Liquid chromatography-mass spectrometry apparatus and control method therefor

Abstract

The present application is applicable to the field of medical devices, and discloses a liquid chromatography-mass spectrometry apparatus and a control method for the liquid chromatography-mass spectrometry apparatus. The liquid chromatography-mass spectrometry apparatus comprises a sample storage device, a pretreatment device, a chromatography device, a mass spectrometry detection device, and a controller. The chromatography device comprises a test solution preparation channel, a test solution transfer assembly, a liquid phase fluid delivery assembly, and a chromatography column. An operating pressure outputted by the liquid phase fluid delivery assembly is less than or equal to 20 MPa. The length of the chromatography column is greater than or equal to 3 mm and less than or equal to 35 mm. A sample comprises a target substance to be measured, and the target substance to be measured comprises at least one of vitamin D, a steroid hormone, and a catecholamine. The present application reduces costs of the liquid chromatography-mass spectrometry apparatus.

Description

Liquid chromatography-mass spectrometry equipment and its control method Technical Field

[0001] This application relates to the field of medical devices, and more particularly to a liquid chromatography-mass spectrometry (LC-MS) device and a control method for the LC-MS device. Background Technology

[0002] In related technologies, clinical mass spectrometry detection of trace substances (concentrations as low as pg / mL) such as vitamin D, steroid hormones, and catecholamines employs ultra-high performance liquid chromatography-mass spectrometry (UPLC / UHPLC) tandem mass spectrometry, equipped with chromatographic columns of long length, small inner diameter, and small particle size (e.g., 2.1mm*100mm, 1.7μm) to meet clinical testing needs. However, the pressure of UPLC / UHPLC systems has also increased significantly, with column pressures generally exceeding 40MPa, and some even reaching baseline pressures above 60MPa and peak pressures exceeding 80MPa. This leads to a substantial increase in the manufacturing difficulty, production cost, and maintenance cost of high-pressure pumps, valves, and pipelines, as well as a higher frequency of failures. Summary of the Invention

[0003] The first objective of this application is to provide a liquid chromatography-mass spectrometry (LC-MS) device that aims to solve the technical problems of high production and maintenance costs in ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS / MS) devices in the related art.

[0004] To achieve the above objectives, the solution provided in this application is: a liquid chromatography-mass spectrometry (LC-MS) device, characterized in that it comprises:

[0005] A sample storage device for holding a sample container loaded with a sample collected from a human or animal body to load the sample, the sample including a target analyte, the target analyte including at least one of vitamin D, steroid hormones, and catecholamines;

[0006] A pretreatment device is provided for pretreating a sample from a sample container of a sample storage device using magnetic separation to obtain a test solution. The pretreatment device includes a magnetic separation component, a magnetic bead elution component, a reagent dispensing component, and a pipetting component. The pipetting component is used to aspirate at least a portion of the sample from the sample container of the sample storage device and dispense all or part of the aspirated sample into a reaction vessel. The reagent dispensing component is used to dispense an internal standard reagent containing an internal standard and a magnetic bead reagent containing magnetic beads into the reaction vessel, respectively. The magnetic separation component is used to perform magnetic separation and washing on a first mixture in the reaction vessel containing at least the sample, the internal standard reagent, and the magnetic bead reagent to obtain a clear liquid and magnetic beads adsorbed with the internal standard and the target analyte, and then aspirates and discards the clear liquid. The magnetic bead elution component is used to elute the magnetic beads adsorbed with the internal standard and the target analyte obtained from the magnetic separation and washing in the reaction vessel to obtain the test solution. The reagent dispensing component and the pipetting component are two independent components or the same component.

[0007] A chromatographic device, comprising a reagent preparation channel, a reagent transfer assembly, a liquid phase fluid delivery assembly, and a chromatographic column, wherein the reagent transfer assembly, the liquid phase fluid delivery assembly, and the chromatographic column are respectively connected to the reagent preparation channel; the reagent transfer assembly is used to aspirate at least a portion of the reagent obtained by the pretreatment device from the reaction vessel and transfer all or part of the aspirated reagent to the reagent preparation channel; the liquid phase fluid delivery assembly is used to drive the reagent in the reagent preparation channel through the chromatographic column to adsorb the reagent onto the chromatographic column, and to drive the liquid phase fluid through the chromatographic column to elute the reagent adsorbed on the chromatographic column to form a test solution;

[0008] A mass spectrometry detection device, which is connected to the chromatographic column, is used to perform mass spectrometry detection on the test solution flowing out of the chromatographic column and obtain mass spectrometry detection information;

[0009] A controller configured to process the mass spectrometry detection information and output the mass spectrometry detection result of the target analyte in the sample;

[0010] The working pressure output by the liquid phase fluid transport component is less than or equal to 20 MPa;

[0011] The length of the chromatographic column is greater than or equal to 3 mm and less than or equal to 35 mm;

[0012] The output of the mass spectrometry detection results of the sample includes: outputting the mass spectrometry detection results of at least one of vitamin D, steroid hormones, and catecholamines in the sample.

[0013] A second objective of this application is to provide a liquid chromatography-mass spectrometry (LC-MS) device, which includes:

[0014] A sample storage device for holding a sample container loaded with a sample collected from a human or animal body to load the sample, the sample including a target analyte;

[0015] A pretreatment device for pretreating the sample from the sample container of the sample storage device to obtain a test solution;

[0016] A chromatographic device, comprising a reagent preparation channel, a reagent transfer assembly, a liquid phase fluid delivery assembly, and a chromatographic column, wherein the reagent transfer assembly, the liquid phase fluid delivery assembly, and the chromatographic column are respectively connected to the reagent preparation channel; the reagent transfer assembly is used to transfer at least a portion of the reagent obtained by the pretreatment device to the reagent preparation channel; the liquid phase fluid delivery assembly is used to drive the reagent in the reagent preparation channel through the chromatographic column to adsorb the reagent onto the chromatographic column, and to drive the liquid phase fluid through the chromatographic column to elute the reagent adsorbed on the chromatographic column to form a test solution;

[0017] A mass spectrometry detection device, which is connected to the chromatographic column, is used to perform mass spectrometry detection on the test solution flowing out of the chromatographic column and obtain mass spectrometry detection information;

[0018] A controller configured to process the mass spectrometry detection information and output the mass spectrometry detection result of the target analyte in the sample;

[0019] The working pressure output by the liquid phase fluid delivery component is less than or equal to 20 MPa.

[0020] A third objective of this application is to provide a liquid chromatography-mass spectrometry (LC-MS) device, which includes:

[0021] A sample storage device is used to place a sample container loaded with a sample to realize the feeding of the sample, the sample including the target analyte;

[0022] A pretreatment device for pretreating the sample from the sample container of the sample storage device to obtain a test solution;

[0023] A chromatographic device, comprising a reagent preparation channel, a reagent transfer assembly, a liquid phase fluid delivery assembly, and a chromatographic column, wherein the reagent transfer assembly, the liquid phase fluid delivery assembly, and the chromatographic column are respectively connected to the reagent preparation channel; the reagent transfer assembly is used to transfer at least a portion of the reagent obtained by the pretreatment device to the reagent preparation channel; the liquid phase fluid delivery assembly is used to drive the reagent in the reagent preparation channel through the chromatographic column to adsorb the reagent onto the chromatographic column, and to drive the liquid phase fluid through the chromatographic column to elute the reagent adsorbed on the chromatographic column to form a test solution;

[0024] A mass spectrometry detection device, which is connected to the chromatographic column, is used to perform mass spectrometry detection on the test solution flowing out of the chromatographic column and obtain detection information;

[0025] A controller configured to process the mass spectrometry detection information and output the mass spectrometry detection result of the target analyte in the sample;

[0026] The working pressure output by the liquid phase fluid transport component is less than or equal to 20 MPa;

[0027] The output of the mass spectrometry detection results of the target analyte in the sample includes: outputting the mass spectrometry detection results of at least one of vitamin D, steroid hormones, and catecholamines in the sample.

[0028] The fourth objective of this application is to provide a control method for a liquid chromatography-mass spectrometry (LC-MS) device, the control method comprising:

[0029] The pretreatment device controls the pretreatment of samples collected from human or animal bodies to obtain a test solution; the sample includes a target analyte, which includes at least one of vitamin D, steroid hormones, and catecholamines;

[0030] The control solution transfer assembly transfers at least a portion of the solution obtained from the pretreatment device to the solution preparation channel.

[0031] The liquid phase fluid delivery assembly is controlled to drive the test solution in the test solution preparation channel through a chromatographic column with a length greater than or equal to 3 mm and less than or equal to 35 mm by liquid phase fluid at a working pressure of less than or equal to 20 MPa, so that the test solution is adsorbed onto the chromatographic column.

[0032] The liquid phase fluid delivery assembly is controlled to drive the liquid phase fluid through the chromatographic column at a working pressure of less than or equal to 20 MPa, so that the liquid phase fluid elutes the test solution adsorbed on the chromatographic column to form the test solution flowing to the mass spectrometry detection device;

[0033] The mass spectrometer detection device is controlled to perform mass spectrometry detection on the test solution flowing out of the chromatographic column and obtain mass spectrometry detection information;

[0034] The mass spectrometry detection information is processed to output the mass spectrometry detection results of the target analyte in the sample;

[0035] The pretreatment device controls the pretreatment of samples collected from human or animal bodies to obtain a test solution, including: controlling a pipetting component to aspirate at least a portion of the sample from the sample container of the sample storage device and distributing all or part of the aspirated sample to a reaction container; controlling a reagent dispensing component to dispense an internal standard reagent containing an internal standard and a magnetic bead reagent containing magnetic beads to the reaction container to obtain a first mixture; controlling a magnetic separation component to perform magnetic separation and cleaning on the first mixture in the reaction container to obtain a clear liquid and the magnetic beads adsorbed with the internal standard and the target analyte; controlling the magnetic separation component to aspirate and drain the clear liquid in the reaction container; and controlling a magnetic bead elution component to elute the magnetic beads adsorbed with the internal standard and the target analyte obtained by the magnetic separation and cleaning in the reaction container to obtain the test solution.

