Method for controlling a liquid chromatograph

Abstract

Provided is a method for controlling a liquid chromatograph, with which it is possible to determine whether bubbles remain in a flow path. This method for controlling a liquid chromatograph (300) comprising a liquid feed pump, a flow path connected to the liquid feed pump, a flow-path switching valve (auto purge valve (205), injection valve (207), stream selection valve (304)) which is provided in the flow path to switch between a plurality of connection destinations of the flow path, a pressure sensor for detecting at least one pressure among a liquid feed pressure of the liquid feed pump, a flow path internal pressure in the flow path, and a pressure acting on the flow-path switching valve, includes: rotating the flow-path switching valve during the liquid feed from the liquid feed pump; and determining whether bubbles remain in the flow path on the basis of a pressure variation when the pressure, which has dropped as a result of the rotation of the flow-path switching valve, rises.

Description

[Technical Field]

[0001] The present disclosure relates to a method for controlling a liquid chromatograph. [Background technology]

[0002] A typical liquid chromatograph (HPLC) consists of a pump that delivers the liquid mobile phase, an injector that introduces the sample, a separation column that separates the sample, a column oven that controls the temperature of the separation column, and the piping that connects them. The pump holds multiple mobile phases and performs gradient delivery, changing the mixture ratio over time to deliver the mobile phase to the separation column. In gradient delivery, the pump first delivers a mobile phase with a low sample elution strength to the separation column, so that the target components in the sample injected into the separation column are adsorbed onto the separation column (adsorption process). Next, the mobile phase is changed to a higher elution strength, and the target components in the sample adsorbed onto the separation column are eluted from the separation column and reach the detector (separation process). After the target components are detected, the pump changes the mobile phase to a higher elution strength to wash away any remaining impurities from the separation column. In this way, gradient elution changes the mobile phase composition in the separation column during a single analysis (washing process). When performing continuous measurements using gradient flow, after one analysis is completed, the composition of the mobile phase in the separation column must be changed to the initial mobile phase in order to start the next analysis (equilibration process). Furthermore, to avoid contamination with impurities, preparatory operations such as cleaning the injector and returning the injector switching valve to its initial position must be performed.

[0003] Some liquid chromatographs are equipped with multiple liquid chromatographs. Each liquid chromatograph is called a stream, and can be integrated into a single detector via a stream select valve, enabling mutual analysis. This liquid chromatograph adjusts the times for the equilibration, adsorption, elution, and cleaning steps for the separation column, as well as the injector cleaning step. It rotates the stream select valve so that the detector is connected at the time of each stream's elution step, allowing the target component from the corresponding stream to be introduced into the detector, eliminating detector waiting time. In this way, this liquid chromatograph achieves high throughput.

[0004] This liquid chromatograph is more complex than a typical liquid chromatograph, making it difficult to identify the location of a malfunction within the device. Malfunctions include clogged flow paths, leaks, and residual air bubbles. When a flow path is clogged, an increase in the pressure value of the pressure sensor attached to each liquid delivery pump indicates the location of the blockage downstream of the pressure sensor. When a leak occurs, the leak can be detected by leak sensors attached to each liquid delivery pump and near the piping flow path. Furthermore, a decrease in the pressure value of the pressure sensor attached to each liquid delivery pump indicates the location of the leak downstream of the pressure sensor. On the other hand, when there are large amounts of residual air bubbles, pulsation in the pressure sensor value attached to each liquid delivery pump is detected during normal liquid delivery, indicating the presence of residual air bubbles. However, when the amount of residual air bubbles is small, pressure fluctuations are not detected during normal liquid delivery, and the presence of residual air bubbles cannot be detected. In such cases, variations in the retention time of the substance being measured or variations in peak intensity can often only be noticed after the data has been acquired, resulting in wasted sample and measurement time.

