Liquid chromatograph and liquid delivery method

Abstract

A liquid chromatograph of the present application includes: a supply pipe connecting a liquid feeding device and a liquid storage container; a circulation pipe connecting a middle of the supply pipe and the liquid storage container; a flow path switching valve provided at a connection portion of the supply pipe and the circulation pipe, which selectively switches either of a liquid feeding state in which the supply pipe on the liquid storage container side and the liquid feeding device side is made to flow, and a circulation state in which the supply pipe on the liquid storage container side and the circulation pipe are made to flow; a bubble detection device provided between the liquid storage container and the flow path switching valve in the supply pipe; and a circulation liquid feeding device provided at the circulation pipe, and a control device switches the flow path switching valve to the circulation state, performs circulation liquid feeding using the circulation liquid feeding device, and switches the flow path switching valve to the liquid feeding state in a case where no bubble of the liquid is detected by the bubble detection device. Thus, bubbles mixed at the time of setting or replacing a mobile phase can be removed more easily and reliably.

Description

Technical Field

[0001] This invention relates to a liquid chromatograph and a liquid delivery method. Background Technology

[0002] Liquid chromatography (LC) separates liquid samples into components by delivering a liquid mobile phase to a column packed with a stationary phase. The separated components are then detected using detectors such as UV / Vis spectrophotometers, fluorometers, and mass spectrometers connected in subsequent stages.

[0003] In a liquid chromatograph, the mobile phase delivered from the delivery device to the column serves the following purpose: accompanying the transport of the analyte sample, it separates the sample into individual components based on the difference in affinity between the mobile phase and the stationary phase packed into the column. In a liquid chromatograph, various mobile phases, such as ultrapure water, organic solvents, and buffer solvents, are selected depending on the purpose of the assay and the type of liquid sample.

[0004] The mobile phase used in liquid chromatography can significantly affect the measurement results depending on its properties. For example, consider the following scenario: air bubbles mixed into the mobile phase are transported to the delivery device or downstream of the delivery device, resulting in a significant reduction in the accuracy of the measurement results.

[0005] For example, air bubbles may enter the mobile phase during operations such as changing the mobile phase supply bottle or supplying the mobile phase. The main reasons for air bubble entry include not only operator oversight or operational errors, but also insufficient operator experience, the equipment's environment, and the type of mobile phase used. Therefore, even with careful operation to prevent air bubbles from entering the supply line, it is difficult to completely eliminate the possibility of air bubble entry.

[0006] Therefore, regardless of whether air bubbles are mixed into the mobile phase, it is preferable to perform the air bubble removal process after the mobile phase supply bottle is changed or after the mobile phase supply operation.

[0007] As a technique for removing bubbles mixed into the mobile phase, the technique described in Patent Document 1 is known, for example. Patent Document 1 discloses a degassing and liquid delivery device, which, from upstream to downstream, at least sequentially includes a degassing mechanism for removing gas from a liquid, a liquid delivery mechanism for delivering liquid, and a branch section that divides into multiple flow paths, and has a confluence section that merges one of the multiple flow paths separated by the branch section into the upstream of the degassing mechanism.

[0008] Existing technical documents

[0009] Patent documents

[0010] Patent Document 1: Japanese Patent Application Publication No. 2014-62827 Summary of the Invention

[0011] The technical problem that the invention aims to solve

[0012] In the aforementioned prior art, a degassing structure is configured along the liquid delivery path of the mobile phase. By repeatedly passing the mobile phase through the degassing mechanism, air bubbles mixed in the mobile phase are removed, and the amount of dissolved air in the mobile phase is reduced. However, it is difficult to determine whether the air bubbles mixed in the mobile phase have been sufficiently removed. In cases where the operator's skill level is low, it can be assumed that unnecessary long-term degassing or insufficient degassing may occur.

[0013] The present invention was made in view of the above circumstances, and its object is to provide a liquid chromatograph and a liquid delivery method that can more easily and reliably remove air bubbles mixed in during mobile phase setup or change operations.

