can further include an information identification mechanism 5, a clamping mechanism 6, and a cap removal mechanism 7. The information identification mechanism 5 is used to identify the information of the sample tube 5000 obtained by the hooking mechanism 4, the clamping mechanism 6 is used to clamp the tube body of the obtained sample tube 5000, and the cap removal mechanism 7 is used to remove the cover of the obtained sample tube 5000.

[0088] The information identification mechanism 5 can include a first code scanning mechanism 101, which can perform horizontal code scanning on the obtained sample tube 5000 along the Y-axis direction, and can include identification of sample rack numbers, identification of quality control and calibration barcodes, etc.

[0089] The control component 1103 can further include a lifting mechanism 15. The lifting mechanism 15 can drive the clamping mechanism 6 to ascend and descend along the Z-axis direction, so that the clamping mechanism 6 has a low position and a high position. When the clamping mechanism 6 with the obtained sample tube 5000 is in the high position, the cap removal mechanism 7 can clamp the cover of the obtained sample tube. When the clamping mechanism 6 descends, the cap removal mechanism 7 can pull the cover out of the tube body.

[0090] The cap removal mechanism 7 can include a first sensor 115, a waste cap disposal mechanism 116, and a waste cap hopper 117. The first sensor 115 can be provided in multiple numbers, for example, to detect whether there is a sample tube 5000 in the corresponding hole of the sample rack 4000, whether the sample tube 5000 includes a cover, whether the sample tube 5000 is a long tube or a short tube, etc. After the cap removal mechanism 7 removes the cover, the clamping mechanism 6 drives the tube body to be placed back into the sample rack 4000; the cap removal mechanism 7 can drop the cover into the waste cap disposal mechanism 116, and the waste cap disposal mechanism 116 can send the waste cap to the waste cap hopper 117.

[0091] The sample table module 1100 can include a first waste box 13 arranged in the sample table frame 1105. A waste cover hopper 117 can be communicated to the first waste box 13. The first waste box 13 is used to collect the discarded cover, and is configured with three sections of tracks and can be pulled out of the sample table frame 1105 for disposal, which is simple and convenient.

[0092] The cover pulling mechanism 7 can be a rotating cover pulling mechanism to pull out the cover. The cover pulling mechanism 7 can include a rotating gripper capable of holding the cover. Exemplarily, the information identification mechanism 5 can further include a second code scanning mechanism 102. In use, the cover pulling mechanism 7 can hold the cover, and the clamping mechanism 6 can release the tube, at which time the entire sample tube 5000 can be controlled by the cover pulling mechanism 7 to rotate. The second code scanning mechanism 102 is used to scan the code of the sample tube 5000 controlled to rotate by the cover pulling mechanism 7, and can achieve 360° rotation code scanning of the sample tube 5000. After scanning, the clamping mechanism 6 clamps the tube and then pulls the cover.

[0093] The tube control assembly 1103 can further include a pushing movement mechanism 14. The pushing movement mechanism 14 can drive the hooking mechanism 4 to move along the X-axis direction to correspond to different tracks in the conveying track assembly 1201 of the pre-processing module 1200, and then can send the controlled sample tube 5000. In another embodiment, the pre-processing module 1200 actively docks with the hooking mechanism 4.

[0094] The sample table module 1100 can achieve at least some of the functions of sample buffering, sample tube 5000 opening, intelligent identification, sample conveying, docking pipeline, emergency queuing, and intelligent quality control insertion.

[0095] Reference Figure 7 and Figure 8 Exemplarily, the pre-processing module 1200 can include a conveying track assembly 1201, a pipetting assembly 1202, a reaction disc assembly 1203, and a sample conveying assembly 1204. Reference Figure 8 The pre-processing module 1200 can further include a pre-processing frame 1212 and a second control element 1213. The pre-processing frame 1212 can include a bottom frame and a mounting panel, mainly used for mounting and positioning other module assemblies, including integrated installation of liquid path parts and electrical parts. The second control element 1213 can be an electrical element, mainly integrated with hardware control devices such as switching power supply, air switch and control PCB, etc., which can control the actions of other assemblies.

[0096] Reference Figure 9 and Figure 10The transport track assembly 1201 includes a normal sample track 8 and an emergency sample track 9, which are respectively connected to the hooking mechanism 4 and used to transport the controlled sample tube 5000. The pipetting assembly 1202 is used to take liquid from the transport track assembly 1201, specifically, from the sample tube 5000; the pipetting assembly 1202 is used for pipetting.

[0097] The transport track assembly 1201 can further include a return track 16 and a track switching mechanism 17. The return track 16 can be connected to the hooking mechanism 4. The normal sample track 8, the emergency sample track 9 and the return track 16 can be arranged side by side, referring to Figure 7 The emergency sample track 9 can be the track closest to the pipetting assembly 1202 along the X-axis direction, and the return track 16 can be the track farthest from the pipetting assembly 1202. Taking the end of the transport track assembly 1201 where the hooking mechanism 4 is located as the head end, the track switching mechanism 17 can be the tail end. The track switching mechanism 17 is used to switch the sample tube 5000 of the normal sample track 8 or the sample tube 5000 of the emergency sample track 9 to the return track 16. Referring to Figure 10 The track switching mechanism 17 can include a track switching lever 131 movable along the X-axis direction and a track switching driving mechanism 130 for controlling the track switching lever 131. The track switching lever can be connected to each track and can fork the sample rack 4000 and move the sample rack 4000.

[0098] In other embodiments, the sample tube 5000 after being taken liquid can be transported from the transport track assembly 1201 to other recycling modules.

[0099] Referring to Figure 10 Each track can further be provided with a manipulating mechanism for accurately positioning the sample rack 4000 for taking liquid. Exemplarily, the transport track assembly 1201 can include a track mounting frame 123, a second sensor 124 and a third sensor 125, which can be sample rack detection photoelectricity and can identify the position and state of the sample rack 4000. The second sensor 124 is located at the head end, and the third sensor 125 is located at the positioning position of the sample rack 4000.

[0100] Each track can include a belt conveying line provided on the track mounting frame 123, and each track can include a respective belt driving mechanism 126 for individual driving. The normal sample track 8 can include a buffer assembly 127 and a normal sample positioning assembly 128. The buffer assembly 127 can include a buffer stop lever and a buffer driving assembly for controlling the buffer stop lever to block or release the sample rack 4000. The normal sample positioning assembly 128 can include a normal sample positioning stop lever and a normal sample positioning driving assembly for driving the normal sample positioning stop lever to block or release the sample rack 4000.

[0101] The pipetting assembly 1202, in conjunction with the standard sample positioning assembly 128, enables precise sample placement, such as through liquid retrieval. The buffer assembly 127 serves as a buffer for the next sample rack 4000. After the sample tube 5000 in the sample rack 4000 at the standard sample positioning assembly 128 has completed its injection, the belt drive mechanism 126 operates, simultaneously sending out the previous sample rack 4000 and receiving the next sample rack 4000. The buffer assembly 127 prevents interference between adjacent sample racks 4000 and allows for rapid connection of the second sample rack 4000 after the previous one has completed its injection, reducing waiting time and accelerating the workflow.

