A full-automatic mass spectrometry detection all-in-one machine device

Abstract

This application relates to a fully automated mass spectrometry detection device. The fully automated mass spectrometry detection device includes a sample stage module, a pretreatment module, a multi-channel liquid chromatography module, and a mass spectrometry detection module. The sample stage module is adapted to interface with a production line to load samples. The pretreatment module is adapted to interface with the sample stage module to obtain samples from the sample stage module, and is used to pre-treat the samples for subsequent liquid chromatography separation. The multi-channel liquid chromatography module is adapted to interface with the pretreatment module to obtain the pre-treated samples for liquid chromatography separation. The mass spectrometry detection module is adapted to interface with the multi-channel liquid chromatography module to obtain the liquid chromatography-separated samples for mass spectrometry detection. The sample stage module, pretreatment module, multi-channel liquid chromatography module, and mass spectrometry detection module are all independent modules, with two or more modules used in combination. This application's solution can improve the equipment's scalability, ease of maintenance, adaptability to different scenarios, and work efficiency.

Description

Technical Field

[0001] This application relates to the field of liquid chromatography-tandem mass spectrometry detection technology, and in particular to a fully automated integrated mass spectrometry detection device. Background Technology

[0002] Mass spectrometry, a crucial detection technique in analytical chemistry, is widely used for analyzing complex samples in clinical medicine, biomedicine, and food safety. However, current sample pretreatment techniques for mass spectrometry are numerous, including protein precipitation, liquid-liquid extraction, and solid-phase extraction for different target compounds, resulting in poor versatility and heavy reliance on manual processes. Therefore, mass spectrometry typically requires batch-wise pretreatment, followed by single-channel injection and analysis, and finally batch-wise result analysis. This workflow suffers from low automation and throughput, leading to inefficient and costly detection. Consequently, samples collected by hospitals often require a following day for clinical results after data analysis and report review, failing to meet the time and cost constraints of clinical diagnosis and treatment, thus limiting the clinical application of mass spectrometry.

[0003] Currently, some technologies are researching integrated structural designs, where sample processing, liquid chromatography separation, and mass spectrometry detection modules are highly coupled within a single system. While this design ensures the continuity of the basic detection process, it has gradually revealed the following shortcomings in practical applications. First, the rigidity of module functions limits system scalability and versatility. For example, when it is necessary to add sample pretreatment types (such as solid-phase extraction, protein precipitation) or improve liquid chromatography separation efficiency, it is often necessary to replace the entire equipment or carry out complex modifications, resulting in resource waste and soaring costs. Second, maintenance and upgrades of each module are difficult to implement independently. Due to the tight integration of the pretreatment unit, liquid chromatography unit, and mass spectrometry detection unit, the maintenance or technical iteration of a single module often requires the shutdown of the entire system, seriously affecting detection efficiency and continuity. Third, there is insufficient adaptability to multiple scenarios. Faced with detection tasks with different sample volumes, different pretreatment requirements, or different throughput requirements, traditional equipment is difficult to flexibly configure through module recombination. It is often necessary to configure multiple sets of dedicated equipment to cover all scenario requirements, exacerbating the problem of low equipment utilization.

[0004] Therefore, it is necessary to propose a new technical solution to overcome the shortcomings of existing technologies. Summary of the Invention

[0005] Based on this, this application provides a fully automated mass spectrometry detection integrated machine, which can improve the scalability, ease of maintenance, adaptability to different scenarios, and work efficiency of the equipment.

[0006] Therefore, this application adopts the following technical solution: a fully automated mass spectrometry detection integrated machine, the fully automated mass spectrometry detection integrated machine comprising: a sample stage module, adapted to be connected to a production line to load samples; a pretreatment module, adapted to be connected to the sample stage module to obtain samples from the sample stage module, the pretreatment module being used to pretreat the samples for subsequent liquid chromatography separation; a multi-channel liquid chromatography module, adapted to be connected to the pretreatment module to obtain the pretreated samples for liquid chromatography separation; a mass spectrometry detection module, adapted to be connected to the multi-channel liquid chromatography module to obtain the liquid chromatography separated samples for mass spectrometry detection; and a control and data processing module for controlling the automatic operation of the integrated machine; wherein the sample stage module, pretreatment module, multi-channel liquid chromatography module and mass spectrometry detection module are all independent modules, and two or more of them are used in combination.

[0007] In some embodiments, the sample stage module, pretreatment module, multi-channel liquid chromatography module, and mass spectrometry detection module are respectively configured to handle batch loading of multiple samples at once and automated sample loading of single samples one by one.

[0008] In some embodiments, the multichannel liquid chromatography module includes: a multichannel injection unit, including a batch loading mechanism for batch loading, a reaction cup gripper mechanism for single-tube automated loading, and an injection mechanism for injection; a reagent delivery unit, including a reagent pump assembly for delivery of mobile phase and sample injection; a column loading unit, including a cartridge loading mechanism and a switching valve for loading and switching cartridges; and a waste liquid unit for collecting waste liquid.

[0009] In some embodiments, the reaction cup gripper mechanism includes: a flexible gripper for gripping and releasing the reaction cup; a gripper drive assembly powerably connected to the flexible gripper to drive the flexible gripper to rotate left and right and translate up and down; and a cup dropping assembly including an electrically controlled telescopic component, an active push rod, a cup dropping rocker, and a passive push rod, wherein the active push rod and the passive push rod are connected to both ends of the cup dropping rocker, the passive push rod is disposed near the flexible gripper, and the active push rod is disposed near the electrically controlled telescopic component; The batch sample loading mechanism includes an insulated box, a temperature control module for controlling the temperature inside the insulated box, and a movable tray located inside the insulated box and drivable along a first direction. The insulated box includes a movable cover and a fixed cover. The movable cover is used to open the insulated box to take out and place a sample tray therein. The fixed cover has a sample inlet slot extending perpendicular to the first direction. The movable tray carries the samples arranged in an array and moves along the first direction so that the samples arranged in an array are exposed one by one below the sample inlet slot for the sample loading mechanism to take samples.

[0010] In some embodiments, the injection mechanism includes at least two injection channels, each including: a valve-pump assembly including an injection valve connected to the column loading unit for injecting a sample into the column loading unit; a sample suction arm assembly for aspirating a sample, one end of which is connected to a sampling needle and the other end to the injection valve; a needle holder and washing unit connected to the injection valve, including an injection chamber for inserting the sampling needle to deliver a sample to the injection valve, and a washing chamber for inserting the sampling needle to wash the sampling needle; and an injection pump connected to the injection valve for providing suction power.

[0011] In some embodiments, the sampling arm assembly includes a sampling arm, an arm drive, a lead screw, a slider, and a guide rail. The arm drive drives the sampling arm to translate via the lead screw, and the slider is connected to the sampling arm and slides in cooperation with the guide rail.

[0012] In some embodiments, the valve-pump assembly includes a cleaning fluid delivery pump, a cleaning fluid suction pump, and a three-way valve. The cleaning fluid delivery pump is connected to a cleaning fluid bottle and a needle washing chamber to supply cleaning fluid to the needle washing chamber. The cleaning fluid suction pump is connected to the needle washing chamber and a waste liquid pipeline to discharge waste liquid from the needle washing chamber to a waste liquid unit. The three-way valve connects the cleaning fluid delivery pump and the cleaning fluid suction pump to switch the connection between the cleaning fluid delivery pump, the cleaning fluid suction pump, and the needle washing chamber.

[0013] In some embodiments, the injection pump includes a pump body, a zero-point sensor disposed on the pump body, and a pump body drive assembly for driving the pump body to move. The pump body is connected to the suction arm assembly and the injection valve. The pump body drive assembly includes a drive motor, a synchronous pulley, a synchronous belt, and a driven pulley. The synchronous pulley is connected to the output end of the drive motor, the driven pulley is connected to the pump body, and the synchronous belt connects the synchronous pulley and the driven pulley.

[0014] In some embodiments, the needle holder and needle washing component includes a main body component, with the injection chamber and the washing chamber formed on the main body component. The injection chamber contains a sealing ring and a sealing ring cover plate that presses the sealing ring. The injection chamber is connected to the injection valve via a pipeline. The washing chamber has a cleaning fluid channel and a washing needle channel communicating near the upper part. Cleaning fluid flows into the cleaning fluid channel and overflows into the washing needle channel. The cleaning fluid channel has an inlet and an outlet for the cleaning fluid to be input and output. The washing needle channel has a waste fluid outlet for waste liquid discharge. The upper end of the injection chamber has an overflow groove communicating with the washing needle channel, allowing liquid overflowing from the sealing ring cover plate to flow into the washing needle channel.

