LC-MS combined mass spectrometer sample injection processing device and working method thereof

Abstract

This invention discloses a sample preparation device for an LC-MS mass spectrometer, comprising a sample pretreatment mechanism connected to the outlet of a chromatographic column in a liquid chromatograph, the outlet of which is connected to the sample inlet of the mass spectrometer. The sample pretreatment mechanism includes a primary microfiltration mechanism, the outlet of which is connected to a secondary desalting mechanism; the outlet of the secondary desalting mechanism is connected to a tertiary variable-speed degassing mechanism; and the outlet of the tertiary variable-speed degassing mechanism is connected to a quaternary sample flow stabilization mechanism. This invention also discloses the operating method of the above device. This invention, through four-stage sample solution processing, significantly improves the accuracy of mass spectrometry detection and avoids interference from impurities, salts, and bubbles on the detection data.

Description

Technical Field

[0001] This invention belongs to the field of LC-MS coupling technology, and particularly relates to the sample processing device and its working method for LC-MS coupled mass spectrometer. Background Technology

[0002] LC-MS, or liquid chromatography-mass spectrometry, utilizes the separation capabilities of high-performance liquid chromatography (HPLC) combined with the molecular detection capabilities of mass spectrometry (MS). This allows for the separation and detection of mixed samples using a single LC-MS system. Therefore, LC-MS has a wide range of industrial applications, primarily used for qualitative and analytical analysis of substances.

[0003] Therefore, many existing technologies report on improvements to LC-MS, such as Chinese patent application CN202422565388.1, which discloses a waste liquid recovery device for a liquid chromatography-mass spectrometry (LC-MS) instrument. This recovery device includes a base with the LC-MS instrument body mounted on top. A first conveying assembly is located on the left side of the LC-MS instrument body, and a stirring tank is connected to the left side of the LC-MS instrument body via the first conveying assembly. A driving assembly is located on top of the stirring tank, and a rotating rod is located inside the stirring tank via the driving assembly. A stirring rod is fixedly mounted on the surface of the rotating rod. A support plate is fixedly mounted on the left side of the stirring tank, and a storage tank is fixedly mounted on top of the support plate. A second conveying assembly is located inside the stirring tank, and a diversion pipe is located on the right side of the stirring tank via the second conveying assembly. A nozzle is fixedly mounted at the bottom of the diversion pipe. The waste liquid from the LC-MS instrument is recovered using the technology disclosed in this patent. However, in actual work, the key reason affecting the accuracy of LC-MS detection is often that if the sample solution is not treated before entering the mass spectrometer after the sample is separated from the chromatographic column, including measures such as impurity removal and degassing, the accuracy of the mass spectrometry detection data will be affected.

[0004] Specifically, in the LC-MS process, the sample solution first passes through a liquid chromatography column for separation. After separation, the sample substances enter the mass spectrometer. Therefore, the current LC-MS essentially connects the chromatographic column in the liquid chromatography column to the injection port of the mass spectrometer. However, in actual operation, it has been found that because the sample is directly separated from the chromatographic column, the column's ability to separate impurities in the sample decreases with increasing column usage time. When the sample solution passes through the column, impurities, including salts, directly enter the mass spectrometer and appear as interfering peaks in the mass spectrometry results, severely interfering with the analysis of chromatographic data. Simultaneously, the introduction of salts also leads to severe scaling of the mass spectrometer, affecting its lifespan.

[0005] Meanwhile, the presence of air bubbles in the sample solution is also a major reason for low detection accuracy. This is because after the sample passes through the chromatographic column and is separated by the column, tiny air bubbles will be expelled from the column along with the eluent and the sample and eventually enter the mass spectrometer, interfering with the accuracy of mass spectrometry detection. Summary of the Invention

[0006] Based on the above background, the purpose of this invention is to provide a sample processing device for LC-MS coupled mass spectrometer.

[0007] To achieve the above objectives, the present invention adopts the following technical solution:

[0008] An LC-MS coupled mass spectrometer sample processing device includes an injection pretreatment mechanism connected to the liquid outlet of a chromatographic column in a liquid chromatograph, wherein the liquid outlet of the injection pretreatment mechanism is connected to the injection end of the mass spectrometer.