[0036] Alternatively, the pretreatment device controls the pretreatment of samples collected from a human or animal body to obtain a test solution, including: controlling a pipetting component to aspirate at least a portion of the sample from the sample container of the sample storage device and dispensing all or part of the aspirated sample into a reaction container; controlling a reagent dispensing component to dispense an internal standard reagent containing an internal standard and a magnetic bead reagent containing magnetic beads into the reaction container to obtain a first mixture; and controlling a magnetic separation component to perform magnetic separation and cleaning on the first mixture in the reaction container to obtain a clear liquid containing the internal standard and the target analyte, using the clear liquid as the test solution.

[0037] The liquid chromatography-mass spectrometry (LC-MS) device and its control method provided in this application pre-treat samples collected from human or animal bodies to obtain purified test solutions using a pre-treatment device. A liquid flow delivery component outputs a working pressure of less than or equal to 20 MPa to drive the liquid flow to elute the test solutions adsorbed on the chromatographic column. This achieves detection performance similar to or even exceeding that of ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS), thereby significantly reducing the manufacturing difficulty, production cost, maintenance cost, and failure frequency of the LC-MS device. This application uses a chromatographic column with a length greater than or equal to 3 mm and less than or equal to 35 mm, and a working pressure of less than or equal to 20 MPa to detect at least one of vitamin D, steroid hormones, and catecholamines. While the working pressure is significantly reduced, its detection performance is superior to that of previous related technologies using high-pressure chromatography. Attached Figure Description

[0038] To more clearly illustrate the technical solutions in the embodiments of this application or the prior art, the drawings used in the description of the embodiments or the prior art 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 the structures shown in these drawings without creative effort.

[0039] Figure 1 is a schematic diagram of the results obtained by the liquid chromatography-mass spectrometry device provided in the embodiments of this application;

[0040] Figure 2 is a schematic diagram of the liquid path of a single chromatographic column provided in an embodiment of this application;

[0041] Figure 3 is a schematic diagram of the dimensions of the chromatographic column provided in an embodiment of this application;

[0042] Figure 4 is a comparative schematic diagram of rapid gradient separation and elution using chromatographic columns of different lengths provided in the embodiments of this application;

[0043] Figure 5 is a comparative schematic diagram of rapid gradient separation and elution using chromatographic columns with different inner diameters provided in the embodiments of this application;

[0044] Figure 6 is a comparative schematic diagram of rapid gradient separation and elution using chromatographic columns of different particle sizes provided in the embodiments of this application;

[0045] Figure 7 is a schematic diagram comparing the detection results of steroid hormones obtained by using the scheme of the embodiment of this application and related technical solutions respectively;

[0046] Figure 8 is a schematic diagram comparing the detection results of vitamin D obtained by using the scheme of the present application embodiment and related technical solutions respectively.

[0047] Explanation of reference numerals in the attached figures: 10, Liquid Chromatography-Mass Spectrometry (LC-MS) equipment; 100, Chromatographic device; 110, Chromatographic column; 111, Inner cavity; 120, Liquid flow delivery assembly; 121, First drive pump; 122, Second drive pump; 123, Merging unit; 130, Reagent preparation channel; 140, Reagent transfer assembly; 200, Mass spectrometry detection device; 300, Pretreatment device; 310, Magnetic separation unit; 320, Magnetic bead elution unit; 330, Reagent storage unit; 340, Reagent dispensing unit; 350, Pipette unit; 360, Reaction vessel supply unit; 400, Sample storage device; 20, First container; 30, Second container; L, Length of chromatographic column; d, Inner diameter. Detailed Implementation

[0048] The technical solutions of the embodiments of this application will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only a part of the embodiments of this application, and not all of the embodiments. Based on the embodiments of this application, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of this application.

[0049] The liquid chromatography-mass spectrometry (LC-MS) device (or liquid chromatography-tandem mass spectrometry device) provided in this application embodiment is suitable for scenarios requiring the detection of trace substances such as vitamin D, steroid hormones, and catecholamines.

[0050] As shown in Figures 1 to 6, a first aspect of this application provides a liquid chromatography-mass spectrometry (LC-MS) device 10, including a chromatographic element 100, a mass spectrometry detection element 200, and a controller. The chromatographic element 100 is used to elute a test solution prepared from a sample using a liquid phase fluid to prepare an analyte. The mass spectrometry detection element 200 is connected to a chromatographic column 110 for mass spectrometry detection of the analyte effluent from the chromatographic column 110 and to obtain mass spectrometry detection information. The controller is configured to process the mass spectrometry detection information and output the mass spectrometry detection results of the sample. The connection between the chromatographic element 100 and the mass spectrometry detection element 200 is specifically a series connection via a liquid path, i.e., the outlet of the chromatographic element 100 and the inlet of the mass spectrometry detection element 200 are connected via a liquid path.

[0051] In one implementation method, the above-mentioned samples are samples collected from human or animal bodies.

[0052] As one implementation method, the above-mentioned sample is a blood sample.

[0053] As one implementation method, the mass spectrometry detection results of the output sample include: the mass spectrometry detection results of at least one of vitamin D, steroid hormones, and catecholamines in the output sample. That is, the liquid chromatography-mass spectrometry device 10 provided in this application embodiment can meet the detection requirements of trace substances such as vitamin D, steroid hormones, and catecholamines.

[0054] In one embodiment, the chromatographic device 100 includes a solution preparation channel 130, a solution transfer assembly 140, a liquid phase fluid delivery assembly 120, and a chromatographic column 110. The solution transfer assembly 140, the liquid phase fluid delivery assembly 120, and the chromatographic column 110 are respectively connected to the solution preparation channel 130. The solution transfer assembly 140 is used to transfer the solution prepared from the sample to the solution preparation channel 130. The liquid phase fluid delivery assembly 120 is used to drive the solution in the solution preparation channel 130 through the chromatographic column 110 to adsorb the solution onto the chromatographic column 110, and to drive the liquid phase fluid through the chromatographic column 110 to elute the solution adsorbed on the chromatographic column 110 to form the test solution.

[0055] In one embodiment, the liquid chromatography-mass spectrometry (LC-MS) apparatus 10 further includes a sample pretreatment device 300, which is used to pretreat the sample to obtain a test solution. A test solution transfer assembly 140 is used to transfer at least a portion of the test solution obtained by the pretreatment device 300 to the test solution preparation channel 130. The sample pretreatment performed by the pretreatment device 300 is mainly used to purify the sample to ensure the accuracy of the mass spectrometry detection results.

[0056] In one embodiment, the liquid chromatography-mass spectrometry (LC-MS) apparatus 10 further includes a sample storage device 400 for holding a sample container containing a sample collected from a human or animal body for sample loading. A pretreatment device 300 is used to pretreat the sample from the sample container in the sample storage device 400 to obtain a test solution.

[0057] In one implementation, the working pressure output by the liquid phase fluid delivery component 120 is less than or equal to 20 MPa. In prior art liquid chromatography-tandem mass spectrometry (LC-MS / MS) devices, ultra-high pressure (40 MPa) liquid phase fluid drive is required to meet the elution and detection requirements of trace substances such as vitamin D, steroid hormones, and catecholamines. However, excessively high pressure leads to a significant increase in the manufacturing difficulty, production cost, and maintenance cost of the high-pressure pump, high-pressure valve, and high-pressure pipeline. The LC-MS / MS device 10 of this embodiment can use a lower-pressure liquid phase drive system, maintaining or even further improving the LC-MS / MS detection performance of trace substances such as vitamin D, steroid hormones, and catecholamines, while greatly reducing the manufacturing difficulty, production cost, maintenance cost, and failure frequency of the LC-MS / MS device 10.

[0058] In one embodiment, the liquid chromatography-mass spectrometry (LC-MS) device 10 includes a sample storage device 400, a pretreatment device 300, a chromatographic device 100, a mass spectrometry detection device 200, and a controller. The sample storage device 400 is used to hold a sample container containing a sample collected from a human or animal body for sample loading. The sample includes a target analyte, which may include at least one of vitamin D, steroid hormones, and catecholamines. The pretreatment device 300 is used to pretreat the sample from the sample container in the sample storage device using magnetic separation to obtain a test solution. The pretreatment device 300 includes a magnetic separation component 310, a magnetic bead elution component 320, and a reagent dispensing unit. The device comprises a sample container 340 and a pipetting component 350; the pipetting component 350 is used to aspirate at least a portion of the sample from the sample container of the sample storage device and to dispense all or part of the aspirated sample into the reaction container; the reagent dispensing component 340 is used to dispense internal standard reagent containing internal standard and magnetic bead reagent containing magnetic beads into the reaction container respectively; the magnetic separation component 310 is used to perform magnetic separation and cleaning on a first mixture containing at least the sample, internal standard reagent and magnetic bead reagent in the reaction container to obtain a clear liquid and magnetic beads adsorbed with internal standard and target analyte, and to aspirate and dispose of the clear liquid; the magnetic bead elution component 320 is used to further elute the magnetic beads adsorbed with internal standard and target analyte obtained by magnetic separation and cleaning in the reaction container. Elution is performed to obtain a test solution; the reagent dispensing component 340 and the pipetting component 350 are two independent components or the same component; the chromatographic device 100 includes a test solution preparation channel 130, a test solution transfer assembly 140, a liquid phase fluid delivery assembly 120, and a chromatographic column 110. The test solution transfer assembly, the liquid phase fluid delivery assembly, and the chromatographic column are respectively connected to the test solution preparation channel. The test solution transfer assembly is used to aspirate at least a portion of the test solution obtained by pretreatment by the pretreatment device from the reaction vessel and transfer all or part of the aspirated test solution to the test solution preparation channel. The liquid phase fluid delivery assembly is used to drive the test solution in the test solution preparation channel through the chromatographic column to adsorb the test solution onto the chromatographic column, and is also used to drive... A liquid-phase fluid flows through the chromatographic column to elute the test solution adsorbed on the column, thereby forming the analyte. A mass spectrometry detection device 200 is connected to the chromatographic column 110 to perform mass spectrometry detection on the analyte flowing from the column and obtain mass spectrometry detection information. The controller is configured to process the mass spectrometry detection information and output the mass spectrometry detection results of the target analyte in the sample. The working pressure output by the liquid-phase fluid delivery assembly is less than or equal to 20 MPa. The length of the chromatographic column 110 is greater than or equal to 3 mm and less than or equal to 35 mm. The output mass spectrometry detection results of the sample include: the mass spectrometry detection results of at least one of vitamin D, steroid hormones, and catecholamines in the sample.

