Liquid chromatograph device and method for removing bubbles from liquid chromatograph device

Abstract

The present invention realizes a liquid chromatograph device that can remove bubbles during the preparation action when the device is started without complicated operations. The liquid chromatograph device includes a liquid delivery pump (1) for delivering a solvent, a syringe (53) for injecting a sample into the solvent delivered by the liquid delivery pump (1), a separation column (54) for supplying a solvent and a sample through the syringe (53) and separating the sample according to components, a detector (55) for detecting the components supplied from the separation column (54), a pressure sensor (51) for measuring the pressure in the solvent flow path of the liquid delivery pump (1), and a controller (50) for controlling the action of the liquid delivery pump (1). The controller (50) controls the bubble removal action in the solvent flow path performed by the liquid delivery pump (1), i.e., the purge action, and determines whether the pressure change in the solvent flow path measured by the pressure sensor (51) during the purge action is greater than a specified change, and when the pressure change is greater than the specified change, the bubble removal action is completed.

Description

Technical Field

[0001] The invention relates to a liquid chromatograph device and a method for removing bubbles from the liquid chromatograph device. Background Art

[0002] Conventionally, when HPLC (liquid chromatography) analysis is started, a purge operation of a liquid delivery pump is performed for the purpose of removing bubbles mixed in a flow path and replacing a solvent.

[0003] In particular, in a liquid chromatograph apparatus, since different solvents are not provided in a certain pipe, purge for the purpose of replacing the solvent is rarely necessary, and a purge operation is performed for the purpose of removing bubbles.

[0004] Usually, the purge operation is to open the purge valve and purge the liquid at a flow rate several to several dozen times the flow rate used for analysis. Even if the system capacity is fully purged, bubbles may remain due to factors such as the structure of the pump and the viscosity of the solvent.

[0005] Patent Document 1 describes a technique for maintaining a constant liquid supply flow rate even when air bubbles are mixed into normal liquid supply.

[0006] Prior art literature

[0007] Patent Literature

[0008] Patent Document 1: Japanese Patent Publication No. 2004-507639 Summary of the invention

[0009] Technical problem to be solved by the invention

[0010] In liquid chromatography, the mixing of bubbles prevents the liquid from being delivered at the correct flow rate and must be avoided. However, it is difficult to determine whether bubbles are mixed in the flow path that cannot be observed with the naked eye. Usually, abnormal liquid delivery is discovered after the start of liquid delivery or analysis, and sometimes re-purging is necessary.

[0011] For example, in a liquid delivery device that delivers liquid at high pressure, the pump room is generally made of metal to withstand the high pressure. Therefore, even if sufficient purging is performed to remove bubbles, it is difficult to determine whether bubbles are mixed in the purging operation.

[0012] In conventional general HPLC, after the purge is completed, normal liquid delivery is performed, and the presence or absence of mixed bubbles is determined by confirming that liquid delivery at a constant flow rate can be performed based on the stability of the liquid delivery pressure.

[0013] However, in a liquid chromatograph apparatus, it is desired to be able to determine the completion of the purge for removing bubbles during the preparatory operation at the start-up of the apparatus.

[0014] In the technology described in Patent Document 1, the presence or absence of bubbles is not determined at the end of the purge. In addition, the technology described in Patent Document 1 is a technology for maintaining a constant liquid delivery flow rate even when bubbles are mixed in the normal liquid delivery, so it is not a technology for removing bubbles, but a technology for allowing the existence of bubbles.

[0015] However, if bubbles are present in the liquid delivery, this usually prevents the liquid delivery rate from being kept constant.

[0016] There is a method in which, when poor liquid delivery cannot be eliminated even after repeated purging operations, the piping is temporarily removed and bubbles are manually removed using a plastic syringe. For example, if the flow path is a flow path using a water-based solvent, an organic solvent such as isopropyl alcohol or methanol is used for purging, and after the bubbles are removed, the water-based solvent is sometimes purged for the purpose of replacing the solvent. In this case, complicated manual work such as removing the piping and replacing the solvent bottle may be required.

[0017] The object of the present invention is to realize a liquid chromatograph device and a bubble removal method for the liquid chromatograph device, which can remove bubbles in the preparation action when the device is started without complicated operations.

[0018] Technical means for solving technical problems

[0019] In order to achieve the above-mentioned object, the present invention is configured as follows.

