JP7331328B2 - Liquid chromatograph equipped with flow switching valve - Google Patents

Description

The present invention relates to a liquid chromatograph equipped with a channel switching valve.

Conventionally, liquid chromatographs equipped with channel switching valves have been proposed that are capable of forming various channels according to their purposes (eg, Patent Documents 1 to 3).

In Patent Document 1, in a high-performance liquid chromatograph equipped with a trap column for concentrating a sample, a channel switching valve, an analysis column, etc., a channel for introducing a sample into the trap column by the channel switching valve, and in the trap column Disclosed is one in which a flow path for introducing a concentrated component into an analysis column can be switched. In the invention described in Patent Document 1, it is described that the arrangement of the ports of the flow path switching valve and the method of connecting the ports are devised so as to prevent the occurrence of shocks due to pressure changes when switching the flow path.

Patent Document 2 discloses a needle, a syringe pump for sucking and discharging a sample through the needle, a needle drive mechanism for moving the needle, a sample loop for holding the sample sucked by the syringe pump, A liquid chromatograph is disclosed that has an autosampler with a channel switching mechanism for switching between a loading mode and an injecting mode. In the invention described in Patent Document 2, when performing high-pressure gradient analysis in which two or more solvents are mixed and sent as a mobile phase, and the ratio of the mixture concentration is gradually changed, the mobile phase flowing through the analysis column is It is described that the analysis can be performed in a short time by shortening the time until the gradient is reflected in the composition.

In Patent Document 3, a sample is introduced into a concentration column through an analysis channel switching valve together with a diluent and concentrated, then the analysis channel switching valve is switched to connect the concentration column to the analysis channel, and the concentration column is In a liquid chromatograph for performing separation analysis by introducing a sample from a sample into an analysis channel, a suction and discharge unit for sucking and discharging a liquid, a diluent container containing a diluent, a channel connected to the suction and discharge unit, and It is disclosed to have a channel selection valve to which a channel leading to the diluent container is connected. By providing this channel selection valve, a mechanism for diluting the sample to be introduced into the concentration column can be realized with a simple configuration.

Japanese Patent No. 4913470 Japanese Patent No. 6409971 Japanese Patent No. 4313501

By the way, when a sample is analyzed by a liquid chromatograph, in a typical liquid chromatograph, after the sample liquid is directly injected into the sample loop or the like, the flow path switching valve is switched to temporarily hold the sample liquid in the sample loop or the like. The mobile phase pushes out the sample and introduces it into the analytical column. However, in such a method of introducing a sample into an analytical column, for example, when the polarity of the solvent in the sample is close to the polarity of the analytical column, the components in the sample flow as they are without being concentrated at the tip of the analytical column. It has been pointed out that the peak becomes broader and the sensitivity decreases.

Regarding such indications, the invention described in Patent Document 1 provides a trap column, and the invention described in Patent Document 3 provides a concentration column. It can be close to the polarity of the analytical column. Moreover, in the invention described in Patent Document 3, the configuration for feeding the liquid to the concentration column is complicated, and there is room for improvement in terms of manufacturing cost, maintenance cost, and the like. The configuration of the invention described in Patent Document 2 cannot deal with the above-mentioned indication.

SUMMARY OF THE INVENTION Accordingly, an object of the present invention is to provide a liquid chromatograph capable of easily changing the polarity of a solvent in a sample and having good sensitivity.

The inventor of the present invention has made intensive studies to solve the problems described above. As a result, the inventors have found that the above-described problem can be solved by using a predetermined flow path switching valve and arranging each configuration connected to the port in a predetermined arrangement.