[0005] In view of this situation, a liquid delivery system for liquid chromatography described in Patent Document 1 has been proposed. This liquid delivery system includes a liquid delivery mechanism, a pressure sensor, and a liquid delivery failure detection unit. The liquid delivery mechanism is configured to continuously deliver liquid using at least one plunger pump that delivers liquid by reciprocating a plunger. The pressure sensor detects the liquid delivery pressure of the liquid delivery mechanism. The liquid delivery failure detection unit is configured to capture the liquid delivery pressure detected by the pressure sensor at a cycle that allows fluctuations within one drive cycle of the liquid delivery mechanism to be read, and to detect a liquid delivery failure of the liquid delivery mechanism using the captured liquid delivery pressure. In this liquid transfer system, the liquid transfer failure detection unit is configured to execute a pulsation detection step and a liquid transfer failure detection step in that order. The pulsation detection step calculates a fluctuation range of the liquid delivery pressure within a constant drive cycle of the liquid delivery mechanism, and detects pulsation when the number of consecutive cycles in which the fluctuation range exceeds a predetermined reference value exceeds a predetermined reference number. The liquid delivery failure detection step detects a liquid delivery failure of the liquid delivery mechanism when the pulsation detection step detects pulsation.

[0006] In the liquid delivery system described in Patent Document 1, if pressure fluctuations exceeding the normal range are detected during analysis, the system switches the discharge port of the plunger pump (liquid delivery pump) to a drain valve to connect it to the drain, and drives the plunger pump at high speed for a certain period of time to perform a purge operation. The system then returns the drain valve to its original position, connects the plunger pump to the separation column, and monitors the pressure fluctuations for a certain period of time. Furthermore, if air bubbles are introduced into the plunger pump, the compressed air prevents normal discharge of the liquid, resulting in a sudden drop in the liquid delivery pressure. During the discharge operation of the other plunger pump, normal liquid delivery occurs, resulting in an increase in the liquid delivery pressure. As a result, fluctuations (pulsations) in the liquid delivery pressure occur that are synchronized with the drive cycle of the liquid delivery mechanism. This liquid delivery system detects such pulsations and detects liquid delivery problems in the liquid delivery mechanism. Note that in this liquid delivery system, the air bubbles that can be expelled by the purge operation are limited to those within the plunger pump. [Prior art documents] [Patent documents]

[0007] [Patent Document 1] International Publication No. 2020 / 183774 Summary of the Invention [Problem to be solved by the invention]

[0008] The liquid transfer system described in Patent Document 1 can detect remaining air bubbles inside the liquid transfer pump. However, with this liquid transfer system, it is difficult to determine whether air bubbles remain in the flow path.

[0009] An object of the present disclosure is to provide a method for controlling a liquid chromatograph that can determine whether bubbles remain in a flow path. [Means for solving the problem]

[0010] In order to solve the above problems, for example, the configurations described in the claims are adopted. The present application includes multiple means for solving the above-mentioned problems, and one example thereof is a control method for a liquid chromatograph comprising a liquid delivery pump, a flow path connected to the liquid delivery pump, a flow path switching valve provided in the flow path and switching between multiple connection destinations of the flow path, and a pressure sensor that detects at least one of the liquid delivery pressure of the liquid delivery pump, the flow path pressure within the flow path, and the pressure applied to the flow path switching valve, in which the flow path switching valve is rotated while liquid is being delivered from the liquid delivery pump, and whether or not air bubbles remain in the flow path is determined based on pressure fluctuations when the pressure, which had decreased due to the rotation of the flow path switching valve, rises. [Effects of the Invention]

[0011] According to the present disclosure, it is possible to provide a method for controlling a liquid chromatograph that can determine whether bubbles remain in a flow path. Problems, configurations, and effects other than those described above will become apparent from the following description of the embodiments. [Brief explanation of the drawings]