[0015] In some embodiments, the needle holder and needle washing component includes a main body component, a base, and an adjustment mechanism. The main body component is movably disposed on the base or fixed to a movable base. The adjustment mechanism drives the main body component to move relative to the base or to move together with the base.

[0016] In some embodiments, the multi-channel sample loading unit includes a batch loading mechanism, which includes an insulated box, a temperature control module for controlling the temperature inside the insulated box, and a movable tray disposed inside the insulated box and drivable to move along a first direction. The insulated box includes a movable cover and a fixed cover. The movable cover is used to open the insulated box to take out and place a sample tray therein. The fixed cover has a sample loading slot extending perpendicular to the first direction. The movable tray carries samples arranged in an array and moves along the first direction so that the samples arranged in an array are exposed column by column below the sample loading slot for the sample loading mechanism to take samples.

[0017] In some embodiments, the temperature control module includes a thermoelectric semiconductor chip, an inner heat sink, an inner fan, an outer heat sink, an outer fan, and a heat insulation component. The heat insulation component surrounds the thermoelectric semiconductor chip, and the thermoelectric semiconductor chip and the heat insulation component are sandwiched between the inner and outer heat sinks. The inner fan drives airflow through the inner heat sink into the heat insulation chamber, and the outer fan drives airflow outside the heat insulation chamber through the outer heat sink.

[0018] In some embodiments, the reagent delivery unit includes a track support, a pull-out track, at least two reagent pump assemblies, a filling pump, a tee connector, and a waste liquid connector. The pull-out track is connected to the reagent pump assemblies and can be pulled and moved on the track support. The tee connector connects the reagent bottle and the two reagent pump assemblies. The inlet of the filling pump is connected to the two reagent pump assemblies, and its outlet is connected to the waste liquid connector.

[0019] In some embodiments, each of the reagent pump groups includes a first unit and a second unit for receiving different reagents, a mixer for mixing different reagents, a waste liquid outlet for discharging waste liquid, and a filling and cleaning valve for switching the direction of reagent flow. The first unit includes a unit proportional valve, a unit primary pump, and a unit secondary pump. The second unit includes a unit proportional valve, a unit primary pump, a unit secondary pump, and a waste liquid discharge port.

[0020] In some embodiments, the cartridge loading mechanism includes a cartridge quick-release assembly, a cartridge control button, and a cartridge indicator light. The cartridge control button is used to trigger the cartridge quick-release assembly to load or release the cartridge, and the cartridge indicator light is used to display the status of the cartridge. The switching valve includes a pre-column switching valve located upstream of the cartridge loading mechanism and two post-column switching valves located downstream of the cartridge loading mechanism.

[0021] In some embodiments, the multichannel liquid phase module further includes a reagent storage unit, which includes a reagent bottle support for carrying the reagent bottle assembly, a weighing component for monitoring the reagent level, and a reading component for identifying reagent information.

[0022] In some embodiments, the multi-channel liquid phase module further includes a pre-vacuum system unit, which includes a soundproof enclosure, a vacuum pump disposed inside the soundproof enclosure and connected to the mass spectrometry detection module, and a fan cooling assembly for blowing air into the soundproof enclosure to dissipate heat. The walls of the soundproof enclosure are provided with a layer of sound-insulating material, and the inlets on the walls of the soundproof enclosure for the fan cooling assembly to enter and exit are provided with filter cotton.

[0023] In some embodiments, the control and data processing module is used to perform fully automatic control of the sample stage module, pretreatment module, multi-channel liquid chromatography module, and mass spectrometry detection module. The control and data processing module is configured to control the integrated device to perform automatic integration, automatic review, automatic alarm and retesting of abnormal samples, and quality control management, so as to realize the laboratory work results of sample entry and exit.

[0024] The fully automated mass spectrometry detection system provided in this application adopts a modular design, allowing for flexible configuration to meet the needs of different users and possessing strong compatibility and functional expandability. The system includes a sample stage module, a pretreatment module, a multi-channel liquid chromatography module, and a mass spectrometry detection module. These modules can be combined according to user requirements to meet the fully automated needs of the entire process from sample input to report output. It is easy to use, significantly reducing the barrier to entry and the professional skills required of users, substantially lowering costs, and improving the equipment's scalability, ease of maintenance, adaptability to various scenarios, and work efficiency. Attached Figure Description

[0025] To more clearly illustrate the technical solutions in the embodiments of this application or in the conventional art, the drawings used in the description of the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of this application. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0026] Figure 1 This is a three-dimensional assembly diagram of the fully automated mass spectrometry detection integrated machine of this application.

[0027] Figure 2 This is a three-dimensional view of the multi-channel liquid chromatography module in the fully automated mass spectrometry detection integrated machine of this application.

[0028] Figure 3 This is a schematic diagram of sample aspiration from the multi-channel liquid chromatography module in the fully automated mass spectrometry detection integrated machine of this application.

[0029] Figure 4 This is a schematic diagram of the sample introduction process in the multi-channel liquid chromatography module of the fully automated mass spectrometry detection system of this application.

[0030] Figure 5 This is a schematic diagram of sample aspiration for another connection method of the multi-channel liquid chromatography module in the fully automated mass spectrometry detection integrated machine of this application.

[0031] Figure 6 This is a schematic diagram of sample introduction for another connection method of the multi-channel liquid chromatography module in the fully automated mass spectrometry detection integrated machine of this application.

[0032] Figure 7 This is a three-dimensional view of the multi-channel sample introduction unit in the fully automated mass spectrometry detection integrated machine of this application.

[0033] Figure 8 This is a perspective view of the reaction cup gripper mechanism in the fully automated mass spectrometry detection integrated machine of this application.

[0034] Figure 9 This is a three-dimensional view of the sample introduction mechanism in the fully automated mass spectrometry detection integrated machine of this application.

[0035] Figure 10 This is a perspective view of the sample suction arm assembly in the fully automated mass spectrometry detection integrated machine of this application.

[0036] Figure 11 This is a perspective view of the valve and pump assembly in the fully automated mass spectrometry detection integrated machine of this application.

[0037] Figure 12 This is a three-dimensional view of the injection pump in the fully automated mass spectrometry detection system of this application.

[0038] Figure 13 This is a perspective view of the needle holder and needle washing component in the fully automated mass spectrometry detection integrated machine of this application.

[0039] Figure 14 This is a perspective view of the needle holder and needle washing component in the fully automated mass spectrometry detection integrated machine of this application.

[0040] Figure 15 To Figure 14A sectional view of the component shown.

[0041] Figure 16 To Figure 14 Another sectional view of the component shown.

[0042] Figure 17 This is a three-dimensional view of the batch loading mechanism in the fully automated mass spectrometry detection integrated machine of this application.

[0043] Figure 18 This is a perspective view of the temperature control module in the fully automated mass spectrometry detection integrated machine of this application.

[0044] Figure 19 This is a perspective view of the reagent delivery unit in the fully automated mass spectrometry detection integrated machine of this application.

[0045] Figure 20 This is a perspective view of the reagent pump assembly in the fully automated mass spectrometry detection integrated machine of this application.

[0046] Figure 21 This is a perspective view of the column loading unit in the fully automated mass spectrometry detection system of this application.

[0047] Figure 22 This is a perspective view of the reagent storage unit in the fully automated mass spectrometry detection integrated machine of this application.

[0048] Figure 23 This is a three-dimensional exploded view of some components of the reagent storage unit in the fully automated mass spectrometry detection integrated machine of this application.

[0049] Figure 24 This is a perspective view of the waste liquid unit in the fully automated mass spectrometry detection integrated machine of this application.

[0050] Figure 25 This is a perspective view of the front-stage vacuum system unit in the fully automated mass spectrometry detection integrated machine of this application.

[0051] Figure 26 This is another perspective view of the front-stage vacuum system unit in the fully automated mass spectrometry detection integrated machine of this application.