A first aspect of the present invention is a sample receiving portion for receiving a sample sent by a sample liquid sending pump, and a mixed solvent liquid sending pump for sending a mixed solvent to be mixed with the sample at a predetermined mixing ratio. a sample loop that temporarily holds a mixture of the sample and the mixed solvent and has one end and the other end; an analysis column that separates the sample into components; and components separated by the analysis column. a mobile phase feed pump that feeds the mobile phase to the analysis column; a load position that temporarily holds the mixture in the sample loop; and the mixture held in the sample loop. a channel switching valve that can be switched between an injection position for sending a liquid to the analysis column, and a switching valve for switching between the sample receiving unit, the mixed solvent liquid sending pump, and the sample loop. one end and the other end of, each port connected to each of the analysis column and the mobile phase pump, and in the load position, one of the mixed solvent pump, the sample receiving unit and the sample loop A flow channel a in which ports connected to ends communicate with each other, and a flow channel b in which ports connected to the mobile phase pump and the analysis column communicate with each other are formed. A channel d in which a port connected to a mixed solvent delivery pump communicates, a channel e in which one end of the sample loop and a port connected to the analysis column communicate, and the other end of the sample loop and the mobile phase delivery The present invention relates to a liquid chromatograph that forms a channel f in which a port connected to a liquid pump communicates.

In an embodiment of the present invention, the channel switching valve has a waste liquid port connected to a waste liquid container for collecting waste liquid, and in the load position, the waste liquid port and the port connected to the other end of the sample loop. may be formed, and the waste liquid port may be configured not to communicate with other ports at the injection position.

In an embodiment of the present invention, a solid-phase cartridge preloaded with a sample, which is detachably installed in the sample receiving portion, and an elution solvent for eluting the sample carried in the solid-phase cartridge are fed. and an elution solvent feeding pump as the sample liquid feeding pump, and a connecting portion connected to the elution solvent feeding pump and detachably connected to the solid phase cartridge.

In an embodiment of the present invention, a solvent switching valve is provided in a flow path between the elution solvent feeding pump and the connection section, and the solvent switching valve is configured to connect the connection section, the elution solvent feeding pump, and each port connected to each of the preparation liquid feeding pumps for feeding the preparation liquid that does not elute the sample supported on the solid-phase cartridge, and the elution solvent liquid feeding pump and the connecting portion communicate with each other. It may be possible to switch to a channel g or a channel i in which the preparation liquid feeding pump and the connecting portion communicate with each other.

In an embodiment of the present invention, instead of the solid phase cartridge, a connection adapter that can be detachably installed in the sample receiving portion and the connection portion is provided, and the mixed solution in the sample loop is sent to the analysis column. After the loading position, an elution solvent can be sent as a washing liquid through the connection adapter. Further, in this case, the preparatory liquid may be further sent as a cleaning liquid.

In an embodiment of the present invention, a sample container containing the sample, a connecting portion having a needle detachably connected to the sample container and the sample receiving portion, and suction and discharge of the sample via the needle are performed. and the sample liquid-sending pump for performing.

Embodiments of the present invention may have a drive mechanism for moving the connecting portion.

In the embodiment of the present invention, the flow path switching valve is set to the load position, and the sample injected by the sample liquid feeding pump and the mixed solvent injected by the mixed solvent liquid feeding pump are transferred to the predetermined flow path a. A mixed solution preparation step of combining so as to achieve a mixing ratio, feeding the mixed solution from one end of the sample loop to the other end, and holding the mixed solution in the sample loop; after the mixed solution preparation step, The flow channel switching valve is set to the injection position, and the mobile phase is fed from the other end to the one end of the sample loop through the flow channel f by the mobile phase feed pump, and held in the sample loop. The controller may have a control unit configured to execute an analysis step of sending the mixed solution obtained through the channel e to the analysis column.

In an embodiment of the present invention, the sample loop may be provided with a vibration imparting mechanism that promotes mixing of the sample and the mixed solvent.

ADVANTAGE OF THE INVENTION According to this invention, the polarity of the solvent in a sample can be easily changed and the liquid chromatograph which has favorable sensitivity can be provided.