[0059] As one implementation, the working pressure output by the liquid phase fluid delivery assembly 120 is greater than or equal to 2 MPa and less than or equal to 15 MPa. Setting the working pressure of the liquid phase fluid delivery assembly 120 between 2 MPa and 15 MPa can meet the elution pressure requirements of the target analyte in the chromatographic column 110, while also preventing the pressure of the liquid circuit system from becoming too high, which helps to reduce costs and the frequency of failures.

[0060] In one embodiment, the liquid phase fluid delivery assembly 120 includes a first drive pump 121 and a second drive pump 122. The first drive pump 121 is used to draw a first liquid from the first container 20 and deliver the drawn first liquid toward the chromatographic column 110. The second drive pump 122 is used to draw a second liquid from the second container 30 and deliver the drawn second liquid toward the chromatographic column 110. The rated operating pressure of the first drive pump 121 and the rated operating pressure of the second drive pump 122 are both less than or equal to 20 MPa.

[0061] In one embodiment, the rated operating pressure of the first drive pump 121 and the rated operating pressure of the second drive pump 122 are both greater than or equal to 2 MPa and less than or equal to 15 MPa.

[0062] In one implementation, the ionic strength of the first liquid is less than that of the second liquid. Specifically, the first liquid may be liquid A, and the second liquid may be liquid B.

[0063] In one embodiment, the first liquid contains a first buffer salt, and the second liquid contains a second buffer salt; the concentration of the first liquid is the concentration of the first buffer salt in the first liquid, and the concentration of the second liquid is the concentration of the second buffer salt in the second liquid. The first buffer salt and the second buffer salt can be the same buffer salt or two different buffer salts; that is, the buffer salt in the first liquid and the buffer salt in the second liquid can be the same buffer salt or different buffer salts. When the buffer salt in the first liquid and the buffer salt in the second liquid are the same buffer salt, the concentration of the liquid phase fluid formed by the first liquid and the second liquid is the concentration of that buffer salt in the liquid phase fluid; when the buffer salt in the first liquid and the buffer salt in the second liquid are different buffer salts, the concentration of the liquid phase fluid formed by the first liquid and the second liquid is the sum of the concentrations of the first buffer salt and the second buffer salt in the liquid phase fluid.

[0064] In one implementation, the controller is also configured to control the liquid phase fluid delivery assembly 120 to drive the liquid phase fluid to perform gradient elution of the test solution adsorbed on the chromatographic column 110 to form the analyte. In this embodiment, the gradient elution scheme facilitates rapid separation and elution of the test solution, thereby improving sample detection efficiency. The applicant's research has found that using a rapid gradient separation elution method, within a certain range, with a shorter chromatographic column 110, provides better clinical detection performance.

[0065] In one implementation, the controller is further configured to: control the liquid phase fluid delivery assembly 120 to prepare liquid phase fluids of different concentrations from at least two liquids according to a preset concentration control method, and drive the liquid phase fluids of different concentrations to perform gradient elution of the sample solution adsorbed on the chromatographic column 110 to form the analyte. The at least two liquids here include, for example, the first liquid and the second liquid described above. This embodiment prepares liquid phase fluids of different concentrations online using at least two liquids to meet the requirements for different concentrations of liquid phase fluid in gradient elution. Since the gradient elution uses the same set of eluents, the only difference being the mixing ratio control method of the first and second liquids, the amount of material and material costs can be effectively reduced.

[0066] In one embodiment, the liquid phase fluid delivery assembly 120 further includes a confluence component 123. A first drive pump 121 and a second drive pump 122 are respectively connected to the confluence component 123. The first drive pump 121 is used to draw a first liquid from the first container 20 and deliver the drawn first liquid toward the confluence component 123 and the chromatographic column 110. The second drive pump 122 is used to draw a second liquid from the second container 30 and deliver the drawn second liquid toward the confluence component 123 and the chromatographic column 110. Before processing the mass spectrometry detection information, the controller is also configured to: control the first drive pump 121 and the second drive pump 122 to operate according to a preset concentration control mode, so that the first liquid and / or the second liquid are made into liquid phase fluids of different concentrations in the confluence component 123, and control the first drive pump 121 and / or the second drive pump 122 to drive the liquid phase fluids of different concentrations in the confluence component 123 to be delivered toward the chromatographic column 110, so as to perform gradient elution of the test solution adsorbed on the chromatographic column 110 to form the test solution.

[0067] In one implementation, the number of chromatographic columns 110 is multiple, meaning there are at least two chromatographic columns 110. The liquid chromatography-mass spectrometry (LC-MS) device 10 also includes a first switching device and a second switching device, with multiple chromatographic columns 110 connected in parallel between the first and second switching devices. The liquid flow delivery assembly 120 can be switched to connect to multiple chromatographic columns 110 via the first switching device; the mass spectrometry detection device 200 can be switched to connect to multiple chromatographic columns 110 via the second switching device. In this embodiment, by setting multiple chromatographic columns 110 in parallel, multiple samples can be detected in parallel, thereby improving the detection efficiency of batch samples. Each chromatographic column 110 requires a set of first drive pumps 121 and second drive pumps 122, meaning the LC-MS device 10 has multiple first drive pumps 121 and multiple second drive pumps 122. If both the first drive pumps 121 and the second drive pumps 122 are ultra-high pressure pumps (operating pressure of 40 MPa), the cost of the LC-MS device 10 will be very high. Therefore, this embodiment uses a first drive pump 121 and a second drive pump 122 with a rated operating pressure of less than or equal to 20 MPa, which can greatly reduce the cost of the liquid chromatography-mass spectrometry (LC-MS) equipment 10. Of course, in specific applications, as an alternative embodiment, the number of chromatographic columns 110 can also be only one.

[0068] As one implementation method, the pretreatment device 300 pretreatments the sample using at least one of the following methods: magnetic separation, solid-phase extraction, liquid-liquid extraction, and protein precipitation. Magnetic separation involves purifying the sample by adsorbing the target analyte with magnetic beads followed by elution, or by adsorbing impurities with magnetic beads. Solid-phase extraction (including magnetic solid-phase extraction) works by adjusting the solvent composition to control the adsorption and dissolution of the target analyte, based on the different adsorption and dissociation coefficients of different substances between the solvent and the solid support, thereby achieving the extraction and enrichment of the target analyte. Liquid-liquid extraction (including solid-liquid extraction: solid-phase supported liquid-liquid extraction) works by separating and extracting the target analyte based on the different partition coefficients of different substances in two immiscible liquids. For example, 25-hydroxyvitamin D has a much higher partition coefficient in hexane than in water, and since hexane is immiscible with water, it can be extracted and separated using hexane. The principle of protein precipitation is as follows: proteins in serum / plasma are precipitated or separated by organic solvents, acids or metal salts, and then separated from the target analytes in the solution by centrifugation or filtration, thereby removing the protein background and extracting the target analytes.

[0069] In one implementation, the pretreatment device 300 uses magnetic separation to pretreatment the sample. The magnetic separation method can be either using magnetic beads to adsorb the target analyte and then elute it to purify the sample, or using magnetic beads to adsorb impurities to purify the sample.

[0070] In a first embodiment of the pretreatment device 300 employing magnetic separation, the pretreatment device 300 pretreatment samples using magnetic separation. The pretreatment device 300 includes a magnetic separation component 310, a magnetic bead elution component 320, a reagent dispensing component 340, and a pipetting component 350. The pipetting component 350 is used to aspirate at least a portion of the sample from the sample container of the sample storage device 400 and dispense all or part of the aspirated sample into the reaction container. The reagent dispensing component 340 is used to dispense the internal standard reagent and the magnetic bead reagent into the reaction container, respectively. The magnetic separation component 310 is used to perform magnetic separation and cleaning on a first mixture containing at least the sample, internal standard reagent, and magnetic bead reagent in the reaction container to obtain a clear liquid and a first magnetic bead liquid, and to aspirate and drain the clear liquid from the reaction container. The magnetic bead elution component 320 is used to elute the first magnetic bead liquid in the reaction container to obtain a test solution. The test solution transfer component 140 is used to aspirate at least a portion of the test solution from the reaction container and transfer all or part of the aspirated test solution to the test solution preparation channel 130. The reagent dispensing component 340 and the pipetting component 350 are either two independent components or the same component. In this embodiment, the magnetic beads are used to adsorb the target analyte, which is in the first magnetic bead solution.

[0071] In one embodiment, the pretreatment device 300 further includes a reagent storage component 330 and a reagent dispensing component 340 for drawing at least a portion of the magnetic bead reagent from a second reagent container from the reagent storage component 330 and dispensing all or part of the drawn magnetic bead reagent to the reaction container.

[0072] In one embodiment, the pretreatment device 300 further includes a reaction vessel providing component 360 and a reaction vessel transferring component. The reaction vessel providing component 360 is used to provide a reaction vessel, and the reaction vessel transferring component is used to transfer the reaction vessel from the reaction vessel providing component 360 to the magnetic separation component 310 and the magnetic bead elution component 320, respectively.