[0012] [Figure 1] Schematic diagram showing a three-stream liquid chromatograph configuration. [Figure 2] A schematic diagram showing the configuration within one stream. [Figure 3A] Schematic diagram of the normal pressure profile. In this figure, the horizontal axis represents time (seconds) and the vertical axis represents pressure value (MPa). [Figure 3B] Schematic diagram of the pressure profile during an abnormality. In this figure, the horizontal axis represents time (seconds) and the vertical axis represents pressure value (MPa). [Figure 4] 1 is a flowchart of air bubble detection. [Figure 5] Graph showing information on changes over time in the deviation of ΔP1, where the horizontal axis represents the time (days) of the change over time, and the vertical axis represents the deviation of ΔP1 (%). [Figure 6] Graph showing information on changes over time in the deviation of ΔP2, where the horizontal axis represents the time (days) of the change over time, and the vertical axis represents the deviation of ΔP2 (%). [Figure 7] Graph showing information on changes in ΔT deviation over time, where the horizontal axis represents time (days) and the vertical axis represents ΔT deviation (%). DETAILED DESCRIPTION OF THE INVENTION

[0013] The method for controlling a liquid chromatograph according to this embodiment will be described in detail below with reference to the accompanying drawings as appropriate. FIG. 1 is a schematic diagram showing the configuration of a liquid chromatograph equipped with three streams. FIG. 2 is a schematic diagram showing the configuration within one stream. FIG. 3A is a schematic diagram of a pressure profile under normal conditions. FIG. 3B is a schematic diagram of a pressure profile under abnormal conditions. FIG. 4 is a flowchart of bubble detection. FIG. 5 is a graph showing information on changes over time in the deviation of ΔP1. FIG. 6 is a graph showing information on changes over time in the deviation of ΔP2. FIG. 7 is a graph showing information on changes over time in the deviation of ΔT.

[0014] First, an example of a liquid chromatograph 300 will be described with reference to Fig. 1. The liquid chromatograph 300 shown in Fig. 1 has three streams: a first stream 301, a second stream 302, and a third stream 303. These streams are connected to a detector 305 via a stream select valve 304, and can be analyzed with each other.

[0015] Each stream will be described with reference to Fig. 2. As shown in Fig. 2, each of the first stream 301 to the third stream 303 is configured to include, as main elements, a first liquid-feed pump 201, a second liquid-feed pump 202, a first pressure sensor 203, a second pressure sensor 204, an auto-purge valve 205, a three-way joint 206, an injection valve 207, a shipper 208, a sample holder 209, a syringe 210, a waste liquid flow path 211, a column 212, a first flow path 213, a second flow path 214, and a third flow path 215.

[0016] The first liquid feed pump 201 is composed of two cylinder pumps, a first cylinder pump and a second cylinder pump, connected in series, and is capable of stable liquid feed by complementarily driving suction and discharge. Similar to the first liquid feed pump 201, the second liquid feed pump 202 is also composed of two cylinder pumps, a first cylinder pump and a second cylinder pump, connected in series. The liquid feed pumps (first liquid feed pump 201 and second liquid feed pump 202) are connected to the flow path.

[0017] A first pressure sensor 203 is disposed downstream of the first liquid feed pump 201. A second pressure sensor 204 is disposed downstream of the second liquid feed pump 202. The first liquid feed pump 201 is connected to an auto-purge valve 205 via the first pressure sensor 203 and a flow path. Similarly, the second liquid feed pump 202 is connected to the auto-purge valve 205 via the second pressure sensor 204 and a flow path. The first pressure sensor 203 and the second pressure sensor 204 detect at least one of the pressures in the flow path and the pressures applied to the flow path switching valves (the auto-purge valve 205, the injection valve 207, and the stream select valve 304).

