Online solid-phase extraction-automated direct injection-nano-current electrospray spectroscopy system

Abstract

This invention discloses an online solid-phase extraction-automated direct sample introduction-nano-current electrospray mass spectrometry (MS / MS) system, relating to the field of organic small molecule analysis and detection. The system includes an online solid-phase extraction module, a nano-current automated sample introduction module, and an ultra-high resolution mass spectrometer (UHS-MS). The UHS-MS has a nano-current electrospray ion source. The online solid-phase extraction module and the nano-current automated sample introduction module are coupled together via a six-way switching valve. The nano-current electrospray ion source and the nano-current automated sample introduction module are coupled together via another six-way switching valve. The online solid-phase extraction module and the nano-current automated sample introduction module can be switched via the piping of the six-way switching valves, allowing for simultaneous or independent pretreatment and sample introduction procedures. This system enables automatic and rapid synchronous processing of sample pretreatment and on-machine testing, effectively reducing the average total analysis time for batches of complex samples and significantly improving the detection efficiency of related complex matrix samples.

Description

Technical Field

[0001] This invention relates to the field of organic small molecule analysis and detection, specifically to an online solid-phase extraction-automatic direct injection-nano-current electrospray mass spectrometry system. Background Technology

[0002] Sample pretreatment is a necessary step in the analysis of most complex samples (such as food, pharmaceuticals, biological samples, or environmental samples). Due to its cumbersome and time-consuming nature, it often accounts for more than half of the total analysis time. Currently, most target analytes in complex samples are at trace levels. Before qualitative or quantitative analysis, samples often need to be purified or enriched using solid-phase extraction (SPE) columns or solid-phase microextraction (SPME) probes to ensure a satisfactory method detection limit. For ultra-trace target analytes analysis in trace samples, patent CN112630289A indicates that using nanofluidic electrospray ionization technology with direct sample introduction can effectively solve the problems of ion signal suppression and loss, thereby improving detection sensitivity. However, this patent CN112630289A is a manual sample introduction method, which cannot meet the high-efficiency detection requirements of batch samples. In addition, ultra-high resolution mass spectrometry (UHDMS) has the characteristics of ultra-high resolution, high throughput, and high sensitivity, making it more suitable for rapid qualitative and quantitative analysis of multiple target analytes in complex matrix samples using direct sample introduction. To meet the need for rapid detection of trace-level target analytes in small batches of samples, there is an urgent need to develop an efficient ultra-high resolution mass spectrometry technology and system that integrates micro-volume pretreatment, automated direct nanofluid injection, and nanofluid electrospray ionization. Summary of the Invention

[0003] To address the shortcomings of existing technologies, this invention provides an online solid-phase extraction-automatic direct sample introduction-nano-current electrospray mass spectrometry system, which can reduce the analysis time of organic matter in batches of complex samples and improve the detection efficiency of related complex matrix samples.

[0004] To achieve the above objectives, the present invention can adopt the following technical solutions:

[0005] An online solid-phase extraction-automated direct injection-nanocurrent electrospray mass spectrometry (SPES) system is disclosed, comprising an online solid-phase extraction module, a nanocurrent automatic injection module, and an ultra-high resolution mass spectrometer. The ultra-high resolution mass spectrometer has a nanocurrent electrospray ion source. The online solid-phase extraction module and the nanocurrent automatic injection module are coupled together via a six-way switching valve. The nanocurrent electrospray ion source and the nanocurrent automatic injection module are coupled together via another six-way switching valve. The online solid-phase extraction module and the nanocurrent automatic injection module can switch between each other via the six-way switching valves, allowing for simultaneous or independent pretreatment and injection procedures.

