Liquid chromatography mass spectrometry device

Abstract

The present disclosure provides a liquid chromatography-mass spectrometry analysis device that can automatically determine the location where the flow path is blocked and restore it in a short time. The liquid chromatography-mass spectrometry analysis device of the present disclosure has: a first flow path, which passes through a separation column; a second flow path, which does not pass through a separation column; a mass spectrometry analysis unit, which is arranged on the downstream side of the first flow path and the second flow path, and analyzes the sample passing through the first flow path; a first valve, which connects any one of the first flow path and the second flow path to the mass spectrometry analysis unit; a control unit, which controls the drive of the first valve; and a pressure gauge, which measures the pressure of the second flow path and outputs it to the control unit. When analyzing the sample in the mass spectrometry analysis unit, the control unit connects the first flow path to the mass spectrometry analysis unit, compares the measured value of the mass spectrometry analysis unit with a predetermined threshold value, and drives the first valve to connect the second flow path to the mass spectrometry analysis unit when it is determined to be abnormal.

Description

Technical Field

[0001] The present disclosure relates to a liquid chromatography-mass spectrometry analysis device. Background Art

[0002] A mass spectrometer is a device that ionizes a sample solution and introduces it into a vacuum device, and then separates and detects the ions based on the mass-to-charge ratio (m / z). It can detect ions with high sensitivity and high accuracy. A mass spectrometer is generally used as a detector for liquid chromatography (LC), for example, and analyzes samples using an analytical method called liquid chromatography-mass spectrometry (LC-MS).

[0003] Liquid chromatography is a method of separating samples by pressurizing a mobile phase containing a sample using a liquid delivery pump and passing it through a separation column, based on the difference in interaction (adsorption, distribution, etc.) with the stationary phase of the separation column. The separation column is densely filled with fine porous particles as a stationary phase to facilitate interaction with the sample. Therefore, sometimes when foreign matter such as dust is mixed in or inclusions such as salt are accumulated, the separation column is clogged, causing a decrease in sensitivity. When the separation column is clogged, the conductivity decreases and the pressure of the solution increases.

[0004] A general LC liquid delivery pump is equipped with a pressure gauge, and therefore, it is possible to detect whether or not the separation column is clogged based on changes in pressure when delivering liquid at a constant flow rate.

[0005] Patent document 1 states that as a method for determining whether a flow path is blocked, "a second flow path 18 that can be switched by a valve 15 is provided on the analysis flow path 8, and a flow meter 17 is provided in the second flow path 18 to measure the flow rate when necessary, thereby determining whether there is blockage" (refer to the abstract of the document).

[0006] Prior art literature

[0007] Patent Literature

[0008] Patent Document 1: Japanese Patent Application Publication No. 2000-249694 Summary of the invention

[0009] Problems to be solved by the invention

[0010] When a flow path for a sample to flow is clogged, in order to recover from the reduced sensitivity caused by the clogged flow path, it is necessary to identify the clogged location and remove the clog. However, in a known liquid chromatography-mass spectrometry apparatus, a user needs to manually identify the clogged location, and identifying the clogged location takes a long time.

[0011] In addition, in Patent Document 1, if the flow rate is constant, the pressure of the solution rises inversely proportional to the conductivity of the flow path, and therefore, the decrease in conductivity caused by the blockage of the flow path can be detected. However, in the method described in Patent Document 1, only the presence or absence of blockage can be confirmed for the separation column, and it is impossible to determine which part of the flow path from LC to the mass spectrometer is blocked. In particular, a method for automatically detecting blockage and leakage of the flow path downstream of the separation column (mass spectrometer side) is not known so far.

[0012] Therefore, the present disclosure provides a liquid chromatography-mass spectrometry analysis apparatus that can automatically identify a location where a flow path is clogged and restore the location in a short time.

[0013] Means for solving problems

[0014] In order to solve the above-mentioned problems, the liquid chromatography-mass spectrometry analysis device disclosed in the present invention comprises: a first flow path, which passes through a separation column; a second flow path, which does not pass through the separation column; a mass spectrometry analysis unit, which analyzes a sample passing through the first flow path; a first valve, which connects any one of the first flow path and the second flow path to the mass spectrometry analysis unit; a control unit, which controls the driving of the first valve; and a pressure gauge, which measures the pressure of the second flow path and outputs it to the control unit, wherein the control unit connects the first flow path to the mass spectrometry analysis unit when the mass spectrometry analysis unit analyzes the sample, compares the measured value of the mass spectrometry analysis unit with a predetermined threshold value, and, if determined to be abnormal, drives the first valve to connect the second flow path to the mass spectrometry analysis unit.