[0014] Technical means for solving technical problems

[0015] This application includes multiple means to solve the above-mentioned problems. As one example, a liquid chromatograph includes: a separation column with a built-in stationary phase; a liquid delivery device for delivering a liquid as a mobile phase to the separation column; a sample injection device for injecting a sample of the analyte 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 supplied to the liquid delivery device; a supply piping connecting the liquid delivery device and the liquid storage container; a circulation piping connecting a portion of the supply piping to the liquid storage container and returning the liquid delivered in the supply piping to the liquid storage container; and a flow path switching valve disposed at... The connection between the supply piping and the circulation piping is selectively switched to either a liquid delivery state, allowing flow between the supply piping on the liquid storage container side and the liquid delivery device side, or a circulation state, allowing flow between the supply piping on the liquid storage container side and the circulation piping. A bubble detection device is disposed between the liquid storage container and the flow path switching valve in the supply piping to detect the presence or absence of bubbles in the liquid being delivered in the supply piping. A circulation delivery device is disposed in the circulation piping to transport 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, utilizes the circulation delivery device for circulation delivery, and switches the flow path switching valve to the liquid delivery state when the bubble detection device does not detect any bubbles in the liquid.

[0016] According to the present invention, the object is to provide a liquid chromatograph and a liquid delivery method that can more easily and reliably remove air bubbles introduced during mobile phase setup or change operations. Attached Figure Description

[0017] Figure 1 This is a schematic diagram illustrating the overall structure of the liquid chromatograph analysis apparatus according to Embodiment 1.

[0018] Figure 2 This is a flowchart illustrating the operation of the liquid supply device according to Embodiment 1.

[0019] Figure 3 This is a schematic diagram illustrating the overall structure of the liquid chromatograph analysis apparatus according to Embodiment 2.

[0020] Figure 4 This is a flowchart illustrating the operation of the liquid supply device according to Embodiment 2.

[0021] Figure 5 This is a schematic diagram illustrating the overall structure of the liquid chromatograph analysis apparatus according to Embodiment 3.

[0022] Figure 6 This is a schematic diagram illustrating the overall structure of the liquid chromatograph analysis apparatus according to Embodiment 3. Detailed Implementation

[0023] The embodiments of the present invention will now be described with reference to the accompanying drawings.

[0024] In this embodiment, a liquid chromatograph (LC) is used as an example of a chromatograph, but it is not limited thereto. For example, the present invention can also be applied to other chromatographs such as high performance liquid chromatograph (HPLC) and ultra-high performance liquid chromatograph (UHPLC).

[0025] <Implementation Method 1>

[0026] Reference Figure 1 and Figure 2 Detailed description of Embodiment 1 of the present invention.

[0027] Figure 1 This is a schematic diagram illustrating the overall structure of the liquid chromatograph analysis apparatus involved in this embodiment.

[0028] Figure 1 The liquid chromatograph analysis apparatus 100 includes: a liquid supply device 110 for providing a solvent as the mobile phase; a separation column 140 containing a stationary phase; a liquid delivery device (liquid delivery pump) 120 for delivering the liquid (solvent) as the mobile phase to the separation column 140; a sample injection device 130 for injecting the analyte sample into the liquid delivered from the liquid delivery device 120 to the separation column; a liquid supply device 110 for supplying the liquid as a solvent to the liquid delivery device 120; an analysis device 150 for analyzing the sample passing through the separation column 140; and a control device 160 for controlling the operation of the liquid chromatograph analysis apparatus 100 as a whole, including the liquid supply device 110, the liquid delivery device 120, and the analysis device 150. The separation column 140 is housed in a constant temperature control device 141.

[0029] The control device 160 includes input devices (keyboard, mouse, etc.) and output devices (monitor, printer, etc.) not shown. Alternatively, devices with both input and display functions, such as a touch panel, can be used as input and output devices provided in the control device 160.

[0030] The liquid supply device 110 includes: a liquid storage container 111 for storing liquid (solvent) supplied to the liquid delivery device 120; supply pipes 112 and 117 connecting the liquid delivery device 120 and the liquid storage container 111; a circulation pipe 114 that connects the middle of the supply pipes 112 and 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 flow path switching valve 116 disposed at the connection between the supply pipes 112 and 117 and the circulation pipe 114. The system selectively switches between a liquid supply state, which allows flow through the supply pipe 112 on the liquid storage container 111 side and the supply pipe 117 on the liquid delivery device 120 side, and a circulation state, which allows flow through the supply pipe 112 on the liquid storage container 111 side and the circulation pipe 114; a bubble detection device (bubble detection sensor) 113, which is disposed between the liquid storage container 111 and the flow path switching valve 116 on the supply pipe 112, detects whether there are bubbles in the liquid being delivered in the supply pipe 112; and a circulation delivery device (circulation delivery pump) 115, which is disposed on the circulation pipe 114, delivers liquid from the flow path switching valve 116 side to the liquid storage container 111 side.