[0018] Flow path switching valves (auto purge valve 205, injection valve 207, stream select valve 304) are provided in the flow paths, and can switch between multiple connection destinations of the flow paths. In the example shown in FIG. 2, the auto-purge valve 205 has two switching positions. In the first position, the flow paths from the first liquid feed pump 201 and the second liquid feed pump 202 can be connected to the three-way joint 206. In the second position, the flow paths from the first liquid feed pump 201 and the second liquid feed pump 202 can be connected to the waste liquid flow path 211. In the second position, in preparation for the liquid feed pump to feed liquid, the flow path is switched to the waste liquid flow path 211, and a purging operation is performed in which the liquid feed pump sends liquid at a high flow rate, thereby removing air bubbles in the liquid feed pump and replacing the liquid in the liquid feed pump flow path. In the first position, the flow paths of the first liquid feed pump 201 and the second liquid feed pump 202 are mixed in the three-way joint 206 and sent to the injection valve 207 via the first flow path 213.

[0019] A sipper 208, a syringe 210, and a sample loop 216 are connected to the injection valve 207. In the example shown in FIG. 2, the injection valve 207 has two switching positions. In the first position, the sipper 208, the sample loop 216, and the syringe 210 are connected. In the second position, the injection valve 207 is connected to the column 212 via a flow path (first flow path 213) from the liquid feed pump, the sample loop 216, and the second flow path 214. In the first position, the syringe 210 is driven, and the sample in a sample container fixed to the sample holder 209 is aspirated from the sipper 208 and introduced into the sample loop 216. In the second position, the flow path from the liquid feed pump is connected to the sample loop 216, so that the sample introduced into the sample loop 216 in the first position is introduced into the column 212.

[0020] The first stream 301, second stream 302, and third stream 303 have the same device configuration, and each stream is connected to a detector 305 via a stream select valve 304 (FIG. 1). By adjusting the injection timing of each stream, the timing of the pump gradient, and the switching timing of the stream select valve 304, high-throughput analysis can be performed without wasting samples.

[0021] Next, a method for controlling a liquid chromatograph according to the present disclosure will be described. In this embodiment, the flow path switching valve is rotated once to detect remaining bubbles. However, it is not necessary to rotate it once; for example, the flow path switching valve may be rotated a specified angle and then returned the same angle in the opposite direction. In this embodiment, the pressure fluctuation when the pressure that has dropped due to the rotation of the flow path switching valve rises is used as an index to detect remaining bubbles.

[0022] As shown in the normal pressure profile in Figure 3A, under normal conditions, after valve switching, the pressure fluctuates by only 10 MPa or less (see the dashed circle in Figure 3A). In contrast, as shown in the abnormal pressure profile in Figure 3B, if bubbles remain, the pressure drops to almost zero after valve switching, and then the bubbles repeatedly compress and expand within the flow path, pulsating between 0 and 10 MPa (see the dashed circle in Figure 3B). If such a pulsating pressure profile is obtained, it is clear that bubbles remain in the flow path.

[0023] The threshold of the pressure profile is calculated using [Equation 1]-[Equation 3] and determined as follows: [Equation 1]<10 MPa, [Equation 2]<10 MPa, and [Equation 3]<50 s. ΔP1=P Max -P1…[Formula 1] ΔP2=P1-P min …[Formula 2] ΔT =T2-T1…[Formula 3]

[0024] Here, ΔP1 is the pressure change amount, ΔP2 is the pressure change amount, P Max is the maximum pressure (maximum pressure reached), P minis the minimum pressure (minimum attainable pressure), P1 is the pressure value before valve switching, ΔT is the time change point, T1 is the valve switching time, and T2 is the pressure recovery time (valve switching time, time to return to P1 x 80%). In other words, in this embodiment, it is possible to determine whether or not bubbles remain in the flow path based on pressure fluctuations, i.e., [Equation 1] and [Equation 2]. In addition to this pressure fluctuation, the time fluctuation to return to a specified pressure (for example, P1 x 80%), i.e., [Equation 3], can be used as a determination criterion.

[0025] 1 and 2, a liquid chromatograph 300 is provided with a total of seven flow path switching valves. Specifically, a first stream 301, a second stream 302, and a third stream 303 are each equipped with an auto-purge valve 205 and an injection valve 207. The streams are connected by a stream select valve 304. In this embodiment, as will be described later, the three types of flow path switching valves, the auto-purge valve 205, the injection valve 207, and the stream select valve 304, are rotated, and the presence or absence of bubbles is determined from the pressure fluctuations.