[0020] A liquid delivery pump for delivering a solvent; a syringe for injecting a sample into the solvent delivered from the liquid delivery pump; a separation column for supplying the solvent and the sample from the syringe and separating the sample according to components; a detector for detecting the components supplied from the separation column; a pressure sensor for measuring the pressure in the solvent flow path of the liquid delivery pump; a controller for controlling the operation of the liquid delivery pump, the controller controlling an operation of removing bubbles from the solvent flow path, i.e., a purging operation, performed by the liquid delivery pump, determining whether a pressure change in the solvent flow path measured by the pressure sensor during the purging operation is greater than a specified change, and completing the bubble removal operation when the pressure change is greater than the specified change.

[0021] A liquid delivery pump for delivering a solvent; a separation column for supplying the solvent and a sample and separating the sample according to components; a detector for detecting the components; and a pressure sensor for measuring the pressure in a solvent flow path of the liquid delivery pump, wherein an action of removing bubbles from the solvent flow path, i.e., a purge action, performed by the liquid delivery pump is started, and it is determined whether a pressure change in the solvent flow path measured by the pressure sensor during the purge action is greater than a specified change, and when the pressure change is greater than the specified change, the bubble removal action is completed.

[0022] Effects of the Invention

[0023] According to the present invention, a liquid chromatograph apparatus and a bubble removal method for a liquid chromatograph apparatus can be realized, which can remove bubbles in a preparatory operation at the time of starting the apparatus without requiring complicated work. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 This is a structural diagram of the liquid chromatograph device of Example 1.

[0025] Figure 2A 1 is a diagram showing an example of a purge valve according to Embodiment 1.

[0026] Figure 2B FIG. 1 is a diagram showing another example of the purge valve of Embodiment 1. FIG.

[0027] Figure 3A 1 is a diagram showing the operation of the first plunger and the second plunger in the purge operation in the first embodiment.

[0028] Figure 3B It shows that Figure 3A The diagram shows the pressure change caused by the operation of the first plunger and the second plunger, and the case where air bubbles are mixed in.

[0029] Figure 3C It shows that Figure 3A The pressure change shown in the figure by the operation of the first plunger 2 and the second plunger 3 is a diagram of a case where no air bubbles are mixed.

[0030] Figure 3D It is shown that in order to find Figure 3B The graph shown is a graph showing the result of differentiating the time change in pressure when bubbles are mixed and calculating the moving average.

[0031] Figure 3E It is shown that in order to find Figure 3C The graph shown is a graph showing the result of differentiating the time change in pressure when no bubbles are mixed and calculating the moving average.

[0032] Figure 4 : is a flowchart showing the process of determining whether the bubble removal is completed.

[0033] Figure 5 This is a structural diagram of the liquid chromatography device of Example 2. DETAILED DESCRIPTION

[0034] Hereinafter, embodiments of the present invention will be described using the drawings.

[0035] [Example]

[0036] (Example 1)

[0037] Figure 1 It is a structural diagram of a liquid chromatograph apparatus according to the first embodiment of the present invention, and is a diagram showing in detail the liquid delivery pump 1 which is a main part of the first embodiment.

[0038] exist Figure 1 , the liquid delivery pump 1 includes a first plunger pump 101, a second plunger pump 102, a first solenoid valve 81, a second solenoid valve 82, a degasser 83, a purge valve 311, a controller 50, a display unit 52, a motor driver 106, a solenoid valve driver 107, and a purge valve driver 312. The first plunger pump 101 and the second plunger pump 102 are connected in series with each other.

[0039] The first plunger pump 101 includes a first pump head 111. The first pump head 111 includes a first suction passage 10, a first discharge passage 103, and a first pressurizing chamber 12. A first check valve 4 is provided on the passage of the first suction passage 10, and a second check valve 5 is provided on the passage of the first discharge passage 103, and the flow direction of the solvent is restricted by the first check valve 4 and the second check valve 5.

[0040] The second plunger pump 102 includes a second pump head 112. The second pump head 112 includes a second suction passage 104, a second discharge passage 11, and a second pressurizing chamber 13. The second check valve 5 and the second suction passage 104 are connected via a connecting flow path 24. That is, the first plunger pump 101 and the second plunger pump 102 are arranged in series with each other, and the first plunger pump 101 is arranged on the upstream side.