[0031] The supply piping 112 is configured such that its upstream end is close to the bottom of the liquid storage container 111. Furthermore, a circulation piping 114 is provided such that its downstream end is located above the upstream end of the supply piping 112 within the liquid storage container 111.

[0032] In the liquid delivery state, the flow path switching valve 116 connects the supply pipes 112 and 117, and disconnects the connection between the supply pipes 112, 117 and the circulation pipe 114. In this state, driven by the liquid delivery device 120, the liquid in the liquid storage container 111 is drawn into the liquid delivery device 120 via the supply pipes 112, 117 and transported to the downstream side (sample injection device 130 side).

[0033] Furthermore, in the circulation state, the flow path switching valve 116 connects the supply pipe 112 and the circulation pipe 114, and disconnects the supply pipe 112 and the circulation pipe 114 from the supply pipe 117. In this state, driven by the circulation delivery device 115, the liquid in the liquid storage container 111 is drawn into the circulation delivery device 115 via the supply pipe 112 and the circulation pipe 114, and is then transported back to the liquid storage container 111.

[0034] Figure 2 This is a flowchart illustrating the actions involved in the liquid supply device.

[0035] Figure 2 In the process, after the operator has performed operations such as replacing the liquid storage container 111, when the input device of the control device 160 instructs the start of the bubble discharge process (step S100), the control device 160 first switches the flow path switching valve 116 to the circulation state, sets the supply pipe 112 and the circulation pipe 114 to the flow state (step S110), and then drives the circulation liquid delivery device 115 to draw in the liquid from the liquid storage container 111 through the supply pipe 112 and the circulation pipe 114 and deliver it to the liquid storage container 111 (step S120).

[0036] At this time, the liquid in the liquid storage container 111 circulates through the supply pipe 112 and the circulation pipe 114. Therefore, air bubbles in the solution mixed into the supply pipe 112 and the circulation pipe 114 are discharged into the liquid storage container 111 and removed. That is, for example, even if air bubbles are mixed into the solution in the supply pipe 112 due to the replacement operation of the liquid storage container 111, the air bubbles can be removed.

[0037] Next, when conveying a predetermined volume of liquid through the circulating liquid delivery device 115, it is determined whether the bubble detection device 113 detects bubbles (step S130). If the determination result is negative, that is, if bubbles have been mixed into the liquid flowing from the liquid storage container 111 through the supply pipe 112, the liquid delivery continues through the circulating liquid delivery device 115 until the determination result of step S130 is positive. Furthermore, the volume of liquid conveyed through the circulating liquid delivery device 115 can be calculated based on the delivery capacity of the circulating liquid delivery device 115 per unit time and the elapsed time.

[0038] Furthermore, if the determination result in step S130 is yes, that is, if no air bubbles are mixed in the liquid 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 the supply state, the supply pipes 112 and 117 are set to the flow state (step S150), the operator is notified of the end of the air bubble removal process through the display device of the control device 160, etc. (step S160), and the process is terminated.

[0039] In addition, after the bubble discharge process is completed, if the bubble detection device 113 detects bubbles during the analysis operation driven by the liquid delivery device 120, it is determined that the liquid stored in the liquid storage container 111 is below a specified amount (here, the liquid level drops to a position lower than the end of the supply pipe 112), the liquid delivery device 120 is stopped, and the operator is urged to replace the liquid storage container 111.

[0040] The effects of this embodiment constructed in the above manner will be explained.

[0041] In the existing technology, it is difficult to determine whether the bubbles mixed in the mobile phase have been sufficiently removed. In cases where the operator's skill level is low, it can be assumed that unnecessary long-term degassing or insufficient degassing will occur.