[0102] The emergency sample delivery track 9 may include an emergency sample positioning component 129, which may include an emergency sample positioning stop and an emergency sample positioning drive component for driving the emergency sample positioning stop to block or release the sample rack 4000. The sample rack 4000 of the emergency sample delivery track 9 can directly reach the positioning position of the track. The pipetting assembly 1202 can accurately position the sample for delivery. Based on the information identified by the control component 1103, it can be determined which sample rack 4000 or which sample tube 5000 should be prioritized for emergency delivery.

[0103] refer to Figure 7 and Figures 11 to 14 For example, the pipetting assembly 1202 may include a three-axis motion mechanism 18 and a pipetting mechanism 19. Support legs 110 of the three-axis motion mechanism 18 are arranged on both sides of the reaction tray assembly 1203 along the Y-axis direction. The three-axis motion mechanism 18 can be fixed to the pretreatment frame 1212 via the two support legs 110. The pretreatment module 1200 has an integral structure, and the three-axis motion mechanism 18 occupies a small area. The pipetting mechanism 19 is fixed to the end of the three-axis motion mechanism 18.

[0104] refer to Figure 11 and Figure 12 The three-axis motion mechanism 18 may include a Y-axis transmission mechanism 132, an X-axis transmission mechanism 134, and a Z-axis lifting mechanism 136. The Y-axis transmission mechanism 132 may be mounted on the support leg 110 and supported by the inclined bracket 137, and driven by the Y-axis drive mechanism 133 to move the X-axis transmission mechanism 134 along the Y-axis direction. The X-axis transmission mechanism 134 is driven by the X-axis drive mechanism 135 to move the Z-axis lifting mechanism 136 along the X-axis direction. The Z-axis lifting mechanism 136 is used to move the pipetting mechanism 19 up and down along the Z-axis direction.

[0105] refer to Figure 13 and Figure 14The pipetting mechanism 19 includes a driver 111, a pipette 112, and a rejector 113. The driver 111 is used to drive the pipette 112 to aspirate and dissipate liquid, and the rejector 113 is used to reject the pipette tip installed at the pipette 112. The pipette tip can also be called a TIP tip.

[0106] The pipetting mechanism 19 may also include a pipetting mounting base 140 and a drive mechanism disposed on the pipetting mounting base 140. Specifically, the driver 111 may be a drive motor, which drives the pipette 112 to move through a first-stage reduction gear mechanism 141, a second-stage reduction gear mechanism 142, and a third-stage reduction gear mechanism 143, thus helping to achieve high-precision pipetting. The pipette 112 may be a precision plunger pipette, which can achieve high-precision pipetting under the control of the driver 111, ensuring pipetting accuracy and consistency. The pipetting mechanism 19 may be equipped with a pipetting control board 138 to control the operation.

[0107] The pipetting mechanism 19 may also include a detection control board 139, which may be a pressure detection control board. This board can perform multiple functions, including pipetting, automatic liquid level detection during pipetting, liquid level following during aspiration, and blockage detection. The pipetting assembly 1202 can move the pipetting mechanism 19 to any point within its range, enabling the picking up and dropping of pipette tips. (See reference...) Figure 7 The pretreatment module 1200 also includes a second waste bin 43, where discarded pipette tips can be collected. The pipetting assembly 1202 also performs liquid extraction and injection operations at different points.

[0108] refer to Figure 7 In some embodiments, the pretreatment module 1200 further includes a loading module 1205 for providing new pipette tips to the pipetting mechanism 19. The loading module 1205 and the transport track assembly 1201 may be located on opposite sides of the pipetting mechanism 19. (See reference...) Figure 15 and Figure 16 The loading module 1205 may include a feed chamber 103, a waste chamber 104, a vertical pushing mechanism 105, a guide support 106, a horizontal pushing mechanism 107, a centering clamping mechanism 108, and a receiving component 109.

[0109] The feed chamber 103 and the waste chamber 104 are arranged side by side, with the waste chamber 104 positioned closer to the conveyor track assembly 1201. Operators place entire boxes of pipette tips stacked in the feed chamber 103. The loading module 1205 is used to automatically feed and unload the pipette tips; in conjunction with the pipetting mechanism 19, it enables automatic installation and rejection.

[0110] A vertical pushing mechanism 105 is installed in the feed chamber 103. The vertical pushing mechanism 105 can be a vertical pushing clamp mechanism and can be equipped with a scanning photoelectric switch. The scanning photoelectric switch can identify whether there is a pipette tip support on the vertical pushing mechanism 105 and how many layers there are. The vertical pushing mechanism 105 can push one layer of pipette tip support upwards at a time and can also retract a certain distance.

[0111] A guide support 106 is positioned above the vertical pushing mechanism 105 and can be pushed open from below. The guide support 106 can be a flap or a wedge-shaped block, and can support one layer of pipette tip holders. A horizontal pushing mechanism 107 is positioned above the guide support 106 and is used to push one layer of pipette tip holders on the guide support 106 to the centering clamping mechanism 108. (Reference) Figure 16 A fourth sensor 144 may be provided, specifically a lifting position detection photoelectric sensor, which pushes the pipette tip horizontally after detecting that it has reached the correct position. A fifth sensor 145 may be provided, specifically a horizontal position detection photoelectric sensor. After the horizontal position detection photoelectric sensor detects that the pipette tip has reached the correct position, the centering clamping mechanism 108 clamps and positions the pipette tip support, ensuring that the pipetting mechanism 19 accurately installs the new pipette tip.

[0112] To achieve a compact structure, the centering clamping mechanism 108 can be mounted on the waste bin 104. After the pipette tips within the centering clamping mechanism 108 are used up, the mechanism prevents loosening, allowing the pipette tip holder to be discarded. A receiving member 109 is located within the waste bin 104 and is capable of receiving the discarded holder. Exemplarily, the horizontal pushing mechanism 107 can be driven by the horizontal pushing drive mechanism 146 to perform horizontal pushing and return. The centering clamping mechanism 108 can be driven by the clamping drive mechanism 147 to perform clamping and prevent loosening.

[0113] The feed chamber 103 and waste chamber 104 can be fixed together as a whole hopper. The loading module 1205 may include a push-pull three-section rail 148 and a magnet assembly 149. The hopper can be slidably connected to the pretreatment frame 1212 along the X-axis via the push-pull three-section rail 148, facilitating the insertion of new pipette tips or the removal of the support. The magnet assembly 149 may include a high-strength electromagnet that automatically engages when the hopper is pushed in; when the hopper needs to be pulled out, the magnetic attraction can be released via a button. The movement of the hopper can be electrically controlled. The loading module 1205 may include a cable chain 150 to ensure the electrical control of each mechanism of the loading module 1205 by the second control element 1213. The loading module 1205 can realize functions such as automatic identification, automatic replacement, material shortage identification alarm, and waste identification alarm.