[0041] The first plunger pump 101 slidably holds the first plunger 2 as a pressurizing member via the bearing 71 .

[0042] The second plunger pump 102 slidably holds the second plunger 3 as a pressurizing member via the bearing 72 .

[0043] The first seal 61 in the first plunger pump 101 prevents liquid leakage from the first pressurizing chamber 12 , and the second seal 62 in the second plunger pump 102 prevents liquid leakage from the second pressurizing chamber 13 .

[0044] When the first plunger pump 101 sucks the solvent, one of the first solenoid valve 81 and the second solenoid valve 82 is in an open state and the other is in a closed state, and one of the first solvent 511 and the second solvent 512 is sucked.

[0045] Here, it is also assumed that the types of solvents to be set are 3 or more. In this case, the same number of solenoid valves as the number of solvents to be set are set, only one of which is in an open state, and the others are in a closed state to suck one solvent.

[0046] The sucked solvent is degassed by the degasser 83 provided on the upstream side of the electromagnetic valves 81 and 82, and is sucked into the first pressurizing chamber 12 through the confluence portion 91 provided on the downstream side of the electromagnetic valves 81 and 82, the first check valve 4, and the first suction passage 10. The solvent sucked into the first pressurizing chamber 12 is compressed as the first plunger 2 rises.

[0047] In addition, the "rise" of the plunger indicates the movement in the direction in which the solvent in the pressurized chamber is compressed or discharged ( Figure 1 The “downward” direction indicates the movement of the solvent towards the left. Figure 1 movement to the right).

[0048] When the pressure of the solvent compressed in the first pressurized chamber 12 is greater than the pressure inside the second pressurized chamber 13 , the solvent flows into the second pressurized chamber 13 via the first discharge passage 103 , the second check valve 5 , the connecting flow passage 24 , and the second suction passage 104 , and is discharged from the second discharge passage 11 .

[0049] The pressure sensor 51 is disposed on the downstream side of the second plunger pump 102 , and measures the pressure of the solvent in the solvent flow path 57 from the second discharge passage 11 to the purge valve 311 .

[0050] The controller 50 provides a command value to the motor driver 106 , the solenoid valve driver 107 , and the purge valve driver 312 based on a signal indicating the solvent pressure from the pressure sensor 51 .

[0051] The motor driver 106 supplies driving power to the first motor 211 and the second motor 212 based on the command value of the controller 50. The first motor 211 drives the first plunger 2 via the reduction gear 221 and the linear motion device 231. The second motor 212 drives the second plunger 3 via the reduction gear 222 and the linear motion device 232.

[0052] The solenoid valve driver 107 supplies driving power to the first solenoid valve 81 and the second solenoid valve 82 based on the command value of the controller 50. The purge valve driver 312 supplies driving power to the purge valve 311 based on the command value of the controller 50.

[0053] The sample to be analyzed is injected into the solvent discharged from the purge valve 311 of the liquid delivery pump 1 through the syringe 53. The solvent (sample and solvent) injected into the sample through the syringe 53 is supplied to the separation column 54, and each component is separated by the separation column 54. After that, the sample is supplied from the separation column 54 to the detector 55. Then, the detector 55 detects the sample components and detects the absorbance, fluorescence intensity, refractive index, mass, etc. corresponding to the sample components. The waste liquid of the detector 55 is stored in the waste liquid container 56.

[0054] The separation column 54 is filled with fine particles, and a load pressure is generated by flow resistance when the solvent flows through gaps between the fine particles. The magnitude of the load pressure varies depending on the diameter of the separation column 54 and the flow rate.

[0055] When the solvent used in the liquid chromatograph device is switched from the first solvent 511 to the second solvent 512, the first electromagnetic valve 81 is switched from the open state to the closed state, and then the second electromagnetic valve 82 is switched from the closed state to the open state. As a result, the interior of the liquid delivery pump 1 (the first check valve 4, the first suction passage 10, the first pressurizing chamber 12, the first discharge passage 103, the connecting flow passage 24, the second suction passage 104, the second pressurizing chamber 13, the second discharge passage 11) and the interior of the syringe 53, the separation column 54, the detector 55, and the piping connecting them are replaced from the first solvent 511 to the second solvent 512.