[0042] In contrast, in this embodiment, the liquid supply device 110 is configured to include: a liquid storage container 111 for storing the liquid (solvent) supplied to the liquid delivery device 120; supply pipes 112 and 117 connecting the liquid delivery device 120 and the liquid storage container 111; and a circulation pipe 114 that circulates the supply pipes 112 and 117 along the middle (i.e., between the supply pipes 112 on the liquid storage container 111 side and the supply pipes on the liquid delivery device 120 side) of the supply pipes 112 and 117. The supply pipe 112 (connection point of supply pipe 117) is connected to the liquid storage container 111, and the liquid supplied from the supply pipe 112 on the liquid storage container 111 side is returned to the liquid storage container 111; a flow path switching valve 116 is provided at the connection point of the supply pipes 112, 117 and the circulation pipe 114, and selectively switches to allow flow between the supply pipe 112 on the liquid storage container 111 side and the supply pipe 117 on the liquid delivery device 120 side. The system includes a liquid delivery state and a circulation state in which the supply pipe 112 and circulation pipe 114 on the side of the liquid storage container 111 are circulated; a bubble detection device (bubble detection sensor) 113 is provided between the liquid storage container 111 and the flow path switching valve 116 on the supply pipe 112 to detect whether there are bubbles in the liquid delivered in the supply pipe 112; and a circulation delivery device (circulation delivery pump) 115 is provided on the circulation pipe 114 to deliver liquid from the flow path switching valve 116 side to the liquid storage container 111 side, switching the flow path switching valve 116 to the circulation state, and using the circulation delivery device 115 to perform circulation delivery. If the bubble detection device 113 does not detect bubbles in the liquid, the flow path switching valve 116 is switched to the liquid delivery state. Therefore, it is easier and more reliable to remove bubbles from the mobile phase, regardless of the operator's skill level.

[0043] <Implementation Method 2>

[0044] Reference Figure 3 and Figure 4 Detailed description of Embodiment 2 of the present invention.

[0045] This embodiment is configured to switch between multiple liquid storage containers based on the remaining liquid level.

[0046] Figure 3 This is a schematic diagram illustrating the overall structure of the liquid chromatography analysis apparatus according to this embodiment. In the diagram, components identical to those in Embodiment 1 are labeled with the same reference numerals, and descriptions are omitted.

[0047] Figure 3The liquid chromatograph analysis apparatus 100A includes: a liquid supply device 110A that provides a solvent as the mobile phase; a separation column 140 containing a stationary phase; a liquid delivery device (liquid delivery pump) 120 that delivers the liquid (solvent) as the mobile phase to the separation column 140; a sample injection device 130 that injects the analyte sample into the liquid delivered from the liquid delivery device 120 to the separation column; a liquid supply device 110 that supplies the liquid as a solvent to the liquid delivery device 120; an analysis device 150 that analyzes the sample passing through the separation column 140; and a control device 160 that controls the operation of the liquid chromatograph analysis apparatus 100, including the liquid supply device 110, the liquid delivery device 120, and the analysis device 150. The separation column 140 is housed in a constant temperature control device 141.

[0048] In addition to the liquid storage container 111, supply piping 112, 117 (117a), circulation piping 114, flow path switching valve 116, bubble detection device 113, and circulation delivery device 115 described in Embodiment 1, the liquid supply device 110A includes: a liquid storage container 211 for storing the liquid (solvent) supplied to the delivery device 120; a supply piping 117 (117b) connecting the delivery device 120 and the liquid storage container 211; and a circulation piping 214 that connects the supply piping 212, 117 (117a), ... The middle section of pipe 117b (i.e., the connection between the supply pipe 212 on the liquid storage container 211 side and the supply pipe 117b on the liquid delivery device 120 side) is connected to the liquid storage container 211, and the liquid delivered from the supply pipe 212 on the liquid storage container 211 side is returned to the liquid storage container 211; a flow path switching valve 216 is provided at the connection between the supply pipe 212, 117b and the circulation pipe 214, and selectively switches to allow the supply pipe 212 on the liquid storage container 211 side and the liquid delivery device 117b to connect. The system includes either a liquid delivery state where the supply pipe 117b on side 20 flows through, or a circulation state where the supply pipe 212 and circulation pipe 214 on side 211 flow through; a bubble detection device (bubble detection sensor) 213, which is located between the liquid storage container 211 and the flow path switching valve 216 on the supply pipe 212, to detect whether there are bubbles in the liquid being delivered in the supply pipe 212; and a circulation delivery device (circulation delivery pump) 215, which is located on the circulation pipe 21. 4. The liquid is transported from the flow path switching valve 216 side to the liquid storage container 211 side; and the liquid delivery flow path switching valve 218 is provided at the branch of the supply pipes 117a and 117b of the supply pipe 117, and can selectively switch to either a first liquid delivery state that allows the supply pipe 117 to flow to the liquid storage container 111 side (i.e., the supply pipe 117a side) or a second liquid delivery state that allows the supply pipe 117 to flow to the liquid storage container 211 side (i.e., the supply pipe 117b side).