[0009] The sample pretreatment mechanism includes a primary microfiltration mechanism, the outlet of which is connected to a secondary desalination mechanism; the outlet of the secondary desalination mechanism is connected to a tertiary variable-speed degassing mechanism; and the outlet of the tertiary variable-speed degassing mechanism is connected to a quaternary sample flow stabilization mechanism.

[0010] The primary microfiltration mechanism includes a primary housing with a filter membrane structure installed inside; the secondary desalination mechanism includes a secondary housing detachably mounted on the primary housing with a polymer desalination structure installed inside; and the tertiary variable-speed debubbling mechanism includes a tertiary housing detachably mounted on the secondary housing.

[0011] The three-stage housing is equipped with a fluid variable speed defoaming structure, which includes a first variable speed unit and a second variable speed unit connected to the first variable speed unit.

[0012] Both the first and second transmission units include symmetrically arranged conical tubes, and a bubble-expelling structure is installed between the conical tubes;

[0013] An exhaust chamber is formed between the conical tube and the three-stage shell, and an exhaust pipe is connected to the top of the three-stage shell.

[0014] Preferably, the liquid inlet end of the primary housing is connected to a liquid inlet pipe, which is connected to the liquid outlet end of the chromatographic column.

[0015] The secondary shell is integrally formed with a threaded neck tube, which is threadedly connected to the primary shell.

[0016] A sealing ring is installed between the side walls of the secondary shell and the primary shell that face each other.

[0017] Preferably, the filter membrane structure includes a membrane sleeve threadedly connected to a primary housing, and a filter membrane is fixedly installed inside the membrane sleeve.

[0018] Preferably, the polymer desalination structure includes a packing sleeve threadedly connected within the secondary housing;

[0019] The two ends of the packing sleeve are respectively threaded with filter screen structures, and the packing sleeve is filled with polymer microspheres that adsorb salt.

[0020] Preferably, the filter structure includes a support ring threadedly connected to the opening of the packing sleeve, and a filter screen is fixedly connected inside the support ring.

[0021] Preferably, a threaded neck is integrally formed on the side wall of the third-level housing facing the second-level housing, and the threaded neck is threadedly connected inside the second-level housing;

[0022] A sealing ring is installed between the side walls of the third-level shell and the second-level shell that face each other.

[0023] Preferably, both the first transmission unit and the second transmission unit include a first conical tube and a second conical tube arranged symmetrically to each other;

[0024] The second conical tube of the first transmission unit is sealed and welded to the first conical tube of the second transmission unit;

[0025] An exhaust chamber is formed inside the third-stage shell by sealing and welding the open ends of the first and second conical tubes to the inner wall of the shell.

[0026] A bubble venting tube is integrally formed between the first conical tube and the second conical tube; the bubble venting structure is located on the bubble venting tube.

[0027] Preferably, the bubble removal structure includes a plurality of bubble removal holes formed on the bubble removal tube, and a breathable membrane is fixedly connected to the inner end of the bubble removal hole;

[0028] The outer end of the bubble vent is connected to the bubble venting pipe; the bubble venting pipe is located inside the exhaust chamber.

[0029] Preferably, the liquid outlet end of the third-stage shell is connected to a fluid outlet pipe;

[0030] The four-stage injection flow stabilization mechanism includes a flow stabilization tube connected to the outlet tube, and a flow stabilization structure is fixedly connected inside the flow stabilization tube;

[0031] The flow stabilizing structure includes a thin tube support fixed inside the flow stabilizing tube. The thin tube support has several through holes, and the flow stabilizing thin tube is fixedly installed inside the through holes.

[0032] The outlet end of the flow stabilizing tube is integrally formed with a conical tube, which is connected to a pre-injection tube, which is connected to the injection port of the mass spectrometer.