[0056] By changing the opening ratio of the first solenoid valve 81 and the second solenoid valve 82, the first solvent 511 and the second solvent 512 can be used while being mixed. Furthermore, even when three or more kinds of solvents are used in the liquid chromatograph apparatus, each solvent can be used in a changed ratio by configuring a solenoid valve for each solvent and switching these solenoid valves.

[0057] Next, a normal liquid feeding process of the liquid feeding pump 1 will be described.

[0058] Normally, liquid feeding is a liquid feeding method for causing the solvent discharged from the liquid feeding pump 1 to flow to the syringe 53, the separation column 54, and the detector 55 when analyzing a sample or preparing for analysis.

[0059] At this time, if the discharge flow rate pulsates, the detection accuracy will decrease, so it is necessary to make the discharge flow rate constant. In the interval where the first plunger 2 descends and sucks the solvent, and in the interval where the first plunger 2 ascends and compresses the solvent, since the solvent is not discharged from the first pressurizing chamber 12, the second plunger 3 ascends and discharges the solvent. Thereafter, in the interval where the second plunger 3 descends and sucks the solvent, the first plunger 2 ascends and discharges the solvent of the portion sucked by the second plunger 3 and the portion discharged to the downstream of the pump. Thereafter, the first plunger 2 ascends and discharges the solvent, and the second plunger 3 stops.

[0060] Through these operations, the discharge flow rate from the liquid feeding pump 1 is kept constant. By keeping the discharge flow rate constant, the discharge pressure also becomes constant.

[0061] In the normal liquid feeding process, both the first plunger 2 and the second plunger 3 operate based on the lower limit point. The lower limit point indicates the position where the plunger has dropped the most within the movable range of the pressurized chamber. On the other hand, the upper limit point indicates the position where the plunger has risen the most within the movable range of the pressurized chamber. In contrast, the lower dead center / upper dead center generally indicate the two ends of the plunger's stroke.

[0062] Therefore, if the stroke range changes, the bottom dead center and top dead center will also change. In this specification, the bottom dead center / upper limit point and the bottom dead center / top dead center are used to have different meanings.

[0063] The pressure sensor 51 is provided downstream of the second plunger pump 102 , and the purge valve 311 is connected downstream.

[0064] The purge valve 311 includes a plurality of ports, and by switching the ports to a plurality of positions, it switches whether to deliver the solvent to the syringe 53. In addition, the purge valve 311 can selectively deliver the solvent to the waste tank 313. In addition, as described below, it can be set to a closed position.

[0065] exist Figure 2A An example of the purge valve 311 is shown in Figure 2B Another example is shown in FIG.

[0066] exist Figure 2A In the purge valve a shown, the solvent discharged from the liquid delivery pump 1 enters the port 611. For example, the port 612 is connected to the syringe 53 side, the port 613 is connected to the waste liquid tank 313 side, and the sealing plug is set on the port 614.

[0067] Port 611 is connected to port 612 during normal liquid feeding or after analysis starts, and is connected to port 613 during purge operation. When the purge operation is performed using the closed position to effectively discharge bubbles, port 611 is connected to port 614. One port 614 among the plurality of ports 612, 613, and 614 is sealed, and the sealed port 614 is used for the closed position.

[0068] exist Figure 2B In the purge valve b shown, the solvent discharged from the liquid delivery pump 1 enters the port 615 and is discharged to either the port 616 or the port 617. For example, the port 616 is connected to the syringe 53 side, and the port 617 is connected to the waste liquid tank 313 side.

[0069] The closed position between the port 615 and the port 616 or the port 615 and the port 617 provided with the purge valve b does not release the flow path (the flow path is closed), and is switched to the closed position, so that it can be used in the same way as the port 614 with the sealing plug provided with the purge valve a. That is, for example, if it is a valve that changes the port by rotating 60 degrees, it can be set to the closed position (used for the closed position) by rotating, for example, 30 degrees.

[0070] In the process of the purging operation, if the liquid is transferred from the normal liquid feeding, the first plunger 2 and the second plunger 3 are temporarily stopped, and the purge valve 311 is switched to the waste liquid tank 313. Then, after the first plunger 2 rises to the upper limit point, the second plunger 3 rises to the upper limit point. After that, when the solenoid valve 81 or the solenoid valve 82 of the solvent to be purged is set to the open state, the purging operation is started.

[0071] The purging operation is performed by reciprocating only the first plunger 2 between the upper limit point and the lower limit point while the second plunger 3 is stopped. At this time, the discharge flow rate is intermittent, and the pressure pulsates accordingly.

