Liquid chromatograph and liquid delivery method

Abstract

This liquid chromatograph comprises a supply pipe for connecting a liquid feeding device and liquid storage container, a circulation pipe for connecting an intermediate part of the supply pipe and the liquid storage container, a flow path switching valve that is provided at the part where the supply pipe and circulation pipe are connected and is for selectively switching to a liquid feeding state in which flow between the liquid storage container side and liquid feeding device side of the supply pipe is allowed or a circulation state in which flow between the liquid storage container side of the supply pipe and the circulation pipe is allowed, a bubble detection device that is provided in a part of the supply pipe between the liquid storage container and flow path switching valve, and a circulation liquid feeding device provided in the circulation pipe. A control device switches the flow path switching valve to the circulation state, causes the circulation liquid feeding device to carry out circulation liquid feeding, and then switches the flow path switching valve to the liquid feeding state after the bubble detection device stops detecting bubbles in the liquid. As a result, it is possible to more simply and reliably remove bubbles introduced during mobile phase placement or replacement work.

Description

[Technical field]

[0001] The present invention relates to a liquid chromatograph and a liquid delivery method. [Background technology]

[0002] A liquid chromatograph (LC) separates the liquid sample to be measured into its individual components by pumping a liquid mobile phase through a column packed with a packing material (stationary phase), and then detects the separated components using a detector connected downstream, such as an ultraviolet-visible absorption spectrometer, a fluorometer, or a mass spectrometer.

[0003] In liquid chromatography, the mobile phase delivered from the liquid delivery device to the column plays a role in separating the sample to be measured into its components due to differences in affinity with the stationary phase packed in the column as the sample is transported. In liquid chromatography, various types of mobile phases, such as ultrapure water, organic solvents, and buffer solvents, are selected according to the purpose of measurement and the type of liquid sample.

[0004] The properties of the mobile phase used in liquid chromatography can have a significant effect on the measurement results. For example, air bubbles mixed into the mobile phase can be transported to the liquid delivery device or the flow path downstream of the liquid delivery device, which can significantly reduce the accuracy of the measurement results.

[0005] Air bubbles may be mixed into the mobile phase, for example, when an operator replaces a mobile phase supply bottle, supplies a mobile phase, etc. The causes of air bubbles being mixed into the mobile phase include not only the operator's overlooking of air bubbles or operational mistakes, but also the operator's lack of operational experience, the installation environment of the device, the type of mobile phase used, etc. Therefore, even if the operator proceeds with the work with the utmost care to prevent air bubbles from being mixed into the supply tube, it is difficult to completely eliminate the possibility of air bubbles being mixed into the mobile phase.

[0006] Therefore, regardless of whether or not air bubbles are mixed into the mobile phase, it is preferable to carry out a process for removing air bubbles after replacing the mobile phase supply bottle or after performing a mobile phase supply operation.

[0007] Known technology for removing bubbles mixed in a mobile phase is, for example, that described in Patent Document 1. Patent Document 1 discloses a degassing and liquid delivery device that has, from upstream to downstream, at least a degassing mechanism for removing gas from liquid, a liquid delivery mechanism for delivering liquid, and a branching section that branches into multiple flow paths, in that order, and that has a junction section where one of the multiple flow paths branched by the branching section joins upstream of the degassing mechanism. [Prior art documents] [Patent documents]

[0008] [Patent Document 1] JP 2014-62827 A Summary of the Invention [Problem to be solved by the invention]

[0009] In the above-mentioned conventional technology, a degassing mechanism is disposed on the liquid delivery path of the mobile phase, and the mobile phase is repeatedly passed through the degassing mechanism to remove air bubbles mixed in the mobile phase and reduce the amount of dissolved air in the mobile phase. However, it is difficult to judge whether air bubbles mixed in the mobile phase have been sufficiently removed, and if the operator has low skill, it is considered that degassing may be performed for an unnecessarily long time or may be insufficient.