[0006] As described above, the online solid-phase extraction-automatic direct injection-nanocurrent electrospray mass spectrometry (SPES) system further includes, in this case, a first six-way switching valve, a second six-way switching valve, a first movable sampling needle, a large-volume quantitative loop, a large-volume analytical pump head containing a three-way switching valve, a first needle holder, a first sample tray, a quaternary high-pressure pump, a three-way switching valve, and an SPE column fixing device. Positions 1 to 6 of the first six-way switching valve are respectively connected to the first needle holder, position 2 of the three-way switching valve, position 3 of the large-volume analytical pump head containing the three-way switching valve, the waste liquid tank, the nitrogen switch valve, and position 3 of the second six-way switching valve. The pipelines are connected, and the two ends of the large-volume quantitative loop are respectively connected to the pipelines at position 2 of the first movable sampling needle and the large-volume analytical pump head containing the three-way switching valve. The first movable sampling needle can be inserted into the first needle seat under a specified command. The quaternary high-pressure pump is connected to the pipeline at position 1 of the three-way switching valve. The three-way switching valve at position 3 is connected to the pipeline at position 1 of the second six-way switching valve. The inlet and outlet ends of the SPE column fixing device are respectively connected to the pipelines at positions 2 and 5 of the second six-way switching valve. The pipelines at positions 4 and 6 of the second six-way switching valve are respectively connected to the waste liquid tank and position 2 of the third six-way switching valve.

[0007] As described above, the online solid-phase extraction-automatic direct injection-nanocurrent electrospray mass spectrometry system further includes a nanocurrent automatic injection module comprising a third six-way switching valve, a second movable sampling needle, a micro-quantitative loop, a nanocurrent micro-analytical pump head with a three-way switching valve, a second needle holder, and a second sample tray. The second movable sampling needle can be inserted into the second needle holder upon a specified command. The tubing at positions 2 and 3 of the nanocurrent micro-analytical pump head with the three-way switching valve is connected to position 1 of the third six-way switching valve and the micro-quantitative loop, respectively. The other end of the micro-quantitative loop is connected to the tubing of the second movable sampling needle. The tubing at positions 3, 4, and 6 of the third six-way switching valve is connected sequentially to the waste liquid tank, the second needle holder, and the waste liquid tank, respectively.

[0008] As described above, in the online solid-phase extraction-automatic direct injection-nanocurrent electrospray mass spectrometry system, the quaternary high-pressure pump, through the switching of the connected three-way switching valve and the first six-way switching valve, the second six-way switching valve and the third six-way switching valve, can respectively clean the first and second movable sampling needles, the large-volume quantitative loop and the micro-quantitative loop, the large-volume analytical pump head with the three-way switching valve and the nanocurrent micro-analytical pump head with the three-way switching valve, the first needle holder and the second needle holder, the solid-phase extraction column in the SPE column fixing device, and multiple pipelines.

[0009] As described above, in the online solid-phase extraction-automatic direct injection-nanocurrent electrospray mass spectrometry system, when the third six-way switching valve is switched to position 1-6, the online solid-phase extraction module and the nanocurrent automatic injection module can operate independently. When the three-way switching valve and the third six-way switching valve in the nanocurrent micro-analysis pump head containing the three-way switching valve are simultaneously switched to positions 1-3 and 1-6 respectively, the sample solution absorbed in the micro-quantitative loop can be injected into the nanocurrent electrospray ion source of the ultra-high resolution mass spectrometer.

[0010] As described above, in the online solid-phase extraction-automatic direct injection-nano-current electrospray mass spectrometry system, when the nitrogen switch valve is opened, the first six-way switching valve is switched to position 1-2, the second six-way switching valve is switched to position 1-6, and the third six-way switching valve is switched to position 1-6, nitrogen gas is blown into the solid-phase extraction column in the SPE column fixing device through the pipeline.

[0011] Compared with the prior art, the advantages of this invention are as follows:

[0012] 1. This invention addresses the limitations of existing online solid-phase extraction-mass spectrometry (SPME-MS) technologies, which suffer from large sample volumes and low sensitivity due to direct injection. It employs nanofluidic direct injection electrospray ionization (ESI) technology, combined with a mass spectrometer possessing ultra-high resolution, high throughput, and high sensitivity, to develop an online SPME-automatic direct injection-nanofluidic ESI-MS system. This system enables automated, rapid, and simultaneous sample pretreatment and on-machine testing, effectively reducing the average total analysis time for batches of complex samples and significantly improving the detection efficiency, sensitivity, and peak throughput for related complex matrix samples. It is particularly suitable for samples with small volumes.