[0026] In this embodiment, the flow path switching valves used are a first switching valve located upstream with respect to the flow of the fluid, and a second switching valve connected downstream of the first switching valve via a flow path. As an example of the first and second switching valves, when the first switching valve is the auto-purge valve 205, the second switching valve is the injection valve 207. As an example of the first and second switching valves, when the first switching valve is the injection valve 207, the second switching valve is the stream select valve 304.

[0027] With regard to such a liquid chromatograph 300, a process for detecting remaining air bubbles in the liquid chromatograph 300 and checking the integrity of the device before measurement will be described with reference to Fig. 4. Detection of remaining air bubbles in the device is performed when switching each valve during operation, and the operator can also select and start air bubble detection maintenance on the device's GUI (Graphical User Interface) screen as one of the maintenance items.

[0028] First, air bubble detection during maintenance will be described with reference to FIG. First, a reset operation is performed to return all valves to their home positions (step S1). Next, the first liquid feed pump 201 and the second liquid feed pump 202 of each stream begin to feed liquid. Simultaneously with the liquid feed, pressure log acquisition by a pressure sensor attached to the liquid feed pump begins (step S2). This pressure sensor detects the liquid feed pressure of the liquid feed pump. The liquid feed conditions are ultrapure water fed at a flow rate of 0.44 mL / min, and the system waits until the pressure stabilizes at approximately 50 MPa (step S3). Pressure stabilization refers to the integration of pressure information obtained every 0.1 seconds, with fluctuations over 30 seconds falling within a range of ±1 MPa. After the pressure stabilizes, the stream select valve 304 is rotated (step S4). The pressure value of each liquid feed pump is acquired (step S5), and the presence or absence of bubbles is determined from the pressure fluctuation value, i.e., the amount of pressure decrease and increase (step S6). The liquid transfer by the first liquid transfer pump 201 and the second liquid transfer pump 202 of each stream in which no air bubbles remain is stopped (No in step S7, step S8).

[0029] On the other hand, in the stream where residual bubbles are confirmed, the injection valve 207 is rotated (Yes in step S7, step S9). The pressure value of each liquid delivery pump is acquired (step S10), and the presence or absence of bubbles is determined from the pressure fluctuation value, the amount of pressure decrease and increase (step S11). In addition, before rotating the injection valve 207 in the stream in which residual bubbles are confirmed (i.e., before step S9), the liquid delivery by the first liquid delivery pump 201 and the second liquid delivery pump 202 in the stream in which no residual bubbles are confirmed may be stopped.

[0030] If it is determined that no bubbles remain when the injection valve 207 is rotated (No in step S12), it is determined that bubbles remain between the stream select valve 304 and the injection valve 207 of the corresponding stream (i.e., in the flow path from the second switching valve to the first switching valve) (step S13, see part A in FIG. 1). Thereafter, the liquid transfer of the first liquid transfer pump 201 and the second liquid transfer pump 202 of the corresponding stream is stopped (step S20).

[0031] If it is determined that bubbles remain (Yes in step S12), the auto-purge valve 205 for the corresponding stream is rotated (step S14). The pressure value of each liquid delivery pump is acquired (step S15), and the presence or absence of bubbles is determined from the pressure fluctuation value, i.e., the amount of pressure decrease and increase (step S16).

[0032] If it is determined that no bubbles remain when the auto-purge valve 205 is rotated, it is determined that bubbles remain between the injection valve 207 and the auto-purge valve 205 of the stream in question (i.e., the flow path from the second switching valve to the first switching valve) (No in step S17, step S18, see part B in FIG. 1). Thereafter, the liquid transfer of the first liquid transfer pump 201 and the second liquid transfer pump 202 of the stream in question is stopped (step S20).