[0010] The present invention has been made in consideration of the above, and has an object to provide a liquid chromatograph and a liquid delivery method that can more easily and reliably remove air bubbles that are mixed in during mobile phase installation or replacement work. [Means for solving the problem]

[0011] The present application includes a number of means for solving the above problems. One example of such a means is a liquid chromatograph including a separation column incorporating a stationary phase, a liquid delivery device for delivering a liquid that is a mobile phase to the separation column, a sample injection device for injecting a sample to be analyzed into the liquid delivered from the liquid delivery device to the separation column, a liquid supply device for supplying the liquid to the liquid delivery device, and a control device for controlling the operation of the liquid delivery device and the liquid supply device. The liquid supply device includes a liquid storage container for storing the liquid to be delivered to the liquid delivery device, a supply pipe connecting the liquid delivery device and the liquid storage container, a circulation pipe connecting the middle of the supply pipe to the liquid storage container and returning the liquid delivered through the supply pipe to the liquid storage container, and a connection between the supply pipe and the circulation pipe. a flow path switching valve provided in a supply section for selectively switching between a liquid delivery state in which flow is passed through the supply piping on the liquid storage container side and the liquid delivery device side, and a circulation state in which flow is passed through the supply piping on the liquid storage container side and the circulation piping; an air bubble detection device provided in the supply piping between the liquid storage container and the flow path switching valve for detecting the presence or absence of air bubbles in the liquid delivered through the supply piping; and a circulating liquid delivery device provided in the circulation piping for delivering the liquid from the flow path switching valve side to the liquid storage container side, and the control device switches the flow path switching valve to the circulation state to perform circulating liquid delivery by the circulating liquid delivery device, and when air bubbles in the liquid are no longer detected by the air bubble detection device, switches the flow path switching valve to the liquid delivery state. Effect of the Invention

[0012] An object of the present invention is to provide a liquid chromatograph and a liquid delivery method that can more easily and reliably remove air bubbles that are mixed in during installation or replacement of a mobile phase. [Brief description of the drawings]

[0013] [Figure 1] 1 is a diagram illustrating an overall configuration of a liquid chromatograph analyzer according to a first embodiment. [Diagram 2]5 is a flowchart showing the operation of the liquid supply device according to the first embodiment. [Diagram 3] FIG. 1 is a diagram illustrating an overall configuration of a liquid chromatograph according to a second embodiment. [Figure 4] 10 is a flowchart showing the operation of a liquid supplying apparatus according to a second embodiment. [Diagram 5] FIG. 13 is a diagram illustrating an overall configuration of a liquid chromatograph according to a third embodiment. [Figure 6] FIG. 13 is a diagram illustrating an overall configuration of a liquid chromatograph according to a third embodiment. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0014] Hereinafter, an embodiment of the present invention will be described with reference to the drawings.

[0015] In this embodiment, a liquid chromatograph (LC: Liquid Chromatograph) will be described as an example of a chromatograph, but the present invention is not limited to this, and can be applied to other chromatographs such as a high performance liquid chromatograph (HPLC: High Performance Liquid Chromatograph) and an ultra-high performance liquid chromatograph (UHPLC: Ultra-High Performance Liquid Chromatograph).

[0016] <First embodiment> A first embodiment of the present invention will be described in detail with reference to FIGS.

[0017] FIG. 1 is a diagram showing a schematic overall configuration of a liquid chromatograph analyzer according to the present embodiment.

[0018] In FIG. 1, the liquid chromatograph 100 includes a liquid supplying device 110 that supplies a solvent that serves as a mobile phase, a separation column 140 that contains a stationary phase, a liquid delivery device (liquid delivery pump) 120 that delivers the liquid (solvent) that serves as the mobile phase to the separation column 140, a sample injection device 130 that injects a sample to be analyzed into the liquid delivered from the liquid delivery device 120 to the separation column, the liquid supplying device 110 that supplies the liquid that serves as the solvent to the liquid delivery device 120, and an analysis device that analyzes the sample that has passed through the separation column 140. analysis device 150, a liquid supply device 110, a liquid delivery device 120, and analysis and a control device 160 that controls the overall operation of the liquid chromatograph analysis device 100 including the device 150. The separation column 140 is housed in a constant temperature control device 141.

[0019] The control device 160 has input devices (such as a keyboard and a mouse) and output devices (such as a display device such as a monitor and a printer) that are not shown. Note that the input devices and output devices provided in the control device 160 may be devices that have both an input function and a display function, such as a touch panel.