[0052] Figure 27 This is a perspective view of the mass spectrometry detection module in the fully automated mass spectrometry detection integrated machine of this application.

[0053] Figure 28 This is another perspective view of the mass spectrometry detection module in the fully automated mass spectrometry detection integrated machine of this application.

[0054] The component labels are as follows:

[0055] 1. Sample stage module; 2. Pretreatment module; 3. Multichannel liquid chromatography module; 4. Mass spectrometry detection module; 5. Reaction cup; 6. Reaction cup gripper mechanism; 7. Batch loading mechanism; 8. Suction arm assembly; 9. Valve pump assembly;

[0056] 31. Multi-channel injection unit; 32. Reagent delivery unit; 33. Column loading unit; 34. Waste liquid unit; 35. Pre-vacuum system unit; 36. Reagent storage unit; 37. Consumable information entry unit; 38. Status indicator unit; 41. Mass spectrometry detection unit; 42. Ion source maintenance platform; 43. Gas supply system; 65. Guide rod; 66. Flexible gripper; 71. Insulation box; 72. Temperature control module; 73. Moving tray; 74. Sample tray; 91. Substrate; 92. Cleaning solution delivery pump; 93. Three-way valve; 94. Cleaning solution suction pump;

[0057] 310. Mounting plate; 311. Sampling arm; 312. Injection pump; 313. Injection valve; 314. Needle washing chamber; 315. Needle seat and needle washing assembly; 317. Filter; 318. Lead screw; 321. Reagent pump assembly; 322. T-connector; 323. Waste liquid connector; 324. Track support; 325. Pull-out track; 326. Infusion pump; 331. Pre-column switching valve; 332. Post-column switching valve one; 333. Post-column switching valve two; 334. Chromatography cartridge; 335. Chromatography cartridge quick-release assembly; 336. Control... 337. Button mounting plate; 338. Chromatography box control button; 341. Chromatography box indicator light; 342. Waste liquid tray; 343. Waste liquid bucket; 344. Waste liquid pipe; 345. Air filter; 356. Soundproof enclosure; 357. Front panel; 358. Casters; 359. Oil collection box; 350. Bottom panel; 351. Rear panel air inlet; 351. Exhaust fan; 362. Reagent bottle; 363. Reagent bottle support; 364. Weighing base; 415. Weighing module interlayer; 416. Vacuum tube interface; 417. 413 Compressed air interface; 414 Exhaust gas support port; 415 Exhaust gas port; 416 Nitrogen port; 431 Caster assembly; 432 Cooling fan; 433 Main pipe interface; 611 Lifting motor; 612 Lifting synchronous belt; 613 Rotary motor; 614 Rotary main wheel; 615 Rotary synchronous belt; 616 Rotary driven wheel; 621 Lifting origin sensor baffle; 622 Lifting origin sensor; 623 Rotary origin sensor; 624 Rotary origin sensor baffle; 631 Fixed... Fixed plate; 632, Electrically controlled telescopic component; 641, Active push rod; 642, Cup dropping rocker; 643, Passive push rod; 711, Movable cover plate; 712, Sample inlet; 721, Thermoelectric semiconductor chip; 722, Temperature control adapter plate; 723, Inner heat sink; 724, Inner fan; 725, Insulation component; 726, Outer heat sink; 727, Outer fan; 731, Drive belt; 931, First interface; 932, Second interface; 933, Third interface; 941, Pump inlet; 942, Pump outlet;

[0058] 3121. Pump body; 3122. Pump bracket; 3123. Drive motor; 3124. Synchronous pulley; 3125. Synchronous belt; 3126. Driven pulley; 3127. Zero-point sensor; 3141. Needle cleaning channel; 3142. Cleaning fluid channel; 3143. Cleaning fluid outlet; 3144. Waste liquid outlet; 3150. Overflow tank; 3151. Main component; 3152. Base; 3153. Calibration screw; 3154. Limit ring; 3155. Screw seat; 3156. Reinforcing block; 3157. Piping; 3158. Sealing ring cover plate; 3159. Sealing ring; 3161. Arm drive component; 3162. Arm drive synchronous belt; 3163. Arm drive wheel; 3181. Guide rail; 3182. Slider; 3211. Unit proportional valve; 3212. Unit 1 Primary Pump; 3213. Unit 1 Secondary Pump; 3214. Mixer; 3215. Filling and Cleaning Valve; 3216. Unit 2 Proportional Valve; 3217. Unit 2 Primary Pump; 3218. Unit 2 Secondary Pump; 3219. Waste Liquid Discharge Port; 3521. Front Panel Air Inlet; 3522. Brush; 3523. Viewing Window; 3524. Temperature Display; 3531. Air Inlet Fan; 3532. Main Switch; 3533. Light Switch; 3551. Right Bracket; 3552. Left Bracket; 3641. Reagent Bottle Tray; 3642. Tray Sealing Ring; 3643. Load Cell; 3644. Load Cell Bracket; 3645. Antenna Tray; 3646. Reader; 7211. Temperature Fuse; 7212. Temperature Sensor. Detailed Implementation

[0059] To make the above-mentioned objectives, features, and advantages of this application more apparent and understandable, the specific embodiments of this application are described in detail below with reference to the accompanying drawings. Many specific details are set forth in the following description to provide a thorough understanding of this application. However, this application can be implemented in many other ways different from those described herein, and those skilled in the art can make similar modifications without departing from the spirit of this application. Therefore, this application is not limited to the specific embodiments disclosed below.

[0060] It should be noted that when a component is referred to as being "fixed to" or "set on" another component, it can be directly on the other component or there may be an intermediate component. When a component is considered to be "connected to" another component, it can be directly connected to the other component or there may be an intermediate component present. The terms "vertical," "horizontal," "upper," "lower," "left," "right," and similar expressions used in this application's specification are for illustrative purposes only and do not represent the only possible implementation.

[0061] Furthermore, the terms "first" and "second" are used for descriptive purposes only and should not be construed as indicating or implying relative importance or implicitly specifying the number of technical features indicated. Thus, a feature defined as "first" or "second" may explicitly or implicitly include at least one of that feature. In the description of this application, "multiple" means at least two, such as two, three, etc., unless otherwise explicitly specified.

[0062] In this application, unless otherwise expressly specified and limited, "above" or "below" the second feature can mean that the first feature is in direct contact with the second feature, or that the first feature and the second feature are in indirect contact through an intermediate medium. Furthermore, "above," "over," and "on top" the second feature can mean that the first feature is directly above or diagonally above the second feature, or simply indicates that the first feature is at a higher horizontal level than the second feature. "Below," "below," and "under" the second feature can mean that the first feature is directly below or diagonally below the second feature, or simply indicates that the first feature is at a lower horizontal level than the second feature.

[0063] Unless otherwise defined, all technical and scientific terms used in this application have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. The terminology used in this application is for the purpose of describing particular embodiments only and is not intended to be limiting of the application. The term "and / or" as used in this application includes any and all combinations of one or more of the associated listed items.

[0064] Please see Figure 1 As shown, this application provides a fully automated mass spectrometry detection integrated device, which includes a sample stage module 1, a pretreatment module 2, a multi-channel liquid chromatography module 3, a mass spectrometry detection module 4, and a control and data processing module. The sample stage module 1 is adapted to connect to a production line to load samples; the pretreatment module 2 is adapted to connect to the sample stage module 1 to obtain samples from the sample stage module 1, and the pretreatment module 2 is used to pre-treat the samples for subsequent liquid chromatography separation; the multi-channel liquid chromatography module 3 is adapted to connect to the pretreatment module 2 to obtain the pre-treated samples for liquid chromatography separation; the mass spectrometry detection module 4 is adapted to connect to the multi-channel liquid chromatography module 3 to obtain the samples separated by liquid chromatography for mass spectrometry detection. The sample stage module 1, pretreatment module 2, multi-channel liquid chromatography module 3, and mass spectrometry detection module 4 are all independent modules, with two or more modules used in combination. The control and data processing module is used to control the automatic operation of the integrated device.

[0065] The fully automated mass spectrometry detection system provided in this application adopts a modular design, allowing for flexible configuration to meet the needs of different users and possessing strong compatibility and functional expandability. The fully automated mass spectrometry detection system includes a sample stage module 1, a pretreatment module 2, a multi-channel liquid chromatography module 3, and a mass spectrometry detection module 4. These modules can be combined according to user requirements to meet the fully automated needs of the entire process from sample input to report output. It is simple to use, greatly reducing the barrier to entry and the professional skills required of users, significantly lowering costs, and improving the equipment's scalability, ease of maintenance, adaptability to different scenarios, and work efficiency.