[0114] refer to Figure 7 , Figure 17 and Figure 18The reaction disk assembly 1203 is generally located at the core of the pretreatment module 1200, with the other modules arranged around it. The reaction disk assembly 1203 is used for magnetic bead-based pretreatment of samples pipetted into the reaction vessel 6000. (Reference) Figure 19 and Figure 20 In some embodiments, the reaction disk assembly 1203 may include a first outer disk 31, a first inner disk 32, a first mixing assembly 33, a first magnetic attraction assembly 34, and a rinsing assembly 35.

[0115] The first outer disk 31 and the first inner disk 32 are used to limit the corresponding reaction cup 6000 and adjust its position. The first outer disk 31 can serve as an integral frame for integrating and installing other functional mechanisms. The first inner disk 32 can rotate around its axis and can be controlled by the first inner disk drive mechanism 167, so that the reaction cup 6000 constrained by the holes of the first inner disk 32 stops at a set circumferential position, realizing the scheduling of the reaction cup 6000. Specifically, there may be positions for picking up and placing cups, liquid injection, water injection, and mixing.

[0116] Mixing positions can be set after different addition positions. The first mixing component 33 is used to mix the substances in the reaction cup 6000. The substances in the reaction cup 6000 at the mixing position may include samples, magnetic beads, and various reagents. The first mixing component 33 may include a first pressing cup mechanism 166 to prevent the reaction cup 6000 from dislodging from the hole of the first inner disk 32 during mixing.

[0117] The first magnetic adsorption component 34 is used to adsorb magnetic beads inside the reaction cup 6000. Its main function is to adsorb the magnetic beads and retain the adsorbed substance during liquid extraction after the reaction, facilitating the extraction process. Different substances require different pretreatment methods; in some embodiments, the retained substance may be an effective substance.

[0118] The rinsing assembly 35 is used for rinsing the magnetic beads and for removing waste liquid. The rinsing assembly 35 may include rinsing injection needles 151, for example, six rinsing injection needles 151 and one waste liquid needle. The ratio of the reaction reagents can be adjusted according to rinsing requirements. The rinsing assembly 35 may include a rinsing lifting mechanism 152, which can simultaneously drive the three sets of rinsing injection needles 151 to rise and fall. The rinsing assembly 35 may include a rinsing water injection needle 153, which can be used for dilution.

[0119] The reaction disk assembly 1203 is mainly used to perform functions such as sample rinsing and purification, mixing, magnetic attraction, and elution extraction. The reaction disk assembly 1203 may also include a sixth sensor 154, specifically a photoelectric sensor for detecting whether a reaction cup 6000 is present in a hole in the first inner disk 32; this hole can be a cup placement / removal position. The rinsing assembly 35 can be located in the reaction disk assembly 1203 away from the transport track assembly 1201.

[0120] Exemplarily, the pretreatment module 1200 may further include a cup-picking and placing assembly 1207, capable of picking up and placing reaction cups 6000 along the Z-axis direction. For example, the cup-picking and placing assembly 1207 can place an empty reaction cup 6000 onto the reaction tray assembly 1203, remove the reaction cup 6000 from the reaction tray assembly 1203, and place the reaction cup 6000 onto the sample delivery assembly 1204. The cup-picking and placing assembly 1207 may be located between the reaction tray assembly 1203 and the delivery track assembly 1201, saving space and avoiding the pipetting assembly 1202. In other embodiments, the cups may be picked up and placed laterally.

[0121] refer to Figure 7 , Figure 8 and Figure 18 The sample delivery assembly 1204 is used to provide the mass spectrometer 2000 with a sample that has undergone magnetic bead pretreatment. Exemplarily, the sample delivery assembly 1204 includes a reaction vessel delivery assembly 41, which can deliver a single reaction vessel 6000 and retrieve the reaction vessel 6000 after the mass spectrometer 2000 has obtained the pretreated sample.

[0122] For example, the sample delivery assembly 1204 may include a 96-well plate placement position 42. The pipetting assembly 1202 is used to inject liquid into the 96-well plate at the 96-well plate placement position 42, which can then be used for subsequent detection, experiments, etc.

[0123] The sample delivery assembly 1204 can be located on the side of the reaction disk assembly 1203 opposite to the sample stage module 1100. The mass spectrometry device 2000 can be located on the side of the pretreatment module 1200 opposite to the sample stage module 1100.

[0124] The pretreatment module 1200 primarily performs sample dilution, purification, and extraction functions. Finally, the processed extract is sent to a back-end detector for analysis, such as mass spectrometry. The magnetic bead pretreatment method utilizes surface-modified magnetic particles to specifically adsorb target analytes, combined with magnetic field separation technology, enabling extraction in a short time and significantly shortening the experimental cycle. The selective adsorption mechanism of the magnetic bead pretreatment method effectively removes impurities such as proteins and salts, obtaining high-purity products and reducing interference in subsequent experiments. This method eliminates the need for complex centrifugation or vacuum filtration steps, requiring only simple mixing, magnetic separation, and washing operations to complete the extraction.

[0125] The mass spectrometry pretreatment device 1000 of this embodiment, by setting up a normal placement position 1, an emergency placement position 2, a normal sample injection track 8, and an emergency sample injection track 9, can realize different sample delivery methods and can process sample tubes 5000 placed at the emergency placement position 2 in a queue. By setting up a control component 1103, the automatic docking of the sample stage module 1100 and the pretreatment module 1200 is realized, effectively arranging the pulsed operation of the entire mass spectrometry pretreatment device 1000.

[0126] refer to Figure 7 and Figure 8 For example, the pretreatment module 1200 may also include a reaction cup loading assembly 1206, a reagent tray assembly 1208, a reagent needle assembly 1209, and a washing tank assembly 1210. These components are also mounted on the pretreatment frame 1212, generally surrounding the reaction tray assembly 1203.

[0127] refer to Figure 21 and Figure 22 For example, the reaction cup feeding assembly 1206 may include a hopper 20, a vertical pushing mechanism 21, a horizontal conveying mechanism 22, and a rotating cup-dividing mechanism 23. The reaction cup feeding assembly 1206 is capable of adjusting the bulk reaction cups 6000 to a posture suitable for accurate feeding.

[0128] The hopper 20 contains bulk reaction cups 6000, all of which can be empty. The hopper 20 has a limit-selection discharge port 201 to ensure that the output reaction cups 6000 are in a straight position, and reaction cups 6000 in an inclined position will fall back into the hopper 20.

[0129] The horizontal conveying mechanism 22 may include a buffer adjustment mechanism 163 and a flat belt conveyor assembly 164. The flat belt conveyor assembly 164 may be located inside the hopper 20 to ensure that the reaction cup 6000 is conveyed to the limit-selective discharge port 201. The buffer adjustment mechanism 163 may be located outside the hopper 20 to adjust the reaction cup 6000 to a position suitable for pickup by the cup pick-up and drop-off assembly 1207.