[0020] The liquid supply device 110 includes a liquid storage container 111 for storing a liquid (solvent) to be supplied to the liquid delivery device 120, supply pipes 112, 117 connecting the liquid delivery device 120 and the liquid storage container 111, a circulation pipe 114 which connects the middle of the supply pipes 112, 117 (i.e., the connection between the supply pipe 112 on the liquid storage container 111 side and the supply pipe 117 on the liquid delivery device 120 side) to the liquid storage container 111 and returns the liquid delivered from the supply pipe 112 on the liquid storage container 111 side to the liquid storage container 111, and a supply pipe 114 which is provided at the connection between the supply pipes 112, 117 and the circulation pipe 114 and returns the liquid delivered from the supply pipe 112 on the liquid storage container 111 side to the liquid storage container 111, The system is equipped with a flow path switching valve 116 that selectively switches between a liquid delivery state in which flow is made through the tube 112 and the supply piping 117 on the liquid delivery device 120 side, and a circulation state in which flow is made through the supply piping 112 on the liquid storage container 111 side and the circulation piping 114, an air bubble detection device (air bubble detection sensor) 113 that is provided between the liquid storage container 111 of the supply piping 112 and the flow path switching valve 116 and detects the presence or absence of air bubbles in the liquid delivered through the supply piping 112, and a circulating liquid delivery device (circulating liquid delivery pump) 115 that is provided in the circulation piping 114 and delivers liquid from the flow path switching valve 116 side to the liquid storage container 111 side.

[0021] The supply pipe 112 is disposed such that its upstream end is located near the bottom of the liquid storage container 111. Moreover, the circulation pipe 114 is provided such that its downstream end is located higher in the liquid storage container 111 than the upstream end of the supply pipe 112.

[0022] In the liquid delivery state, the flow path switching valve 116 connects the supply pipe 112 to the supply pipe 117, and disconnects the supply pipes 112, 117 from the circulation pipe 114. In this state, the liquid delivery device 120 is driven, so that the liquid in the liquid storage container 111 is sucked up into the liquid delivery device 120 via the supply pipes 112, 117 and delivered to the downstream side (the sample injection device 130 side).

[0023] In addition, in the circulation state, the flow path switching valve 116 is connected between the supply pipe 112 and the circulation pipe 114and disconnects the supply pipe 112 and the circulation pipe 114 from the supply pipe 117. In this state, the circulating liquid sending device 115 is driven, so that the liquid in the liquid storage container 111 is sucked up into the circulating liquid sending device 115 via the supply pipe 112 and the circulation pipe 114, and is sent back to the liquid storage container 111.

[0024] FIG. 2 is a flowchart showing the operation of the liquid supplying apparatus.

[0025] In FIG. 2, after an operator performs work such as replacing the liquid storage container 111, the control device 160 instructs the start of the bubble discharge process using its input device (step S100). The control device 160 first switches the flow path switching valve 116 to a circulation state to bring the supply piping 112 and the circulation piping 114 into a flow-through state (step S110), and then drives the circulation liquid delivery device 115 to suck up the liquid in the liquid storage container 111 through the supply piping 112 and the circulation piping 114 and deliver it to the liquid storage container 111 (step S120).

[0026] At this time, since the liquid in the liquid storage container 111 is circulated via the supply pipe 112 and the circulation pipe 114, air bubbles mixed in the solution inside the supply pipe 112 and the circulation pipe 114 are removed by being discharged into the liquid storage container 111. That is, even if air bubbles have mixed in the solution in the supply pipe 112 due to, for example, the replacement work of the liquid storage container 111, the air bubbles can be removed.

[0027] Next, when a predetermined volume of liquid is delivered by the circulating liquid delivery device 115, it is determined whether or not air bubbles are detected by the air bubble detection device 113 (step S130), and if the determination result is NO, that is, if air bubbles are mixed in the liquid flowing from the liquid storage container 111 through the supply pipe 112, delivery of the liquid by the circulating liquid delivery device 115 is continued until the determination result of step S130 becomes YES. The volume of the liquid delivered by the circulating liquid delivery device 115 can be calculated from the delivery capacity per unit time of the circulating liquid delivery device 115 and the elapsed time.

[0028] Furthermore, if the judgment result in step S130 is YES, i.e., if no air bubbles are mixed in the liquid flowing from the liquid storage container 111 through the supply pipe 112, the circulating liquid delivery device 115 is stopped (step S140), the flow path switching valve 116 is switched to a supply state, the supply pipes 112, 117 are put into a flowing state (step S150), and the end of the bubble discharge process is notified to the operator via a display device or the like of the control device 160 (step S160), and the processing is terminated.