[0066] In some embodiments, the sample stage module 1, the pretreatment module 2, the multi-channel liquid chromatography module 3, and the mass spectrometry detection module 4 are respectively configured to be suitable for batch loading of multiple samples at once and automated sample loading of single samples one by one.

[0067] Specifically, the sample station module 1 and the preprocessing module 2 have the ability to independently load and test samples and connect to automated testing lines. When loading samples independently, the sample station module 1 can match different modules according to throughput requirements and implement automatic retesting functions according to software instructions. In this embodiment, the sample station module 1 includes functions such as loading, scanning, opening, retesting, and docking with automated testing lines for routine and emergency samples, with a maximum sample buffer capacity of no less than 350 samples, enabling unattended operation for 12 hours or even longer. Furthermore, it can also have a sample channel for docking with biochemical and immunoassay automated testing lines, allowing seamless docking with fully automated testing lines. Further, the sample station module 1 is equipped with a high-performance self-backup computer and a touch screen display to facilitate information input, storage, and other operations.

[0068] The pretreatment module 2 is suitable for processing various sample types, including blood, tissue, saliva, and environmental samples. Its processing methods are adaptable to different experimental needs, and it features functions such as sample, internal standard, magnetic bead, and reagent addition, washing, rinsing, magnetic bead removal, mixing, dilution, waste liquid extraction, cup changing, and cup discarding. It is compatible with both solid-phase magnetic bead and immunomagnetic bead pretreatment processes, and transports samples to the multi-channel liquid chromatography module 3 using reaction cups as carriers. Furthermore, this module is compatible with a second connection mode to the automated production line, i.e., direct sample aspiration from the production line, rather than from the sample stage.

[0069] In this embodiment, the multi-channel liquid chromatography module 3 and the mass spectrometry detection module 4 also support two docking modes. One is the pipeline mode, which docks with the reaction cup output by the pretreatment module 2 and injects samples one by one. The other is the traditional batch loading mode, which supports the loading of multiple samples in large batches, and is compatible with the needs of high-throughput LC-MS detection only. It not only supports samples extracted by magnetic beads, but also samples processed by protein precipitation.

[0070] In this embodiment, the multi-channel liquid chromatography module 3 employs unique multi-channel technology and flow path design, featuring rapid and efficient operation with a small dead volume, significantly improving detection efficiency and providing stable and consistent results. Furthermore, unique noise reduction, temperature control, and filtration designs ensure efficient operation of the mechanical vacuum pump while creating a cleaner environment, reducing the risk of abnormal detection results. The equipment provided in this application supports high-throughput detection of large batches of similar items and mixed detection of different items. Combined with integrated control software, it achieves fully automated and efficient sample detection, with samples entering and reports exiting, greatly reducing the barrier to entry, space requirements, and costs. The following provides a detailed description of each component and its function.

[0071] Please see Figure 2 As shown, in this embodiment, the multi-channel liquid chromatography module 3 includes a multi-channel injection unit 31, a reagent delivery unit 32, a column loading unit 33, and a waste liquid unit 34. Furthermore, it also includes a pre-vacuum system unit 35, a reagent storage unit 36, a consumable information input unit 37, and a status indicator unit 38.

[0072] The multi-channel injection unit 31 includes a reaction cup gripper mechanism 6 (such as...). Figure 7 (as shown) and a sample injection mechanism for sample gripping and injection; the reagent delivery unit 32 includes a reagent pump assembly 321 (as shown) Figure 20 As shown), it is used for the delivery of the mobile phase and sample injection; the column loading unit 33 includes a cartridge loading mechanism and a switching valve, for the cartridge 334 (as shown) Figure 21 The loading and switching of (as shown); the waste liquid unit 34 is used to collect waste liquid.

[0073] Please see Figures 3 to 6 As shown, the multi-channel liquid phase module 3 has two specific liquid circuit connection methods, among which... Figure 3 and Figure 4 The diagram shown illustrates sample aspiration and injection under one connection method. Figure 5 and Figure 6 The diagram shows a sample aspiration and injection process under another connection method.

[0074] like Figure 3 and Figure 4As shown, the reagent delivery unit 32 provides power for the delivery of the mobile phase and the sample injection, that is, the mobile phase carries the sample together. The injection process is as follows: 1) The injection valve 313 is in the aspiration mode; 2) The aspiration arm 311 completes needle washing in the needle washing chamber 314; 3) The injection pump 312 completes sample aspiration through the aspiration arm 311; 4) The aspiration arm 311 completes two needle washings in the needle washing chamber 314; 5) The aspiration arm 311 moves to the injection position of the needle holder needle washing component 315 and inserts into the injection position in the needle holder; 6) The injection valve 313 switches to the injection mode; 7) The reagent pump group 321 provides power to deliver the sample into the pre-column switching valve 331; 8) The pre-column switching valve 331 and the post-column switching valve one 332 switch synchronously to select the chromatographic cartridge 334 (as shown in the figure, column 3 and column 4 are selected), and the post-column switching valve two 333 switches to select column 3 or column 4 to enter the mass spectrometry detection module 4 for detection; when the pre-column switching valve 331 and the post-column switching valve one 332 switch synchronously to another position, column 1 and column 2 are selected.

[0075] In some embodiments, the post-column switching valve 332 and post-column switching valve 333 can be replaced by a four-position nine-way valve to achieve rapid switching of the four chromatographic cartridges 334. This flow path design can minimize the dead volume of the tubing, which is beneficial to ensuring the stability and good precision of batch injection. The multi-channel liquid chromatography module 3 switches the chromatographic cartridges 334 according to the gradient time. Both chromatographic cartridges 334 are in the sample injection gradient. When one chromatographic cartridge 334 completes detection and enters equilibrium, the other chromatographic cartridge 334 is immediately switched, and the sample enters the mass spectrometry detection module 4. Through software scheduling and calculation, seamless switching of sample injection and acquisition is achieved, which is highly efficient.

[0076] like Figure 5 and Figure 6 As shown, it is similar to Figure 3 and Figure 4 The main difference between the illustrated embodiments lies in the connection position of the injection pump 312. In this embodiment, the injection pump 312 is not on the high-pressure path of the reagent pump assembly 321, does not need to withstand high pressure, reduces wear on the sealing ring, and has a relatively longer lifespan. Figure 5 and Figure 6 The specific sample aspiration and injection process of the connection method shown is the same as Figure 3 and Figure 4 The embodiments shown are similar and can be understood with reference to the above text, so they will not be repeated here.

[0077] Please see Figure 7 As shown, the multi-channel sample injection unit 31 includes a mounting plate 310 and a reaction cup gripper mechanism 6, a sample injection mechanism, and a batch sample loading mechanism 7 disposed on the mounting plate 310, which can realize batch sample loading and single-tube automated sample loading.

[0078] like Figure 8As shown, in this embodiment, the reaction cup gripper mechanism 6 includes a flexible gripper 66, a gripper drive assembly, and a cup dropping assembly. The flexible gripper 66 is used to grip and release the reaction cup 5; the gripper drive assembly is power-transmittedly connected to the flexible gripper 66 to drive the flexible gripper 66 to rotate left and right and translate up and down; the cup dropping assembly is used to drive the flexible gripper to release the reaction cup 5. Specifically, the gripper drive assembly includes a lifting motor 611, a lifting synchronous belt 612, a rotary motor 613, a rotary main wheel 614, a rotary synchronous belt 615, a rotary driven wheel 616, a lifting origin sensor baffle 621, a lifting origin sensor 622, a rotary origin sensor 623, a rotary origin sensor baffle 624, and a guide rod 65. The cup dropping assembly includes a fixed plate 631, an electrically controlled telescopic component 632, an active push rod 641, a cup dropping rocker 642, and a passive push rod 643. The active push rod 641 and the passive push rod 643 are connected to the two ends of the cup-dropping rocker 642. The passive push rod 643 is located near the flexible gripper 66, and the active push rod 641 is located near the electrically controlled telescopic component 632.