[0013] 2. The system of this embodiment of the invention allows the nano-current autosampler module to operate independently via valve switching. It utilizes a nano-current electrospray ionization source to ionize target peaks in the sample solution, significantly reducing sample volume and organic solvent usage. Furthermore, for samples with low salt content, the system of this embodiment allows for direct nano-current injection ionization testing after simple extraction or solvent dilution, completely avoiding the selective loss of key signals caused by SPE column or SPME probe enrichment and purification processes. Attached Figure Description

[0014] To more clearly illustrate the technical solutions in the embodiments of the present invention, the accompanying drawings used in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of this application. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0015] Figure 1This is a schematic diagram of the online solid-phase extraction-automatic direct injection-nano-current electrospray mass spectrometry system according to an embodiment of the present invention.

[0016] The components include: 1. Online solid-phase extraction module; 2. Nanofluidic automatic sample introduction module; 3. Ultra-high resolution mass spectrometer; 101. First six-way switching valve; 102. Second six-way switching valve; 103. First movable sampling needle; 104. Large-volume quantitative loop; 105. Large-volume analytical pump head with three-way switching valve; 106. First needle holder; 107. First sample tray; 108. Nitrogen switch valve; 109. Quaternary high-pressure pump; 110. Three-way switching valve; 111. SPE column fixing device; 201. Third six-way switching valve; 202. Second movable sampling needle; 203. Micro-quantitative loop; 204. Nanofluidic micro-analytical pump head with three-way switching valve; 205. Second needle holder; 206. Second sample tray; 31. Nanofluidic electrospray ion source. Detailed Implementation

[0017] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of this application, and not all 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.

[0018] Example:

[0019] It should be noted that the terms "first," "second," etc., in the specification, claims, and accompanying drawings of this invention are used to distinguish similar objects and are not necessarily used to describe a specific order or sequence. It should be understood that such data can be interchanged where appropriate so that the embodiments of the invention described herein can be implemented in orders other than those illustrated or described herein. Furthermore, the terms "comprising" and "having," and any variations thereof, in the embodiments of this invention are intended to cover non-exclusive inclusion; for example, a process, method, system, product, or apparatus that comprises a series of steps or units is not necessarily limited to those steps or units explicitly listed, but may include other steps or units not explicitly listed or inherent to such processes, methods, products, or apparatus.

[0020] It should be understood that the terms "center," "longitudinal," "lateral," "length," "width," "thickness," "upper," "lower," "front," "rear," "left," "right," "vertical," "horizontal," "top," "bottom," "inner," "outer," "clockwise," "counterclockwise," "axial," "radial," and "circumferential" indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings. They are used only for the convenience of describing the present invention and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation. Therefore, they should not be construed as limitations on the present invention.

[0021] In the description of this invention, "a plurality of" means at least two, such as two, three, etc., unless otherwise explicitly specified. Furthermore, unless otherwise explicitly specified and limited, the terms "installed," "connected," and "linked" should be interpreted broadly. For example, they can refer to a fixed connection, a detachable connection, or an integral connection; they can refer to a mechanical connection or an electrical connection; they can refer to a direct connection or an indirect connection through an intermediate medium; and they can refer to the internal connection of two components. Those skilled in the art can understand the specific meaning of the above terms in this invention based on the specific circumstances.

[0022] In this invention, unless otherwise explicitly specified and limited, "above" or "below" the second feature can mean that the first feature is in direct contact with the second feature, or that the first feature is in indirect contact with the second feature through an intermediate medium. Furthermore, "above," "over," and "on top" of the second feature can mean that the first feature is directly above or diagonally above the second feature, or simply that the first feature is at a higher horizontal level than the second feature. "Below," "below," and "under" the second feature can mean that the first feature is directly below or diagonally below the second feature, or simply that the first feature is at a lower horizontal level than the second feature.

[0023] See Figure 1 This invention provides an online solid-phase extraction-automatic direct injection-nanocurrent electrospray mass spectrometry (SPES) system, which may include an online solid-phase extraction module 1, a nanocurrent automatic injection module 2, and an ultra-high resolution mass spectrometer 3. The ultra-high resolution mass spectrometer 3 has a nanocurrent electrospray ion source 31. The online solid-phase extraction module 1 and the nanocurrent automatic injection module 2 are coupled together via a six-way switching valve. The nanocurrent electrospray ion source 31 and the nanocurrent automatic injection module 2 are coupled together via another six-way switching valve. The online solid-phase extraction module 1 and the nanocurrent automatic injection module 2 can be switched via the pipeline of the six-way switching valve, and the pretreatment and injection procedures can be performed simultaneously or independently.