[0049] The supply piping 212 is configured such that its upstream end is close to the bottom of the liquid storage container 211. Furthermore, a circulation piping 214 is provided such that its downstream end is located above the upstream end of the supply piping 212 within the liquid storage container 211.

[0050] In the liquid delivery state, the flow path switching valve 216 connects the supply pipe 212 and the supply pipe 117b, and disconnects the connection between the supply pipes 212 and 117b and the circulation pipe 214. When the liquid delivery flow path switching valve 218 switches to the second liquid delivery state, the liquid in the liquid storage container 211 is drawn into the liquid delivery device 120 via the supply pipes 212 and 117b and transported to the downstream side (sample injection device 130 side) by the drive of the liquid delivery device 120.

[0051] Furthermore, in the circulation state, the flow path switching valve 216 connects the supply pipe 212 and the circulation pipe 214, and disconnects the supply pipe 212 and the circulation pipe 214 from the supply pipe 117b. In this state, driven by the circulation delivery device 215, the liquid in the liquid storage container 211 is drawn into the circulation delivery device 215 via the supply pipe 212 and the circulation pipe 214, and is then transported back to the liquid storage container 211.

[0052] In the first liquid supply state, the liquid supply flow path switching valve 218 allows the supply pipe 117 to flow to the side of the liquid storage container 111 (i.e., the supply pipe 117a side), enabling liquid supply from the liquid storage container 111 to the liquid supply device 120. In the second liquid supply state, the supply pipe 117 flows to the side of the liquid storage container 211 (i.e., the supply pipe 117b side), enabling liquid supply from the liquid storage container 111 to the liquid supply device 120.

[0053] Figure 4 This is a flowchart illustrating the operations involved in the liquid supply device of this embodiment.

[0054] First, as an initial state, consider the case where the liquid delivery flow path switching valve 218 is in the first liquid delivery state, and liquid (solvent) from the liquid storage container 111 is supplied to the liquid delivery device 102. In addition, at this time, it is assumed that the air bubbles in the supply pipe 212 of the liquid storage container 211 have been removed in advance and the device is in a standby state.

[0055] Figure 4 If, during the analysis process driven by the liquid delivery device 120, the bubble detection device 113 detects bubbles, that is, detects that the remaining amount of liquid stored in the liquid storage container 111 is less than the predetermined amount (step S170), then the liquid delivery flow path switching valve 218 is switched to the second liquid delivery state, and the liquid supply from the standby liquid storage container 211 to the liquid delivery device 120 begins (step S180), and the operator is notified by the display device of the control device 160 that the liquid storage container 111 needs to be replaced (step S190).

[0056] After the operator has performed operations such as replacing the liquid storage container 111, when the input device of the control device 160 instructs the start of the bubble discharge process (step S200), the control device 160 first switches the flow path switching valve 116 to the circulation state, sets the supply pipe 112 and the circulation pipe 114 to the flow state (step S210), and then drives the circulation liquid delivery device 115 to draw in the liquid from the liquid storage container 111 through the supply pipe 112 and the circulation pipe 114 and deliver it to the liquid storage container 111 (step S220).

[0057] At this time, the liquid in the liquid storage container 111 circulates through the supply pipe 112 and the circulation pipe 114. Therefore, air bubbles in the solution mixed into the supply pipe 112 and the circulation pipe 114 are discharged into the liquid storage container 111 and removed. That is, for example, even if air bubbles are mixed into the solution in the supply pipe 112 due to the replacement operation of the liquid storage container 111, the air bubbles can be removed.