[0079] During operation, the lifting motor 611 rotates, driving the lifting synchronous belt 612 to move up and down, causing the flexible gripper 66 to move up and down following the guide rod 65, completing the movement towards and away from the reaction cup 5. The rotary motor 613 drives the rotating main wheel 614 and the rotating synchronous belt 615 to rotate the driven wheel 616, causing the flexible gripper 66 to rotate following the guide rod 65, realizing the gripping of the reaction cup 5 at different positions. When it is necessary to grasp the reaction cup 5, the weight of the active push rod 641 of the cup-dropping assembly is greater than that of the passive push rod 643, causing the end of the passive push rod 643 to naturally tilt upwards. The flexible gripper 66 descends to the position of the reaction cup 5, and the reaction cup 5 is embedded in the flexible gripper 66, thus completing the grasping of the reaction cup 5. When it is necessary to release the reaction cup 5, the flexible gripper 66 is first lowered to the position where the reaction cup 5 is placed. Then, the electrically controlled telescopic component 632, such as a telescopic electromagnet, extends its telescopic rod, the active push rod 641 moves upwards, and the passive push rod 643 moves downwards due to the lever movement of the cup-dropping rocker 642, squeezing the reaction cup 5 out of the flexible gripper 66, thus realizing the release of the reaction cup 5. As another option, the action of releasing the reaction cup can also be replaced by a linear motor. The shaft of the linear motor is telescopic and can be connected to the passive push rod 643 to realize the function of releasing the reaction cup.

[0080] Please see Figure 9As shown, in this embodiment, the injection mechanism includes at least two injection channels, each including: a valve-pump assembly 9, which includes an injection valve 313 connected to the column loading unit 33 for injecting a sample into the column loading unit 33; a sample suction arm assembly 8 for aspirating a sample, one end of which is connected to a suction needle and the other end of which is connected to the injection valve 313; a needle holder and needle washing assembly 315 connected to the injection valve 313, including an injection chamber for inserting the suction needle to deliver a sample to the injection valve 313, and a needle washing chamber 314 for inserting the suction needle to wash the suction needle; and an injection pump 312 connected to the injection valve 313 for providing suction power.

[0081] Please see Figure 10 As shown, the sampling arm assembly 8 includes a sampling arm 311, an arm drive component 3161, a lead screw 318, a slider 3182, and a guide rail 3181. The arm drive component 3161 drives the sampling arm 311 to translate via the lead screw 318. The slider 3182 is connected to the sampling arm 311 and slides in cooperation with the guide rail 3181. In this embodiment, the arm drive component 3161 includes a motor, an arm drive timing belt 3162 driven by the motor, and an arm drive wheel 3163.

[0082] Please see Figure 11 As shown, the valve-pump assembly 9 includes a cleaning fluid delivery pump 92, a cleaning fluid suction pump 94, and a three-way valve 93. The cleaning fluid delivery pump 92 is connected to the cleaning fluid bottle and the needle washing chamber 314 to supply cleaning fluid into the needle washing chamber 314. The cleaning fluid suction pump 94 is connected to the needle washing chamber 314 and the pipeline 3157 to discharge waste liquid in the needle washing chamber 314 to the waste liquid unit 34. The three-way valve 93 connects the cleaning fluid delivery pump 92 and the cleaning fluid suction pump 94 to switch the connection between the cleaning fluid delivery pump 92, the cleaning fluid suction pump 94, and the needle washing chamber 314. Specifically, the valve-pump assembly 9 includes a base plate 91, an injection valve 313 mounted on the base plate 91, a cleaning fluid delivery pump 92, a cleaning fluid suction pump 94, and a three-way valve 93. The injection valve 313 has six ports, which are respectively connected to the quantitative loop of the aspiration arm 311, the injection pump 312, the filter 317, the reagent pump group 321 of the reagent delivery unit 32, the post-column switching valve 332, and the waste liquid tube. The cleaning solution delivery pump 92 is connected to the cleaning solution bottle to provide cleaning reagent to the needle holder washing component 315. The cleaning solution aspiration pump 94 is connected to the waste liquid tube to aspirate the waste liquid from the needle holder washing component 315. The three-way valve 93 has three ports: a first port 931, a second port 932, and a third port 933. The two ports are connected to the cleaning solution delivery pump 92 and the cleaning solution aspiration pump 94, and the middle port is connected to the needle holder washing component 315. Both the cleaning solution delivery pump 92 and the cleaning solution aspiration pump 94 have two ports: a pump inlet 941 and a pump outlet 942.

[0083] Please see Figure 12 As shown, in this embodiment, the sample injection pump 312 includes a pump bracket 3122, a pump body 3121 disposed on the pump bracket 3122, a zero-point sensor 3127 disposed on the pump body 3121, and a pump body 3121 drive assembly for driving the pump body 3121. The pump body 3121 is connected to the sample suction arm assembly 8 and the sample injection valve 313. The pump body 3121 drive assembly includes a drive motor 3123, a synchronous pulley 3124, a synchronous belt 3125, and a driven pulley 3126. The synchronous pulley 3124 is connected to the output end of the drive motor 3123, the driven pulley 3126 is connected to the pump body 3121, and the synchronous belt 3125 connects the synchronous pulley 3124 and the driven pulley 3126.

[0084] Please see Figure 13 As shown, the needle holder and needle washing component 315 includes a main body component 3151, a base 3152, and an adjustment mechanism. The main body component 3151 is movably disposed on the base 3152 or fixed to the movable base 3152. The adjustment mechanism drives the main body component 3151 to move relative to the base 3152 or to move together with the base 3152, so as to facilitate adjustment to the relative position with the sampling arm 311. In this embodiment, the adjustment mechanism includes a calibration screw 3153, a limiting ring 3154, and a screw seat 3155. The calibration screw 3153 can be manually turned and rotated. The calibration screw 3153 is supported by the screw seat 3155 and threadedly connected to the base 3152. A reinforcing block 3156 is provided at the lower part of the main body component 3151 to strengthen the main body component 3151 and ensure the structural stability of the main body component 3151.

[0085] Please see Figures 14 to 16As shown, in this embodiment, the needle holder and needle washing component 315 includes a main body component 3151, and the injection chamber and the needle washing chamber 314 are formed on the main body component 3151. That is, in this embodiment, the needle holder for injection and the needle washing chamber are constructed on the same component; in other embodiments, they can be set as separate parts. In this embodiment, a sealing ring 3159 and a sealing ring cover plate 3158 for pressing the sealing ring 3159 are provided in the injection chamber, and the injection chamber is connected to the injection valve 313 through a pipeline 3157. The needle washing chamber 314 has a cleaning fluid channel 3142 and a needle washing channel 3141 that are connected near the upper part. The cleaning fluid channel 3142 is filled with cleaning fluid and overflows into the needle washing channel 3141. The cleaning fluid channel 3142 has an inlet for input of cleaning fluid and an outlet for output of cleaning fluid. The needle washing channel 3141 has a waste fluid outlet 3144 for discharge of waste fluid. The upper end of the injection chamber has an overflow groove 3150 communicating with the needle washing channel 3141, so that the liquid overflowing from the sealing ring cover plate 3158 flows to the needle washing channel 3141. In use, cleaning fluid is injected into the cleaning fluid channel 3142, and the cleaning fluid overflows into the needle washing channel 3141, where the sampling needle completes the needle washing process.

[0086] Please see Figure 17 As shown, in this embodiment, the multi-channel sample loading unit 31 includes a batch loading mechanism 7, which includes an insulated box 71, a temperature control module 72 for controlling the temperature inside the insulated box 71, and a movable tray 73 disposed inside the insulated box 71 and drivable along a first direction. The insulated box 71 includes a movable cover 711 and a fixed cover. The movable cover 711 is used to open the insulated box 71 to load and unload sample trays 74 therein. The fixed cover has a sample loading slot 712 extending perpendicular to the first direction. The movable tray 73 carries samples arranged in an array and moves along the first direction so that the samples arranged in an array are exposed column by column below the sample loading slot 712 for the sample loading mechanism to pick up. The sample tray 74 is used to load processed samples that can be directly injected, and it can be a standard specification such as a 96-well deep well plate, a 96-well shallow well plate, or a 48-well sample bottle. Furthermore, it also includes a sample tray, which is mounted on a movable tray 73 and is retractable for easy loading of the sample tray 74. Additionally, different tooling can be mounted for loading sample containers of special sizes. The movable tray 73 is driven by a transmission belt 731 to allow the sample to pass through the injection slot 712. When the sample moves to the injection slot 712, the suction arm 311 of the suction arm assembly 8 can perform a suction operation. After the movable cover plate 711 is closed, the temperature control module 72 controls the temperature of the chamber inside the insulation box 71 to ensure the stability of the sample during the injection process.