[0072] However, since the flow resistance of the pipe connecting the purge valve 311 and the waste liquid tank 313 is smaller than the fluid resistance of the separation column 54, the maximum pressure during the purge operation is lower than the pressure during normal liquid delivery.

[0073] Furthermore, since the sample is not analyzed during the purge operation and the solvent does not flow to the separation column 54 and the detector 55 , there is no problem even if the flow rate and pressure pulsate.

[0074] Figure 3A 1 is a diagram showing the operation of the first plunger 2 and the second plunger 3 in the purge operation in the first embodiment.

[0075] exist Figure 3A , the movement of the first plunger 2 indicated by the dotted line repeatedly performs suction and discharge, while the second plunger 3 indicated by the solid line stops at the upper limit point. Figure 3B Shows the Figure 3A The pressure change in response to the operation of the first plunger 2 and the second plunger 3 shown is a case where air bubbles are mixed. Figure 3C Shows the Figure 3A The pressure change shown in FIG. 1 with respect to the operation of the first plunger 2 and the second plunger 3 is a diagram showing a case where no air bubbles are mixed.

[0076] Figure 3D Show that in order to find Figure 3B The result of differentiating the time change in pressure when bubbles are mixed is calculated by moving average. Figure 3E Show that in order to find Figure 3CThe result of differentiating the time change in pressure when no bubbles are mixed is shown and calculating the moving average.

[0077] The calculation method for obtaining the time variation of pressure is not limited to this method as long as the difference between the time variation of pressure during purging and the time variation of pressure during discharge when no bubbles are mixed is clearly understood.

[0078] During the period of mixing bubbles in the solvent, Figure 3D As shown, the temporal variation of pressure does not change significantly.

[0079] However, when there is no air bubble mixing, Figure 3E As shown in FIG. 1 , at the timing when the first plunger 2 moves in the ascending direction, i.e., at the timing when the discharge starts, the time variation of the pressure changes greatly. If the time variation of the pressure at the start of the discharge is N times (predetermined times) or more of the average variation, and this situation is observed for a predetermined number of times, i.e., M times or more, it can be determined that the pressure variation in the solvent flow path is greater than the predetermined variation, and it can be determined that the bubble removal is completed.

[0080] Here, N is an arbitrary value that can clearly distinguish noise greater than 1, and M is set to an arbitrary integer greater than 2. The value of N can be changed according to the type of solvent, such as 3 times for aqueous solvents and 2 times for organic solvents, depending on the type of solvent.

[0081] In order to prevent erroneous determination due to noise in the average value, the value of M may be set to an arbitrary value such as 5.

[0082] Figure 4 FIG. 5 is a flowchart showing the process of determining whether the bubble removal is completed. Figure 4 The actions shown in the flowchart shown are controlled.

[0083] exist Figure 4 In step S1, when the device is started or when the device is restored from a standby state where the device has been stopped for several hours, the bubble removal and bubble removal determination process is implemented.

[0084] In step S2, the purge operation is started. The purge operation may be started automatically during the process of the device starting up or returning from the standby state, or may be started at an arbitrary timing.

[0085] After the purge operation is started, in step S3 , it is determined whether the number of times the pressure change amount detected by the pressure sensor 51 becomes N times the average change amount within a predetermined time is M times or more.

[0086] When it is determined that the number of times the average change amount is N times or more is M times, it is determined that the bubble removal is completed, and in step S4, the purging is completed.

[0087] In step S3 , when the number of times the average change amount is N times within the predetermined time is not M times or more, it is determined that the bubble removal is not completed, and the process proceeds to step S5 .

[0088] In step S5 , it is determined whether the number of trials (the number of repeated trials of bubble removal when it is determined that bubble removal is not completed) is less than L. If it is determined that the number of trials is less than L, the process proceeds to step S6 .

[0089] In step S6, the purge valve 311 is switched to the closed position ( Figure 2A Sealed port 614 or Figure 2B The purge valve 311 is in the closed position where the flow path between the ports is not released. This action causes the pressure in the solvent flow path to rise. When the pressure in the solvent flow path exceeds the set pressure, the purge valve 311 is switched to the port 613 or the port 617 (the position where the solvent is discarded) connected to the waste liquid tank 313, and the flow path is released at once, thereby effectively removing bubbles. Here, the set pressure is set to a value that does not exceed the upper limit pressure specified in the device structure.