[0033] This invention also discloses the operating method of the above-mentioned LC-MS coupled mass spectrometer sample processing device, including the following steps:

[0034] (1) Primary filtration: After the sample solution exits the chromatographic column of the liquid chromatography, it passes through the primary microfiltration mechanism to filter impurities and then enters the secondary polymer desalting structure.

[0035] (2) Desalination: After the salt in the sample solution is removed in the secondary polymer desalination structure, it enters the tertiary variable speed degassing mechanism;

[0036] (3) In the three-stage variable speed degassing mechanism, the sample solution generates fluid turbulence by continuously accelerating and decelerating the flow rate, and removes the bubbles in the fluid before entering the four-stage sample injection and flow stabilization mechanism to stabilize the flow rate.

[0037] (4) The sample solution enters the mass spectrometer's injection port after being stabilized in the four-stage injection stabilization mechanism.

[0038] The present invention has the following beneficial effects:

[0039] 1. The sample solution is preliminarily filtered through a primary microfiltration mechanism to remove impurities (after entering the mass spectrometer, there are many impurity peaks in the detection spectrum, which seriously interferes with the interpretation of sample data), especially small insoluble impurities.

[0040] Subsequently, the salt in the sample solution is removed by a secondary desalting mechanism. Salt removal not only effectively protects the mass spectrometer, but also further reduces the impurity peaks in the spectrum.

[0041] Finally, the bubbles in the sample liquid are removed by a three-stage variable speed degassing mechanism. The fluid turbulence effect is generated by the continuous change of flow rate, and the small bubbles in the fluid are detached from the fluid under the turbulence.

[0042] 2. A filter membrane structure is installed inside the primary housing. Specifically, the filter membrane structure includes a membrane sleeve threadedly connected inside the primary housing, and a filter membrane is fixedly installed inside the membrane sleeve, so as to filter out small impurities in the sample solution.

[0043] 3. By filling the packing sleeve with polymer microspheres that adsorb salts, the sample solution enters the packing sleeve after passing through the secondary shell. During the process of passing through the polymer microspheres in the packing sleeve, the salts in the sample solution will exchange with the resin microspheres, and the metal ions of the salts will be adsorbed in the resin microspheres. This method achieves purification and desalination, further reducing the impact of salts on the detection structure.

[0044] 4. A variable-speed defoaming structure is installed within the three-stage shell. This structure allows the fluid to continuously accelerate and decelerate within the three-stage shell, resulting in drastic changes in flow velocity. These drastic changes create an turbulence effect, which, combined with the turbulence, rapidly separates air bubbles. This achieves drastic changes in fluid velocity within a limited shell length path, improving bubble removal efficiency. The variable-speed defoaming structure includes a first variable-speed unit and a second variable-speed unit connected to the first variable-speed unit.

[0045] That is, the fluid first passes through the first speed change unit for a first-stage drastic speed change to complete the initial bubble discharge, and then passes through the second speed change unit for a second-stage drastic speed change to discharge the bubbles again. Through the two-stage drastic speed change, the bubbles in the fluid can be completely discharged.

[0046] 5. The first and second speed change units are formed by two conical tubes, so they are similar in structure to Venturi tubes. When the fluid passes through the first and second speed change units, the Venturi effect is generated. Under this method, the turbulence amplitude of the fluid is very large, and the air bubbles in the fluid will be quickly expelled. Attached Figure Description

[0047] To more clearly illustrate the technical solutions in the embodiments of the present invention 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 the present invention. For those skilled in the art, other drawings can be obtained based on the structures shown in these drawings without creative effort.