[0015] Further features related to the present disclosure will become apparent from the description and drawings of this specification. In addition, the present disclosure is achieved and implemented through the combination of elements and multiple elements and the following detailed description and the scope of the attached patent claims.

[0016] The descriptions in this specification are merely typical examples, and it should be understood that they do not limit the scope of patent protection or application examples of the present disclosure in any sense.

[0017] Effects of the Invention

[0018] According to the present disclosure, it is possible to automatically identify a location where a flow path is clogged in a liquid chromatograph-mass spectrometer and restore the location in a short time.

[0019] Other problems, structures, and effects than those described above will become apparent from the following description of the embodiments. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 It is a schematic diagram showing the structure of the liquid chromatograph-mass spectrometer according to the first embodiment.

[0021] Figure 2 It is a schematic diagram showing an example of connection of flow paths by a selector valve.

[0022] Figure 3 This is a flowchart showing the operation of the liquid chromatograph-mass spectrometer according to the first embodiment.

[0023] Figure 4 It is a schematic diagram showing the structure of a liquid chromatograph-mass spectrometer according to a second embodiment.

[0024] Figure 5 It is a schematic diagram showing the structure of a liquid chromatograph-mass spectrometer according to a third embodiment.

[0025] Figure 6 It is a schematic diagram showing the structure of a mass spectrometer according to a fourth embodiment. DETAILED DESCRIPTION

[0026] [First embodiment]

[0027] <Device Structure>

[0028] Figure 1 Schematic diagram showing the structure of the liquid chromatography-mass spectrometry analysis device of the first embodiment. The liquid chromatography-mass spectrometry analysis device includes: solution tanks 1a to 1c, a mass spectrometry analysis unit 2, liquid delivery pumps 3a to 3c, a separation column 4, a selection valve 5 (first valve), a first flow path 11, a second flow path 12, pressure gauges 13a to 13c, a sampler 14, and a control unit 100.

[0029] The solution tanks 1a and 1b contain a solution that becomes a mobile phase. As the solution that becomes a mobile phase, a solution generally used in liquid chromatography can be used according to the sample, for example, water, an aqueous solution of salts, methanol, acetonitrile, an organic solvent such as hexane, etc. can be used alone or in combination. The solution tanks 1a and 1b are connected to the first flow path 11 via liquid delivery pumps 3a and 3b (first liquid delivery pump).

[0030] The solution tank 1c stores a solution to be sent to the second flow path 12, and is connected to the second flow path 12 via a solution sending pump 3c (second solution sending pump). The solution stored in the solution tank 1c may be the same as or different from the solutions stored in the solution tanks 1a and 1b.

[0031] Liquid feeding pumps 3a to 3c pressurize and feed the solution in solution tanks 1a to 1c. Pressure gauges 13a and 13b are connected to liquid feeding pumps 3a and 3b for feeding the first flow path 11, respectively, and pressure gauge 13c is connected to liquid feeding pump 3c for feeding the second flow path 12.

[0032] The pressure gauges 13a to 13c measure the pressure of the solution flowing in the flow path, respectively. As the pressure gauges 13a to 13c, it is preferable to use a pressure gauge that can measure the pressure in the range that can be pressurized by the liquid feeding pumps 3a to 3c, typically a pressure of about 0 to 200 MPa. In addition, when the dead volume of the pressure gauges 13a to 13c is large, the time required until the pressure of the solution is stabilized becomes longer, so it is preferable to reduce the dead volume of the pressure gauges 13a to 13c, and typically it is preferable to suppress it to less than 10 μL.

[0033] The first flow path 11 and the second flow path 12 are composed of, for example, pipes. The first flow path 11 is connected to a sampler 14, and the separation column 4 is connected to the downstream side of the sampler 14. As the sampler 14, for example, an automatic sampler, a manual syringe, etc. can be used. The sample is introduced into the first flow path 11 through the sampler 14. The second flow path 12 is a flow path that does not pass through the separation column 4, and the sample is not introduced into the second flow path 12.