[0090] After that, the process returns to step S2 and performs the purge operation again using the purge valve 311. Then, the process proceeds to step S3, and when it is determined that the number of times the average change amount is N times or more is M times, it is determined that the bubble removal is completed, and in step S4, the purge is considered to be completed.

[0091] In step S3 , when the number of times the average change amount is N times within the predetermined time is not M times or more, it is determined that the bubble removal is not completed, and the process proceeds to step S5 .

[0092] In step S5 , if the purge by switching the purge valve 311 to the closed position is performed a certain number of times, namely L times, and the bubble removal is not determined to be complete, the process proceeds to step S7 , and an error is displayed on the display unit 52 .

[0093] Here, the number of determinations L can be set to any number. When an error display is shown on the display unit 52, for example, the deterioration of the seals 61 and 62 as consumable parts, the failure of the components constituting the first solenoid valve 81, the second solenoid valve 82, the pressure sensor 51, etc., is displayed, and it is determined that maintenance is required. The display unit 52 may also display that maintenance is required.

[0094] In the liquid chromatograph apparatus, when three or more liquid feeding solvents are set, it is necessary to perform the determination process of whether the bubble removal is completed for all the set solvents. The reason is that when a plurality of HPLC flow paths are set from the degasser 83 and connected to one detector 55 using a switch valve or the like, it is necessary to perform the determination process of whether the bubble removal is completed in all the flow paths.

[0095] After it is determined that the bubble removal is complete, as long as the liquid supply is continued, the solvent degassed by the degasser 83 will continue to flow, so when normal liquid supply is performed, there is no worry that bubbles will be mixed after the analysis starts.

[0096] However, in the liquid chromatograph, if the standby state for stopping sample analysis continues and several hours pass while the liquid feeding pump 1 stops feeding liquid, bubbles may be mixed in, and therefore it is necessary to perform the process of determining whether the bubble removal is completed again.

[0097] As described above, the liquid chromatograph device according to Example 1 of the present invention is constructed so that, in the preparation action when the device is started, the pressure sensor 51 detects the pressure change in the solvent flow path during the purge action, calculates the time change of the pressure, determines whether there are bubbles in the solvent, and if bubbles exist, increases the pressure in the solvent flow path to remove the bubbles.

[0098] However, according to the first embodiment of the present invention, a liquid chromatograph apparatus and a bubble removal method for a liquid chromatograph apparatus can be realized, which can remove bubbles in the preparation operation at the start-up of the apparatus without complicated work.

[0099] Furthermore, even after the bubbles are removed by increasing the pressure in the solvent flow path, it is determined whether bubbles exist in the solvent. If it is determined that the bubble removal process is not completed, an error display is made on the display unit 52 .

[0100] This can avoid the liquid feeding operation being performed in a state where bubbles exist in the solvent, and can also determine the deterioration of the components.

[0101] (Example 2)

[0102] Next, Example 2 of the present invention will be described.

[0103] Figure 5 It is a structural diagram of a liquid chromatograph apparatus according to a second embodiment of the present invention, and is a diagram showing in detail a liquid delivery pump 1 a which is a main part of the second embodiment.

[0104] exist Figure 1 In the illustrated embodiment 1, the pressure sensor 51 of the liquid delivery pump 1 is provided only in the solvent flow path from the second plunger pump 102 .

[0105] In contrast, in Figure 5 In the liquid delivery pump 1a of the second embodiment shown in FIG. 1 , the first pressure sensor 105 is provided on the first discharge passage 103, which is the solvent flow path in the first plunger pump 101, and measures the pressure of the solvent in the first pressurizing chamber 12. Figure 5In the second embodiment shown, the second pressure sensor 160 is provided in the second discharge passage 11 which is the solvent flow path in the second plunger pump 102 , and measures the pressure in the second pressurizing chamber 13 .

[0106] The determination process of the completion of bubble removal in Example 2 is the same as Figure 4 The flowcharts shown are the same, so detailed description will be omitted.

[0107] In the second embodiment, two pressure sensors, namely the first pressure sensor 105 and the second pressure sensor 160 are provided.