[0130] The reaction cup 6000 flows reliably by gravity to the flat belt conveyor assembly 164. Exemplarily, the limit-selective discharge port 201 is located high within the hopper 20, and the vertical pusher mechanism 21 can push material upwards from the lowest point. The vertical pusher mechanism 21 is used to feed material from the hopper 20 to the flat belt conveyor assembly 164, indirectly pushing the reaction cup 6000 towards the limit-selective discharge port 201. The vertical pusher mechanism 21 helps to maintain the feeding posture, facilitates continuous feeding, and avoids blockage at the limit-selective discharge port 201.

[0131] The vertical pusher mechanism 21 may include a vertical pusher mechanism mounting base 156, a crank-slider mechanism 157, a vertical pusher drive assembly 158, a first-stage pusher plate 159, a second-stage pusher plate 160, and a third-stage pusher plate 161.

[0132] The vertical feeding mechanism mounting base 156 is connected to the hopper 20, and together with the hopper 20, it defines the space for holding the reaction cup 6000. (Reference) Figure 20The first-stage pusher plate 159, the second-stage pusher plate 160, and the third-stage pusher plate 161 are fixed and increase in height sequentially, with the first-stage pusher plate 159 positioned at its lowest point along the Z-axis. The vertical pusher mechanism mounting base 156 may include a first partition plate disposed between the first-stage pusher plate 159 and the second-stage pusher plate 160, and a second partition plate disposed between the second-stage pusher plate 160 and the third-stage pusher plate 161. The first-stage pusher plate 159 can feed material to the top surface of the first partition plate; the second-stage pusher plate 160 can descend to the height of the first partition plate and feed material to the top surface of the second partition plate; the third-stage pusher plate 161 can descend to the height of the second partition plate and feed material to the flat belt conveyor assembly 164. (Reference) Figure 20 The top surface of each plate can be angled downwards to the right. The plate thickness can be approximately the diameter of a reaction cup of 6000 mm. Through the repeated raising and lowering of the pusher plate, continuous and orderly feeding of the cup can be achieved.

[0133] The bottom surface of the hopper 20 can be tilted. The vertical pushing mechanism 21 may include a through-beam detection photoelectric sensor, which is located at the lowest point of the hopper 20 and is used to detect whether there is a reaction cup 6000.

[0134] The vertical pusher drive assembly 158 can drive the three pusher plates to slide and rise via the crank-slider mechanism 157. The crank can be designed as a disc for rotational balancing. A spring can also be provided for reset.

[0135] Exemplarily, the buffer adjustment mechanism 163 may include a synchronous belt mechanism on two opposing sides, with a gap between the two synchronous belts capable of accommodating the reaction cup 6000 and supporting its rim. A height difference exists between the buffer adjustment mechanism 163 and the flat belt conveyor assembly 164, allowing the reaction cup 6000 discharged from the limit-selective discharge port 201 to fall and adjust its posture by gravity, ensuring the cup opening faces upwards. The two synchronous belts can rub against the cup walls to transport the reaction cup 6000 to the rotating cup-separating mechanism 23. The buffer adjustment mechanism 163 can buffer a line of reaction cups 6000.

[0136] The horizontal conveying mechanism 22 may also include a seventh sensor 162, located in the buffer adjustment mechanism 163 near the limit-selective discharge port 201. When the seventh sensor 162 does not detect the reaction cup 6000, it indicates a shortage in the buffer. In response, at least the flat belt conveyor assembly 164 in the vertical pushing mechanism 21 and the horizontal conveying mechanism 22 can be activated to replenish the buffer with new reaction cups 6000. When the seventh sensor 162 detects a reaction cup 6000, the cup feeding operation can be stopped. The horizontal conveying mechanism 22 may also include an eighth sensor, located in the buffer adjustment mechanism 163 near the rotating cup dispensing mechanism 23. When the eighth sensor does not detect a reaction cup 6000, the second control element 1213 can issue a cup shortage alarm signal.

[0137] The horizontal conveyor mechanism 22 may include a horizontal conveyor drive assembly 165 for driving the flat belt conveyor assembly 164, and may also include two additional drive assemblies for driving the synchronous belt mechanism.

[0138] The rotating cup-separating mechanism 23 separates a continuous row of reaction cups 6000 into multiple discrete units. For example, the rotating cup-separating mechanism 23 includes a turntable with four holes, where the central angle between adjacent holes is 90°, making the separated reaction cups 6000 easy to grasp. Sensors can be installed to detect whether a reaction cup 6000 is present at a corresponding rotation position. If no reaction cup 6000 is detected, the turntable rotates, acquiring the buffered reaction cup 6000 through rotation. If a reaction cup 6000 is detected, the turntable stops.

[0139] refer to Figure 18 The hopper 20 is located on the side of the reaction plate assembly 1203 opposite to the conveyor track assembly 1201, and the horizontal conveying mechanism 22 extends toward the conveyor track assembly 1201. The buffer adjustment mechanism 163 is located between the reaction plate assembly 1203 and the buffer plate assembly 1211.

[0140] refer to Figure 7 , Figure 18 , Figure 23 and Figure 24 The pretreatment module 1200 may also include a buffer tray assembly 1211. The buffer tray assembly 1211 can be arranged side-by-side with the reaction tray assembly 1203, located between the reaction tray assembly 1203 and the sample delivery assembly 1204. The buffer tray assembly 1211 can be used for cup handling by the cup handling assembly 1207 and for pipetting by the pipetting assembly 1202. The buffer tray assembly 1211 and the reaction tray assembly 1203 can be operated similarly by other components, exhibiting good compatibility. Transferring the processed liquid from the reaction tray assembly 1203 to the buffer tray assembly 1211 achieves cup replacement, enabling further sample processing and increasing the production pulsation capacity of the mass spectrometry pretreatment equipment 1000. The mass spectrometry pretreatment equipment 1000 has a compact structure, with short execution times for each component and rapid and smooth material flow. The buffer disk component 1211 can be configured to buffer multiple reaction cups 6000. Whether the subsequent sample feeding process is paused or the sample in the previous process is adjusted, the sample of the current process can be buffered through the buffer disk component 1211.

[0141] The buffer assembly 1211 may include a second outer disk 36, a second inner disk 37, a dilution assembly 38, a second mixing assembly 39, and a second magnetic attraction assembly 40. The second outer disk 36 can serve as a frame for supporting and mounting other functional mechanisms. The second outer disk 36 may have an inlet and an outlet for the cup, and each can be equipped with a sensor, such as a ninth sensor 170, to detect the presence of a cup. The ninth sensor 170 may be a reflective sensor. (Reference) Figure 24The second inner disk 37 can be driven to rotate by the second inner disk drive mechanism 169, which can drive the reaction cups 6000 at each hole to rotate relative to the second outer disk 36. The second outer disk 36 and the second inner disk 37 are used to limit the corresponding reaction cups 6000 and adjust the position of the reaction cups 6000.