[0073] In one embodiment, the pretreatment device 300 further includes a mixing component; the controller is also configured to control the pretreatment device 300 to perform the following pretreatment actions: control the pipetting component 350 to aspirate at least a portion of the sample from the sample container of the sample storage device 400 and distribute all or part of the aspirated sample to the reaction container; control the reagent dispensing component 340 to dispense the internal standard reagent to the reaction container; control the mixing component to mix the sample and the internal standard reagent in the reaction container to obtain a second mixture; control the reagent dispensing component 340 to dispense the magnetic bead reagent into the second mixture in the reaction container to obtain a first mixture; control the magnetic separation component 310 to perform magnetic separation and washing on the first mixture in the reaction container to obtain a clear liquid and a first magnetic bead liquid; control the magnetic separation component 310 to aspirate and drain the clear liquid in the reaction container; control the magnetic bead elution component 320 to elute the first magnetic bead liquid in the reaction container to obtain a test solution.

[0074] In a second embodiment of the pretreatment device 300 employing magnetic separation, the pretreatment device 300 pretreatments samples using magnetic separation. The pretreatment device 300 includes a magnetic separation component 310, a reagent dispensing component 340, and a pipetting component 350. The pipetting component 350 aspirates at least a portion of the sample from the sample container of the sample storage device 400 and dispenses all or part of the aspirated sample into the reaction container. The reagent dispensing component 340 dispenses internal standard reagent and magnetic bead reagent into the reaction container respectively. The magnetic separation component 310 performs magnetic separation and cleaning on a first mixture containing at least the sample, internal standard reagent, and magnetic bead reagent in the reaction container to obtain a clear liquid and a second magnetic bead liquid, the clear liquid being used as the test solution. The test solution transfer component 140 aspirates at least a portion of the test solution from the reaction container and transfers all or part of the aspirated test solution to the test solution preparation channel 130. The reagent dispensing component 340 and the pipetting component 350 are either two independent components or the same component. In this embodiment, the magnetic beads are used to adsorb impurities, and the target analyte is in the clear liquid.

[0075] In one embodiment, the chromatographic column 110 includes a column having an inner cavity 111 and packing material filled in the inner cavity 111; the chromatographic column 110 satisfies at least two of the following conditions: the length L of the chromatographic column is greater than or equal to 5 mm and less than or equal to 30 mm; the inner diameter d of the inner cavity 111 is greater than 2.1 mm and less than or equal to 4.0 mm.

[0076] The volume of the inner cavity 111 is greater than or equal to 0.063 mL and less than or equal to 0.38 mL.

[0077] In one implementation, the length L of the chromatographic column is greater than 0 mm and less than 50 mm. The chromatographic column 110 has a first end and a second end spaced apart and opposite to each other. The first end forms a first inlet, and the second end forms a first outlet. The test solution and liquid phase fluid can flow into the chromatographic column 110 through the first inlet, and the analyte or waste liquid formed by elution can flow out of the chromatographic column 110 through the first outlet. The distance between the first end and the second end is the length L of the chromatographic column. In prior art, liquid chromatography-tandem mass spectrometry (LC-MS / MS) devices used for detecting trace amounts of substances such as vitamin D, steroid hormones, and catecholamines required a relatively long chromatographic column 110 (e.g., a column 110 with a length greater than 50 mm and less than or equal to 150 mm) to increase the theoretical plate number. This theoretical plate number is suitable for long-duration separation requirements with partial isocratic elution, such as the detection and analysis of complex scientific samples; alternatively, given a longer chromatographic column 110, the sample detection and analysis time can be appropriately shortened by increasing the flow rate, but this results in extremely high system pressure. In this application, the embodiments address the need for rapid and efficient clinical testing. From another perspective, the rapid gradient separation elution method, using a shorter chromatographic column 110 (less than 50 mm) within a certain range, actually provides better clinical testing performance: analysis can be completed quickly by maintaining a low flow rate (0.3-0.6 mL / min), the separated analyte peaks are more favorable, and the shorter chromatographic column 110 can bring lower system pressure, which is a significant advantage.

[0078] In one implementation method, the length L of the chromatographic column is greater than or equal to 3 mm and less than or equal to 35 mm. Using a chromatographic column 110 within this length range, the detection requirements for trace substances such as vitamin D, steroid hormones, and catecholamines can be met under low-pressure conditions.

[0079] In one implementation method, the length L of the chromatographic column is greater than or equal to 5 mm and less than or equal to 30 mm. This implementation method, by selecting a suitable effective length, can reduce the diffusion of excess column volume and the non-specific adsorption loss of excess packing material, while significantly reducing column pressure. This facilitates maintaining or even further improving the performance of liquid chromatography-tandem mass spectrometry (LC-MS / MS) detection of trace substances such as vitamin D, steroid hormones, and catecholamines under low-pressure conditions.

[0080] In one implementation, the inner diameter d of the inner cavity 111 is greater than 2.1 mm and less than 4.6 mm. In prior art, liquid chromatography-tandem mass spectrometry (LC-MS / MS) for detecting trace amounts of substances such as vitamin D, steroid hormones, and catecholamines required a column 110 with a smaller inner diameter d (e.g., a column 110 with an inner diameter d greater than or equal to 1.0 mm and less than or equal to 2.1 mm) to reduce lateral diffusion during separation, decrease column bed volume (i.e., the volume of the inner cavity 111), and shorten latency (dead time). However, a very small inner diameter d leads to a significant increase in column pressure, increasing system pressure, and also increases the length of the target analyte bonded to the packing material, resulting in a broader peak and affecting resolution. In this embodiment, a column 110 with an inner diameter d (greater than 2.1 mm and less than 4.6 mm) different from both ultra-high efficiency HPLC (1.0 mm–2.1 mm) and conventional HPLC (4.6 mm–10 mm) in related technologies is selected, thus achieving both low pressure and high resolution.

[0081] In one implementation, the inner diameter d of the inner cavity 111 is greater than 2.1 mm and less than or equal to 4.0 mm. In this implementation, by selecting a suitable inner diameter d for the chromatographic column 110, the length of the binding region between the target analyte and the packing material is narrowed, which helps to reduce peak width and improve resolution. Simultaneously, it can significantly reduce column pressure, thereby improving the performance of liquid chromatography-tandem mass spectrometry detection of trace substances such as vitamin D, steroid hormones, and catecholamines under low-pressure conditions.

[0082] In one implementation, the length L of the chromatographic column is greater than or equal to 5 mm and less than or equal to 30 mm, and the inner diameter d of the inner cavity 111 is greater than 2.1 mm and less than or equal to 4.0 mm.

[0083] In one implementation, the diameter of the packing material is greater than or equal to 1.7 μm and less than or equal to 1.8 μm. This application's embodiments, targeting the sample type, analyte content, and sensitivity requirements for clinical detection of trace substances such as vitamin D, steroid hormones, and catecholamines, select and design key column material (packing material) parameters (particle size 1.7, 1.8 μm) to maintain a small packing material particle size and increase specific surface area. This balances column pressure and specific surface area to achieve better retention of the target analyte and better resolution.

[0084] In one embodiment, the packing has through holes, the diameter of which is greater than or equal to... (Aemi) and less than or equal to In this implementation scheme, by designing the pore diameter of the through holes on the packing to be smaller, it is beneficial to increase the specific surface area of ​​the packing.

[0085] In one implementation, the volume of the inner cavity 111 is greater than or equal to 0.063 mL and less than or equal to 0.38 mL. If the column bed volume (i.e., the volume of the inner cavity 111) is too large, it will lead to excessive retention of the target analyte by the chromatographic column 110, which is not conducive to the rapid elution and separation of the target analyte, and will also increase the loss due to non-specific adsorption of the target analyte, resulting in a decrease in recovery rate and sensitivity. If the column bed volume is too small, it will lead to insufficient retention of the target analyte by the chromatographic column 110 or supersaturation, resulting in sample loss and affecting the retention separation effect and sensitivity. In this implementation, the volume of the inner cavity 111 is set to be greater than or equal to 0.063 mL and less than or equal to 0.38 mL, so that the chromatographic column 110 can meet the rapid separation requirements for clinical detection of trace substances such as vitamin D, steroid hormones, and catecholamines.

[0086] In one implementation, the mass spectrometry detection device 200 includes a triple quadrupole tandem mass spectrometer.

[0087] As one implementation method, the length of the chromatographic column is greater than or equal to 3 mm and less than or equal to 35 mm.

[0088] In one implementation, the length of the chromatographic column is 25 mm, 3 mm, 30 mm, 20 mm, 10 mm, or 15 mm.

[0089] In one implementation, the working pressure output by the liquid phase fluid transport component is 10 MPa, 15 MPa, or 20 MPa.

[0090] In one embodiment, the pretreatment device further includes a reagent storage component for loading a first reagent container containing an internal standard reagent and a second reagent container containing magnetic bead reagents. The reagent dispensing component is used to draw at least a portion of the internal standard reagent from the first reagent container of the reagent storage component and dispense all or part of the drawn internal standard reagents into the reaction vessel, and to draw at least a portion of the magnetic bead reagents from the second reagent container of the reagent storage component and dispense all or part of the drawn magnetic bead reagents into the reaction vessel.

[0091] In one implementation, the preprocessing device further includes a mixing component; the controller is also configured to control the preprocessing device to perform the following preprocessing actions:

[0092] Control the pipetting component to aspirate at least a portion of the sample from the sample container of the sample storage device and to dispense all or part of the aspirated sample into the reaction container;

[0093] The reagent dispensing unit controls the dispensing of internal standard reagents into the reaction vessel;

[0094] The mixing unit is controlled to mix the sample and internal standard reagent in the reaction vessel to obtain a second mixture;

[0095] The reagent dispensing component controls the magnetic bead reagent to be dispensed into the second mixture in the reaction vessel to obtain the first mixture.