[0087] Please see Figure 18 As shown, in this embodiment, the temperature control module 72 includes a thermoelectric semiconductor chip 721, a temperature control adapter plate 722, an inner heat sink 723, an inner fan 724, an outer heat sink 726, an outer fan 727, and a heat insulation component 725. The heat insulation component 725 surrounds the thermoelectric semiconductor chip 721, and the thermoelectric semiconductor chip 721 and the heat insulation component 725 are sandwiched between the inner heat sink 723 and the outer heat sink 726. The inner fan 724 drives airflow through the inner heat sink 723 into the insulation box, and the outer fan 727 drives airflow outside the insulation box through the outer heat sink 726. The thermoelectric semiconductor chip 721, also known as a semiconductor cooling chip or Peltier, has a cold side and a hot side, which can be switched according to cooling or heating needs. The outer heat sink 726 and the inner heat sink 723 are attached to its two sides respectively, and the temperature is controlled by the fan blowing air. Furthermore, the temperature control module 72 also includes a temperature sensor 7212 and a temperature fuse 7211, which are installed near the thermoelectric semiconductor chip 721 to detect the temperature and provide power-off protection when the temperature is too high, thus ensuring the safety of temperature control.

[0088] Please see Figure 19 and Figure 20 As shown, in this embodiment, the reagent delivery unit 32 includes a track support 324, a pull-out track 325, at least two reagent pump sets 321, a filling pump 326, a three-way connector 322, and a waste liquid connector 323. The pull-out track 325 is connected to the reagent pump sets 321 and can be pulled and moved on the track support 324. The three-way connector 322 connects the reagent bottle 361 and the two reagent pump sets 321. The inlet of the filling pump 326 is connected to the two reagent pump sets 321, and its outlet is connected to the waste liquid connector 323. Furthermore, each of the reagent pump units 321 includes a first unit and a second unit for receiving different reagents, a mixer 3214 for mixing different reagents, a waste liquid outlet 3144 for discharging waste liquid, and a filling and cleaning valve 3215 for switching the direction of reagent flow. The first unit includes a unit proportional valve 3211, a unit primary pump 3212, and a unit secondary pump 3213. The second unit includes a unit proportional valve 3216, a unit primary pump 3217, a unit secondary pump 3218, and a waste liquid discharge port 3219.

[0089] The reagent pump assembly 321 is used to assist in the power delivery of the mobile phase and samples. It is equipped with a pull-out rail 325 for easy removal for maintenance operations. The perfusion pump 326 is used for rapid replacement of mobile phase reagents, which can quickly meet the reagent requirements of new projects and shorten the changeover time. It is connected to the perfusion cleaning valve 3215 on the two reagent pump assemblies 321. The perfusion cleaning valve 3215 is commonly referred to as a purge valve in the industry. Both the first and second units include a primary pump and a secondary pump, which are connected in series to accelerate reagent replacement and perfusion.

[0090] In practical applications, the above structure allows for flexible switching and proportion adjustment of different reagents by connecting different reagents to the unit proportional valve 3211 and the unit proportional valve 3216, supporting the reagent requirements of different detection projects. Taking the first unit as an example, the reagents sequentially enter the unit primary pump 3212, the unit secondary pump 3213, and the perfusion cleaning valve 3215; similarly, the reagents of the second unit pass through the perfusion cleaning valve 3215 in a similar process. The perfusion cleaning valve 3215 is a two-position six-way valve, which allows the reagents of each unit to have two states: one is entering the mixer 3214, and the other is entering the waste liquid connector 323 of the reagent delivery unit 32, realizing the automatic mixing of the reagents of the two units. After the reagents of the two units are fully mixed in the mixer 3214, they enter the injection valve 313, realizing the reagent balance and sample delivery of the liquid phase module flow path.

[0091] Please see Figure 21 As shown, in this embodiment, the column loading unit 33 includes a cartridge loading mechanism and a switching valve for loading and switching cartridges 334. The cartridge loading mechanism includes a cartridge quick-release assembly 335, a cartridge control button 337, a control button mounting plate 336, and a cartridge indicator light 338. The cartridge control button 337 triggers the cartridge quick-release assembly 335 to load or release the cartridge 334, and the cartridge indicator light 338 displays the status of the cartridge 334. The switching valve includes a pre-column switching valve 331 located upstream of the cartridge loading mechanism and two post-column switching valves located downstream of the cartridge loading mechanism, namely, post-column switching valve one 332 and post-column switching valve two 333.

[0092] Specifically, the number of chromatographic cartridges 334 loaded at one time can be increased or decreased; the larger the number, the greater the throughput, and the corresponding number of pre-column switching valves 331 and post-column switching valves increases accordingly. During operation, the pre-column switching valve 331 and post-column switching valve one 332 switch synchronously, selecting chromatographic cartridge 334. The post-column switching valve two selects different chromatographic cartridges 334 for detection in the mass spectrometry detection module 4. Specifically, the chromatographic cartridges 334 can be switched according to the gradient time. Both chromatographic cartridges 334 are in the sample injection gradient. When one chromatographic cartridge 334 completes detection and reaches equilibrium, the other chromatographic cartridge 334 is immediately switched. Through software scheduling and calculation, seamless switching of sample acquisition is achieved, maximizing efficiency. In some embodiments, the post-column switching valve one 332 and post-column switching valve two 333 can be replaced by a four-position nine-way valve to achieve rapid switching of the four chromatographic cartridges 334. This flow path design can minimize the dead volume of the tubing, which is beneficial for ensuring the stability and good precision of batch injection.

[0093] The control button mounting plate 336 is equipped with the chromatography cartridge control button 337 and the chromatography cartridge indicator light 338, which are used to control the loading and unloading of the chromatography cartridge 334. There are multiple chromatography cartridge control buttons 337. Pressing a chromatography cartridge control button 337 will drive the corresponding chromatography cartridge quick-release assembly 335 to move, thereby loading the chromatography cartridge 334. After insertion, the sealing action is completed. Finally, the chromatography cartridge indicator light 338 will light up to indicate that the loading is complete. In the non-injection state, pressing the chromatography cartridge control button 337 will drive the chromatography cartridge quick-release assembly 335 to switch to the unloaded state, and the chromatography cartridge 334 can be removed.

[0094] Furthermore, in this embodiment, the quick-release assembly 335 of the chromatographic cartridge of the column loading unit 33 includes an RFID reading module for convenient direct information reading. The chromatographic cartridge 334 is affixed with an RFID tag or barcode tag, which can be directly read by the RFID reading module or manually scanned to enter the chromatographic cartridge information, preventing incorrect loading of the chromatographic cartridge. In addition, the quick-release assembly 335 also includes temperature control components such as silicone rubber heating pads, heating wires, or Peltiers, as well as temperature sensors and temperature fuses, to achieve independent temperature control of the chromatographic cartridge 334. The temperature of different chromatographic cartridges 334 can be controlled at different temperatures to support different detection methods, ensuring that they do not interfere with each other when different projects are performed together.

[0095] Please see Figure 22 and Figure 23As shown, in this embodiment, the multi-channel liquid chromatography module 3 further includes a reagent storage unit 36. The reagent storage unit 36 ​​includes a reagent bottle support 362 for supporting reagent bottles 361, a weighing component for monitoring reagent levels, and a reading component for identifying reagent information. The reagent bottle support 362 is provided with several accommodating cavities to allow the lower half of the reagent bottle 361 to be inserted into it, ensuring that the reagent bottle 361 will not tip over. The weighing component includes a weighing base 363 and a weighing module interlayer 364, which is mounted on the weighing base 363. The weighing module interlayer includes a reagent bottle tray 3641, a tray sealing ring 3642, a weighing sensor 3643, and a weighing sensor bracket 3644. The reading component includes an antenna tray 3645 and a reader 3646. In this embodiment, the reader 3646 is an RFID reading module, and the antenna tray 3645 is an RFID antenna tray. Reagent bottle 361 contains various reagents required for the testing. An RFID tag and barcode are affixed to the bottom for tracking reagent information. A reagent bottle tray 3641 and an RFID reader module are mounted on an RFID antenna tray, which is installed on top of a weighing sensor 3643. This enables real-time detection of the weight of reagent bottle 361 and its contents, monitoring reagent levels and identifying the type and specifications of reagent bottle 361 to prevent incorrect reagent placement and testing errors.