[0024] Specifically, this invention addresses the limitations of existing online solid-phase extraction-mass spectrometry (SPME-MS) technologies, such as large sample volumes and low sensitivity of direct injection. It employs nanofluid electrospray ionization (SPE) technology with direct injection, combined with a mass spectrometer offering ultra-high resolution, high throughput, and high sensitivity, to develop an online SPME-automated direct injection-nanofluid electrospray ionization (NSIE-MS) system. In this system, the online SPME module 1 and the nanofluid automated injection module 2 are switched via a valve, allowing the two modules to perform pretreatment and injection procedures simultaneously or independently. This enables automated and rapid synchronous processing of sample pretreatment and on-machine testing, effectively reducing the average total analysis time for batches of complex samples. This significantly improves the detection efficiency, sensitivity, and peak throughput for complex matrix samples, making it particularly suitable for small-volume samples. Furthermore, through a six-way switching valve, the nanofluid automated injection module 2 can operate independently. By utilizing the nanofluid electrospray ionization source 31 to ionize target peaks in the sample solution, it can significantly reduce sample volume and organic solvent usage. Furthermore, the system of this invention allows for direct nanofluid injection testing of samples with low salt content after simple extraction or solvent dilution, completely avoiding the selective loss of key signals caused by the enrichment and purification process of SPE columns or SPME probes.

[0025] See you again Figure 1 , Figure 1 An online solid-phase extraction-automated direct injection-nanocurrent electrospray mass spectrometry (SSPMS) system is demonstrated, which may include an online solid-phase extraction module 1, a nanocurrent automated injection module 2, and an ultra-high resolution mass spectrometer 3. For example, the ultra-high resolution mass spectrometer 3 may be a Fourier transform ion cyclotron resonance mass spectrometer, a triple quadrupole-linear ion trap combined mass spectrometer, or a Bruker 7.0T Solarix XR FTICR-MS mass spectrometer, etc. The ultra-high resolution mass spectrometer 3 includes a nanocurrent electrospray ion source 31, which is connected to position 5 of a third six-way switching valve 201. In this embodiment of the invention, the nanocurrent automated injection module 2 and the online solid-phase extraction module 1 can perform pretreatment and injection procedures simultaneously or independently via the six-way switching valve.

[0026] It is understood that the system in this embodiment of the invention can be a system in which the nanofluid autosampler module 2 is simultaneously connected to the online solid-phase extraction module 1 and the ultra-high resolution mass spectrometer 3, or it can be a system in which the online solid-phase extraction module 1 can be used independently and the nanofluid autosampler module 2 is connected to the ultra-high resolution mass spectrometer 3 separately. For example, except that the waste liquid tube is made of polypropylene, the other connecting pipes in the combined system can be made of stainless steel, polytetrafluoroethylene, or polyetheretherketone.

[0027] Specifically, the online solid-phase extraction module 1 may include a first six-way switching valve 101, a second six-way switching valve 102, a first movable sampling needle 103, a large-volume quantitative loop 104, a large-volume analytical pump head 105 containing a three-way switching valve, a first needle holder 106, a first sample tray 107, a quaternary high-pressure pump 109, a three-way switching valve 110, and an SPE column fixing device 111. Positions 1 to 6 of the first six-way switching valve 101 are sequentially connected to the pipelines of the first needle holder 106, position 2 of the three-way switching valve 110, position 3 of the large-volume analytical pump head 105 containing the three-way switching valve, a waste liquid tank, a nitrogen switch valve 108, and position 3 of the second six-way switching valve 102. Large-volume quantitative... The two ends of the ring 104 are respectively connected to the first movable sampling needle 103 and the 2nd position of the large volume analytical pump head 105 containing a three-way switching valve. The first movable sampling needle 103 can be inserted into the first needle seat 106 under a specified command. The quaternary high pressure pump 109 is connected to the 1st position of the three-way switching valve 110. The 3rd position of the three-way switching valve 110 is connected to the 1st position of the second six-way switching valve 102. The inlet and outlet ends of the SPE column fixing device 111 are respectively connected to the 2nd and 5th positions of the second six-way switching valve 102. The 4th and 6th positions of the second six-way switching valve 102 are respectively connected to the waste liquid tank and the 2nd position of the third six-way switching valve 201 in the nano-flow automatic sampling module 2.