[0108] Therefore, according to the second embodiment, the pressure in the first pressurized chamber 12 and the pressure in the second pressurized chamber 13 can be measured separately. Therefore, as in the first embodiment, by a purging method in which the second plunger 3 is not stopped near the upper limit point, for example, by setting the flow rate of normal liquid delivery to a high flow rate, or by a liquid delivery method in which the first plunger 2 and the second plunger 3 are independently operated for effective purging, the pressure change amount during solvent discharge can be detected, thereby determining whether or not bubbles are mixed into the first pressurized chamber 12 and the second pressurized chamber 13, respectively.

[0109] Furthermore, during normal liquid feeding and after analysis starts, it is possible to monitor the possibility of bubbles being mixed in. If bubbles are detected after analysis starts, normal liquid feeding is stopped once, and a determination process of bubble removal is performed, thereby preventing loss of the sample to be analyzed.

[0110] In the second embodiment, in addition to the same effects as those of the first embodiment, the above-mentioned effects can also be obtained.

[0111] (Regarding Modifications of the Present Invention)

[0112] In addition, the present invention is not limited to the above-mentioned embodiments, and includes various modifications. For example, the above-mentioned embodiments are described in detail to facilitate understanding and explanation of the present invention, and the present invention is not necessarily limited to including all the described structures.

[0113] That is, various changes, additions, and omissions may be made to a part of the configuration of the embodiment.

[0114] According to the present invention, the following effects can also be obtained.

[0115] By determining that bubble removal is complete during the purge operation, it is possible to reduce unnecessary purge operation time, reduce the amount of solvent used, and reduce the need for return work due to poor liquid delivery after starting normal liquid delivery and after starting analysis.

[0116] Furthermore, by purging using the closed position of the purge valve 311, bubbles can be removed without the need for complex manual work such as disassembling the piping or replacing the solvent bottle. In other words, the consumption of the piping connection and the risk of taking the wrong solvent bottle are also reduced.

[0117] The first discharge passage 103 and the second discharge passage 11 may also be defined as solvent flow passages in the same manner as the solvent flow passage 57 .

[0118] In addition, in the above-mentioned embodiment, whether the bubble removal is completed is determined based on whether the time change of the pressure at the beginning of discharge is observed to be more than N times the average change, and this situation continues for more than M times, but it is not limited to this determination. As long as it is determined whether the pressure change in the solvent flow path measured by the pressure sensor 51, 105, 160 is more than the specified change, and the example of determining that the bubble removal is completed when it is above the specified change is included in the embodiments of the present invention.

[0119] Description of symbols

[0120] 1, 1a…liquid delivery pump, 2…first plunger, 3…second plunger, 11…second discharge passage, 12…first pressurizing chamber, 13…second pressurizing chamber, 50…controller, 51…pressure sensor, 52…display unit, 53…syringe, 54…separation column, 55…detector, 56…waste liquid container, 57…solvent flow path, 81…first solenoid valve, 82…second solenoid valve, 83…degasser, 101…first plunger pump, 102…second plunger pump, 103…first discharge passage, 105…first pressure sensor, 106…motor driver, 107…solenoid valve driver, 160…second pressure sensor, 211…first motor, 212…second motor, 311…purge valve, 312…purge valve driver, 511…first solvent, 512…second solvent.

Claims

1. A liquid chromatograph device, comprising: A liquid delivery pump for delivering solvent; a syringe for injecting a sample into the solvent fed from the liquid feeding pump; A separation column for supplying the solvent and the sample via the syringe and separating the sample into components; a detector for detecting the components supplied from the separation column; a pressure sensor for measuring the pressure in the solvent flow path of the liquid delivery pump; as well as A controller for controlling the action of the liquid delivery pump, wherein the liquid chromatograph device is characterized in that: The controller controls a purge operation to remove bubbles from the solvent flow path by the liquid delivery pump. determining whether the pressure change amount in the solvent flow path measured by the pressure sensor during the purge operation is greater than or equal to a predetermined change amount, and completing the bubble removal operation when the pressure change amount is greater than or equal to the predetermined change amount; The liquid delivery pump includes a purge valve having multiple ports and switching between a position for delivering the solvent to the syringe, a waste position, and a closed position. When the average pressure change does not exceed a specified number of times within a specified time for more than a specified number of times, the controller switches the purge valve to the closed position. When the pressure in the solvent flow path exceeds a set pressure, the controller switches the purge valve to the waste position.