[0096] Please see Figure 24 As shown, in this embodiment, the waste liquid unit 34 includes a waste liquid tray 341, a waste liquid bucket 342, a waste liquid pipe 343, and an air filter 344. The waste liquid bucket 342 collects all waste liquid generated by the equipment; all waste liquid from the instrument is connected to the waste liquid pipe 343 and enters the waste liquid bucket 342. The waste liquid tray 341 holds the waste liquid bucket 342 to prevent it from breaking or tipping over. The air filter 344 ensures that the waste liquid bucket 342 is open to the atmosphere, but filters the gas to prevent toxic and harmful gases from evaporating into the air.

[0097] Please see Figure 25 and Figure 26 As shown, in this embodiment, the multi-channel liquid phase module 3 further includes a pre-vacuum system unit 35. The pre-vacuum system unit 35 includes a soundproof box 351, a vacuum pump disposed inside the soundproof box 351 and connected to the mass spectrometry detection module 4, and a fan cooling assembly for blowing air into the soundproof box 351 to dissipate heat. The wall of the soundproof box 351 is provided with a sound insulation material layer, and the inlet on the wall of the soundproof box 351 for the fan cooling assembly to enter and exit is provided with filter cotton.

[0098] Specifically, the soundproof enclosure 351 is generally a cuboid structure, comprising a front panel 352, a top panel, a bottom panel 356, a rear panel, and left and right side panels. The bottom panel 356 is equipped with casters 354 to facilitate movement of the pre-vacuum system unit 35, and also includes an oil collection box 355. The front panel 352 features a front air inlet 3521, a brush 3522, an acrylic glass viewing window 3523, and a temperature display 3524. The right side panel includes an intake fan 3531, a main switch 3532, and a light switch 3533. The bottom panel 356 houses the oil collection box 355, along with a right bracket 3551 and a left bracket 3552 supporting the oil collection box 355. The rear panel has a rear air inlet 357, and the left side panel has an exhaust fan 358.

[0099] The pre-vacuum system unit 35 is equipped with a mechanical vacuum pump, which is connected to the mass spectrometry detection module 4 via piping to draw in air and create a low vacuum environment. The inner wall of the soundproof enclosure 351 is lined with sound-absorbing cotton, such as polyurethane or EVA, to reduce the noise of the mechanical vacuum pump. The front panel air inlet 3521 and the rear panel air inlet 357 face the mechanical vacuum pump to ensure the normal operation of its built-in fan. Both the intake fan 3531 and the exhaust fan 358 contain filter cotton, ensuring airflow while providing sound insulation and filtering gases emitted by the mechanical vacuum pump, such as lubricating oil vapor, to prevent them from affecting the performance of the mass spectrometry detection module 4 and causing environmental pollution. The temperature display 3524 is used to detect and display temperature values ​​in real time. The pipeline cable of the mechanical vacuum pump passes through the brush 3522 and connects to the mass spectrometry detection module 4. During equipment operation, the status indicator unit 38 displays the instrument's operating status, such as normal operation, instrument malfunction, standby, etc., facilitating instrument management and maintenance.

[0100] Please see Figure 27 and Figure 28 As shown, in this embodiment, the mass spectrometry detection module 4 includes a mass spectrometry detection unit 41, an ion source maintenance platform 42, and a gas supply system 43. The mass spectrometry detection unit 41 has a vacuum tube interface 411 for connecting to the pre-vacuum system unit 35. The gas supply system 43 outputs three gases: dry compressed gas, zero-stage air, and nitrogen. These gases are connected to the compressed air interface 412, exhaust gas support port 413, exhaust gas port 414, and nitrogen port 415 of the mass spectrometry detection unit 41 via pipelines passing through the main pipeline interface 433 of the gas supply system 43, providing gas support for the detector mass spectrometry detection unit 41. The cooling fan 432 provides heat dissipation for the gas supply system 43. The mass spectrometry detection unit 41 is positioned above the gas supply system 43, and the gas supply system 43 is equipped with caster assemblies 431 to facilitate the overall movement of the mass spectrometry detection module 4.

[0101] The control and data processing module is a hardware and software integrated system that controls the automatic operation of the integrated machine and analyzes sample data. During use, it can be matched with a workstation, and the software is installed in the workstation to achieve fully automatic control of four modules: sample stage module 1, pretreatment module 2, multi-channel liquid chromatography module 3, and mass spectrometry detection module 4. The system integrates automatic integration, automatic review, and automatic alarm and retesting functions for abnormal samples. Test results are automatically reviewed and transmitted to the LIMS, ultimately achieving a "sample in, report out" laboratory work result. Combining internal quality control and patient-based real-time quality control, the system is designed with automatic quality control functions, including traditional internal laboratory quality control and patient-based real-time quality control (PBRTQC). Based on a fully automated workflow, the system ensures the quality of test results and the overall quality control level of the laboratory, significantly improving the efficiency and reliability of automated testing.

[0102] As described above, the fully automated mass spectrometry detection integrated machine provided in this application adopts a modular design, allowing for flexible configuration to meet the needs of different users and possessing strong compatibility and functional expandability. The fully automated mass spectrometry detection integrated machine provided in this application includes a sample stage module 1, a pretreatment module 2, a multi-channel liquid chromatography module 3, and a mass spectrometry detection module 4. These modules can be combined according to user needs to meet the fully automated requirements of the entire process from sample input to report output. It is simple to use, greatly reducing the barrier to entry and the professional skills required of users, significantly lowering costs, and improving the equipment's scalability, ease of maintenance, adaptability to different scenarios, and work efficiency.

[0103] Furthermore, the equipment is compatible with liquid chromatography-mass spectrometry (LC-MS) technologies using protein precipitation and magnetic bead solid-phase extraction, supporting the detection of multiple items. The equipment features multi-layer integrated multi-channel injection technology and a convenient column loading and switching module, enabling high-throughput sample processing. It is fast and efficient, and its unique flow path design results in a small dead volume, significantly improving detection efficiency and providing stable and consistent results. Unique noise reduction, temperature control, and filtration designs ensure efficient operation of the mechanical vacuum pump while creating a cleaner environment, reducing the risk of abnormal test results. The equipment supports high-throughput detection of large batches of similar items and mixed detection of different items; flexible reagent combinations and switching automatically and quickly match different detection items; real-time monitoring of consumable usage status using RFID and barcode dual-mode, intelligent consumable information management, and convenient operation; and integrated control software enables fully automated and efficient sample detection and intelligent data interpretation, with sample input and report output, greatly reducing the barrier to entry, space requirements, and costs.

[0104] The embodiments described above are merely illustrative of 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 the patent 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 protection of this application. Therefore, the patent protection scope of this application should be determined by the appended claims.