[0028] The nanofluid autosampler module 2 includes a third six-way switching valve 201, a second movable sampling needle 202, a micro-quantitative loop 203, a nanofluid micro-analytical pump head 204 with a three-way switching valve, a second needle holder 205, and a second sample tray 206. The second movable sampling needle 202 can be inserted into the second needle holder 205 under a specified command. The tubing at positions 2 and 3 of the nanofluid micro-analytical pump head 204 with the three-way switching valve is connected to position 1 of the third six-way switching valve 201 and the micro-quantitative loop 203, respectively. The other end of the micro-quantitative loop 203 is connected to the tubing of the second movable sampling needle 202. The tubing at positions 3, 4, and 6 of the third six-way switching valve 201 is connected to the waste liquid tank, the second needle holder 205, and the waste liquid tank, respectively.

[0029] In this embodiment, when the third six-way switching valve 201 is switched to the 1-6 position connection, the online solid phase extraction module 1 and the nano-current automatic sampling module 2 independently perform pretreatment and injection procedures. The injection procedure of the nano-current automatic sampling module 2 is as follows: 1. The second movable sampling needle 202 is inserted into the sample bottle containing the solution in the second sample tray 206, and the nano-current micro-analytical pump head 204 with the three-way switching valve is turned on to perform the aspiration and purging procedure. At the same time, its three-way switching valve is switched to the 1-2 position and the 1-3 position connection state, and the micro-quantitative loop 203 is rinsed; 2. After the micro-quantitative loop 203 aspirates the solution, the second movable sampling needle 202 is inserted into the second needle seat 205, which can be used to clean the pipeline connected to the nano-current electrospray ion source 31 or perform the injection procedure.

[0030] When the third six-way switching valve 201 is switched to position 1-6, the pretreatment procedure of the online solid-phase extraction module 1 is as follows: 1. Switch the first six-way switching valve 101 to position 1-2, the second six-way switching valve 102 to position 1-2, and the three-way switching valve 110 to position 1-3. Turn on the quaternary high-pressure pump 109, select the appropriate mobile phase for column washing according to the requirements before loading the SPE column, and simultaneously start the aspiration and purging procedure of the large-volume analytical pump head 105 containing the three-way switching valve. Switch its three-way switching valve to positions 1-2 and 1-3 respectively, so that a certain amount of sample original solution is aspirated into the quantitative loop; 2. Change the first six-way switching valve 101 to position 1-6, the second six-way switching valve 102 to position 1-6, and the large-volume analytical pump head 105 containing the three-way switching valve to position 1-3. 1. Change the three-way switching valve of the analytical pump head 105 to 2-3 connection, and change the three-way switching valve 110 to 1-2 connection. The original sample solution enters the SPE column fixation device 111 for enrichment and column cleaning. 2. Change the first six-way switching valve 101 to 1-2 connection, open the nitrogen switch valve 108, and dry the SPE column at regular intervals. 3. Close the nitrogen switch valve 108, change the second six-way switching valve 102 to 1-2 connection, and change the three-way switching valve 110 to 1-3 connection. At the same time, start the aspiration and purging program of the large-volume analytical pump head, and switch its three-way switching valves to 1-2 and 1-3 connection respectively, so that a certain amount of original sample solution is aspirated into the quantitative loop. This state is the state of step 1 of the pretreatment program of the online solid phase extraction module 1 mentioned above, and this cycle continues to the next sample.

[0031] Simultaneously, before step 4 of the pretreatment procedure of the above-mentioned online solid-phase extraction module 1, the nano-current automatic sampling module 2 quickly performs the following operations in sequence: the second movable sampling needle 202 is inserted into the designated sample vial; the third six-way switching valve 201 is changed to a 1-2 connection; and the three-way switching valve of the nano-current micro-analytical pump head is changed to a 2-3 connection. At this moment, the eluent from the SPE column enters the sample vial and is quantitatively collected. After the eluent collection is completed, the third six-way switching valve 201 is quickly changed to a 1-6 connection; the second movable sampling needle 202 is inserted into the second needle holder 205; and the third six-way switching valve 201 is changed back to a 1-2 connection to clean the second movable sampling needle 202, the micro-quantitative loop 203, and the second needle holder 205. After cleaning for a period of time, the above-mentioned sample injection procedure of the nano-current automatic sampling module 2 can be restarted cyclically.