2. The liquid chromatograph device according to claim 1, characterized in that: If the pressure change at the start discharge timing of the solvent of the liquid delivery pump is more than the specified times of the average pressure change for more than the specified number of times within the specified time, the controller determines that the pressure change in the solvent flow path is greater than the specified change and completes the bubble removal action.

3. The liquid chromatograph device according to claim 1, characterized in that: One of the plurality of ports is sealed, the sealed port being for the closed position.

4. The liquid chromatograph device according to claim 1, characterized in that: A position where a port among the plurality of ports and a flow path between the ports are closed is used for the closed position.

5. The liquid chromatograph device according to claim 1, characterized in that: The liquid delivery pump comprises: a first plunger pump that sucks or discharges the solvent by sliding in a space between an upper limit point and a lower limit point; and a second plunger pump that sucks or discharges the solvent by sliding in a space between an upper limit point and a lower limit point, the first plunger pump and the second plunger pump are connected in series to each other and to the solvent flow path, the pressure sensor is connected to the downstream side of the second plunger pump, the purge valve is connected to the downstream side of the pressure sensor, and the controller controls the purge action in such a way that the plunger of the first plunger pump reciprocates between the upper limit point and the lower limit point when the plunger of the second plunger pump stops at the upper limit point.

6. The liquid chromatograph device according to claim 1, characterized in that: Also includes a display unit, The controller switches the purge valve to the closed position, and when the pressure in the solvent flow path exceeds the set pressure, switches the purge valve to the discard position, and then performs the purge action, and when the situation in which the average pressure change amount does not exceed the specified times within the specified time for a certain number of times continues for more than the specified times, an error is displayed on the display unit.

7. The liquid chromatograph device according to claim 1, characterized in that: The liquid delivery pump comprises: a first plunger pump that sucks or discharges the solvent by sliding in a space between an upper limit point and a lower limit point; and a second plunger pump, which sucks or discharges the solvent by sliding in the space between the upper limit point and the lower limit point, the first plunger pump and the second plunger pump are connected to each other in series and connected to the solvent flow path, and the pressure sensor has: a first pressure sensor, which measures the pressure in the solvent flow path of the first plunger pump; and a second pressure sensor, which measures the pressure in the solvent flow path of the second plunger pump.

8. A method for removing bubbles from a liquid chromatograph device, the liquid chromatograph device comprising: a liquid delivery pump for delivering a solvent; and a syringe for injecting a sample into the solvent delivered from the liquid delivery pump; A separation column for supplying the solvent and the sample and separating the sample according to the components; a detector for detecting the components; and a pressure sensor for measuring the pressure in the solvent flow path of the liquid feeding pump. The bubble removal method of the liquid chromatograph device is characterized in that: starting a purge operation to remove bubbles from the solvent flow path by the liquid delivery pump, determining whether the pressure change amount in the solvent flow path measured by the pressure sensor during the purge operation is greater than a predetermined change amount, When the pressure change amount is greater than the predetermined change amount, the bubble removal operation is completed. The liquid delivery pump includes a purge valve having multiple ports and switching between a position for delivering the solvent to the syringe, a waste position, and a closed position. When the average pressure change does not exceed a specified number of times within a specified time for more than a specified number of times, the purge valve is switched to the closed position. When the pressure in the solvent flow path exceeds a set pressure, the purge valve is switched to the waste position.

9. The method for removing bubbles from a liquid chromatograph according to claim 8, wherein: If the pressure change amount at the start of discharging the solvent of the liquid delivery pump becomes the specified times or more of the average pressure change amount for more than the specified number of times within the specified time, it is determined that the pressure change amount in the solvent flow path is greater than the specified change amount, and the bubble removal operation is completed.

10. The method for removing bubbles from a liquid chromatograph according to claim 9, wherein: When the number of times the average pressure change amount becomes more than the specified number of times within the specified time does not continue for more than the specified number of times, the pressure in the solvent flow path is increased, and when the pressure in the solvent flow path exceeds the set pressure, the solvent flow path is released to remove the bubbles in the solvent flow path.

11. The method for removing bubbles from a liquid chromatograph according to claim 10, wherein: When the pressure in the solvent flow path exceeds the set pressure, the solvent flow path is released and the purge action is performed. When the number of times that the average pressure change amount does not continue to exceed the specified number of times within the specified time reaches a certain number, an error is displayed on the display unit.

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