[0048] Figure 1 This is a schematic diagram of the structure of the sample pretreatment mechanism connecting the chromatographic column of the liquid chromatograph and the sample injection port of the mass spectrometer in an embodiment of the present invention;

[0049] Figure 2 This is a schematic diagram of the sample pretreatment mechanism in an embodiment of the present invention;

[0050] Figure 3 This is a schematic diagram of the structure of the primary microfiltration mechanism in an embodiment of the present invention;

[0051] Figure 4 This is a schematic diagram of the secondary desalination mechanism in an embodiment of the present invention;

[0052] Figure 5 This is a schematic diagram of the structure of polymer microspheres filled inside the filler sleeve in an embodiment of the present invention;

[0053] Figure 6 This is a schematic diagram of the dispersed structure of the three-stage shell and the two-stage shell in an embodiment of the present invention;

[0054] Figure 7 This is a schematic diagram of the fluid variable speed defoaming structure in an embodiment of the present invention;

[0055] Figure 8 This is a schematic diagram of the structure of the first transmission unit and the second transmission unit in an embodiment of the present invention;

[0056] Figure 9 This is a schematic diagram of the structure forming an exhaust chamber within the three-stage housing in an embodiment of the present invention;

[0057] Figure 10 This is a schematic diagram of the four-stage sample feeding and stabilization mechanism in an embodiment of the present invention;

[0058] Figure 11 This is an embodiment of the present invention. Figure 2 Front view in the middle;

[0059] Figure 12 This is an embodiment of the present invention. Figure 2 The top view in the image.

[0060] The realization of the objective, functional features and advantages of the present invention will be further explained in conjunction with the embodiments and with reference to the accompanying drawings. Detailed Implementation

[0061] 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 a part of the embodiments of the present invention, and not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present invention.

[0062] It should be noted that all directional indications (such as up, down, left, right, front, back, etc.) in the embodiments of the present invention are only used to explain the relative positional relationship and movement of each component in a certain specific posture (as shown in the figure). If the specific posture changes, the directional indication will also change accordingly.

[0063] Furthermore, in this invention, descriptions involving "first," "second," etc., are for descriptive purposes only and should not be construed as indicating or implying their relative importance or implicitly specifying the number of technical features indicated. Therefore, a feature defined with "first" or "second" may explicitly or implicitly include at least one of that feature. Additionally, the technical solutions of the various embodiments can be combined with each other, but only on the basis of being achievable by those skilled in the art. When the combination of technical solutions is contradictory or impossible to implement, such a combination of technical solutions should be considered non-existent and not within the scope of protection claimed by this invention.

[0064] Example 1

[0065] like Figure 1-12 As shown, an LC-MS coupled mass spectrometer sample processing device includes an injection pretreatment mechanism 3 connected to the liquid outlet of the chromatographic column 11 in the liquid chromatograph 1. The injection pretreatment mechanism 3 performs pre-purification of the sample liquid before it enters the mass spectrometer 2, including three-stage treatment of microfiltration, desalting, and degassing. The fluid is also stabilized before entering the mass spectrometer 2, thereby improving the accuracy of LC-MS detection.

[0066] Therefore, the liquid outlet of the sample pretreatment mechanism 3 is connected to the sample inlet port 21 of the mass spectrometer 2.

[0067] Specifically, the sample pretreatment mechanism 3 includes a primary microfiltration mechanism 31, the outlet of which is connected to a secondary desalination mechanism 32; the outlet of the secondary desalination mechanism 32 is connected to a tertiary variable speed degassing mechanism 33, and the outlet of the tertiary variable speed degassing mechanism 33 is connected to a quaternary sample flow stabilization mechanism 34.

[0068] First, the sample solution passes through a primary microfiltration mechanism 31 to filter out impurities in the sample solution (after impurities enter the mass spectrometer 2, there are many impurity peaks in the detection spectrum, which seriously interferes with the interpretation of sample material data). In particular, small insoluble impurities pass through the primary microfiltration mechanism 31.

[0069] Subsequently, the salt in the sample solution is removed by the secondary desalting mechanism 32. Salt removal not only effectively protects the mass spectrometer 2, but also further reduces the impurity peaks in the spectrum.

[0070] Finally, the bubble removal mechanism 33 removes the bubbles from the sample liquid by using a three-stage variable speed debubbling mechanism. The fluid turbulence effect is generated by the continuous change of flow rate, and the small bubbles in the fluid are detached from the fluid under the turbulence.