[0032] For example, the volumes of the large-volume quantitative loop 104 and the micro-volume quantitative loop 203 are 1–10 mL and 10–100 μL, respectively. The large-volume analytical pump head 105 with a three-way switching valve and the nano-flow micro-analytical pump head 204 with a three-way switching valve include an adjustable quantitative aspiration range, a fixed aspiration rate, and an adjustable evacuation rate. The adjustable quantitative aspiration ranges are 0.2–10 mL and 2–100 μL, respectively. The fixed aspiration rates are 200 μL / sec and 10 μL / sec, respectively. The adjustable evacuation rates are 2–200 μL / sec and 0.02–10 μL / sec, respectively.

[0033] In some embodiments, the quaternary high-pressure pump 109 can clean the first movable sampling needle 103, the second movable sampling needle 202, the large-volume quantitative loop 104 and the micro-quantitative loop 203, the large-volume analytical pump head 105 with a three-way switching valve and the nano-flow micro-analytical pump head 204 with a three-way switching valve, the first needle seat 106, the second needle seat 205, the solid-phase extraction column in the SPE column fixing device 111, and multiple pipelines by switching the connected three-way switching valve 110 and the first six-way switching valve 101, the second six-way switching valve 102, and the third six-way switching valve 201.

[0034] Specifically, when the three-way switching valve of the large-volume analytical pump head 105 containing the three-way switching valve is switched to position 2-3, the first six-way switching valve 101 is switched to position 1-6, the second six-way switching valve 102 is switched to position 1-2, the third six-way switching valve 201 is switched to position 1-2, the three-way switching valve of the nano-flow micro-analytical pump head 204 containing the three-way switching valve is switched to position 2-3, and the first movable sampling needle 103 and the second movable sampling needle 202 are respectively inserted into the first needle seat 106 and the second needle seat 205, by turning on the quaternary high-pressure pump 109, the three-way switching valve 110 is switched to positions 1-2 and 1-3 respectively, which can clean the pipeline of the system and thus solve the problem of sample residue after injection.

[0035] In some embodiments, when the third six-way switching valve 201 in the nano-flow autosampler module 2 is switched to the 1-6 position connection, the online solid phase extraction module 1 and the nano-flow autosampler module 2 can operate independently. When the three-way switching valve in the nano-flow micro-analysis pump head 204 containing the three-way switching valve and the third six-way switching valve 201 in the nano-flow autosampler module 2 are switched to the 1-3 position and the 1-6 position connection respectively, the sample solution drawn in the micro-quantitative loop 203 can be injected into the nano-flow electrospray ion source 31 of the ultra-high resolution mass spectrometer 3.

[0036] Furthermore, simultaneously, the nitrogen switch valve 108 is opened, the first six-way switching valve 101 in the online solid phase extraction module 1 is switched to position 1-2, the second six-way switching valve 102 in the online solid phase extraction module 1 is switched to position 1-6, and the third six-way switching valve 201 in the nano-flow automatic injection module 2 is switched to position 1-6. Nitrogen gas is then blown into the solid phase extraction column in the SPE column fixing device 111 through the pipeline.

[0037] In the description of this specification, the references to terms such as "one embodiment," "some embodiments," "example," "specific example," or "some examples," etc., indicate that a specific feature, structure, material, or characteristic described in connection with that embodiment or example is included in at least one embodiment or example of the present invention. In this specification, the illustrative expressions of the above terms do not necessarily refer to the same embodiment or example. Furthermore, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in one or more embodiments or examples. Moreover, without contradiction, those skilled in the art can combine and integrate the different embodiments or examples described in this specification, as well as the features of different embodiments or examples.

[0038] The above embodiments are merely illustrative of the technical concept and features of the present invention, and are intended to enable those skilled in the art to understand the content of the present invention and implement it accordingly. They should not be construed as limiting the scope of protection of the present invention. All equivalent changes or modifications made based on the essence of the content of the present invention should be covered within the scope of protection of the present invention.