[0034] The first flow path 11 has a separation column 4 with a low conductivity on the flow path, and therefore, in order to obtain a flow rate sufficient for analysis, it is typically preferred to use a liquid-feeding pump 3a or 3b that can deliver liquid at a pressure of about 0.1 to 100 MPa. On the other hand, the second flow path 12 has a higher conductivity than the first flow path 11, and therefore, as the liquid-feeding pump 3c that delivers liquid to the second flow path 12, a liquid-feeding pump having a lower upper limit of the pressure that can be pressurized than the liquid-feeding pumps 3a or 3b that deliver liquid to the first flow path 11 can be used.

[0035] The first flow path 11 and the second flow path 12 are connected to the selector valve 5, and by switching the selector valve 5, either the first flow path 11 or the second flow path 12 is connected to the mass spectrometer 2. The details of the selector valve 5 will be described later. Hereinafter, in the liquid chromatograph-mass spectrometer of the present embodiment, the portion from the solution tanks 1a and 1b to immediately before the mass spectrometer 2 is sometimes referred to as a "liquid chromatograph (LC)".

[0036] Although not shown in the figure, the mass spectrometer 2 has the structure of a general mass spectrometer (MS), such as an ion source, a vacuum chamber, and an ion detection unit. The mass spectrometer 2 ionizes the sample introduced from the first flow path 11 using the ion source, introduces it into the vacuum chamber, separates the ions according to the mass-to-charge ratio (m / z), and detects the ion intensity using the ion detection unit. The ion detection unit outputs the detection signal of the ion intensity to the control unit 100. In addition, the ion detection unit can also output the ion current as a detection signal to the control unit 100.

[0037] Examples of the ion source include an electrospray ionization ion source, an atmospheric pressure chemical ionization ion source, an atmospheric pressure photoionization ion source, etc. In any ionization method, a solution containing a sample is sprayed into a vacuum chamber through a capillary of an ion source probe.

[0038] The inner diameter of the appropriate capillary depends on the flow rate of the liquid chromatography (LC), and it is preferred to use a thinner capillary as the flow rate decreases. The inner diameter of a typical capillary is about 30 μm to 150 μm. When a capillary thicker than 150 μm is used, the ionization efficiency decreases. In addition, the distribution of the sample spreads due to diffusion while the solution flows through the capillary, so the separation ability of LC may also deteriorate. The inner diameter of the capillary is thin and is heated according to the conditions of ionization, so it is easy to be clogged due to the mixing of foreign matter and the accumulation of inclusions.

[0039] The control unit 100 is a computer terminal such as a personal computer, and is configured to control the overall operation of the liquid chromatography-mass spectrometry analysis device. Although not shown in the figure, the control unit 100 includes the following parts, etc.: a data processing unit that processes the detection signal (measurement value) of the ion detection unit of the mass spectrometry analysis unit 2; a storage unit that stores various data; an input unit for the user to input instructions to the liquid chromatography-mass spectrometry analysis device; and a display unit that displays the results of mass spectrometry analysis, various GUI screens, etc.

[0040] Figure 2 1 and 10 are schematic diagrams showing examples of connection of flow paths based on the selector valve 5 , wherein (a) shows a state where the first flow path 11 is connected to the mass spectrometer 2 , and (b) shows a state where the second flow path 12 is connected to the mass spectrometer 2 .

[0041] The control unit 100 drives the selection valve 5 to switch the flow path connected to the mass spectrometer 2. As a result, either the first flow path 11 or the second flow path 12 is introduced into the mass spectrometer 2. Figure 2 As shown, the flow path not connected to the mass spectrometer 2 is connected to the waste liquid tank 15, thereby preventing the solution from flowing out to the outside.

[0042] <Action>

[0043] Figure 3 1 is a flowchart showing the operation of the liquid chromatograph-mass spectrometer according to the first embodiment. The operation when an automatic sampler is used as the sampler 14 will be described below.

[0044] First, the user prepares the sample in advance and introduces it into the sampler 14. By adding an internal standard substance of known concentration to the sample, the influence of adsorption and ionization instability on the flow path can be eliminated, so the signal intensity of the sample can be accurately quantified. After the user introduces the sample into the sampler 14, the user inputs an instruction to start the operation from the input unit of the mass spectrometer 2.