[0071] Example 2

[0072] like Figure 1-12 As shown, based on the structure of Embodiment 1, the primary microfiltration mechanism 31 includes a primary housing 311. An inlet pipe is connected to the inlet end of the primary housing 311, and the inlet pipe is connected to the outlet end of the chromatographic column 11. Specifically, according to existing methods, the inlet end of the inlet pipe is connected to the outlet end of the chromatographic column 11 via a connector with PEEK fittings at both ends.

[0073] A filter membrane structure is installed inside the primary housing 311. Specifically, the filter membrane structure includes a membrane sleeve 312 (made of stainless steel, with its outer wall connected to the cylindrical cavity of the primary housing 311 via threads) threadedly connected inside the primary housing 311. A filter membrane 313 is fixedly installed inside the membrane sleeve 312. The filter membrane 313 is a microfiltration membrane disclosed in the prior art, capable of filtering impurities with a particle size in the micrometer range.

[0074] The sample solution is first separated from the chromatographic column 11 and enters the primary housing 311, where it undergoes preliminary filtration of insoluble impurities through the filter membrane 313. Subsequently, it proceeds to the next stage, the secondary desalting mechanism 32.

[0075] Example 3

[0076] like Figure 1-12 As shown, based on the structure of Embodiment 2, the secondary desalination mechanism 32 includes a secondary housing 321 detachably mounted on the primary housing 311. Specifically, the secondary housing 321 has an integrally formed threaded neck tube, which is threadedly connected to the primary housing 311 (within the housing cavity). To enhance sealing after connection, a sealing ring B is installed between the facing sidewalls of the secondary housing 321 and the primary housing 311 (grooves A are respectively formed on the facing sidewalls of the secondary housing 321 and the primary housing 311; when the secondary housing 321 is threaded onto the primary housing 311, the sealing ring B enhances sealing as the primary and secondary housings 321 are tightly joined).

[0077] Meanwhile, a polymer desalination structure is installed inside the secondary housing 321; specifically, the polymer desalination structure includes a packing sleeve 322 threadedly connected inside the secondary housing 321 (the packing sleeve 322 is also made of stainless steel, with a threaded structure on its outer wall). At the same time, filter screen structures are threadedly connected to both ends (inlet and outlet ends) of the packing sleeve 322. The filter screen structure specifically includes a support ring threadedly connected to the opening of the packing sleeve 322, and a filter screen 3221 (stainless steel filter screen) is fixedly connected inside the support ring.

[0078] After removing the packing sleeve 322, the removable support ring allows the polymer microspheres in the packing sleeve 322 to be emptied and replaced.

[0079] Meanwhile, the packing sleeve 322 is filled with polymer microspheres 3222 that adsorb salt. The polymer microspheres 3222 are conventional adsorption and desalination materials disclosed in the prior art, such as anion exchange resin microspheres, which are used to exchange with metal ions for desalination.

[0080] After passing through the secondary shell 321, the sample solution enters the packing sleeve 322. During the process of passing through the polymer microspheres filled in the packing sleeve 322, the salt in the sample solution will exchange with the resin microspheres, and the metal ions of the salt will be adsorbed in the resin microspheres. This method achieves purification and desalting, further reducing the impact of salt on the detection structure.

[0081] Example 4

[0082] like Figure 1-12 As shown, based on the structure of Embodiment 3, the above-mentioned three-stage speed-changing de-bubbling mechanism 33 includes a three-stage housing 331 that is detachably installed on the two-stage housing 321; the length of the three-stage housing 331 is greater than that of the first and second stage housings 321, and its installation method is the same as that between the first and second stage housings 321. Specifically, a threaded neck tube is integrally formed on the side wall of the three-stage housing 331 facing the two-stage housing 321, and the threaded neck tube is threadedly connected inside the two-stage housing 321.

[0083] Similarly, in the same way as the structure in which a sealing ring B is provided between the primary and secondary housings 321, a sealing ring B is installed between the side walls of the tertiary housing 331 and the secondary housing 321 that face each other.