[0029] Furthermore, if the bubble detection device 113 detects air bubbles during an analysis operation or the like performed by driving the liquid delivery device 120 after the bubble discharge process is completed, it may determine that the liquid stored in the liquid storage container 111 has fallen below a specified amount (in this case, the liquid level has dropped to a position below the end of the supply piping 112), stop the liquid delivery device 120, and prompt the operator to replace the liquid storage container 111.

[0030] The effects of the present embodiment configured as above will be described.

[0031] In conventional techniques, it is difficult to determine whether air bubbles mixed in the mobile phase have been sufficiently removed, and if the operator is not very skilled, degassing may be performed for an unnecessarily long time or may be insufficient.

[0032] In contrast, in this embodiment, liquid supply device 110 comprises liquid storage container 111 for storing liquid (solvent) to be supplied to liquid delivery device 120, supply pipes 112, 117 connecting liquid delivery device 120 and liquid storage container 111, circulation pipe 114 connecting the middle of supply pipes 112, 117 (i.e., the connection between supply pipe 112 on the liquid storage container 111 side and supply pipe 117 on the liquid delivery device 120 side) to liquid storage container 111 and returning liquid delivered from supply pipe 112 on the liquid storage container 111 side to liquid storage container 111, and a liquid delivery state in which liquid is passed through supply pipe 112 on the liquid storage container 111 side and supply pipe 117 on the liquid delivery device 120 side, and a liquid delivery state in which liquid is passed through supply pipe 112 on the liquid storage container 111 side and circulation pipe 114. the flow path switching valve 116 selectively switches between a circulation state and a circulating state in which the liquid is circulated, an air bubble detection device (air bubble detection sensor) 113 is provided between the liquid storage container 111 of the supply piping 112 and the flow path switching valve 116 and detects the presence or absence of air bubbles in the liquid being pumped through the supply piping 112, and a circulating liquid delivery device (circulating liquid delivery pump) 115 is provided in the circulation piping 114 and delivers liquid from the flow path switching valve 116 side to the liquid storage container 111 side. When the flow path switching valve 116 is switched to the circulation state and circulating liquid delivery is performed by the circulating liquid delivery device 115, and when air bubbles in the liquid are no longer detected by the air bubble detection device 113, the flow path switching valve 116 is switched back to the liquid delivery state, air bubbles in the mobile phase can be removed more easily and reliably regardless of the skill of the operator.

[0033] <Second embodiment> A second embodiment of the present invention will be described in detail with reference to FIGS.

[0034] In this embodiment, a plurality of liquid storage containers are configured to be switched depending on the remaining amount of liquid.

[0035] 3 is a diagram showing the overall configuration of a liquid chromatograph according to this embodiment, in which the same members as those in the first embodiment are given the same reference numerals and their explanations are omitted.

[0036] In FIG. 3, the liquid chromatograph 100A includes a liquid supplying device 110A that supplies a solvent that is a mobile phase, a separation column 140 that contains a stationary phase, a liquid delivery device (liquid delivery pump) 120 that delivers the liquid (solvent) that is the mobile phase to the separation column 140, a sample injection device 130 that injects a sample to be analyzed into the liquid delivered from the liquid delivery device 120 to the separation column, a liquid supplying device 110 that supplies the liquid that is the solvent to the liquid delivery device 120, and a sample analyzer 130 that analyzes the sample that has passed through the separation column 140. analysis device 150, a liquid supply device 110, a liquid delivery device 120, and analysis and a control device 160 that controls the overall operation of the liquid chromatograph analysis device 100 including the device 150. The separation column 140 is housed in a constant temperature control device 141.