[0058] Next, when conveying a predetermined volume of liquid through the circulating liquid delivery device 115, it is determined whether the bubble detection device 113 detects bubbles (step S230). If the determination result is negative, that is, if bubbles have been mixed into the liquid flowing from the liquid storage container 111 through the supply pipe 112, the liquid delivery continues through the circulating liquid delivery device 115 until the determination result of step S230 is positive. Furthermore, the volume of liquid conveyed through the circulating liquid delivery device 115 can be calculated based on the delivery capacity of the circulating liquid delivery device 115 per unit time and the elapsed time.

[0059] Furthermore, if the determination result in step S230 is yes, that is, if no air bubbles are mixed in with the liquid 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, the supply pipes 112 and 117a are set to the flow state (step S250), the operator is notified of the end of the air bubble removal process through the display device of the control device 160, etc. (step S260), and the process is terminated.

[0060] Therefore, the liquid delivery flow path switching valve 218 is in the second liquid delivery state, and liquid (solvent) from the liquid storage container 211 is supplied to the liquid delivery device 102. Air bubbles in the supply pipe 112 of the liquid storage container 111 are removed, and the system enters a standby state. If the liquid in the liquid storage container 211 is less than a predetermined amount, the same operation is performed to switch the liquid delivery switching valve 218 so that liquid is supplied from the liquid storage container 111 to the liquid delivery device 20. The system then performs an air bubble removal process by replacing the liquid storage container 211, thus entering a standby state. This allows for the alternating switching of multiple (here, two) liquid storage containers 111 and 211. In other words, the analysis operation can continue without waiting for the liquid storage containers to be replaced.

[0061] The other structures are the same as in Implementation Method 1.

[0062] In this embodiment configured as described above, the same effects as in embodiment 1 can also be obtained.

[0063] Furthermore, the ability to continue analysis without waiting for the liquid storage container to be replaced improves the throughput of analysis results.

[0064] In addition, in this embodiment, the bubble detection devices 113 and 213 detect bubbles to determine whether the liquid storage containers 111 and 211 are less than the predetermined capacity. However, this is not the only method. For example, a method can be considered to calculate the remaining amount of the liquid storage containers 111 and 211 based on the set flow rate and delivery time of the liquid delivery device 120 in the control device 160, a method to configure a weight sensor on the setting part of each liquid storage container and to know the remaining amount of liquid (solvent) based on the weight, or a method to insert a liquid level sensor into the liquid storage container to detect the remaining amount of liquid (solvent).

[0065] <Implementation Method 3>

[0066] Reference Figure 5 and Figure 6 Detailed description of Embodiment 3 of the present invention.

[0067] This embodiment uses a flow path switching valve that combines the functions of the liquid delivery flow path switching valve and the switching valve in embodiment 2.

[0068] Figure 5 and Figure 6 This is a schematic diagram illustrating the overall structure of the liquid chromatograph analysis apparatus according to this embodiment. In the diagram, components identical to those in Embodiments 1 and 2 are labeled with the same reference numerals, and descriptions are omitted.

[0069] Figure 5 and Figure 6The liquid chromatograph analysis apparatus 100B includes: a liquid supply device 110B that provides a solvent as the mobile phase; a separation column 140 containing a stationary phase; a liquid delivery device (liquid delivery pump) 120 that delivers the liquid (solvent) as the mobile phase to the separation column 140; a sample injection device 130 that injects the analyte sample into the liquid delivered from the liquid delivery device 120 to the separation column; a liquid supply device 110 that supplies the liquid as a solvent to the liquid delivery device 120; an analysis device 150 that analyzes the sample passing through the separation column 140; and a control device 160 that controls the operation of the liquid chromatograph analysis apparatus 100, including the liquid supply device 110, the liquid delivery device 120, and the analysis device 150. The separation column 140 is housed in a constant temperature control device 141.

[0070] Figure 5 and Figure 6 In embodiment 2, the functions of flow path switching valves 116 and 216 and liquid delivery flow path switching valve 218 are concentrated in flow path switching valve 318.