[0142] The pipetting assembly 1202 is used to transfer samples from the reaction tray assembly 1203 to the buffer tray assembly 1211, specifically transferring the supernatant. The buffer tray assembly 1211 is equipped with a new reaction cup 6000 to receive the supernatant after elution from the reaction tray assembly 1203, which greatly reduces the impact of magnetic bead residue on the test results. (Reference) Figure 23 The dilution component 38 is used to dilute the substance in the reaction cup 6000, and can dilute it proportionally. The second mixing component 39 is used to mix the substance in the reaction cup 6000, and may include a second pressing mechanism 168 to press the reaction cup 6000 for mixing. The second magnetic adsorption component 40 is used to adsorb magnetic beads in the reaction cup 6000, which can reduce the influence of magnetic bead residue and remove interference by aggregating the magnetic beads.

[0143] The buffer disk assembly 1211 can hold a number of reaction cups that is greater than or equal to the number of reaction cups that the reaction disk assembly can hold. When the cycle time of subsequent steps is slow or certain processes are abnormal, it ensures that normal samples that have already been injected can be processed and buffered to prevent sample waste.

[0144] The pipetting assembly 1202 can pipe liquids into a 96-well plate. Exemplarily, the pick-and-place cup assembly 1207 of the pretreatment module 1200 is used to transport reaction cups 6000 containing samples from the buffer tray assembly 1211 to the reaction cup delivery assembly 41.

[0145] refer to Figure 18 and Figure 7 The reagent tray assembly 1208 is located between the reaction tray assembly 1203 and the sample stage module 1100. The working order of the reagent tray assembly 1208 can be set sequentially in a counterclockwise rotation direction. The mass spectrometry pretreatment device 1000 has a compact structure and a short reagent transfer stroke.

[0146] refer to Figure 25 and Figure 26 The reagent tray assembly 1208 may include a third outer tray 45, a third inner tray 46, a third mixing component 47, a cooling mechanism 48, and an insulation layer 49. The third outer tray 45 can serve as a frame to support and connect other components. The insulation layer 49 can enclose the third outer tray 45, the third inner tray 46, and the third mixing component 47. The cooling mechanism 48 can be located at the lower part of the third outer tray 45 and may have four constant-temperature cooling mechanisms. The cooling mechanism 48, in conjunction with the insulation layer 49, helps to achieve constant temperature control and ensure the effectiveness of the reagents in the reagent kit.

[0147] The third inner disk 46 can be rotated by the third inner disk drive mechanism 171, enabling the scheduling of reagent kits. The reagent disk assembly 1208 may also include a mixing toothed plate 172 mounted on the third inner disk drive mechanism 171. The mixing toothed plate 172 is used to drive the third mixing assembly 47, which can achieve mixing of the magnetic bead solution and prevent precipitation.

[0148] refer to Figure 26 The upper cover of the reagent tray assembly 1208 may include a fixed cover 173 and a window cover 174. The fixed cover has a reagent dispensing hole for the reagent needle assembly 1209 to dispense reagents. Each part of the upper cover may be provided with a heat-insulating layer 49. The reagent tray assembly 1208 can maintain a constant temperature within the range of 2°C to 8°C.

[0149] For example, the reagent tray assembly 1208 includes a third scanning mechanism 114. The third scanning mechanism 114 can be mounted on the side of the third outer tray 45 for scanning reagent kits within the reagent tray assembly 1208. The third scanning mechanism 114, the first scanning mechanism 101, and the second scanning mechanism 102 work together to effectively control the sample pretreatment steps.

[0150] refer to Figure 18 , Figure 8 and Figure 7 The pretreatment frame 1212 may also be equipped with a button indicator component 122, which can be used to conveniently control the rotation of the third inner disk 46 for easy loading and unloading, and the indicator light can conveniently display the status of the reagent disk assembly 1208 in real time. The pretreatment frame 1212 may also be equipped with a refrigeration cycle component 44, which can be used in conjunction with the refrigeration mechanism 48 to realize the temperature control of the reagent disk assembly 1208.

[0151] refer to Figure 18 and Figure 7 The reagent needle assembly 1209 is located between the reagent tray assembly 1208 and the reaction tray assembly 1203, close to the transport track assembly 1201. The reagent needle assembly 1209 is used to transfer reagents from the reagent tray assembly 1208 to the reaction tray assembly 1203. The cleaning tank assembly 1210 is located close to the reaction cup loading assembly 1206, and the cleaning tank assembly 1210 is used to clean the reagent needles 30 of the reagent needle assembly 1209.

[0152] refer to Figure 27The reagent needle assembly 1209 includes a lifting drive mechanism 26, a rotating drive mechanism 27, a splined shaft 28, a swing arm 29, and a reagent needle 30. The splined shaft 28 is slidably connected to the rotating drive mechanism 27 and can be a ball spline, allowing the splined shaft 28 to rotate under the drive of the rotating drive mechanism 27. The lifting drive mechanism 26 is also rotatably connected to the splined shaft 28, but both are axially positioned along the splined shaft 28. The lifting drive mechanism 26 drives the splined shaft 28 to slide. The swing arm 29 extends radially along the splined shaft 28, with its two ends fixed to the splined shaft 28 and the reagent needle 30, respectively. The reagent needle 30 extends downwards for easy liquid collection. The lifting drive mechanism 26 and the rotating drive mechanism 27 cooperate to ultimately rotate the reagent needle 30, allowing it to rise and fall at different rotation positions. The reagent needle 30 is connected to a pipette pump and is controlled by the pipette pump to accurately collect and dispense liquid.

[0153] For example, the reagent needle assembly 1209 may also include a liquid detection control board 175, which can perform accurate liquid level detection and liquid level tracking functions; it may also include a tenth sensor 176, which may be an anti-collision detection photoelectric sensor, which can effectively identify collision anomalies against the reagent needle 30 and realize the protection of the reagent needle 30.

[0154] refer to Figure 28 The cup-taking and placing assembly 1207 includes a robotic arm 24 and a waste liquid suction needle 25. Specifically, the cup-taking and placing assembly 1207 may also include a horizontal displacement drive mechanism 50 and a vertical pick-and-place drive mechanism 51. The horizontal displacement drive mechanism 50 can drive the vertical pick-and-place drive mechanism 51 to translate approximately along the Y-axis direction. The vertical pick-and-place drive mechanism 51 can drive the robotic arm 24 and the waste liquid suction needle 25 to rise and fall as a whole. The robotic arm 24 and the waste liquid suction needle 25 can also move independently. For example, the waste liquid suction needle 25 can be controlled by the waste liquid suction vertical drive mechanism 177 to achieve vertical movement, enabling it to extract waste liquid from the reaction cup 6000. The robotic arm 24 can be controlled by the cup-dropping linkage 178 to place or drop the cup at a designated position. (Refer to...) Figure 18 The horizontal shifting drive mechanism 50 moves the robotic arm 24 to the corresponding position of the buffer disk assembly 1211. The other end of the cup-dropping linkage 178 is directly opposite a preset fixed rod, and when triggered, the robotic arm 24 drops the cup. Fixed rods can also be preset in other positions to meet the requirement of dropping cups at various preset positions.