[0037] The liquid supply device 110A includes, in addition to the liquid storage container 111, supply pipes 112, 117 (117a), circulation pipe 114, flow path switching valve 116, air bubble detection device 113, and circulation liquid sending device 115 described in the first embodiment, a liquid storage container 211 that stores a liquid (solvent) to be supplied to the liquid sending device 120, a supply pipe 117 (117b) that connects the liquid sending device 120 and the liquid storage container 211, and a pipe (pipe) intermediate (intermediate) between the supply pipes 212, 117b. That is, a circulation pipe 214 that connects the liquid storage container 211 to the connection portion of the supply pipe 212 on the liquid storage container 211 side and the supply pipe 117b on the liquid delivery device 120 side and returns the liquid delivered from the supply pipe 212 on the liquid storage container 211 side to the liquid storage container 211, and a liquid delivery state that is provided at the connection portion of the supply pipes 212, 117b and the circulation pipe 214 and allows a liquid to flow between the supply pipe 212 on the liquid storage container 211 side and the supply pipe 117b on the liquid delivery device 120 side. a flow path switching valve 216 that selectively switches between a supply state in which the liquid is passed through the supply pipe 212 on the liquid storage container 211 side and a circulation state in which the liquid is passed through the circulation pipe 214; an air bubble detection device (air bubble detection sensor) 213 that is provided between the liquid storage container 211 of the supply pipe 212 and the flow path switching valve 216 and detects the presence or absence of air bubbles in the liquid being sent through the supply pipe 212; The liquid supply system is equipped with a circulating liquid supply device (circulating liquid supply pump) 215 that supplies the liquid, and a liquid supply flow path switching valve 218 that is provided at the branching point of supply pipes 117a, 117b of supply pipe 117 and selectively switches between a first liquid supply state in which supply pipe 117 is caused to flow to the liquid storage container 111 side (i.e., supply pipe 117a side) and a second liquid supply state in which supply pipe 117 is caused to flow to the liquid storage container 211 side (i.e., supply pipe 117b side).

[0038] The supply pipe 212 is disposed such that its upstream end is located near the bottom of the liquid storage container 211. In addition, the circulation pipe 214 is provided such that its downstream end is located higher in the liquid storage container 211 than the upstream end of the supply pipe 212.

[0039] In the liquid delivery state, the flow path switching valve 216 connects the supply pipe 212 to the supply pipe 117b, and blocks the connection between the supply pipes 212, 117b and the circulation pipe 214. When the liquid delivery flow path switching valve 218 is switched to the second liquid delivery state, the liquid delivery device 120 is driven, and the liquid in the liquid storage container 211 is sucked up into the liquid delivery device 120 via the supply pipes 212, 117b and delivered to the downstream side (the sample injection device 130 side).

[0040] In addition, in the circulation state, the flow path switching valve 216 is connected between the supply pipe 212 and the circulation pipe 213. 214 and disconnects the supply pipe 212 and the circulation pipe 214 from the supply pipe 117b. In this state, the circulating liquid sending device 215 is driven, so that the liquid in the liquid storage container 211 is sucked up into the circulating liquid sending device 215 via the supply pipe 212 and the circulation pipe 214, and is sent back to the liquid storage container 211.

[0041] In a first liquid delivery state, the liquid delivery flow path switching valve 218 allows flow through the supply piping 117 to the liquid storage container 111 side (i.e., the supply piping 117a side) to enable liquid to be supplied from the liquid storage container 111 to the liquid delivery device 120, and in a second liquid delivery state, allows flow through the supply piping 117 to the liquid storage container 211 side (i.e., the supply piping 117b side) to enable liquid to be supplied from the liquid storage container 111 to the liquid delivery device 120.

[0042] FIG. 4 is a flowchart showing the operation of the liquid supplying device of the present embodiment.

[0043] First, consider a case where, as an initial state, the liquid sending flow path switching valve 218 is in the first liquid sending state and liquid (solvent) is being supplied from the liquid storage container 111 to the liquid sending device 102. Also, at this time, it is assumed that air bubbles have been removed in advance from within the supply pipe 212 of the liquid storage container 211 and the liquid storage container 211 is in a standby state.

[0044] In FIG. 4, when the bubble detection device 113 detects an air bubble while performing an analysis operation or the like by driving the liquid delivery device 120, that is, when it detects that the remaining amount of liquid stored in the liquid storage container 111 is less than a predetermined amount (step S170), it switches the liquid delivery flow path switching valve 218 to the second liquid delivery state to start supplying liquid from the waiting liquid storage container 211 to the liquid delivery device 120 (step S180), and notifies the operator via a display device or the like of the control device 160 that the liquid storage container 111 needs to be replaced (step S190).

[0045] After the operator has performed the replacement work for the liquid storage container 111, the control device 160 instructs the start of the bubble discharge process using its input device (step S200). The control device 160 first switches the flow path switching valve 116 to a circulation state to bring the supply piping 112 and the circulation piping 114 into a flow-through state (step S210), and then drives the circulation liquid delivery device 115 to suck up the liquid in the liquid storage container 111 through the supply piping 112 and the circulation piping 114 and deliver it to the liquid storage container 111 (step S220).