[0096] The magnetic separation component is controlled to perform magnetic separation and cleaning of the first mixture in the reaction vessel to obtain a clear liquid and magnetic beads adsorbed with internal standard and target analyte;

[0097] The magnetic separation component is controlled to draw in and drain the clear liquid from the reaction vessel;

[0098] The magnetic bead elution unit controls the elution of magnetic beads containing internal standards and target analytes in the reaction vessel to obtain the test solution.

[0099] Compared with previous technical solutions, the key innovations in the technical performance of the liquid chromatography-mass spectrometry (LC-MS) device 10 provided in this application are as follows:

[0100] 1) Previous chromatographic techniques used longer columns (e.g., 50 mm) to increase the theoretical plate number of the separation. However, this theoretical plate number is suitable for long-duration separations requiring partial isocratic elution, such as the analysis of complex research samples, or for increasing the flow rate to appropriately shorten the analysis time, but this results in extremely high system pressure. In contrast, this application addresses the need for rapid and efficient clinical testing. From another perspective, it employs a rapid gradient separation elution method. Within a certain range, using a shorter column (e.g., 5 mm-30 mm) provides better clinical testing performance. Furthermore, it only requires a lower flow rate (e.g., 0.3 mL / min-0.6 mL / min) to quickly complete the analysis, resulting in better peak widths of the separated analytes. Simultaneously, the shorter column (110) leads to lower system pressure, demonstrating significant advantages. See Figure 4 for specific results.

[0101] 2) Previous chromatographic techniques used columns with smaller inner diameters to minimize lateral diffusion during separation and reduce column bed volume, thus shortening dead time. However, excessively small inner diameters lead to a significant increase in column pressure, increasing system pressure, and also increase the longitudinal width of the target analyte binding with the column material, resulting in broader peaks and affecting resolution. Therefore, this application employs a 2.1mm-4.0mm column with an inner diameter of 110, which differs from previous ultra-high efficiency UHPLC techniques (column inner diameter of 1.0mm-2.1mm) and conventional HPLC techniques (column inner diameter of 4.6mm-10mm). This achieves both low pressure and high resolution, as shown in Figure 5.

[0102] 3) In this embodiment of the application, the sample type, analyte content and sensitivity requirements of clinical detection of vitamin D and steroid hormones are selected and the key column material (packing material) parameters (particle size 1.7, 1.8 μm) are designed. The balance between column pressure and specific surface area is achieved to obtain better analyte retention and resolution. The specific effect is shown in Figure 6.

[0103] 4) Balanced control of overall column bed volume: If the column bed volume is too large, the retention of the target analyte will be too strong, which is not conducive to rapid elution and separation. At the same time, it will increase the loss of the target analyte due to non-specific adsorption, resulting in a decrease in recovery rate and sensitivity. If the column bed volume is too small, the retention of the target analyte will be too weak or supersaturation will occur, resulting in sample loss and affecting retention, separation and sensitivity. The embodiments of this application optimize the design of column bed volume (0.063mL-0.38mL) suitable for rapid separation in clinical detection of vitamin D and steroid hormones.

[0104] 5. The specific optimization parameters and beneficial effects are shown in Table 1 below:

[0105] Table 1

[0106] To verify the beneficial effects of the liquid chromatography-mass spectrometry (LC-MS) device 10 provided in the embodiments of this application, the applicant conducted the following experiments:

[0107] (1) Example 1

[0108] The sample from the same sample container was divided into two parts. One part of the sample was placed in a first liquid chromatography-mass spectrometry (LC-MS) device (i.e., the LC-MS device 10 provided in the embodiments of this application) with a chromatographic column 110 with an inner diameter of 3.0 mm and a length of 25 mm and a working column pressure of 10 MPa for steroid hormone detection. The other part of the sample was placed in a second liquid chromatography-mass spectrometry (LC-MS) device (i.e., the LC-MS device provided in the prior art of this application) with a chromatographic column with an inner diameter of 2.1 mm and a length of 50 mm and a working column pressure of 40 MPa for steroid hormone detection. The detection data are shown in Figure 7 and Table 2 below.

[0109] Table 2

[0110] As shown in Figure 7 and Table 2, for the LC-MS detection of steroid hormones, the low-pressure chromatography separation technique of this application embodiment, besides significantly reducing the working column pressure from 40 MPa to 10 MPa, also exhibits superior performance compared to the high-pressure chromatography separation of previous related techniques, such as significantly reduced peak width, increased peak height, and slightly improved resolution. Furthermore, the low-pressure chromatography separation technique of this application embodiment can achieve an earlier first peak elution time, resulting in higher separation and detection efficiency.

[0111] Example 2:

[0112] The sample from the same sample container was divided into two parts. One part of the sample was placed in a first liquid chromatography-mass spectrometry (LC-MS) device (i.e., the LC-MS device 10 provided in the embodiments of this application) with a chromatographic column of 3.0 mm inner diameter and 25 mm length and a working column pressure of 10 MPa for vitamin D detection. The other part of the sample was placed in a second liquid chromatography-mass spectrometry (LC-MS) device (i.e., the LC-MS device provided in the prior art of this application) with a chromatographic column of 2.1 mm inner diameter and 50 mm length and a working column pressure of 40 MPa for vitamin D detection. The detection data are shown in Figure 8 and Table 3 below.

[0113] Table 3

[0114] As shown in Figure 8 and Table 3, for the LC-MS detection of vitamin D, the low-pressure chromatography separation technology of this application embodiment, except for a significant decrease in working column pressure from 40 MPa to 10 MPa, maintains or even outperforms the high-pressure chromatography separation performance of previous related technologies, such as peak width, peak height, and resolution. Furthermore, the low-pressure chromatography separation technology of this application embodiment can achieve an earlier first peak elution time, resulting in higher separation and detection efficiency.

[0115] A second aspect of this application provides a liquid chromatography-mass spectrometry (LC-MS) device 10, which includes:

[0116] The sample storage device 400 is used to place a sample container containing a sample to achieve sample loading.

[0117] The pretreatment device 300 is used to pretreat the sample from the sample container of the sample storage device 400 to obtain a test solution.

[0118] The chromatographic device 100 includes a solution preparation channel 130, a solution transfer assembly 140, a liquid phase fluid delivery assembly 120, and a chromatographic column 110. The solution transfer assembly 140, the liquid phase fluid delivery assembly 120, and the chromatographic column 110 are respectively connected to the solution preparation channel 130. The solution transfer assembly 140 is used to transfer at least a portion of the solution obtained by the pretreatment device 300 to the solution preparation channel 130. The liquid phase fluid delivery assembly 120 is used to drive the solution in the solution preparation channel 130 through the chromatographic column 110 to adsorb the solution onto the chromatographic column 110, and to drive the liquid phase fluid through the chromatographic column 110 to elute the solution adsorbed onto the chromatographic column 110 to form the test solution.

[0119] Mass spectrometry detection device 200 is connected to chromatographic column 110 to perform mass spectrometry detection on the test solution flowing out of chromatographic column 110 and obtain mass spectrometry detection information.

[0120] The controller is configured to process mass spectrometry detection information and output the mass spectrometry detection results of the sample.

[0121] The working pressure output by the liquid phase fluid transport component 120 is less than or equal to 20MPa;

[0122] The output sample's mass spectrometry detection results include: the mass spectrometry detection results of at least one of vitamin D and catecholamines in the output sample.

[0123] The liquid chromatography-mass spectrometry (LC-MS) apparatus 10 provided in the second aspect of this application focuses on limiting vitamin D and catecholamines to an operating pressure of less than or equal to 20 MPa.

[0124] In one embodiment, the working pressure output by the liquid phase fluid transport assembly 120 is greater than or equal to 2 MPa and less than or equal to 15 MPa.

[0125] As one implementation method, the preprocessing device 300 uses magnetic separation to preprocess the sample.

[0126] Apart from the above, other parts and principles of the control method of the liquid chromatography-mass spectrometry (LC-MS) device 10 provided in the second aspect of the embodiments of this application can be referred to the control scheme and principle of the controller in the liquid chromatography-mass spectrometry (LC-MS) device 10 provided in the first aspect, and will not be described in detail here.

[0127] A third aspect of this application provides a control method for a liquid chromatography-mass spectrometry (LC-MS) device 10, the control method comprising:

[0128] The pretreatment device 300 is controlled to pretreatment samples collected from human or animal bodies to obtain test solutions;

[0129] The control solution transfer assembly 140 transfers at least a portion of the solution obtained by the pretreatment device 300 to the solution preparation channel 130;

[0130] The liquid phase fluid delivery component 120 is controlled to drive the test solution in the test solution preparation channel 130 through the chromatographic column 110 at a working pressure of less than or equal to 20 MPa, so that the test solution is adsorbed on the chromatographic column 110.

[0131] The liquid phase fluid delivery assembly 120 is controlled to drive the liquid phase fluid through the chromatographic column 110 at a working pressure of less than or equal to 20 MPa, so that the liquid phase fluid elutes the test solution adsorbed on the chromatographic column 110 to form the test solution flowing to the mass spectrometry detection device 200.

[0132] The mass spectrometry detection device 200 is controlled to perform mass spectrometry detection on the test solution flowing out of the chromatographic column 110 and obtain mass spectrometry detection information;

[0133] The mass spectrometry detection information is processed to output the mass spectrometry detection results of the sample.

[0134] In one implementation, the aforementioned pretreatment device 300 pretreatments samples collected from human or animal bodies to obtain a test solution, including:

[0135] The control pipetting component 350 aspirates at least a portion of the sample from the sample container of the sample storage device 400 and dispenses all or part of the aspirated sample into the reaction container;

[0136] The reagent dispensing unit 340 controls the dispensing of the internal standard reagent into the reaction vessel;

[0137] The mixing unit is controlled to mix the sample and internal standard reagent in the reaction vessel to obtain a second mixture;

[0138] The reagent dispensing component 340 dispenses the magnetic bead reagent into the second mixture in the reaction vessel to obtain the first mixture.