[0033] If it is determined that bubbles remain, it is determined that bubbles remain between the auto-purge valve 205 and the liquid feed pump of the stream in question (i.e., in the flow path from the first switching valve to the liquid feed pump) (Yes in step S17, step S19, see part C in FIG. 1). Thereafter, the liquid feed of the first liquid feed pump 201 and the second liquid feed pump 202 of the stream in question is stopped (step S20).

[0034] As described above, the control method for the liquid chromatograph 300 according to this embodiment can determine whether or not bubbles remain in the flow path by sequentially rotating the flow path selector valve starting from the downstream side (detector 305 side) during bubble detection during maintenance. Furthermore, if bubbles remain, this control method identifies their location because the flow path is separated by the flow path selector valve as described above. When bubble detection during maintenance is started, this control method automatically performs the series of steps described above. The remaining bubbles and their location are displayed on the GUI screen, prompting the operator to proceed.

[0035] Next, air bubble detection during operation will be described. Air bubble detection during operation differs from air bubble detection during maintenance, as the order of valve switching is random depending on the measurement order. The auto purge valve 205 switches during the purging operation before measurement. The injection valve 207 switches during sample injection. The stream select valve 304 switches when switching between the three streams. Therefore, although it is possible to detect whether or not air bubbles remain, it is not possible to determine where the bubbles remain. When remaining air bubbles are detected, new measurement reservations cannot be made for the corresponding stream.

[0036] Meanwhile, the currently scheduled measurement is carried out. When the scheduled measurement is completed, the corresponding stream is masked, and the liquid delivery pump and column oven temperature control are stopped. After the operation is completed and the device enters standby mode, the operator selects and performs bubble detection maintenance from the maintenance screen on the device's GUI. This causes the liquid chromatograph 300 to automatically perform the series of steps described above during maintenance, identify the location of the bubble, and perform the work to remove the bubble. The details of this work are explained below.

[0037] If air bubbles remain between the stream select valve 304 and the injection valve 207, the result and remedy (Remedy) are displayed on the maintenance screen. The maintenance screen displays the result: "Air bubbles remain between the stream select valve and injection valve of stream ***," and the remedy: "Perform air purge maintenance and then perform air bubble detection maintenance again," and "If air bubbles remain, contact service personnel." Air purge maintenance is selected from the maintenance screen of the device's GUI. For this maintenance, a stream can be selected and an air purge can be performed for the relevant stream. After air purge maintenance, perform air bubble detection maintenance again to check for the presence of bubbles. The work up to this point can be performed by either the operator or service personnel. If air bubbles remain after air purging, service personnel should perform the following work.

[0038] Check the piping connection between the stream select valve 304 and the injection valve 207 for looseness. Disconnect the affected piping and reconnect it. ·Perform air bubble detection maintenance again and check for the presence of air bubbles. Replace the affected piping. Replace the stream select valve 304. Replace the injection valve 207. ·Perform air bubble detection maintenance again and check for the presence of air bubbles.

[0039] If air bubbles remain between the injection valve 207 and the auto-purge valve 205, the result and remedy (Remedy) are displayed on the maintenance screen. The maintenance screen displays the result: "Air bubbles remain between the injection valve and auto-purge valve of stream ***," and the remedy: "Perform air purge maintenance and then perform air bubble detection maintenance again," and "If air bubbles remain, contact service personnel." Air purge maintenance is selected from the maintenance screen of the device's GUI. For this maintenance, a stream can be selected and air purging can be performed for the relevant stream. After air purge maintenance, air bubble detection maintenance is performed again to check for the presence or absence of bubbles. The work up to this point can be performed by either the operator or service personnel. If air bubbles remain even after air purging, service personnel should perform the following work.

[0040] Check the piping connection between the injection valve 207 and the auto-purge valve 205 for looseness. Disconnect the affected piping and reconnect it. ·Perform air bubble detection maintenance again and check for the presence of air bubbles. Replace the affected piping. Replace the injection valve 207. Replace the auto purge valve 205. ·Perform air bubble detection maintenance again and check for the presence of air bubbles.