[0071] The flow path switching valve 318 has five ports 318a to 318e. The supply pipe 117 connected to the liquid delivery device 120 is connected to port 318a, the supply pipe 112 connected to the liquid storage container 111 is connected to port 318b, the circulation pipe 114 connected to the liquid storage container 111 is connected to port 318c, the supply pipe 212 connected to the liquid storage container 211 is connected to port 318d, and the circulation pipe 214 connected to the liquid storage container 211 is connected to port 318e.

[0072] When the flow path switching valve 318 is switched to Figure 5 In the position shown, supply pipes 112 and 117 are in a flow state (that is, equivalent to the case in Embodiment 2 where flow path switching valve 116 is in the liquid delivery state and liquid delivery flow path switching valve 218 is in the first liquid delivery state), and supply pipe 212 and circulation pipe 214 are in a flow state (that is, equivalent to the case in Embodiment 2 where flow path switching valve 216 is in the circulation state).

[0073] Furthermore, when the flow path switching valve 318 is switched to Figure 6 In the position shown, supply pipes 212 and 117 are in a flow state (that is, equivalent to the case in Embodiment 2 where flow path switching valve 216 is in the liquid delivery state and liquid delivery flow path switching valve 218 is in the second liquid delivery state), and supply pipe 112 and circulation pipe 114 are in a flow state (that is, equivalent to the case in Embodiment 2 where flow path switching valve 116 is in the circulation state).

[0074] That is, by simply switching the flow path switching valve 318 in this embodiment, the switching functions of the flow path switching valves 116 and 216 and the liquid delivery flow path switching valve 218 in embodiment 2 can be achieved in one integrated manner.

[0075] The other structures are the same as in embodiments 1 and 2.

[0076] In this embodiment configured as described above, the same effects as in embodiments 1 and 2 can also be obtained.

[0077] <Postscript>

[0078] Furthermore, the present invention is not limited to the embodiments described above, and includes various modifications or combinations without departing from its spirit. Moreover, the present invention is not limited to having all the structures described in the above embodiments, but also includes structures after deleting a portion of their structure. Additionally, the aforementioned structures and functions can also be implemented, for example, using integrated circuit design, in part or in whole. Furthermore, the aforementioned structures and functions can also be implemented in software by a processor interpreting and executing programs that implement their respective functions.

[0079] Label Explanation

[0080] 100, 100A, 100B Liquid Chromatography Analytical System

[0081] 102 Liquid delivery device

[0082] 110 Liquid supply device

[0083] 110A and 110B Liquid Supply Units

[0084] 111 Liquid storage containers

[0085] 112 Supply piping

[0086] 113 Bubble Detection Device (Bubble Detection Sensor)

[0087] 114 Circulation Piping

[0088] 115 Circulating Liquid Delivery Device (Circulating Liquid Delivery Pump)

[0089] 116 Flow path switching valve

[0090] 117 Piping supply

[0091] 117a and 117b supply piping

[0092] 120 liquid delivery device (liquid delivery pump)

[0093] 130 Sample Injection Device

[0094] 140 Separation Column

[0095] 141 Constant Temperature Control Device

[0096] 150 Analytical apparatus

[0097] 160 Control Device

[0098] 211 Liquid storage containers

[0099] 212 Supply piping

[0100] 213 Bubble Detection Device (Bubble Detection Sensor)

[0101] 214 Circulation Piping

[0102] 215 Circulating Liquid Delivery Device (Circulating Liquid Delivery Pump)

[0103] 216 Flow path switching valve

[0104] 218 Liquid delivery flow path switching valve

[0105] 318 Flow path switching valve

[0106] Ports 318a to 318e.

Claims

1. A liquid chromatograph, comprising: A separation column with a built-in stationary phase; A liquid delivery device that delivers the liquid, which serves as the mobile phase, to the separation column; A sample injection device for injecting the analyte 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 chromatograph is characterized in that... The liquid supply device includes: A liquid storage container for storing the liquid supplied to the liquid delivery device; A supply piping connection is provided between the liquid delivery device and the liquid storage container; A circulation piping that connects the supply piping midway to the liquid storage container and returns the liquid delivered in the supply piping to the liquid storage container; A flow path switching valve is disposed at the connection between the supply pipe and the circulation pipe, and selectively switches to either a liquid delivery state that allows the supply pipe to flow between the liquid storage container side and the liquid delivery device side, or a circulation state that allows the supply pipe to flow between the liquid storage container side and the circulation pipe. A bubble detection device, disposed between the liquid storage container and the flow path switching valve in the supply piping, detects whether bubbles are present in the liquid being supplied in the supply piping; and A circulating liquid delivery device, installed in the circulating piping, 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 and uses the circulation liquid delivery device to perform circulation liquid delivery. If the bubble detection device does not detect any bubbles in the liquid, the flow path switching valve is switched to the liquid delivery state.