[0046] At this time, since the liquid in the liquid storage container 111 is circulated via the supply pipe 112 and the circulation pipe 114, air bubbles mixed in the solution inside the supply pipe 112 and the circulation pipe 114 are removed by being discharged into the liquid storage container 111. That is, even if air bubbles have mixed in the solution in the supply pipe 112 due to, for example, the replacement work of the liquid storage container 111, the air bubbles can be removed.

[0047] Next, when a predetermined volume of liquid is delivered by the circulating liquid delivery device 115, it is determined whether or not air bubbles are detected by the air bubble detection device 113 (step S230), and if the determination result is NO, that is, if air bubbles are mixed in the liquid flowing from the liquid storage container 111 through the supply pipe 112, delivery of the liquid by the circulating liquid delivery device 115 is continued until the determination result of step S230 becomes YES. The volume of the liquid delivered by the circulating liquid delivery device 115 can be calculated from the delivery capacity per unit time of the circulating liquid delivery device 115 and the elapsed time.

[0048] Furthermore, if the judgment result in step S230 is YES, i.e., if no air bubbles are mixed in the liquid flowing from the liquid storage container 111 through the supply pipe 112, the circulating liquid delivery device 115 is stopped (step S240), the flow path switching valve 116 is switched to the supply state to place the supply pipes 112, 117a in a flowing state (step S250), and the end of the bubble discharge process is notified to the operator via a display device or the like of the control device 160 (step S260), and the processing is terminated.

[0049] As a result, the liquid sending flow path switching valve 218 is in the second liquid sending state, liquid (solvent) is being supplied from the liquid storage container 211 to the liquid sending device 102, and air bubbles are removed from the supply pipe 112 of the liquid storage container 111, resulting in a standby state. Then, when the amount of liquid in the liquid storage container 211 becomes less than a predetermined amount, the liquid sending flow path switching valve 218 is switched to supply liquid from the liquid storage container 111 to the liquid sending device 120 by a similar operation, and the liquid storage container 211 is replaced and a bubble removal process is performed to return to a standby state, thereby allowing multiple (here, two) liquid storage containers 111, 211 to be alternately switched. In other words, the analysis operation can be continued without waiting for the replacement of the liquid storage container.

[0050] The other configurations are similar to those of the first embodiment.

[0051] In the present embodiment configured as above, the same advantages as those in the first embodiment can be obtained.

[0052] Furthermore, the analysis operation can be continued without waiting for replacement of the liquid storage container, and the throughput of the analysis results can be improved.

[0053] In this embodiment, it is determined that the liquid storage container 111, 211 has become less than a predetermined capacity by detecting air bubbles with the air bubble detection device 113, 213. However, this is not limited to this, and other possible methods may be used, such as a method in which the control device 160 calculates the remaining amount of the liquid storage container 111, 211 from the set flow rate and liquid delivery time of the liquid delivery device 120, a method in which a weight sensor is placed at the installation portion of each liquid storage container to determine the remaining amount of liquid (solvent) by weight, or a method in which a liquid level sensor is inserted into the liquid storage container to detect the remaining amount of liquid (solvent).

[0054] <Third embodiment> A third embodiment of the present invention will be described in detail with reference to FIGS.

[0055] This embodiment uses a flow path switching valve that combines the functions of the liquid sending flow path switching valve and the switching valve in the second embodiment.

[0056] 5 and 6 are diagrams showing the overall configuration of a liquid chromatograph according to this embodiment. In the drawings, the same members as those in the first and second embodiments are given the same reference numerals, and the description thereof will be omitted.

[0057] 5 and 6, the liquid chromatograph 100B includes a liquid supplying device 110B that supplies a solvent that is a mobile phase, a separation column 140 that contains a stationary phase, a liquid delivery device (liquid delivery pump) 120 that delivers the liquid (solvent) that is the mobile phase to the separation column 140, a sample injection device 130 that injects a sample to be analyzed into the liquid delivered from the liquid delivery device 120 to the separation column, a liquid supplying device 110 that supplies the liquid that is the solvent to the liquid delivery device 120, and a sample injection device 130 that analyzes the sample that has passed through the separation column 140. analysis device 150, a liquid supply device 110, a liquid delivery device 120, and analysis and a control device 160 that controls the overall operation of the liquid chromatograph analysis device 100 including the device 150. The separation column 140 is housed in a constant temperature control device 141.