[0084] A variable-speed defoaming structure is installed inside the three-stage shell 331. Through the variable-speed defoaming structure, when the fluid reaches the three-stage shell 331, the fluid continuously accelerates and decelerates in the three-stage shell 331. This continuous acceleration and deceleration causes the fluid velocity to change drastically. Under the drastic change, the fluid generates an agitation effect. With the agitation effect, the bubbles in the fluid will be separated quickly.

[0085] Therefore, in order to make the fluid velocity change drastically within a limited shell length path range and improve the bubble removal efficiency, the above-mentioned fluid variable speed defoaming structure includes a first variable speed unit 332 and a second variable speed unit 333 connected to the first variable speed unit 332.

[0086] That is, the fluid first undergoes a first-stage drastic speed change through the first speed change unit 332 to complete the initial bubble discharge, and then passes through the second speed change unit 333 to complete a second-stage drastic speed change to discharge the bubbles again. Through the two-stage drastic speed change, the bubbles in the fluid can be completely discharged.

[0087] Example 5

[0088] like Figure 1-12 As shown, based on the structure of Embodiment 4, both the first transmission unit 332 and the second transmission unit 333 include conical tubes arranged symmetrically, and a bubble removal structure is installed between the conical tubes.

[0089] Specifically, both the first transmission unit 332 and the second transmission unit 333 include a first conical tube 3321 and a second conical tube arranged symmetrically (front and back symmetrically). The opening end of the first conical tube 3321 faces forward, and the opening end of the second conical tube 3322 faces backward.

[0090] Since the first speed change unit 332 and the second speed change unit 333 are formed by two conical tubes, their structure is similar to a venturi tube. When the fluid passes through the first speed change unit 332 and the second speed change unit 333, the venturi effect is generated. Under this method, the turbulence amplitude of the fluid is very large, and the air bubbles in the fluid will be quickly expelled.

[0091] Example 6

[0092] like Figure 1-12 As shown, in this embodiment, based on the structure of embodiment 5, in order to further improve the emission of bubble gas, an exhaust chamber C is formed between the above-mentioned conical tube and the three-stage shell 331, and the top of the three-stage shell 331 is connected to an exhaust pipe 3311.

[0093] Specifically, the second conical tube 3322 of the first transmission unit 332 is sealed and welded to the first conical tube 3321 of the second transmission unit 333. That is, the four conical tubes are welded to the inner wall of the three-stage housing 331 respectively. In the three-stage housing 331, since the shape of the second conical tube 3322 of the first transmission unit 332 is similar to a dumbbell structure, the recessed part of the dumbbell structure forms an exhaust chamber C with the inner wall of the three-stage housing 331, providing a basis for fluid exhaust to the external environment.

[0094] Specifically, an exhaust chamber C is formed inside the third-stage housing 331 by sealing and welding the open ends of the first conical tube 3321 and the second conical tube 3322 to the inner wall of the third-stage housing 331.

[0095] A bubble-venting pipe 334 is integrally formed between the first conical tube 3321 and the second conical tube 3322; the bubble-venting structure is located on the bubble-venting pipe 334.

[0096] Example 7

[0097] like Figure 1-12 As shown, in this embodiment, based on the structure of embodiment 6, in order to achieve air bubble removal, the air bubble removal structure includes a plurality of air bubble removal holes formed on the air bubble removal tube 334, and the inner end of the air bubble removal hole is fixedly connected to a breathable membrane 3351; the breathable membrane 3351 is a thin film disclosed in the prior art that can only release air and can prevent liquid from passing through. At the same time, the outer end of the air bubble removal hole is connected to the air bubble removal tube 335; the air bubble removal tube 335 is located in the exhaust chamber C.

[0098] During operation, the gas generated by fluid turbulence will remain in the exhaust chamber C. Therefore, in order to further improve the exhaust effect, the exhaust pipe 3311 can be connected to a small air pump to create a negative pressure state in the exhaust chamber C.

[0099] Because of the barrier provided by the breathable membrane 3351, the sample liquid will not overflow into the exhaust chamber C.