[0045] When the control unit 100 receives the start instruction of the action, in step S1, the liquid chromatography-mass spectrometry device is activated to start the normal measurement. That is, the control unit 100 confirms that the first flow path 11 is connected to the mass spectrometry unit 2 through the selection valve 5, drives the liquid delivery pumps 3a and 3b, and introduces the solution from the solution tanks 1a and 1b to the first flow path 11. The pressure gauges 13a and 13b output the pressure values ​​of the liquid delivery pumps 3a and 3b to the control unit 100. In addition, the control unit 100 drives the sampler 14 to introduce the sample into the first flow path 11, so that the mass spectrometry unit 2 analyzes the sample. The ion detection unit of the mass spectrometry unit 2 outputs the signal intensity of the sample and the signal intensity of the internal standard substance to the control unit 100. The output signal of the ion detection unit can be an ion intensity or an ion current.

[0046] The data processing unit of the control unit 100 obtains a chromatogram based on the output signal of the ion detection unit. The display unit of the control unit 100 may receive the chromatogram from the data processing unit and display the chromatogram.

[0047] In step S2, the control unit 100 compares the signal intensity of the internal standard substance, or the output value of the pressure gauge 13a and 13b, with a predetermined threshold value stored in the storage unit. Thus, the control unit 100 determines whether there is an abnormality in the measurement. The predetermined threshold value is, for example, a value set according to a measurement value or its deviation obtained by past measurement, and the upper limit of the range of values ​​obtained by normal measurement can be set as the threshold value. When it is determined that there is no abnormality (no), the control unit 100 returns to step S1 and continues normal measurement.

[0048] When the control unit 100 detects an abnormality (yes), there is a high possibility that a blockage has occurred in the LC or the mass spectrometer 2, so in order to identify the location where the blockage has occurred, the process moves to step S3. In step S3, the control unit 100 switches the selector valve 5, connects the second flow path 12 to the mass spectrometer 2, drives the liquid delivery pump 3c, and delivers the solution from the solution tank 1c to the mass spectrometer 2 at a constant flow rate. In addition, the control unit 100 receives the pressure value of the liquid delivery pump 3c from the pressure gauge 13c.

[0049] In step S4, the control unit 100 compares the output value of the pressure gauge 13c with a predetermined threshold value stored in the storage unit. For example, the predetermined threshold value to be compared with the output value of the pressure gauge 13c is set according to the pressure in the case where no blockage occurs. When blockage occurs between the selector valve 5 and the outlet of the capillary of the ion source, in particular, the capillary of the ion source, the pressure measured by the pressure gauge 13c rises. Therefore, according to whether the pressure measured by the pressure gauge 13c is above the threshold value, it can be determined whether there is blockage between the selector valve 5 and the outlet of the capillary of the ion source.

[0050] When the pressure measured by the pressure gauge 13c is less than the threshold value (No), it can be assumed that there is no blockage between the selector valve 5 and the capillary outlet of the ion source, and the blockage occurs on the LC side, that is, the separation column 4. Then, the process moves to step S5, and the user replaces the separation column 4. When the control unit 100 detects that the separation column 4 has been replaced, it switches the selector valve 5 to connect the first flow path 11 to the mass spectrometer 2, and returns to step S1 to resume normal measurement.

[0051] If the pressure measured by the pressure gauge 13c is greater than the threshold value (yes), it is known that there is a blockage between the selector valve 5 and the capillary outlet of the ion source. At this time, the control unit 100 displays a message requesting maintenance for eliminating the blockage of the ion source on the display unit, for example, and stops the measurement operation.

[0052] Afterwards, the process is transferred to step S6, and the user performs a recovery process for removing the blockage. As a recovery process, for example, the type and flow rate of the solution in the solution tank 1c are changed. The second flow path 12 does not have a portion with a small conductivity such as a separation column 4 on the flow path. Therefore, it is possible to directly apply pressure to the blocked portion by increasing the flow rate, and the blockage can be effectively washed away. In addition, as a solution introduced into the second flow path 12, a solvent that easily dissolves the inclusions (salts, polymers) that are the cause of the blockage is used, thereby efficiently removing the blockage. Specifically, as a solution introduced into the second flow path 12, pure water is suitable for dissolving salts, and organic solvents such as isopropyl alcohol are suitable for dissolving polymers. In this step, the control unit 100 determines whether the output value of the pressure gauge 13c is less than a predetermined threshold value.