Claims

1. An online solid phase extraction-automated direct injection-nanoliter electrospray mass spectrometry system, characterized in that, The online solid phase extraction module includes a first six-way switching valve, a second six-way switching valve, a first movable sampling needle, a large-volume quantitative ring, a large-volume analysis pump head with a three-way switching valve, a first needle seat, a first sample disc, a four-element high-pressure pump, a three-way switching valve, and an SPE column fixing device, wherein the 1-6 positions of the first six-way switching valve are connected in sequence with the first needle seat, the 2 position of the three-way switching valve, the 3 position of the large-volume analysis pump head with the three-way switching valve, a waste liquid barrel, a nitrogen on-off valve, and the 3 position of the second six-way switching valve; the two ends of the large-volume quantitative ring are connected with the first movable sampling needle and the 2 position of the large-volume analysis pump head with the three-way switching valve; the first movable sampling needle can be inserted into the first needle seat under a specified password; the four-element high-pressure pump is connected with the 1 position of the three-way switching valve; the 3 position of the three-way switching valve is connected with the 1 position of the second six-way switching valve; the inlet end and the outlet end of the SPE column fixing device are connected with the 2 position and the 5 position of the second six-way switching valve; the 4 position and the 6 position of the second six-way switching valve are connected with the waste liquid barrel and the 2 position of the third six-way switching valve of the nanoflow automatic sampling module; the online solid phase extraction module includes a first six-way switching valve, a second six-way switching valve, a first movable sampling needle, a large-volume quantitative ring, a large-volume analysis pump head with a three-way switching valve, a first needle seat, a first sample disc, a four-element high-pressure pump, a three-way switching valve, and an SPE column fixing device, wherein the 1-6 positions of the first six-way switching valve are connected in sequence with the first needle seat, the 2 position of the three-way switching valve, the 3 position of the large-volume analysis pump head with the three-way switching valve, a waste liquid barrel, a nitrogen on-off valve, and the 3 position of the second six-way switching valve; the two ends of the large-volume quantitative ring are connected with the first movable sampling needle and the 2 position of the large-volume analysis pump head with the three-way switching valve; the first movable sampling needle can be inserted into the first needle seat under a specified password; the four-element high-pressure pump is connected with the 1 position of the three-way switching valve; the 3 position of the three-way switching valve is connected with the 1 position of the second six-way switching valve; the inlet end and the outlet end of the SPE column fixing device are connected with the 2 position and the 5 position of the second six-way switching valve; the 4 position and the 6 position of the second six-way switching valve are connected with the waste liquid barrel and the 2 position of the third six-way switching valve; the ultra-high resolution mass spectrometer has a nanoflow electrospray ion source; the online solid phase extraction module and the nanoflow automatic sampling module are coupled and connected through the second six-way switching valve; the nanoflow electrospray ion source and the nanoflow automatic sampling module are coupled and connected through the third six-way switching valve; the online solid phase extraction module and the nanoflow automatic sampling module can perform pretreatment and sampling procedures simultaneously or independently through the pipeline switching of the third six-way switching valve.

2. The online solid phase extraction-automated direct injection-nanoflow electrospray mass spectrometry system according to claim 1, wherein, The four high-pressure pumps can clean the first movable sampling needle and the second movable sampling needle, the large-volume quantitative ring and the micro-quantitative ring, the large-volume analytical pump head containing a three-way switching valve and the nanoflow micro-analytical pump head containing a three-way switching valve, the first needle seat and the second needle seat, the solid-phase extraction column in the SPE column fixing device, and multiple pipelines by switching the connected three-way switching valve and the first six-way switching valve, the second six-way switching valve and the third six-way switching valve.

3. The online solid phase extraction-automated direct injection-nanoflow electrospray mass spectrometry system according to claim 1, wherein, When the third six-way switching valve is switched to the 1-6 position connection, the online solid-phase extraction module and the nanoflow automatic sampling module can be independently operated, and when the three-way switching valve in the nanoflow micro-analytical pump head containing a three-way switching valve and the third six-way switching valve are switched to the 1-3 position and the 1-6 position connection respectively, the sample solution sucked in the micro-quantitative ring can be injected into the nanoflow electrospray ion source of the ultra-high resolution mass spectrometer.

4. The online solid phase extraction-automated direct injection-nanoflow electrospray mass spectrometry system of claim 1, wherein, When the nitrogen switch valve is opened, the first six-way switching valve is switched to the 1-2 position connection, the second six-way switching valve is switched to the 1-6 position connection, and the third six-way switching valve is switched to the 1-6 position connection, nitrogen is blown into the solid-phase extraction column in the SPE column fixing device through the pipeline.

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