[0155] Exemplarily, the robotic arm 24 is used to transport reaction cups 6000 from the reaction cup loading assembly 1206 to the reaction tray assembly 1203, and to remove discarded reaction cups 6000 from the reaction cup conveying assembly 41; further, it is also used to transport reaction cups 6000 from the reaction cup loading assembly 1206 to the buffer tray assembly 1211, and to transport reaction cups 6000 from the buffer tray assembly 1211 to the reaction cup conveying assembly 41. A waste liquid suction needle 25 is used to suction waste liquid from the discarded reaction cups 6000 in the reaction cup conveying assembly 41, and the waste liquid suction needle 25 can also be used to suction waste liquid from the reaction cups 6000 in the reaction tray assembly 1203.

[0156] The pick-and-place cup assembly 1207 is positioned between the reaction tray assembly 1203 and the transport track assembly 1201, and can be positioned lower than the typical movement path of the pipetting assembly 1202. The pick-and-place cup assembly 1207 is primarily used for grasping, transferring, and rejecting the reaction cups 6000. Waste reaction cups 6000 can be collected in the second waste bin 43.

[0157] refer to Figure 7 and Figure 8 For example, the pretreatment frame 1212 of the pretreatment module 1200 may also be provided with a waste liquid pump 118, a solvent bottle 119, a liquid path pump valve assembly 120, and a liquid path conversion assembly 121. The waste liquid pump 118 may be connected to the waste liquid suction needle 25. The solvent bottle 119 is used to hold the reagents and solvents for the extraction reaction and may be connected to the rinsing assembly 35, etc. For example, the reaction disk assembly 1203 includes a wiring transfer plate 155, which can mount, gather, and classify the liquid path pipes and wires.

[0158] The liquid circuit pump and valve assembly 120 is used in the liquid circuit system, integrating components such as pumps, valves, and pipelines to realize the liquid supply and injection of the whole system, and can be connected to the liquid transfer mechanism 19. The liquid circuit conversion assembly 121 is used for the transfer and distribution of pure water, integrating a liquid level switch to monitor the remaining liquid volume in real time, and can be connected to the dilution assembly 38.

[0159] refer to Figure 29 This application provides a mass spectrometry pretreatment method. In an exemplary embodiment, the mass spectrometry pretreatment method S7000 may be based on the aforementioned mass spectrometry pretreatment device 1000 or mass spectrometry system.

[0160] The mass spectrometry pretreatment method S700 may include the following steps.

[0161] Step S710: Sample tube 5000 is delivered to control component 1103.

[0162] For example, step S710 includes: conveying the sample tube 5000 placed at the normal placement position 1 to the control component 1103; in response to the sample tube 5000 being placed at the emergency placement position 2, receiving the sample tube 5000 placed at the emergency placement position 2 and being able to insert it before the sample tube 5000 placed at the normal placement position 1 to be conveyed, and conveying it to the control component 1103. For example, the step of conveying sample tubes 5000 to the control component 1103 further includes: in response to the sample tubes 5000 being placed at the quality control placement position 10 of the sample stage module 1100, conveying the sample tubes 5000 placed at the quality control placement position 10 of the sample stage module 1100 to the control component 1103, specifically, inserting them before the sample tubes 5000 placed at the normal placement position 1 to be conveyed; conveying the sample tubes 5000 received from the biochemical and immunological automated line 3000 at the inlet / outlet interface 11 of the sample stage module 1100 to the control component 1103; and using the reversing turntable 12 of the sample stage module 1100 to convert the sample tubes 5000 arranged in reverse in front of the control component 1103 into a forward arrangement. The S7000 mass spectrometry pretreatment method can process samples in high capacity and supports online loading and unloading; the maximum sample buffer capacity is 320 samples, enabling unattended operation for 8 to 12 hours; it can realize functions such as emergency priority and intelligent insertion quality control, and can meet the needs of more complex application scenarios; in addition, it can also connect to the sample channel of the 3000 biochemical and immunoassay automated line, and can seamlessly connect to the fully automated detection line; it can intelligently grab the 4000 sample racks to ensure reliable processing of 5000 sample tubes.

[0163] Step S720: Control the sample tube 5000 to be transferred to the forward processing module 1200. Step S720 may include: using the control component 1103 to identify the information of the acquired sample tube 5000, the clamping mechanism 6 of the control component 1103 clamping the tube body of the acquired sample tube 5000, and the cap removal mechanism 7 of the control component 1103 removing the cap of the acquired sample tube 5000.

[0164] For example, step S720, before capping, may further include: using the first scanning mechanism 101 of the control component 1103 to perform horizontal scanning of the acquired sample tube 5000; using the capping mechanism 7 of the control component 1103 to clamp the sample tube 5000 and control the sample tube 5000 to rotate one revolution; and using the second scanning mechanism 102 of the control component 1103 to scan the controlled rotating sample tube 5000. The mass spectrometry pretreatment method S7000 can achieve fully automated processing; it reduces human error and improves efficiency; utilizing the advantages of the magnetic bead method, the mass spectrometry pretreatment method S7000 adopts a streamlined operation mode, realizing parallel processing of each process, thus significantly increasing the throughput of pretreatment.

[0165] Step S730: Transporting the controlled sample tube 5000. Step S730 may include: transporting the controlled sample tube 5000 from the normal placement position 1 using the normal sample delivery track 8; and transporting the controlled sample tube 5000 from the emergency placement position 2 using the emergency sample delivery track 9. This effectively bypasses normal samples and prioritizes the processing of emergency samples.

[0166] In step S740, liquid is taken from and pipetted from the transport track assembly 1201. Specifically, liquid can be pipetted from the sample tube 5000 to the reaction cup 6000.

[0167] Step S750: Perform magnetic bead pretreatment on the sample transferred to reaction vessel 6000. Magnetic bead pretreatment includes the use of immunomagnetic beads or solid-phase magnetic beads. Magnetic bead extraction is a pretreatment method that is compatible with both solid-phase and immunomagnetic beads, offering good compatibility. Magnetic bead extraction can be completed quickly, significantly shortening the experimental cycle. Its selective adsorption mechanism yields high-purity products, reducing interference in subsequent experiments. Magnetic bead extraction eliminates the need for complex centrifugation or vacuum filtration steps, requiring only simple mixing, magnetic separation, and washing operations. Magnetic bead extraction is suitable for various sample types, including blood, tissue, saliva, and environmental samples, and can adapt to different experimental needs.