[0058] 5 and 6, the functions of the flow path switching valves 116 and 216 and the liquid sending flow path switching valve 218 shown in the second embodiment are integrated into a flow path switching valve 318.

[0059] The flow path switching valve 318 has five ports 318a to 318e, with the supply pipe 117 connected to the liquid delivery device 120 connected to port 318a, the supply pipe 112 connected to the liquid storage container 111 connected to port 318b, the circulation pipe 114 connected to the liquid storage container 111 connected to port 318c, the supply pipe 212 connected to the liquid storage container 211 connected to port 318d, and the circulation pipe 214 connected to the liquid storage container 211 connected to port 318e.

[0060] When the flow path switching valve 318 is switched to the position shown in FIG. 5, the supply pipes 112, 117 are in a flow-through state (i.e., this corresponds to the case in the second embodiment where the flow path switching valve 116 is in a liquid delivery state and the liquid delivery flow path switching valve 218 is in a first liquid delivery state), and the supply pipe 212 and the circulation pipe 214 are in a flow-through state (i.e., this corresponds to the case in the second embodiment where the flow path switching valve 216 is in a circulation state).

[0061] Furthermore, when the flow path switching valve 318 is switched to the position shown in FIG. 6, the supply pipes 212, 117 are in a flow-through state (i.e., this corresponds to the case in the second embodiment where the flow path switching valve 216 is in a liquid delivery state and the liquid delivery flow path switching valve 218 is in a second liquid delivery state), and the supply pipe 112 and the circulation pipe 114 are in a flow-through state (i.e., this corresponds to the case in the second embodiment where the flow path switching valve 116 is in a circulation state).

[0062] That is, the switching functions of the flow path switching valves 116, 216 and the liquid sending flow path switching valve 218 in the second embodiment can be integrally realized by only switching the flow path switching valve 318 in this embodiment.

[0063] The other configurations are similar to those of the first and second embodiments.

[0064] The present embodiment configured as above can also provide the same effects as the first and second embodiments.

[0065] <Additional Notes> The present invention is not limited to the above-described embodiments, and includes various modifications and combinations within the scope of the gist of the present invention. The present invention is not limited to those having all the configurations described in the above-described embodiments, and includes those in which some of the configurations are deleted. The above-described configurations, functions, etc. may be realized by designing some or all of them as an integrated circuit, for example. The above-described configurations, functions, etc. may be realized by software, in which a processor interprets and executes a program that realizes each function. [Explanation of symbols]

[0066] 100, 100A, 100B... liquid chromatograph analysis apparatus, 102... liquid delivery device, 110... liquid supply device, 110A, 110B... liquid supply device, 111... liquid storage container, 112... supply piping, 113... air bubble detection device (air bubble detection sensor), 114... circulation piping, 115... circulation liquid delivery device (circulation liquid delivery pump), 116... flow path switching valve, 117... supply piping, 117a, 117b... supply piping, 120... liquid delivery device (liquid delivery pump), 130... sample injection device, 140... separation column, 141... constant temperature control device, 150... analysis device, 160... control device, 211... liquid storage container, 212... supply piping, 213... bubble detection device (bubble detection sensor), 214... circulation piping, 215... circulating liquid delivery device (circulating liquid delivery pump), 216... flow path switching valve, 218... liquid delivery flow path switching valve, 318... flow path switching valve, 318a to 318e... ports

Claims

1. A separation column incorporating a stationary phase; A liquid delivery device that delivers a liquid that is a mobile phase to the separation column; a sample injection device that injects a sample to be analyzed into the liquid sent from the liquid sending device to the separation column; a liquid supplying device for supplying the liquid to the liquid delivery device; A liquid chromatograph including a control device for controlling operations of the liquid delivery device and the liquid supply device, The liquid supply device includes: a liquid storage container that stores the liquid to be supplied to the liquid delivery device; A supply pipe connecting the liquid delivery device and the liquid storage container; a circulation pipe that connects a middle portion of the supply pipe to the liquid storage container and returns the liquid delivered through the supply pipe to the liquid storage container; a flow path switching valve provided at a connection between the supply pipe and the circulation pipe, selectively switching between a liquid delivery state in which the supply pipe on the liquid storage container side and the supply pipe on the liquid delivery device side are caused to flow, and a circulation state in which the supply pipe on the liquid storage container side and the circulation pipe are caused to flow; an air bubble detection device provided in the supply pipe between the liquid storage container and the flow path switching valve, the air bubble detection device detecting the presence or absence of air bubbles in the liquid being delivered through the supply pipe; a circulation liquid delivery device that is provided in the circulation piping and delivers the liquid from the flow path switching valve side to the liquid storage container side, The control device switches the flow path switching valve to the circulation state, performs circulatory liquid delivery using the circulating liquid delivery device, and switches the flow path switching valve to the liquid delivery state when air bubbles in the liquid are no longer detected by the bubble detection device.