[0100] Example 8

[0101] like Figure 1-12 As shown, in this embodiment, based on the structure of embodiment 7, the liquid outlet end of the three-stage housing 331 is connected to an outlet pipe; the four-stage sample injection flow stabilizing mechanism 34 includes a flow stabilizing pipe 341 connected to the outlet pipe 35, and a flow stabilizing structure is fixedly connected inside the flow stabilizing pipe 341.

[0102] Specifically, the flow stabilization structure includes a thin tube support 342 fixed inside the flow stabilization tube 341. The thin tube support 342 has several through holes, and flow stabilization thin tubes 344 (connected) are fixedly installed inside these through holes. Because the fluid flow velocity changes drastically during the bubble removal process, the fluid flow rate is stabilized before sample injection. Specifically, the flow stabilization structure splits the fluid. The split fluid passes through each flow stabilization tube 341, which is 6-8 cm long. Within the narrow flow stabilization tube 341, the fluid velocity rapidly decreases, and the fluid's kinetic energy drops quickly. Finally, the fluid flowing out of each flow stabilization thin tube 344 has a lower flow velocity and converges. Therefore, to slightly accelerate fluid injection, a conical tube 345 is integrally formed at the outlet end of the aforementioned flow stabilization tube 341. The conical tube is connected to a pre-injection tube 3451, which is connected to the injection port of the mass spectrometer 2.

[0103] Specifically, the method is the same as the existing method, with the pre-injection tube 3451 connected to the injection port of the mass spectrometer 2 via a stainless steel connecting tube.

[0104] Example 9

[0105] like Figure 1-12 As shown, this embodiment discloses the working method of the above-mentioned LC-MS coupled mass spectrometer 2 sample processing device, including the following steps:

[0106] (1) Primary filtration: After the sample solution exits from the column 11 of the liquid chromatography 1, it passes through the primary microfiltration mechanism 31 to filter impurities and then enters the secondary polymer desalting structure.

[0107] (2) Desalination: After the salt in the sample solution is removed in the secondary polymer desalination structure, it enters the tertiary variable speed degassing mechanism 33;

[0108] (3) In the three-stage variable speed degassing mechanism 33, the sample solution generates fluid turbulence by continuously accelerating and decelerating the flow rate, and removes the bubbles in the fluid before entering the four-stage sample injection and flow stabilization mechanism 34 to stabilize the flow rate.

[0109] (4) The sample solution enters the injection port of the mass spectrometer 2 after being stabilized in the four-stage injection stabilization mechanism 34.

[0110] The above method enables the sample solution to be pre-purified before entering the mass spectrometer 2, including three-stage treatment of microfiltration, desalting, and degassing. The fluid is also stabilized before entering the mass spectrometer 2, thereby improving the accuracy of LC-MS detection.

[0111] Of course, the above description is not intended to limit the present invention, and the present invention is not limited to the examples given above. Any changes, modifications, additions or substitutions made by those skilled in the art within the scope of the present invention should also fall within the protection scope of the present invention.

Claims

1. A sample processing device for LC-MS coupled mass spectrometry, characterized in that, It includes an injection pretreatment mechanism connected to the liquid outlet of the chromatographic column in liquid chromatography, with the liquid outlet of the injection pretreatment mechanism connected to the injection port of the mass spectrometer. The sample pretreatment mechanism includes a primary microfiltration mechanism, the outlet of which is connected to a secondary desalination mechanism; the outlet of the secondary desalination mechanism is connected to a tertiary variable-speed degassing mechanism; and the outlet of the tertiary variable-speed degassing mechanism is connected to a quaternary sample flow stabilization mechanism. The primary microfiltration mechanism includes a primary housing with a filter membrane structure installed inside; the secondary desalination mechanism includes a secondary housing detachably mounted on the primary housing with a polymer desalination structure installed inside; and the tertiary variable-speed debubbling mechanism includes a tertiary housing detachably mounted on the secondary housing. The three-stage housing is equipped with a fluid variable speed defoaming structure, which includes a first variable speed unit and a second variable speed unit connected to the first variable speed unit. Both the first and second transmission units include symmetrically arranged conical tubes, and a bubble-expelling structure is installed between the conical tubes; An exhaust chamber is formed between the conical tube and the three-stage shell, and an exhaust pipe is connected to the top of the three-stage shell.