[0139] The magnetic separation component 310 is controlled to perform magnetic separation and cleaning on the first mixture in the reaction vessel to obtain a clear liquid and a first magnetic bead liquid;

[0140] The magnetic separation component 310 is controlled to draw in and drain the clear liquid from the reaction vessel;

[0141] The magnetic bead elution unit 320 is used to elute the first magnetic bead liquid in the reaction vessel to obtain the test solution.

[0142] Alternatively, as another implementation, the above-described pretreatment device 300 pretreatments samples collected from human or animal bodies to obtain a test solution, including:

[0143] The control pipetting component 350 aspirates at least a portion of the sample from the sample container of the sample storage device 400 and dispenses all or part of the aspirated sample into the reaction container;

[0144] The reagent dispensing unit 340 controls the dispensing of the internal standard reagent into the reaction vessel;

[0145] The mixing unit is controlled to mix the sample and internal standard reagent in the reaction vessel to obtain a second mixture;

[0146] The reagent dispensing component 340 dispenses the magnetic bead reagent into the second mixture in the reaction vessel to obtain the first mixture.

[0147] The magnetic separation component 310 is controlled to perform magnetic separation and cleaning on the first mixture in the reaction vessel to obtain a clear liquid and a second magnetic bead liquid, and the clear liquid is used as a test solution.

[0148] As one implementation method, the mass spectrometry detection results of the output sample include: the mass spectrometry detection results of at least one of vitamin D, steroid hormones, and catecholamines in the output sample.

[0149] In one implementation, the liquid phase fluid delivery assembly 120 is controlled to drive the liquid phase fluid through the chromatographic column 110 at a working pressure of less than or equal to 20 MPa, so that the liquid phase fluid elutes the test solution adsorbed on the chromatographic column 110 to form the test solution flowing to the mass spectrometry detection device 200. This includes: controlling the liquid phase fluid delivery assembly 120 to prepare liquid phase fluids of different concentrations according to a preset concentration control method, and driving the liquid phase fluids of different concentrations to be delivered toward the chromatographic column 110 at a working pressure of less than or equal to 20 MPa, so as to perform gradient elution of the test solution adsorbed on the chromatographic column 110, thereby forming the test solution.

[0150] As one implementation method, a control method for a liquid chromatography-mass spectrometry (LC-MS) device includes:

[0151] The pretreatment device controls the pretreatment of samples collected from human or animal bodies to obtain a test solution; the sample includes a target analyte, which includes at least one of vitamin D, steroid hormones, and catecholamines.

[0152] The control solution transfer assembly transfers at least a portion of the solution obtained from pretreatment by the pretreatment device to the solution preparation channel.

[0153] The liquid phase fluid delivery component is controlled to drive the test solution in the test solution preparation channel through a chromatographic column with a length greater than or equal to 3 mm and less than or equal to 35 mm at a working pressure of less than or equal to 20 MPa, so that the test solution is adsorbed on the chromatographic column.

[0154] The liquid phase fluid delivery assembly is controlled to drive the liquid phase fluid through the chromatographic column at a working pressure of less than or equal to 20 MPa, so that the liquid phase fluid elutes the test solution adsorbed on the chromatographic column to form the test solution flowing to the mass spectrometry detection device.

[0155] The mass spectrometry detection device is controlled to perform mass spectrometry detection on the test solution flowing out of the chromatographic column and obtain mass spectrometry detection information;

[0156] The mass spectrometry detection information is processed to output the mass spectrometry detection results of the target analyte in the sample;

[0157] The pretreatment device controls the pretreatment of samples collected from human or animal bodies to obtain a test solution, including: controlling a pipetting component to aspirate at least a portion of the sample from a sample container from a sample storage device and distributing all or part of the aspirated sample to a reaction container; controlling a reagent dispensing component to dispense an internal standard reagent containing an internal standard and a magnetic bead reagent containing magnetic beads to the reaction container to obtain a first mixture; controlling a magnetic separation component to perform magnetic separation and cleaning on the first mixture in the reaction container to obtain a clear liquid and magnetic beads adsorbed with the internal standard and the target analyte; controlling the magnetic separation component to aspirate and drain the clear liquid in the reaction container; and controlling a magnetic bead elution component to elute the magnetic beads adsorbed with the internal standard and the target analyte obtained from the magnetic separation and cleaning in the reaction container to obtain the test solution.

[0158] Alternatively, the pretreatment device can be controlled to pretreat samples collected from human or animal bodies to obtain a test solution, including: controlling a pipetting component to aspirate at least a portion of the sample from a sample container from a sample storage device and dispensing all or part of the aspirated sample into a reaction container; controlling a reagent dispensing component to dispense an internal standard reagent containing an internal standard and a magnetic bead reagent containing magnetic beads into the reaction container to obtain a first mixture; and controlling a magnetic separation component to perform magnetic separation and cleaning of the first mixture in the reaction container to obtain a clear liquid containing the internal standard and the target analyte, which is used as the test solution.

[0159] In one embodiment, the reagent dispensing component controls the dispensing of an internal standard reagent containing an internal standard and a magnetic bead reagent containing magnetic beads into a reaction vessel, comprising: controlling the reagent dispensing component to dispense the internal standard reagent into the reaction vessel; controlling the mixing component to mix the sample and the internal standard reagent in the reaction vessel to obtain a second mixture; and controlling the reagent dispensing component to dispense the magnetic bead reagent into the second mixture in the reaction vessel to obtain a first mixture.

[0160] As one implementation method, the mass spectrometry detection results of the target analyte in the output sample include: the mass spectrometry detection results of at least one of vitamin D, steroid hormones, and catecholamines in the output sample.

[0161] In one implementation, controlling the liquid phase fluid delivery component to drive the liquid phase fluid through the chromatographic column at a working pressure of less than or equal to 20 MPa, so that the liquid phase fluid elutes the test solution adsorbed on the chromatographic column to form a test solution flowing to the mass spectrometry detection device, includes: controlling the liquid phase fluid delivery component to prepare liquid phase fluids of different concentrations according to a preset concentration control method, and driving the liquid phase fluids of different concentrations to be delivered towards the chromatographic column at a working pressure of less than or equal to 20 MPa, so as to perform gradient elution of the test solution adsorbed on the chromatographic column, thereby forming a test solution.

[0162] Apart from the above, other parts and principles of the control method of the liquid chromatography-mass spectrometry (LC-MS) device 10 provided in the third aspect of the embodiments of this application can be referred to the control scheme and principle of the controller in the LC-MS device 10 provided in the first and second aspects above, and will not be described in detail here.

[0163] A fourth aspect of this application provides a liquid chromatography-mass spectrometry (LC-MS) device 10, which includes:

[0164] The sample storage device 400 is used to hold a sample container containing samples collected from a human or animal body for sample loading, the sample including the target analyte.

[0165] The pretreatment device 300 is used to pretreat a sample from a sample container in a sample storage device to obtain a test solution.

[0166] The chromatographic device 100 includes a test solution preparation channel 130, a test solution transfer assembly 140, a liquid phase fluid delivery assembly 140, and a chromatographic column 110. The test solution transfer assembly, the liquid phase fluid delivery assembly, and the chromatographic column are respectively connected to the test solution preparation channel. The test solution transfer assembly is used to transfer at least a portion of the test solution obtained by the pretreatment device to the test solution preparation channel. The liquid phase fluid delivery assembly is used to drive the test solution in the test solution preparation channel through the chromatographic column to adsorb the test solution onto the chromatographic column, and to drive the liquid phase fluid through the chromatographic column to elute the test solution adsorbed on the chromatographic column to form the test solution.

[0167] Mass spectrometry detection device 200, which is connected to a chromatographic column, is used to perform mass spectrometry detection on the test solution flowing out of the chromatographic column and obtain mass spectrometry detection information;

[0168] The controller is configured to process mass spectrometry detection information and output the mass spectrometry detection results of the target analyte in the sample.

[0169] The working pressure output by the liquid phase fluid transport component is less than or equal to 20 MPa.

[0170] As one implementation method, the target analyte of the sample includes at least one of vitamin D, steroid hormones, and catecholamines.

[0171] As one implementation method, the pretreatment device uses at least one of magnetic separation, solid phase extraction, liquid-liquid extraction, and protein precipitation to pretreatment the sample.

[0172] In one embodiment, the pretreatment device employs magnetic separation to pretreat samples. The pretreatment device includes a magnetic separation component, a magnetic bead elution component, a reagent dispensing component, and a pipetting component. The pipetting component aspirates at least a portion of the sample from a sample container in a sample storage device and dispenses all or part of the aspirated sample into a reaction container. The reagent dispensing component dispenses internal standard reagent containing an internal standard and magnetic bead reagent containing magnetic beads into the reaction container, respectively. The magnetic separation component performs magnetic separation and cleaning on a first mixture in the reaction container containing at least the sample, internal standard reagent, and magnetic bead reagent to obtain a clear liquid and magnetic beads adsorbed with the internal standard and the target analyte, then aspirates and discards the clear liquid. The magnetic bead elution component elutes the magnetic beads adsorbed with the internal standard and the target analyte obtained from the magnetic separation and cleaning process in the reaction container to obtain a test solution. The reagent dispensing component and the pipetting component are either two independent components or the same component.

[0173] Alternatively, the pretreatment device includes a magnetic separation component, a reagent dispensing component, and a pipetting component; the pipetting component is used to aspirate at least a portion of the sample from the sample container of the sample storage device and dispense all or part of the aspirated sample into the reaction container; the reagent dispensing component is used to dispense an internal standard reagent containing an internal standard and a magnetic bead reagent containing magnetic beads into the reaction container respectively; the magnetic separation component is used to magnetically separate and clean a first mixture containing at least the sample, the internal standard reagent, and the magnetic bead reagent in the reaction container to obtain a clear liquid containing the internal standard and the target analyte, the clear liquid being used as the test solution; the test solution transfer component is used to aspirate at least a portion of the test solution from the reaction container and transfer all or part of the aspirated test solution to the test solution preparation channel; the reagent dispensing component and the pipetting component are two independent components or the same component.