[0053] The control unit 100 determines that the pressure gauge 13c is not blocked at the time point when the value is less than the threshold value, switches the selector valve 5 to connect the first flow path 11 to the mass spectrometry unit 2, returns to step S1, and can resume normal measurement. In addition, in step S6, an internal standard substance of known concentration can also be added to the solution flowing through the second flow path 12. In this case, in addition to the value of the pressure of the solution, the signal intensity of the internal standard substance is also monitored, thereby determining whether the state of the flow path has returned to normal.

[0054] <Technical Effect>

[0055] As described above, the liquid chromatography mass spectrometry analysis device of the present embodiment has the following structure: when an abnormality is detected, the first flow path 11 is switched to the second flow path 12 that does not pass through the separation column 4, and the pressure of the second flow path 12 is measured. When the pressure of the second flow path 12 is greater than a predetermined threshold value, it can be determined that the part where the blockage has occurred is the ion source. Therefore, according to the present embodiment, the part where the blockage has occurred can be automatically determined, and the blockage can be recovered in a short time.

[0056] [Second embodiment]

[0057] <Device Structure>

[0058] Figure 4 Schematic diagram showing the structure of a liquid chromatography-mass spectrometry analysis device according to a second embodiment. Figure 4 As shown, the difference between the liquid chromatography-mass spectrometry analysis device of this embodiment and the first embodiment is that the first flow path 11 branches into three, and has three separation columns 4 respectively passing through the first flow path 11 branched out, and selection valves 6 and 7 (second valves) are respectively provided on the upstream and downstream sides of the three separation columns 4. The characteristics of the multiple separation columns 4 can be the same or different. The control unit 100 controls the drive of the selection valves 6 and 7 to select the separation column 4 for measurement. The number of separation columns 4 is not limited to 3, and other structures and actions are the same as those of the first embodiment, so the description is omitted.

[0059] <Technical Effect>

[0060] In the liquid chromatography mass spectrometry analysis apparatus of this embodiment, since a plurality of separation columns 4 are provided, the characteristics of the plurality of separation columns 4 can be made different, and the separation column 4 can be selected according to the characteristics of the sample to be measured. Alternatively, a plurality of separation columns 4 having the same characteristics can be used for analysis in parallel, and can be introduced into the mass spectrometry analysis unit 2 only at a time near the peak, thereby having the advantage of being able to improve productivity.

[0061] In addition, the liquid chromatograph mass spectrometer of this embodiment has a plurality of separation columns 4, which increases the number of selector valves and complicates the flow path. In addition, the selector valves 6 and 7 may become clogged, or carryover contamination may occur due to samples remaining in the selector valves 6 and 7.

[0062] Here, in the liquid chromatography fractionation device described in Patent Document 1, even if a plurality of separation columns are provided as in the present embodiment and the pressure of the liquid delivery pump is measured to detect blockage, it is still impossible to determine whether the blockage occurs in the selector valve, the separation column, or the ion source. Therefore, it is necessary for the user to determine the blockage location, which takes time.

[0063] On the other hand, according to the present embodiment, when an abnormality is detected, the first flow path 11 is switched to the second flow path 12 that does not pass through the separation column 4, and the pressure of the second flow path 12 is measured. When the pressure of the second flow path 12 is above a predetermined threshold, it can be determined that the ion source is clogged, and when the pressure of the second flow path 12 is less than the predetermined threshold, it can be determined that any one of the separation column 4 and the selection valves 6 and 7 is clogged. Therefore, according to the present embodiment, the clogged portion can be automatically determined, and the clogged portion can be recovered in a short time.

[0064] [Third Embodiment]

[0065] <Device Structure>

[0066] Figure 5 Schematic diagram showing the structure of a liquid chromatography-mass spectrometry analysis device according to a third embodiment. Figure 5 As shown, in this embodiment, at least one of the plurality of separation columns 4 of the liquid chromatography-mass spectrometry analysis apparatus of the second embodiment is set as a hollow dummy column 10, and the flow path can be switched by the selector valves 6 and 7 (second valves) respectively provided on the upstream and downstream sides of the separation column 4 and the dummy column 10. In this embodiment, the flow path passing through the separation column 4 in the flow path between the selector valve 6 and the selector valve 7 is used as the first flow path 11, and the flow path passing through the dummy column 10 is used as the second flow path 12. In other words, the dummy column 10 is provided in parallel with the plurality of separation columns 4, and the second flow path 12 is the flow path passing through the dummy column 10.