[0041] If air bubbles remain between the auto purge valve 205 and the liquid feed pump, the result and remedy (Remedy) are displayed on the maintenance screen. The maintenance screen displays the result: "Air bubbles remain between the auto purge valve and the liquid feed pump of stream ***," and the remedy: "Perform air purge maintenance and then perform air bubble detection maintenance again," and "If air bubbles remain, contact service personnel." Air purge maintenance is selected from the maintenance screen of the device's GUI. For this maintenance, a stream can be selected and air purging can be performed for the relevant stream. After air purge maintenance, perform air bubble detection maintenance again and check for the presence or absence of bubbles. The work up to this point can be performed by the operator or service personnel. If air bubbles remain even after air purging, service personnel will perform the following work.

[0042] Check for loose piping connections between the auto-purge valve 205 and the liquid feed pump. Disconnect the affected piping and reconnect it. ·Perform air bubble detection maintenance again and check for the presence of air bubbles. Replace the affected piping. Replace the auto purge valve 205. · Replace the pump head (replacement part) of the liquid transfer pump. ·Perform air bubble detection maintenance again and check for the presence of air bubbles.

[0043] The results of the air bubble detection maintenance, i.e., the information (ΔP1, ΔP2, ΔT) obtained when determining whether or not air bubbles remain in the flow path, are stored in a database in the CU (Computer Unit) 307. Figures 5 to 7 each show a graph 501 (601, 701) of the changes over time in the maintenance results stored in the database. As shown in Figures 5 to 7, the graph 501 (601, 701) plots the time (days) 502 (602, 702) of the changes over time and the deviation 503 (603, 703) of the maintenance result information (ΔP1, ΔP2, ΔT). 0% of the deviation is the average value of each predetermined value. Here, for example, a threshold value within ±7% of the deviation (dotted line in Figures 5 to 7) is set as the threshold value at which there is no possibility of air bubble generation. Based on the transition of the information on the changes over time in the deviation, if the deviation approaches the threshold value, even if it is within the threshold value, it can be diagnosed as the possibility of air bubble generation. Therefore, according to this embodiment, the above-mentioned information can be used to diagnose the possibility of bubble generation at an early stage, or to make such predictions at an early stage, and then perform maintenance work such as adjusting or replacing the liquid chromatograph 300 or its components.

[0044] The various controls described above are performed by the CU 307 (FIG. 1). The CU 307 may be a single device or may be composed of multiple devices. The CU 307 may be built into the liquid chromatograph 300 or may be provided externally to the liquid chromatograph 300.

[0045] Below, the differences between the prior art and the technology according to the present disclosure will be summarized once again. Patent Document 1 is configured to switch between directing the mobile phase from the liquid delivery system to a separation column or discharging it to a drain by switching a switching valve. It also states that a switching valve is not necessarily required to detect liquid delivery failure. On the other hand, the technology disclosed herein does not require discharging the mobile phase to a drain by switching a flow path switching valve, and instead uses the pressure fluctuations that occur when the pressure, which has decreased due to the rotation of the flow path switching valve, rises as an indicator. In other words, the technology disclosed herein and Patent Document 1 have different device components.

[0046] Furthermore, the technology disclosed herein can detect remaining air bubbles by using the pressure fluctuations that occur when the pressure that has dropped due to the rotation of the flow path switching valve rises as an indicator, making it possible to detect air bubbles remaining not only inside the liquid feed pump but also in the flow path between the liquid feed pump and the flow path switching valve. Furthermore, in a device having a configuration with multiple flow path switching valves, by using the pressure fluctuations that occur when the pressure that has dropped due to the rotation of each flow path switching valve rises as an indicator, it is possible to detect air bubbles remaining in the flow path from the liquid feed pump to the downstream flow path switching valve and in the flow paths between multiple flow path switching valves. In this way, the technology disclosed herein can determine the location of remaining air bubbles in the flow path.