[0174] As one implementation method, the length of the chromatographic column is greater than or equal to 3 mm and less than or equal to 35 mm.

[0175] In one embodiment, the chromatographic column includes a column having an inner cavity and packing material filled in the inner cavity, wherein the inner diameter of the inner cavity is greater than 2.1 mm and less than 4.6 mm.

[0176] In addition to the above, other parts and principles of the control method of the liquid chromatography-mass spectrometry (LC-MS) device 10 provided in the fourth aspect of the embodiments of this application can be referred to the control scheme and principle of the controller in the LC-MS device 10 provided in the first, second and third aspects, and will not be described in detail here.

[0177] A fourth aspect of this application provides a computer-readable storage medium storing a computer program. When the computer program is executed by a processor (e.g., the controller described above), it causes the processor to implement the steps of the control method for the liquid chromatography-mass spectrometry (LC-MS) apparatus 10 described above. The computer-readable storage medium may be an internal storage unit of the LC-MS apparatus 10, such as a hard disk or memory of the LC-MS apparatus 10; or, it may be an external storage device of the LC-MS apparatus 10, such as a pluggable hard disk, smart media card (SMC), secure digital card (SD), flash card, etc., provided on the LC-MS apparatus 10.

[0178] The above description is merely a preferred embodiment of this application and does not limit the patent scope of this application. Any equivalent structural transformations made based on the inventive concept of this application and the contents of the specification and drawings of this application, or direct / indirect applications in other related technical fields, are included within the patent protection scope of this application.

Claims

1. A liquid chromatography-mass spectrometry (LC-MS) device, characterized in that: include: A sample storage device for holding a sample container loaded with a sample collected from a human or animal body to load the sample, the sample including a target analyte, the target analyte including at least one of vitamin D, steroid hormones, and catecholamines; A pretreatment device is provided for pretreating a sample from a sample container of a sample storage device using magnetic separation to obtain a test solution. The pretreatment device includes a magnetic separation component, a magnetic bead elution component, a reagent dispensing component, and a pipetting component. The pipetting component is used to aspirate at least a portion of the sample from the sample container of the sample storage device and dispense all or part of the aspirated sample into a reaction vessel. The reagent dispensing component is used to dispense an internal standard reagent containing an internal standard and a magnetic bead reagent containing magnetic beads into the reaction vessel, respectively. The magnetic separation component is used to perform magnetic separation and washing on a first mixture in the reaction vessel containing at least the sample, the internal standard reagent, and the magnetic bead reagent to obtain a clear liquid and magnetic beads adsorbed with the internal standard and the target analyte, and then aspirates and discards the clear liquid. The magnetic bead elution component is used to elute the magnetic beads adsorbed with the internal standard and the target analyte obtained from the magnetic separation and washing in the reaction vessel to obtain the test solution. The reagent dispensing component and the pipetting component are two independent components or the same component. A chromatographic device, comprising a reagent preparation channel, a reagent transfer assembly, a liquid phase fluid delivery assembly, and a chromatographic column, wherein the reagent transfer assembly, the liquid phase fluid delivery assembly, and the chromatographic column are respectively connected to the reagent preparation channel; the reagent transfer assembly is used to aspirate at least a portion of the reagent obtained by the pretreatment device from the reaction vessel and transfer all or part of the aspirated reagent to the reagent preparation channel; the liquid phase fluid delivery assembly is used to drive the reagent in the reagent preparation channel through the chromatographic column to adsorb the reagent onto the chromatographic column, and to drive the liquid phase fluid through the chromatographic column to elute the reagent adsorbed on the chromatographic column to form a test solution; A mass spectrometry detection device, which is connected to the chromatographic column, is used to perform mass spectrometry detection on the test solution flowing out of the chromatographic column and obtain mass spectrometry detection information; A controller configured to process the mass spectrometry detection information and output the mass spectrometry detection result of the target analyte in the sample; The working pressure output by the liquid phase fluid transport component is less than or equal to 20 MPa; The length of the chromatographic column is greater than or equal to 3 mm and less than or equal to 35 mm; The output of the mass spectrometry detection results of the sample includes: outputting the mass spectrometry detection results of at least one of vitamin D, steroid hormones, and catecholamines in the sample.

2. The liquid chromatograph-mass spectrometer apparatus of claim 1, wherein: The working pressure output by the liquid phase fluid transport component is greater than or equal to 2MPa and less than or equal to 15MPa.

3. The liquid chromatograph-mass spectrometer of claim 1, wherein: The liquid phase fluid delivery assembly includes a first drive pump and a second drive pump. The first drive pump is used to draw a first liquid from a first container and deliver the drawn first liquid toward the chromatographic column. The second drive pump is used to draw a second liquid from a second container and deliver the drawn second liquid toward the chromatographic column. The rated operating pressure of the first drive pump and the rated operating pressure of the second drive pump are both less than or equal to 20 MPa.

4. The liquid chromatograph-mass spectrometer of claim 3, wherein: The liquid phase fluid delivery assembly further includes a confluence component. The first drive pump and the second drive pump are respectively connected to the confluence component. The first drive pump is used to draw the first liquid from the first container and deliver the drawn first liquid toward the confluence component and the chromatographic column. The second drive pump is used to draw the second liquid from the second container and deliver the drawn second liquid toward the confluence component and the chromatographic column. Before processing the mass spectrometry detection information, the controller is further configured to: control the first drive pump and the second drive pump to operate according to a preset concentration control method, so that the first liquid and / or the second liquid are made into liquid phase fluids of different concentrations in the confluence component, and control the first drive pump and / or the second drive pump to drive the liquid phase fluids of different concentrations in the confluence component to be delivered toward the chromatographic column respectively, so as to perform gradient elution of the test solution adsorbed on the chromatographic column to form the test solution.

5. The liquid chromatograph-mass spectrometer of claim 1, wherein: The number of chromatographic columns is multiple, and the liquid chromatography-mass spectrometry device further includes a first switching device and a second switching device, with the multiple chromatographic columns connected in parallel between the first switching device and the second switching device; The liquid phase fluid delivery assembly can be switched to connect to the multiple chromatographic columns via the first switching device; The mass spectrometer detection device can be switched to connect to the multiple chromatographic columns via the second switching device.

6. The liquid chromatograph-mass spectrometer of any one of claims 1 to 5, wherein: The pretreatment device further includes a reagent storage component, which is used to load a first reagent container containing the internal standard reagent and a second reagent container containing the magnetic bead reagent. The reagent dispensing component is used to draw at least a portion of the internal standard reagent from the first reagent container from the reagent storage component and dispense all or part of the drawn internal standard reagent into the reaction vessel, and to draw at least a portion of the magnetic bead reagent from the second reagent container from the reagent storage component and dispense all or part of the drawn magnetic bead reagent into the reaction vessel. And / or, the pretreatment device further includes a reaction vessel providing component and a reaction vessel transferring component, wherein the reaction vessel providing component is used to provide the reaction vessel, and the reaction vessel transferring component is used to transfer the reaction vessel from the reaction vessel providing component to the magnetic separation component and the magnetic bead elution component, respectively.

7. The liquid chromatograph-mass spectrometer of any one of claims 1 to 5, wherein: The pre-processing device further includes a mixing component; The controller is also configured to control the preprocessing device to perform the following preprocessing actions: The pipetting component is controlled to aspirate at least a portion of the sample from the sample container of the sample storage device and to dispense all or part of the aspirated sample into the reaction container; The reagent dispensing component is controlled to dispense the internal standard reagent into the reaction vessel; The mixing component is controlled to mix the sample and the internal standard reagent in the reaction vessel to obtain a second mixture; The reagent dispensing component is controlled to dispense the magnetic bead reagent into the second mixture in the reaction vessel to obtain the first mixture; The magnetic separation component is controlled to perform magnetic separation and cleaning on the first mixture in the reaction vessel to obtain the clear liquid and the magnetic beads adsorbed with the internal standard and the target analyte; The magnetic separation component is controlled to draw in and drain the clear liquid from the reaction vessel; The magnetic bead elution unit is controlled to elute the magnetic beads in the reaction vessel, which adsorb the internal standard and the target analyte, to obtain the test solution.

8. The liquid chromatograph-mass spectrometer of claim 1, wherein: The length of the chromatographic column is greater than or equal to 5 mm and less than or equal to 30 mm.

9. The liquid chromatograph-mass spectrometer of any one of claims 1 to 5 or 8, wherein: The chromatographic column includes a column body having an inner cavity and packing material filling the inner cavity, wherein the inner diameter of the inner cavity is greater than 2.1 mm and less than 4.6 mm.

10. The liquid chromatograph-mass spectrometer of claim 9, wherein: The inner diameter of the cavity is greater than 2.1 mm and less than or equal to 4.0 mm.

11. The liquid chromatograph-mass spectrometer apparatus of claim 10, wherein: The diameter of the filler is greater than or equal to 1.7 μm and less than or equal to 1.8 μm; and / or the filler forms through-holes having a hole diameter greater than or equal to and less than or equal to 12. The liquid chromatograph-mass spectrometer of any one of claims 1 to 5 or 8, wherein: The chromatographic column includes a column having an inner cavity and packing material filled in the inner cavity, wherein the volume of the inner cavity is greater than or equal to 0.063 mL and less than or equal to 0.38 mL.

13. The liquid chromatograph-mass spectrometer of any one of claims 1 to 5 or 8, wherein: The sample was a blood sample; And / or, the mass spectrometry detection device includes a triple quadrupole tandem mass spectrometer.