[0067] The dummy column 10 is a hollow column without a filler inside. Therefore, the conductivity of the dummy column 10 is greater than that of the separation column 4.

[0068] The control unit 100 connects any one of the plurality of first flow paths 11 or second flow paths 12 to the mass spectrometer 2 by switching the selector valves 6 and 7. The other device structures are the same as those of the first and second embodiments, and thus description thereof is omitted.

[0069] <Action>

[0070] The operation of the liquid chromatography mass spectrometry analysis device of this embodiment is described. In this embodiment, during normal measurement ( Figure 3 In step S1 shown in the figure, the liquid is sent from the solution tank 1a by the liquid sending pump 3a (first liquid sending pump). Figure 3 The control unit 100 switches the selector valves 6 and 7 (step S3), connects the second flow path 12 passing through the dummy column 10 to the mass spectrometry unit 2, uses the liquid delivery pump 3b (second liquid delivery pump) to deliver liquid from the solution tank 1b, and uses the pressure gauge 13b to measure the pressure of the second flow path 12 (step S4). The other actions are the same as those in the first embodiment, so detailed description is omitted.

[0071] <Technical Effect>

[0072] As described above, according to the present embodiment, the second flow path 12 is not provided as a pipe as in the first embodiment, but is provided as a structure of a dummy column 10 arranged in parallel with the separation column 4 of the first flow path 11, thereby, there is no need to provide a special flow path, the structure of the device becomes simple, and the manufacturing cost can be reduced. In addition, the dummy column 10 can be disassembled like the separation column 4, and therefore, it is also easy to replace it with other columns. Furthermore, since it is possible to determine whether there is a blockage between the liquid delivery pump 3b and the capillary outlet of the ion source, it is possible to automatically determine whether the part where the blockage occurs is the separation column 4 side or the ion source side, and it is possible to recover from the blockage in a short time.

[0073] [Fourth Embodiment]

[0074] <Device Structure>

[0075] A liquid chromatograph-mass spectrometer according to a fourth embodiment will be described. Figure 6 Schematic diagram showing the structure of the mass spectrometry unit of the fourth embodiment. Figure 6 As shown, the liquid chromatography mass spectrometry analysis device of this embodiment is different from the first embodiment in that the mass spectrometry analysis unit 2 has more than two ion source probes 9 and has a selection valve 8 (third valve) for switching multiple ion source probes. The selection valve 8 is switched by the control unit 100. Although omitted from the illustration, the ion source probe 9 has a capillary, and the outlet of the capillary is arranged toward the vacuum chamber 16. The other device structures are the same as those of the first embodiment, so the description is omitted.

[0076] <Action>

[0077] The operation of the liquid chromatography mass spectrometry analysis device of this embodiment is described. The operation of this embodiment is substantially the same as that of the first embodiment, but the difference from the first embodiment is that, during normal measurement (step S1 in the first embodiment), when one of the multiple ion source probes 9 is used and it is determined that the ion source is clogged (yes in step S4), in step S5, the control unit 100 switches the selection valve 8 to connect the other ion source probes to the mass spectrometry unit 2. In this way, when it is determined that the ion source is clogged, by switching the ion source probe 9, it is possible to recover from the clog more reliably and in a short time.

[0078] <Technical Effect>

[0079] As described above, in this embodiment, as in the first embodiment, the following structure is provided: when an abnormality is detected, the first flow path 11 is switched to the second flow path 12 that does not pass through the separation column 4, and the pressure of the second flow path 12 is measured. Thus, according to this embodiment, the location where the blockage has occurred can be automatically determined, and the blockage can be recovered in a short time. In addition, this embodiment has the following structure: when it is determined that there is a blockage between the selection valve 5 and the capillary outlet of the ion source, the flow path is switched to another ion source probe 9. Thus, it is possible to recover from the blockage more reliably and in a short time.