Claims

1. A fully automated mass spectrometry detection integrated machine, characterized in that, The fully automated mass spectrometry detection integrated machine includes: The sample stage module is designed to interface with a production line to load samples. A pretreatment module, adapted to interface with the sample stage module to obtain a sample from the sample stage module, the pretreatment module being used to pretreat the sample for subsequent liquid chromatography separation; A multi-channel liquid chromatography module is adapted to interface with the pretreatment module to obtain pretreated samples for liquid chromatography separation. The mass spectrometry detection module is adapted to interface with the multi-channel liquid chromatography module to acquire samples separated by liquid chromatography for mass spectrometry detection; and, The control and data processing module is used to control the automatic operation of the all-in-one machine. The sample stage module, pretreatment module, multi-channel liquid chromatography module, and mass spectrometry detection module are all independent modules, and two or more of them are used in combination. The sample stage module, pretreatment module, multi-channel liquid chromatography module, and mass spectrometry detection module are respectively configured to be suitable for batch loading of multiple samples at one time and batch loading of single samples one by one on the production line. The multi-channel liquid chromatography module includes a multi-channel injection unit and a column loading unit. The multi-channel injection unit is suitable for batch loading of multiple samples at once and sequential loading of single samples on a production line to support mixed loading of different detection items. The column loading unit is used for loading and switching of chromatographic cartridges. It includes a temperature control device for independently controlling the temperature of different chromatographic cartridges, so as to control different chromatographic cartridges to different temperatures and meet the different temperature requirements of chromatographic cartridges when different detection items are mixed for detection. The multi-channel sample introduction unit includes a batch sample introduction mechanism for batch sample introduction, a reaction cup gripper mechanism for single-tube automated sample introduction, and a sample introduction mechanism for sample introduction. The reaction cup gripper mechanism is mounted on the mounting plate and is used to dock with the reaction cups output by the pretreatment module to realize sample introduction one by one. The batch sample introduction mechanism is mounted on the mounting plate and located below the sample introduction mechanism so that the sample introduction mechanism can directly take samples. The reaction cup gripper mechanism includes: Flexible grippers are used to grasp and release reaction cups; A gripper drive assembly is powerably connected to the flexible gripper to drive the flexible gripper to rotate left and right and translate up and down; and, The cup-dropping assembly includes an electrically controlled telescopic component, an active push rod, a cup-dropping rocker, and a passive push rod. The active push rod and the passive push rod are connected to both ends of the cup-dropping rocker. The passive push rod is positioned close to the flexible gripper, and the active push rod is positioned close to the electrically controlled telescopic component. The batch sample loading mechanism includes an insulated box, a temperature control module for controlling the temperature inside the insulated box, and a movable tray located inside the insulated box and drivable along a first direction. The insulated box includes a movable cover and a fixed cover. The movable cover is used to open the insulated box to take out and place a sample tray therein. The fixed cover has a sample inlet slot extending perpendicular to the first direction. The movable tray carries the samples arranged in an array and moves along the first direction so that the samples arranged in an array are exposed one by one below the sample inlet slot for the sample loading mechanism to take samples.

2. The fully automated mass spectrometry detection integrated machine according to claim 1, characterized in that, The column loading unit includes a cartridge loading mechanism and a switching valve; the multi-channel liquid chromatography module also includes: A reagent delivery unit, including a reagent pump assembly, is used for the delivery of the mobile phase and sample injection; and, Waste liquid unit, used to collect waste liquid.

3. The fully automated mass spectrometry detection integrated machine according to claim 2, characterized in that, The sample introduction mechanism includes at least two sample introduction channels, each of which includes: A valve pump assembly, including an injection valve connected to the column loading unit for injecting an sample into the column loading unit; A sampling arm assembly for aspirating samples, one end of which is connected to a sampling needle and the other end to the injection valve; A needle holder and cleaning chamber, connected to the injection valve, includes a sample injection chamber for inserting the sampling needle to deliver a sample to the injection valve, and a cleaning chamber for inserting the sampling needle to clean the sampling needle; and, A sample pump, connected to the sample injection valve, is used to provide the power for sample suction.

4. The fully automated mass spectrometry detection integrated machine according to claim 3, characterized in that, The sampling arm assembly includes a sampling arm, an arm drive, a lead screw, a slider, and a guide rail. The arm drive drives the sampling arm to translate via the lead screw, and the slider is connected to the sampling arm and slides in cooperation with the guide rail.

5. The fully automated mass spectrometry detection integrated machine according to claim 4, characterized in that, The valve-pump assembly includes a cleaning fluid delivery pump, a cleaning fluid suction pump, and a three-way valve. The cleaning fluid delivery pump is connected to the cleaning fluid bottle and the needle washing chamber to supply cleaning fluid to the needle washing chamber. The cleaning fluid suction pump is connected to the needle washing chamber and the waste liquid pipeline to discharge the waste liquid in the needle washing chamber to the waste liquid unit. The three-way valve connects the cleaning fluid delivery pump and the cleaning fluid suction pump to switch the connection between the cleaning fluid delivery pump, the cleaning fluid suction pump, and the needle washing chamber.

6. The fully automated mass spectrometry detection integrated machine according to claim 3, characterized in that, The needle holder and needle washing component includes a main body component, and the injection chamber and the needle washing chamber are formed on the main body component, wherein: The injection chamber is equipped with a sealing ring and a sealing ring cover plate that presses the sealing ring together. The injection chamber is connected to the injection valve through a pipeline. The needle washing chamber has a cleaning fluid channel and a needle washing channel connected near the upper part. The cleaning fluid is introduced into the cleaning fluid channel and overflows into the needle washing channel. The cleaning fluid channel has an inlet and an outlet for the input and output of the cleaning fluid. The needle washing channel has a waste liquid outlet for the discharge of waste liquid. The upper end of the injection chamber has an overflow groove that communicates with the needle washing channel, so that the liquid overflowing from the sealing ring cover plate flows to the needle washing channel. The needle holder and needle washing component includes a main body, a base, and an adjustment mechanism. The main body is movably disposed on the base or fixed to the movable base. The adjustment mechanism drives the main body to move relative to the base or to move together with the base.

7. The fully automated mass spectrometry detection integrated machine according to claim 1, characterized in that, The temperature control module includes a thermoelectric semiconductor chip, an inner heat sink, an inner fan, an outer heat sink, an outer fan, and an insulation component. The insulation component surrounds the thermoelectric semiconductor chip, and the thermoelectric semiconductor chip and the insulation component are sandwiched between the inner and outer heat sinks. The inner fan drives airflow through the inner heat sink into the insulation box, and the outer fan drives airflow outside the insulation box through the outer heat sink.

8. The fully automated mass spectrometry detection integrated machine according to claim 2, characterized in that, The reagent delivery unit includes a track support, a pull-out track, at least two reagent pump sets, a filling pump, a T-connector, and a waste liquid connector. The pull-out track is connected to the reagent pump sets and can be pulled and moved on the track support. The T-connector connects the reagent bottle and the two reagent pump sets. The inlet of the filling pump is connected to the two reagent pump sets, and its outlet is connected to the waste liquid connector.

9. The fully automated mass spectrometry detection integrated machine according to claim 8, characterized in that, Each of the reagent pump units includes a first unit and a second unit for receiving different reagents, a mixer for mixing different reagents, a waste liquid outlet for discharging waste liquid, and a filling and cleaning valve for switching the direction of reagent flow. The first unit includes a proportional valve, a primary pump, and a secondary pump. The second unit includes a proportional valve, a primary pump, a secondary pump, and a waste liquid outlet.

10. The fully automated mass spectrometry detection integrated machine according to claim 2, characterized in that, The chromatography cartridge loading mechanism includes a chromatography cartridge quick-release assembly, a chromatography cartridge control button, and a chromatography cartridge indicator light. The chromatography cartridge control button is used to trigger the chromatography cartridge quick-release assembly to load or release the chromatography cartridge, and the chromatography cartridge indicator light is used to display the status of the chromatography cartridge. The switching valve includes a pre-column switching valve located upstream of the chromatogram loading mechanism and two post-column switching valves located downstream of the chromatogram loading mechanism.

11. The fully automated mass spectrometry detection integrated machine according to claim 2, characterized in that, The multi-channel liquid phase module also includes a reagent storage unit, which includes a reagent bottle support for carrying the reagent bottle assembly, a weighing component for monitoring the reagent level, and a reading component for identifying reagent information.

12. The fully automated mass spectrometry detection integrated machine according to claim 2, characterized in that, The multi-channel liquid phase module also includes a pre-vacuum system unit, which includes a soundproof box, a vacuum pump located inside the soundproof box and connected to the mass spectrometry detection module, and a fan cooling assembly for blowing air into the soundproof box to dissipate heat. The walls of the soundproof box are provided with a layer of sound-insulating material, and the inlets on the walls of the soundproof box for the fan cooling assembly to enter and exit are provided with filter cotton.

13. The fully automated mass spectrometry detection integrated machine according to claim 1, characterized in that, The control and data processing module is used to perform fully automatic control of the sample stage module, pretreatment module, multi-channel liquid chromatography module and mass spectrometry detection module. The control and data processing module is configured to control the integrated device to perform automatic integration, automatic review and automatic alarm and retesting of abnormal samples, and quality control management, so as to realize the laboratory work results of sample entry and exit.

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