2. The liquid chromatograph as described in claim 1, characterized in that, The liquid supply device includes: Other liquid storage containers that store the liquid supplied to the liquid delivery device; Other supply piping connects the supply piping between the liquid delivery device and the flow path switching valve to the other liquid storage container; Other circulation piping connects the supply piping to the other liquid storage container midway and returns the liquid delivered in the other supply piping to the other liquid storage container. Other flow path switching valve, which is disposed at the connection between the other supply piping and the other circulation piping, selectively switches to either a liquid delivery state that allows the other supply piping to flow between the other liquid storage container side and the liquid delivery device side, or a circulation state that allows the other supply piping to flow between the other liquid storage container side and the other circulation piping. Other bubble detection device, which is installed between the other liquid storage container and the other flow path switching valve in the other supply piping, to detect whether there are bubbles in the liquid being delivered in the other supply piping; Other circulating liquid delivery devices, which are installed in the other circulating piping, deliver the liquid from the other flow path switching valve side to the other liquid storage container side; and A liquid delivery flow path switching valve is disposed at the connection between the supply pipe and the other supply pipes, and selectively switches between a first liquid delivery state, which allows flow through the supply pipes on the liquid storage container side and the liquid delivery device side, and a second liquid delivery state, which allows flow through the other supply pipes on the other liquid storage container side and the supply pipes on the liquid delivery device side. When the liquid delivery flow path switching valve is in the first liquid delivery state, and the control device detects that the remaining amount of liquid stored in the liquid storage container is less than a predetermined amount, the control device switches the liquid delivery flow path switching valve to the second liquid delivery state.

3. The liquid chromatograph as described in claim 1, characterized in that, The liquid supply device includes: Other liquid storage containers that store the liquid supplied to the liquid delivery device; Other supply piping, which connects the flow path switching valve and the other liquid storage container; Other circulation piping connects the flow path switching valve and the other liquid storage container, and returns the liquid supplied in the other supply piping to the other liquid storage container; Other bubble detection devices, disposed between the other liquid storage container in the other supply piping and the flow path switching valve, detect the presence or absence of bubbles in the liquid supplied in the other supply piping; and Other circulating liquid delivery devices, which are installed in the other circulating piping, transport the liquid from the flow path switching valve side to the other liquid storage container side. The flow path switching valve selectively switches between a first liquid delivery cycle state, which allows the supply piping on the liquid storage container side and the liquid delivery device side to flow, and the other supply piping and the other circulation piping on the other liquid storage container side to flow, and a second liquid delivery cycle state, which allows the other supply piping and the supply piping on the liquid delivery device side to flow, and the supply piping and the circulation piping on the liquid storage container side to flow. When the flow path switching valve is in the first liquid delivery cycle state, and the control device detects that the remaining amount of liquid stored in the liquid storage container is less than a predetermined amount, the control device switches the flow path switching valve to the second liquid delivery cycle state.

4. A method for delivering liquid to a liquid chromatograph, the liquid chromatograph comprising: A separation column with a built-in stationary phase; A liquid delivery device that delivers the liquid, which serves as the mobile phase, to the separation column; A sample injection device for injecting the analyte into the liquid delivered from the liquid delivery device to the separation column; A liquid supply device that supplies the liquid to the liquid delivery device; as well as A control device for controlling the operation of the liquid delivery device and the liquid supply device. The liquid delivery method of the liquid chromatograph is characterized by comprising: The step of circulating liquid delivery involves sending the liquid stored in the liquid storage container from the supply piping through the circulation piping to the liquid storage container; as well as The step of supplying the liquid stored in the liquid storage container to the liquid delivery device via the supply pipe, provided that there are no air bubbles in the liquid being delivered in the circulation piping.

Images