2. The LC-MS coupled mass spectrometer sample processing device according to claim 1, characterized in that, The liquid inlet end of the primary housing is connected to a liquid inlet pipe, which is connected to the liquid outlet end of the chromatographic column. The secondary shell is integrally formed with a threaded neck tube, which is threadedly connected to the primary shell. A sealing ring is installed between the side walls of the secondary shell and the primary shell that face each other.

3. The LC-MS coupled mass spectrometer sample processing device according to claim 1, characterized in that, The filter membrane structure includes a membrane sleeve threadedly connected to a primary housing, and a filter membrane is fixedly installed inside the membrane sleeve.

4. The LC-MS coupled mass spectrometer sample processing device according to claim 3, characterized in that, The polymer desalination structure includes a packing sleeve threadedly connected within the secondary housing; The two ends of the packing sleeve are respectively threaded with filter screen structures, and the packing sleeve is filled with polymer microspheres that adsorb salt.

5. The LC-MS coupled mass spectrometer sample processing device according to claim 4, characterized in that, The filter structure includes a support ring threadedly connected to the opening of the packing sleeve, and a filter screen is fixedly connected inside the support ring.

6. The LC-MS coupled mass spectrometer sample processing device according to claim 1, characterized in that, The third-level shell has an integrally formed threaded neck tube on the side wall facing the second-level shell, and the threaded neck tube is threadedly connected inside the second-level shell. A sealing ring is installed between the side walls of the third-level shell and the second-level shell that face each other.

7. The LC-MS coupled mass spectrometer sample processing device according to claim 6, characterized in that, Both the first transmission unit and the second transmission unit include a first conical tube and a second conical tube arranged symmetrically to each other; The second conical tube of the first transmission unit is sealed and welded to the first conical tube of the second transmission unit; An exhaust chamber is formed inside the third-stage shell by sealing and welding the open ends of the first and second conical tubes to the inner wall of the shell. A bubble venting tube is integrally formed between the first conical tube and the second conical tube; the bubble venting structure is located on the bubble venting tube.

8. The LC-MS coupled mass spectrometer sample processing device according to claim 7, characterized in that, The bubble removal structure includes several bubble removal holes opened on the bubble removal tube, and a breathable membrane is fixedly connected to the inner end of the bubble removal hole. The outer end of the bubble vent is connected to the bubble venting pipe; the bubble venting pipe is located inside the exhaust chamber.

9. The LC-MS coupled mass spectrometer sample processing device according to claim 1, characterized in that, The liquid outlet end of the third-stage shell is connected to a fluid outlet pipe; The four-stage injection flow stabilization mechanism includes a flow stabilization tube connected to the outlet tube, and a flow stabilization structure is fixedly connected inside the flow stabilization tube; The flow stabilizing structure includes a thin tube support fixed inside the flow stabilizing tube. The thin tube support has several through holes, and the flow stabilizing thin tube is fixedly installed inside the through holes. The outlet end of the flow stabilizing tube is integrally formed with a conical tube, which is connected to a pre-injection tube, which is connected to the injection port of the mass spectrometer.

10. A method of operating a sample processing device for an LC-MS coupled mass spectrometer as described in any one of claims 1-9, characterized in that, Includes the following steps: (1) Primary filtration: After the sample solution exits the chromatographic column of the liquid chromatography, it passes through the primary microfiltration mechanism to filter impurities and then enters the secondary polymer desalting structure. (2) Desalination: After the salt in the sample solution is removed in the secondary polymer desalination structure, it enters the tertiary variable speed degassing mechanism; (3) In the three-stage variable speed degassing mechanism, the sample solution generates fluid turbulence by continuously accelerating and decelerating the flow rate, and removes the bubbles in the fluid before entering the four-stage sample injection and flow stabilization mechanism to stabilize the flow rate. (4) The sample solution enters the mass spectrometer's injection port after being stabilized in the four-stage injection stabilization mechanism.

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