[0080] [Modifications]

[0081] The present disclosure is not limited to the above-mentioned embodiments, and includes various modified examples. For example, the above-mentioned embodiments are embodiments described in detail in order to explain the present disclosure in an easy-to-understand manner, and do not necessarily need to have all the structures described. In addition, a part of a certain embodiment can be replaced with the structure of other embodiments. In addition, the structure of other embodiments can also be added to the structure of a certain embodiment. In addition, for a part of the structure of each embodiment, a part of the structure of other embodiments can also be added, deleted or replaced.

[0082] Explanation of symbols

[0083] 1a~1c…Solution tank,

[0084] 2…Mass Spectrometry Department,

[0085] 3a~3c…Liquid delivery pump,

[0086] 4…Separation column,

[0087] 5~8…Selection valve,

[0088] 9…Ion source probe,

[0089] 10…Dummy column,

[0090] 11...First flow path,

[0091] 12…Second flow path,

[0092] 13a~13c…pressure gauge,

[0093] 14… Sampler,

[0094] 15…Waste liquid tank,

[0095] 16…Vacuum chamber.

Claims

1. A liquid chromatography-mass spectrometry analysis device, characterized in that: have: a first flow path, which passes through a separation column; a second flow path, which does not pass through the separation column; a mass spectrometer disposed on the downstream side of the first flow path and the second flow path and analyzing the sample passing through the first flow path; a first valve that connects one of the first flow path and the second flow path to the mass spectrometry unit; a first liquid-feeding pump for feeding liquid to the first flow path; a second liquid-feeding pump for feeding liquid to the second flow path; a control unit that controls driving of the first valve, the first liquid-feeding pump, and the second liquid-feeding pump; as well as a pressure gauge that measures the pressure of the second flow path and outputs the pressure to the control unit, When analyzing the sample in the mass spectrometer, the control unit connects the first flow path to the mass spectrometer, and supplies liquid from the first liquid supply pump to the mass spectrometer through the first flow path. The control unit compares the measured value of the mass spectrometer with a predetermined threshold value, and when it is determined to be abnormal, drives the first valve, the first liquid delivery pump, and the second liquid delivery pump to connect the second flow path to the mass spectrometer, and delivers liquid to the mass spectrometer through the second flow path from the second liquid delivery pump, After driving the first valve, the control unit determines that the separation column side is clogged when the pressure of the second flow path measured by the pressure gauge is less than a predetermined pressure threshold, and switches the first valve to connect the first flow path to the mass spectrometry unit to resume normal measurement when it is detected that the separation column has been replaced. When the pressure of the second flow path measured by the pressure gauge is above a predetermined pressure threshold, it is determined that the ion source of the mass spectrometry unit is clogged, and a message requesting maintenance for eliminating the clogged ion source is displayed on the display unit of the control unit, requesting the user to perform a recovery process for removing the clog, and determining whether the state of the flow path has returned to normal based on the pressure value of the solution introduced into the second flow path during the recovery process and the signal intensity of an internal standard substance of known concentration added to the solution. The recovery process includes changing the type and flow rate of the solution introduced into the second flow path or stopping the liquid supply to the second flow path to replace the ion source.

2. The liquid chromatography-mass spectrometry analysis device according to claim 1, characterized in that: The first liquid-feeding pump and the second liquid-feeding pump feed liquid at different pressures.

3. The liquid chromatography-mass spectrometry analysis device according to claim 1, characterized in that: The liquid chromatography-mass spectrometry analysis device also has: a plurality of said first flow paths; a plurality of separation columns, which are respectively disposed in the plurality of first flow paths; and A second valve switches a flow path to any one of the plurality of first flow paths.

4. The liquid chromatography-mass spectrometry analysis device according to claim 3, characterized in that: The liquid chromatography-mass spectrometry analysis device further comprises a hollow column arranged in parallel with the plurality of separation columns. The second flow path is a flow path passing through the hollow column, The second valve switches a flow path to any one of the plurality of first flow paths or the second flow path.

5. The liquid chromatography-mass spectrometry analysis device according to claim 1, characterized in that: The mass spectrometry unit includes a plurality of ion source probes and a third valve for switching the plurality of ion source probes. The control unit drives the third valve to switch the plurality of ion source probes after driving the first valve to connect the second flow path to the mass spectrometer.

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