[0047] Furthermore, the technology disclosed herein makes it possible to easily determine which flow paths contain residual air bubbles, even in complex device configurations. The series of steps for determining which flow paths contain residual air bubbles is automated, and an operator or service person selects and executes this maintenance item on the device's GUI screen. The pressure data obtained by executing this maintenance item is stored in a database, and by analyzing changes over time, it is possible to quickly diagnose or predict operational abnormalities or failures. Therefore, the technology disclosed herein allows for early maintenance work, such as adjustment or replacement of the liquid chromatograph 300 or its components.

[0048] The technology according to the present disclosure is not limited to the above-described embodiments and includes various modifications. For example, the above-described embodiments have been described in detail to clearly explain the technology according to the present disclosure, and are not necessarily limited to those including all of the described configurations. Furthermore, it is possible to replace part of the configuration of one embodiment with the configuration of another embodiment, or to add the configuration of another embodiment to the configuration of one embodiment. Furthermore, it is possible to add, delete, or replace part of the configuration of each embodiment with other configurations. [Explanation of symbols]

[0049] 201 First liquid delivery pump 202 Second liquid delivery pump 203 First pressure sensor 204 Second pressure sensor 205 Auto purge valve (flow path switching valve, first switching valve) 206 Three-way joint 207 Injection valve (flow path switching valve, first switching valve, second switching valve) 208 Shippa 209 Sample Holder 210 Syringe 211 Wastewater flow path 212 Column 213 First Channel 214 Second Channel 215 Third Channel 216 Sample Loop 300 Liquid Chromatograph 301 1st Stream 302 Second Stream 303 Third Stream 304 Stream Select Valve (Flow path switching valve, second switching valve) 305 Detector 501, 601, 701 graphs 502, 602, 702 Aging time (days) 503, 603, 703 deviation

Claims

1. A liquid delivery pump; A flow path connected to the liquid delivery pump; A plurality of streams are provided in the flow paths, each stream including at least a pressure sensor for detecting a pressure in the flow path and a separation column for separating components of a fluid flowing in the flow path; a flow path switching valve for selecting one of the plurality of streams to be used for analysis; A method for controlling a liquid chromatograph comprising: rotating the flow path switching valve while the liquid is being sent from the liquid sending pump, and determining a stream in which air bubbles remain in the flow path based on a pressure fluctuation when the pressure, which has been lowered by the rotation of the flow path switching valve, increases. A method for controlling a liquid chromatograph.

2. 2. A method for controlling a liquid chromatograph according to claim 1, comprising: Each of the plurality of streams includes a first switching valve located upstream with respect to a flow of a fluid, and a second switching valve connected downstream of the first switching valve via the flow path, Based on the pressure fluctuation when the first switching valve is rotated and the pressure fluctuation when the second switching valve is rotated, determining whether or not air bubbles remain in a flow path from the liquid feed pump to the first switching valve, and whether or not air bubbles remain in a flow path from the first switching valve to the second switching valve; A method for controlling a liquid chromatograph.

3. A method for controlling a liquid chromatograph according to claim 2, comprising the steps of: The time lag to return to the specified pressure is used as the judgment criterion. A method for controlling a liquid chromatograph.

4. A method for controlling a liquid chromatograph according to claim 2, comprising the steps of: This can be done during both operation and maintenance. A method for controlling a liquid chromatograph.

5. A method for controlling a liquid chromatograph according to claim 2, comprising the steps of: information obtained when it is determined whether or not air bubbles remain in the flow path is stored in a database, and the possibility of air bubble generation is diagnosed based on the information. A method for controlling a liquid chromatograph.

6. A method for controlling a liquid chromatograph according to claim 2, comprising the steps of: The first switching valve is an auto-purge valve, and the second switching valve is an injection valve. A method for controlling a liquid chromatograph.

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