[0168] Optionally, the reaction vessel loading assembly 1206 of the pretreatment module 1200 is configured to supply at least one thousand reaction vessels 6000, and the reagent tray assembly 1208 of the pretreatment module 1200 is configured to supply at least three thousand reagents, so that the unattended operation time of the mass spectrometry pretreatment method S7000 is greater than or equal to eight hours. For example, when used in a biochemical and immunoassay automated line 3000, the mass spectrometry pretreatment device 1000 can be equipped with more reaction vessels 6000 and reagents, or they can be replenished periodically according to the processing cycle.

[0169] For example, the mass spectrometry pretreatment method S7000 may include step S760, transferring a sample from the reaction plate assembly 1203 to the buffer plate assembly 1211 of the pretreatment module 1200. The pipetting method of the mass spectrometry pretreatment method S7000 can be based on the mass spectrometry pretreatment device 1000; for example, the pick-and-place cup assembly 1207 of the pretreatment module 1200 can be used to transfer a reaction cup 6000 containing the sample from the buffer plate assembly 1211 to the reaction cup delivery assembly 41. The mass spectrometry pretreatment method S7000 is compatible with multiple modes; the front end uses the reaction cup 6000 as the processing unit, allowing for the testing of a minimum single sample, enabling immediate sample testing and significantly reducing reagent waste; simultaneously, the back end can also function as a single reaction cup for transferring samples to a 96-well plate.

[0170] In step S770, the sample pretreated with magnetic beads is provided to the mass spectrometer 2000. Specifically, the supernatant from the previous treatment can be provided through the reaction vessel 6000.

[0171] The mass spectrometry preprocessing method S7000 provided in this application uses a mass spectrometry preprocessing device 1000, which can achieve at least one effect such as automation, high throughput and strong compatibility; it is beneficial to improve the overall performance of mass spectrometry analysis.

[0172] The technical features of the above-disclosed embodiments can be combined in any way. For the sake of brevity, not all possible combinations of the technical features in the above embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0173] In the embodiments disclosed above, unless otherwise explicitly specified and limited, the execution order of each step is not restricted. For example, they can be executed in parallel or sequentially in different orders. The sub-steps of each step can also be executed alternately. Various forms of processes described above can be used, and steps can be reordered, added, or deleted, as long as the desired result of the technical solution provided in this application can be achieved, and this application does not impose any restrictions here.

[0174] The embodiments disclosed above merely illustrate several implementation methods of this application, and while the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of patent protection of this application. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of this application, and these all fall within the scope of patent protection claimed by this application. Therefore, the scope of patent protection of this application should be determined by the appended claims.

Claims

1. A mass spectrometry pretreatment device, used to provide pretreated samples to a mass spectrometry device, characterized in that, The mass spectrometry preprocessing equipment includes a sample stage module and a preprocessing module; The sample stage module includes: The placement area includes a general placement area, a quality control placement area, and an emergency placement area. A transport assembly is used to receive and transport sample tubes placed in the normal placement position; when a sample tube is placed in the emergency placement position, the transport assembly receives and transports the sample tube placed in the emergency placement position; the transport assembly includes a transport vehicle, and the quality control placement position and the emergency placement position are arranged on both sides of the transport vehicle. A control component is used to control sample tubes to be transferred to the preprocessing module. The control component includes a hooking mechanism, an information recognition mechanism, a clamping mechanism, and a cap removal mechanism. The hooking mechanism is used to acquire sample tubes from the transport component. The information recognition mechanism is used to identify information about the acquired sample tubes. The clamping mechanism is used to clamp the body of the acquired sample tubes. The cap removal mechanism is used to remove the caps from the acquired sample tubes. An inlet / outlet interface is provided at an interval from the hooking mechanism. The inlet / outlet interface and the hooking mechanism can be connected via the transport vehicle. The inlet / outlet interface is used to connect to the biochemical and immunological automated line. The preprocessing module includes: The transport track assembly includes a normal sample inlet track and an emergency sample inlet track, wherein the normal sample inlet track and the emergency sample inlet track are respectively connected to the hooking mechanism and are respectively used to transport controlled sample tubes; The reaction tray assembly is used for magnetic bead pretreatment of samples pipetted into reaction cups; The buffer disk assembly includes a second outer disk, a second inner disk, a dilution component, a second mixing component, and a second magnetic attraction component. The second outer disk and the second inner disk are used to limit the corresponding reaction cups and adjust their positions. The dilution component is used to dilute the substances in the reaction cups. The second mixing component is used to mix the substances in the reaction cups. The second magnetic attraction component is used to attract magnetic beads in the reaction cups. The number of reaction cups that the buffer disk assembly can hold is greater than or equal to the number of reaction cups that the reaction disk assembly can hold. A pipetting assembly for taking and pipetting liquid from the transport track assembly, and for transferring samples from the reaction tray assembly to the buffer tray assembly; and A sample delivery assembly for supplying the mass spectrometer with samples that have undergone the magnetic bead pretreatment.

2. The mass spectrometry pretreatment apparatus according to claim 1, characterized in that, The transport component includes the transport vehicle that is movable in a first direction. Along the travel of the transport vehicle, the emergency placement position is arranged at one end, the control component is arranged at the other end, and multiple ordinary placement positions are arranged on both sides.

3. The mass spectrometry pretreatment apparatus according to claim 2, characterized in that, It also includes a sample rack, a sample basket, and a reversing turntable; the sample rack can hold a row of sample tubes, the sample basket is used to place them in the normal placement position, the sample basket can hold a row of sample racks, and the sample basket has an opening on the side facing the transport vehicle; the placement area can simultaneously hold 320 sample tubes placed in the normal placement position; The transport vehicle is equipped with a telescopic part capable of collecting and delivering the sample rack in a second direction; The reversing turntable is spaced apart from the control component and can dock with the transport vehicle. The reversing turntable is used to rotate and change the orientation of the sample rack.

4. The mass spectrometry pretreatment apparatus according to claim 1, characterized in that, The control component also includes a pushing motion mechanism and a lifting mechanism. The pushing motion mechanism drives the hooking mechanism to move to correspond to the normal sample injection track and the emergency sample injection track respectively. The lifting mechanism can drive the clamping mechanism, so that the clamping mechanism has a low position and a high position. The capping mechanism is a rotating capping mechanism. When the clamping mechanism is in the high position, the capping mechanism can hold the cap of the acquired sample tube. The information identification mechanism includes a first scanning mechanism and a second scanning mechanism. The first scanning mechanism is used to scan the acquired sample tube, and the second scanning mechanism is used to scan the sample tube that is held by the capping mechanism and rotated in a controlled manner.