2. 2. The liquid chromatograph according to claim 1, The liquid supply device includes: Another liquid storage container that stores the liquid to be supplied to the liquid delivery device; Another supply pipe connecting the supply pipe between the liquid delivery device and the flow path switching valve and the other liquid storage container; another circulation pipe that connects a midpoint of the other supply pipe to the other liquid storage container and returns the liquid sent through the other supply pipe to the other liquid storage container; a flow path switching valve provided at a connection between the other supply pipe and the other circulation pipe, selectively switching between a liquid delivery state in which the other liquid storage container side and the other supply pipe on the liquid delivery device side are caused to flow, and a circulation state in which the other liquid storage container side and the other supply pipe on the other liquid storage container side are caused to flow; and another air bubble detection device provided between the other liquid storage container and the other flow path switching valve of the other supply pipe, detecting the presence or absence of air bubbles in the liquid being delivered through the other supply pipe; Another circulation liquid delivery device is provided in the other circulation pipe and delivers the liquid from the other flow path switching valve side to the other liquid storage container side; a liquid delivery flow path switching valve provided at a connection between the supply pipe and the other supply pipe, selectively switching between a first liquid delivery state in which the supply pipe on the liquid storage container side and the supply pipe on the liquid delivery device side are caused to flow and a second liquid delivery state in which the other supply pipe on the other liquid storage container side and the supply pipe on the liquid delivery device side are caused to flow, The liquid chromatograph is characterized in that when the control device detects that the remaining amount of liquid stored in the liquid storage container is less than a predetermined amount while the liquid delivery path switching valve is in the first liquid delivery state, the control device switches the liquid delivery path switching valve to the second liquid delivery state.

3. 2. The liquid chromatograph according to claim 1, The liquid supply device includes: Another liquid storage container that stores the liquid to be supplied to the liquid delivery device; Another supply pipe connecting the flow path switching valve and the other liquid storage container; Another circulation pipe that connects the flow path switching valve and the other liquid storage container and returns the liquid sent through the other supply pipe to the other liquid storage container; Another air bubble detection device is provided between the other liquid storage container of the other supply pipe and the flow path switching valve, and detects the presence or absence of air bubbles in the liquid being delivered through the other supply pipe; a second circulation liquid delivery device provided in the second circulation pipe and configured to deliver the liquid from the flow path switching valve side to the second liquid storage container side; the flow path switching valve is capable of selectively switching between a first liquid supply / circulation state in which liquid is passed between the liquid storage container side and the supply piping on the liquid delivery device side and between the other supply piping on the other liquid storage container side and the other circulation piping, and a second liquid supply / circulation state in which liquid is passed between the other supply piping and the supply piping on the liquid delivery device side and between the supply piping on the liquid storage container side and the circulation piping, The liquid chromatograph is characterized in that when the control device detects that the remaining amount of liquid stored in the liquid storage container is less than a predetermined amount while the flow path switching valve is in the first liquid circulation state, the control device switches the flow path switching valve to the second liquid circulation state.

4. A separation column incorporating a stationary phase; A liquid delivery device that delivers a liquid that is a mobile phase to the separation column; a sample injection device that injects a sample to be analyzed into the liquid sent from the liquid sending device to the separation column; a liquid supplying device for supplying the liquid to the liquid delivery device; A liquid delivery method for a liquid chromatograph including the liquid delivery device and a control device for controlling the operation of the liquid supply device, comprising: A step of circulating the liquid stored in a liquid storage container by sending the liquid from a supply pipe to the liquid storage container via a circulation pipe; supplying the liquid stored in the liquid storage container to the liquid delivery device via the supply pipe when there are no more air bubbles in the liquid delivered through the circulation pipe; A liquid delivery method for a liquid chromatograph, comprising:

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