14. A liquid chromatograph-mass spectrometer apparatus, characterized by: include: A sample storage device for holding a sample container loaded with a sample collected from a human or animal body to load the sample, the sample including a target analyte; A pretreatment device for pretreating the sample from the sample container of the sample storage device to obtain a test solution; A chromatographic device, comprising a reagent preparation channel, a reagent transfer assembly, a liquid phase fluid delivery assembly, and a chromatographic column, wherein the reagent transfer assembly, the liquid phase fluid delivery assembly, and the chromatographic column are respectively connected to the reagent preparation channel; the reagent transfer assembly is used to transfer at least a portion of the reagent obtained by the pretreatment device to the reagent preparation channel; the liquid phase fluid delivery assembly is used to drive the reagent in the reagent preparation channel through the chromatographic column to adsorb the reagent onto the chromatographic column, and to drive the liquid phase fluid through the chromatographic column to elute the reagent adsorbed on the chromatographic column to form a test solution; A mass spectrometry detection device, which is connected to the chromatographic column, is used to perform mass spectrometry detection on the test solution flowing out of the chromatographic column and obtain mass spectrometry detection information; A controller configured to process the mass spectrometry detection information and output the mass spectrometry detection result of the target analyte in the sample; The working pressure output by the liquid phase fluid transport component is less than or equal to 20 MPa.

15. The liquid chromatograph-mass spectrometer apparatus of claim 14, wherein: The target analytes in the sample include at least one of vitamin D, steroid hormones, and catecholamines.

16. The liquid chromatograph-mass spectrometer of claim 14 or 15, wherein: The pretreatment device uses at least one of magnetic separation, solid-phase extraction, liquid-liquid extraction, and protein precipitation to pretreat the sample.

17. The liquid chromatograph-mass spectrometer apparatus of claim 16, wherein: The preprocessing device uses magnetic separation to preprocess the sample; The pretreatment device includes a magnetic separation component, a magnetic bead elution component, a reagent dispensing component, and a pipetting component. The pipetting component aspirates at least a portion of the sample from the sample container of the sample storage device and dispenses all or part of the aspirated sample into the reaction container. The reagent dispensing component dispenses an internal standard reagent containing an internal standard and a magnetic bead reagent containing magnetic beads into the reaction container, respectively. The magnetic separation component performs magnetic separation and cleaning on a first mixture in the reaction container containing at least the sample, the internal standard reagent, and the magnetic bead reagent to obtain a clear liquid and magnetic beads adsorbed with the internal standard and the target analyte, then aspirates and discards the clear liquid. The magnetic bead elution component elutes the magnetic beads adsorbed with the internal standard and the target analyte obtained from the magnetic separation and cleaning in the reaction container to obtain the test solution. The reagent dispensing component and the pipetting component are either two independent components or the same component. Alternatively, the pretreatment device includes a magnetic separation component, a reagent dispensing component, and a pipetting component; the pipetting component is used to aspirate at least a portion of the sample from the sample container of the sample storage device and dispense all or part of the aspirated sample into the reaction container; the reagent dispensing component is used to dispense an internal standard reagent containing an internal standard and a magnetic bead reagent containing magnetic beads into the reaction container respectively; the magnetic separation component is used to perform magnetic separation and cleaning on a first mixture in the reaction container containing at least the sample, the internal standard reagent, and the magnetic bead reagent to obtain a clear liquid containing the internal standard and the target analyte, the clear liquid being used as the test solution; the test solution transfer component is used to aspirate at least a portion of the test solution from the reaction container and transfer all or part of the aspirated test solution to the test solution preparation channel; the reagent dispensing component and the pipetting component are two independent components or the same component.

18. The liquid chromatograph-mass spectrometer apparatus as recited in claim 14 or 15, wherein: The length of the chromatographic column is greater than or equal to 3 mm and less than or equal to 35 mm; And / or, the chromatographic column includes a column having an inner cavity and packing material filled in the inner cavity, wherein the inner diameter of the inner cavity is greater than 2.1 mm and less than 4.6 mm.

19. A liquid chromatograph-mass spectrometer apparatus, characterized by: include: A sample storage device is used to place a sample container loaded with a sample to realize the feeding of the sample, the sample including the target analyte; A pretreatment device for pretreating the sample from the sample container of the sample storage device to obtain a test solution; A chromatographic device, comprising a reagent preparation channel, a reagent transfer assembly, a liquid phase fluid delivery assembly, and a chromatographic column, wherein the reagent transfer assembly, the liquid phase fluid delivery assembly, and the chromatographic column are respectively connected to the reagent preparation channel; the reagent transfer assembly is used to transfer at least a portion of the reagent obtained by the pretreatment device to the reagent preparation channel; the liquid phase fluid delivery assembly is used to drive the reagent in the reagent preparation channel through the chromatographic column to adsorb the reagent onto the chromatographic column, and to drive the liquid phase fluid through the chromatographic column to elute the reagent adsorbed on the chromatographic column to form a test solution; A mass spectrometry detection device, which is connected to the chromatographic column, is used to perform mass spectrometry detection on the test solution flowing out of the chromatographic column and obtain detection information; A controller configured to process the mass spectrometry detection information and output the mass spectrometry detection result of the target analyte in the sample; The working pressure output by the liquid phase fluid transport component is less than or equal to 20 MPa; The output of the mass spectrometry detection results of the target analyte in the sample includes: outputting the mass spectrometry detection results of at least one of vitamin D, steroid hormones, and catecholamines in the sample.

20. The liquid chromatograph-mass spectrometer of claim 19, wherein: The working pressure output by the liquid phase fluid transport component is greater than or equal to 2MPa and less than or equal to 15MPa; And / or, the length of the chromatographic column is greater than or equal to 3 mm and less than or equal to 35 mm.

21. The liquid chromatography-mass spectrometry (LC-MS) apparatus as described in claim 19 or 20, characterized in that: The preprocessing device uses magnetic separation to preprocess the sample; And / or, the mass spectrometry detection device includes a triple quadrupole tandem mass spectrometer.

22. A control method for a liquid chromatography-mass spectrometry (LC-MS) device, characterized in that: include: The pretreatment device is controlled to pre-process samples collected from human or animal bodies to obtain a test solution; The sample includes a target analyte, which includes at least one of vitamin D, steroid hormones, and catecholamines. The control solution transfer assembly transfers at least a portion of the solution obtained from the pretreatment device to the solution preparation channel. The liquid phase fluid delivery assembly is controlled to drive the test solution in the test solution preparation channel through a chromatographic column with a length greater than or equal to 3 mm and less than or equal to 35 mm by liquid phase fluid at a working pressure of less than or equal to 20 MPa, so that the test solution is adsorbed onto the chromatographic column. The liquid phase fluid delivery assembly is controlled to drive the liquid phase fluid through the chromatographic column at a working pressure of less than or equal to 20 MPa, so that the liquid phase fluid elutes the test solution adsorbed on the chromatographic column to form the test solution flowing to the mass spectrometry detection device; The mass spectrometer detection device is controlled to perform mass spectrometry detection on the test solution flowing out of the chromatographic column and obtain mass spectrometry detection information; The mass spectrometry detection information is processed to output the mass spectrometry detection results of the target analyte in the sample; The pretreatment device controls the pretreatment of samples collected from human or animal bodies to obtain a test solution, including: controlling a pipetting component to aspirate at least a portion of the sample from the sample container of the sample storage device and distributing all or part of the aspirated sample to a reaction container; controlling a reagent dispensing component to dispense an internal standard reagent containing an internal standard and a magnetic bead reagent containing magnetic beads to the reaction container to obtain a first mixture; controlling a magnetic separation component to perform magnetic separation and cleaning on the first mixture in the reaction container to obtain a clear liquid and the magnetic beads adsorbed with the internal standard and the target analyte; controlling the magnetic separation component to aspirate and drain the clear liquid in the reaction container; and controlling a magnetic bead elution component to elute the magnetic beads adsorbed with the internal standard and the target analyte obtained by the magnetic separation and cleaning in the reaction container to obtain the test solution. Alternatively, the pretreatment device controls the pretreatment of samples collected from a human or animal body to obtain a test solution, including: controlling a pipetting component to aspirate at least a portion of the sample from the sample container of the sample storage device and dispensing all or part of the aspirated sample into a reaction container; controlling a reagent dispensing component to dispense an internal standard reagent containing an internal standard and a magnetic bead reagent containing magnetic beads into the reaction container to obtain a first mixture; and controlling a magnetic separation component to perform magnetic separation and cleaning on the first mixture in the reaction container to obtain a clear liquid containing the internal standard and the target analyte, using the clear liquid as the test solution.

23. The control method for the liquid chromatography-mass spectrometry (LC-MS) apparatus as described in claim 22, characterized in that: The controlled reagent dispensing component dispenses internal standard reagent containing an internal standard and magnetic bead reagent containing magnetic beads into the reaction vessel, including: The reagent dispensing component is controlled to dispense the internal standard reagent into the reaction vessel; the mixing component is controlled to mix the sample and the internal standard reagent in the reaction vessel to obtain a second mixture; the reagent dispensing component is controlled to dispense the magnetic bead reagent into the second mixture in the reaction vessel to obtain a first mixture.

24. The control method for the liquid chromatography-mass spectrometry (LC-MS) apparatus as described in claim 22 or 23, characterized in that: The output of the mass spectrometry detection results of the target analyte in the sample includes: outputting the mass spectrometry detection results of at least one of vitamin D, steroid hormones, and catecholamines in the sample.

25. The control method for the liquid chromatography-mass spectrometry (LC-MS) apparatus as described in claim 22 or 23, characterized in that: The method of controlling the liquid phase fluid delivery component to drive the liquid phase fluid through the chromatographic column at a working pressure of less than or equal to 20 MPa, so that the liquid phase fluid elutes the test solution adsorbed on the chromatographic column to form the test solution flowing to the mass spectrometry detection device, includes: controlling the liquid phase fluid delivery component to prepare liquid phase fluids of different concentrations according to a preset concentration control method, and driving the liquid phase fluids of different concentrations to be delivered toward the chromatographic column at a working pressure of less than or equal to 20 MPa, so as to perform gradient elution of the test solution adsorbed on the chromatographic column, thereby forming the test solution.

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