5. The mass spectrometry pretreatment apparatus according to claim 1, characterized in that, The pretreatment module further includes a loading module, which includes a feed chamber, a waste chamber, a vertical pushing mechanism, a guide support, a horizontal pushing mechanism, a centering clamping mechanism, and a receiving component. The feed chamber and the waste chamber are arranged side by side. The vertical pushing mechanism is located in the feed chamber. The guide support is located on the upper side of the vertical pushing mechanism and can be pushed open from the lower side. The horizontal pushing mechanism is located on the guide support. The centering clamping mechanism is located on the waste chamber and can clamp the pipette tip support. The receiving component is located inside the waste chamber.

6. The mass spectrometry pretreatment apparatus according to claim 1, characterized in that, The pipetting assembly includes a three-axis motion mechanism and a pipetting mechanism. The support legs of the three-axis motion mechanism are arranged on both sides of the reaction tray assembly along the extension direction of the transport track assembly. The pipetting mechanism is fixed to the end of the three-axis motion mechanism. The pipetting mechanism includes a driver, a pipette, and a rejector. The driver is used to drive the pipette to aspirate and dissipate liquid, and the rejector is used to reject the pipette tip installed at the pipette.

7. The mass spectrometry pretreatment apparatus according to claim 1, characterized in that, The sample delivery assembly includes a reaction cup delivery assembly and a 96-well plate placement position; The pretreatment module also includes a reaction cup feeding assembly and a cup picking and placing assembly; The reaction cup feeding assembly includes a hopper, a vertical pushing mechanism, a horizontal conveying mechanism, and a rotary cup separating mechanism. The hopper has a limit-selection discharge port. The vertical pushing mechanism is used to push the reaction cup from the hopper to the limit-selection discharge port. The horizontal conveying mechanism is used to convey the reaction cup from the limit-selection discharge port to the rotary cup separating mechanism. The hopper is located on the side of the reaction plate assembly opposite to the conveying track assembly, and the horizontal conveying mechanism extends towards the conveying track assembly. The cup picking and placing assembly includes a robotic arm and a waste liquid suction needle. The robotic arm is used to transport the reaction cup from the reaction cup feeding assembly to the reaction plate assembly and to remove the waste reaction cup from the reaction cup conveying assembly. The waste liquid suction needle is used to suck up waste liquid from the waste reaction cup and to suck up waste liquid from the reaction cup in the reaction plate assembly. The cup picking and placing assembly is disposed between the reaction plate assembly and the conveying track assembly. The 96-well plate placement position is located on the side of the reaction disk assembly opposite to the sample stage module; the pipetting assembly is used to inject liquid into the 96-well plate at the 96-well plate placement position.

8. The mass spectrometry pretreatment apparatus according to claim 7, characterized in that, The pretreatment module also includes a reagent tray assembly, a reagent needle assembly, and a cleaning tank assembly; The reagent tray assembly includes a third scanning mechanism for scanning the reagent kits within the reagent tray assembly; the reagent tray assembly is located between the reaction tray assembly and the sample stage module. The reagent needle assembly is used to transfer reagents from the reagent tray assembly to the reaction tray assembly; the reagent needle assembly includes a lifting drive mechanism, a rotating drive mechanism, a spline shaft, a swing arm, and a reagent needle; the spline shaft is slidably connected to the rotating drive mechanism and can be driven to rotate; the lifting drive mechanism is used to drive the spline shaft to slide; the two ends of the swing arm are respectively fixed to the spline shaft and the reagent needle; the reagent needle assembly is located between the reaction tray assembly and the reagent tray assembly; The cleaning tank assembly is used to clean the reagent needle.

9. The mass spectrometry pretreatment apparatus according to claim 1, characterized in that, The reaction disk assembly includes a first outer disk, a first inner disk, a first mixing component, a first magnetic attraction component, and a rinsing component; The first outer disk and the first inner disk are used to limit the corresponding reaction cup and adjust the position of the reaction cup. The first mixing component is used to mix the substances in the reaction cup. The first magnetic adsorption component is used to adsorb the magnetic beads in the reaction cup. The rinsing component is used to rinse the magnetic beads and to extract waste liquid.

10. A mass spectrometry pretreatment method, characterized in that, Based on the mass spectrometry preprocessing apparatus as described in any one of claims 1 to 9, the mass spectrometry preprocessing method comprises: The method of feeding sample tubes to the control component includes: feeding a sample tube placed in the normal placement position to the control component; receiving a sample tube placed in the emergency placement position and inserting it before a sample tube placed in the normal placement position to be fed to the control component in response to a sample tube being placed in the emergency placement position; inserting a sample tube placed in the quality control placement position of the sample stage module before a sample tube placed in the normal placement position to be fed to the control component in response to a sample tube being placed in the quality control placement position of the sample stage module and feeding it before a sample tube placed in the normal placement position to be fed to the control component; and feeding a sample tube received from the biochemical and immunological automated line at the inlet / outlet interface of the sample stage module to the control component. Controlling the sample tubes to be transferred to the preprocessing module includes: using the control component to identify the information of the acquired sample tubes, clamping the tube body of the acquired sample tubes by the clamping mechanism of the control component, and removing the caps of the acquired sample tubes by the cap removal mechanism of the control component. The controlled sample tube delivery includes: delivering the controlled sample tube from the normal placement position via the normal sample delivery track; and delivering the controlled sample tube from the emergency placement position via the emergency sample delivery track. Liquid is extracted and transferred from the transport track assembly; The sample transferred into the reaction vessel was pretreated with magnetic beads. Transferring samples from the reaction disk assembly to the buffer disk assembly of the preprocessing module; and The mass spectrometer is supplied with a sample that has undergone the magnetic bead pretreatment.

11. The mass spectrometry pretreatment method according to claim 10, characterized in that, The magnetic bead pretreatment includes the use of immunomagnetic beads or solid-phase magnetic beads.

12. The mass spectrometry pretreatment method according to claim 10, characterized in that, Also includes: The sample-containing reaction cup is transported from the buffer tray assembly to the reaction cup transport assembly of the sample transport assembly using the cup pick-and-place assembly of the pretreatment module, or the liquid is pipetted from the buffer tray assembly to the 96-well plate placement position of the 96-well plate of the sample transport assembly.

13. The mass spectrometry pretreatment method according to any one of claims 10 to 12, characterized in that, The step of delivering sample tubes to the control component further includes: using the reversing turntable of the sample stage module to convert the sample tubes arranged in reverse in front of the control component into a forward arrangement; The step of controlling the sample tube to be transferred to the preprocessing module further includes: using the first scanning mechanism of the control component to perform horizontal scanning of the acquired sample tube; using the capping mechanism of the control component to clamp the sample tube and control the sample tube to rotate one revolution; and using the second scanning mechanism of the control component to scan the controlled rotating sample tube. The reaction cup loading assembly of the pretreatment module is configured to supply at least 1,000 reaction cups, and the reagent tray assembly of the pretreatment module is configured to supply at least 3,000 reagents, so that the unattended operation time of the mass spectrometry pretreatment method is greater than or equal to 8 hours.

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