FIG. 2 is an explanatory diagram for explaining the channel configuration of the liquid chromatograph according to the example of Embodiment 1, and is an explanatory diagram for explaining the channel configuration in a stopped state; FIG. FIG. 5 is an explanatory diagram for explaining the channel configuration when the liquid chromatograph according to the example of Embodiment 1 is performing preparatory processing; FIG. 4 is an explanatory diagram for explaining the channel configuration when the liquid chromatograph according to the example of the first embodiment is performing processing for preparing a mixed liquid; The flow path configuration when the solid phase cartridge is replaced with the connection adapter in parallel with performing the analysis processing by setting the flow path switching valve of the liquid chromatograph according to an example of the first embodiment to the injection position will be described. It is an explanatory diagram for. FIG. 10 is an explanatory diagram for explaining a channel configuration when performing cleaning processing in parallel with performing analysis processing by setting the channel switching valve of the liquid chromatograph according to an example of Embodiment 1 to the loading position; . Description for explaining the channel configuration when performing another cleaning process in parallel with performing analysis processing by setting the channel switching valve of the liquid chromatograph according to an example of the first embodiment to the loading position. It is a diagram. FIG. 4 is an explanatory diagram for explaining the channel configuration of a liquid chromatograph according to another example of Embodiment 1, in which the solid-phase cartridge is installed in parallel with the analytical process performed by setting the channel switching valve to the injection position; FIG. 10 is an explanatory diagram for explaining the flow path configuration when replacing with a connection adapter; FIG. 10 is an explanatory diagram for explaining the channel configuration of a liquid chromatograph according to an example of the second embodiment, and is an explanatory diagram for explaining the channel configuration when preparatory processing is being performed; FIG. 10 is an explanatory diagram for explaining the flow path configuration when a liquid chromatograph according to an example of the second embodiment performs a process of collecting a sample in a sample container in a process of preparing a mixed liquid; FIG. 10 is an explanatory diagram for explaining the channel configuration when a liquid chromatograph according to an example of the second embodiment performs a process of holding a mixed liquid of a sample and a mixed solvent in a sample loop in a process of preparing a mixed liquid; is. FIG. 10 is an explanatory diagram for explaining a channel configuration when performing analysis processing by setting the channel switching valve of the liquid chromatograph according to an example of Embodiment 2 to the injection position; 3 is a block diagram showing an example of an electrical configuration of a liquid chromatograph according to one example of Embodiment 1 and another example; FIG. 4 is a flow chart showing an example of the operation of the liquid chromatograph according to one example of Embodiments 1 and 2. FIG. 8 is a flow chart showing an example of the operation of the liquid chromatograph according to another example of Embodiment 1. FIG.

(Embodiment 1)
A liquid chromatograph (hereinafter sometimes referred to as "liquid chromatograph") according to Embodiment 1 will be described with reference to the drawings.

FIG. 1 is an explanatory diagram for explaining the channel configuration of a liquid chromatograph (liquid chromatograph) 1 according to the first embodiment. Embodiment 1 uses a solid phase cartridge supporting a sample, and in order to deliver the sample to the sample receiving part, an elution solvent for eluting the sample from the solid phase cartridge is delivered by an elution solvent delivery pump. It is an embodiment in the case of doing. The liquid bath 1 having the channel configuration shown in FIG. 1 is one example. The liquid chromatography 1 includes a sample receiving section 11 , a mixed solvent liquid feeding pump 12 , a sample loop 13 , an analysis column 14 , a detector 15 , a mobile phase liquid feeding pump 16 , and a channel switching valve 17 . FIG. 1 shows the liquid clone 1 in a stopped state.

The sample receiving unit 11 receives a sample A sent by an elution solvent sending pump 18 as a sample sending pump. In this embodiment, the sample A is sent together with an elution solvent for eluting the sample A from the solid phase cartridge 19 . Also, the sample receiving part 11 is connected to the port (2) of the channel switching valve 17 as described later. In the example shown in FIG. 1, the sample receiving section 11 has a structure in which a solid-phase cartridge 19 in which the sample A is previously held can be attached and detached. The solid phase cartridge 19 may be directly connected to the sample receiving section 11, or may be connected via a predetermined connecting tool. As such a connector, for example, one having a structure in which the part connected to the sample receiving part 11 is a needle and communicates with the inside of the solid phase cartridge 19 can be mentioned. In addition, the sample receiving section 11 has a structure in which a liquid-tight state is maintained with the solid-phase cartridge 19 (including the case where it is connected to the above-described connector; the same shall apply hereinafter). Known structures can be adopted for the detachable structure and the structure capable of maintaining a liquid-tight state. Further, for the solid phase cartridge 19, for example, those described in Japanese Patent No. 6187133 and Japanese Patent Application Laid-Open No. 2017-090411 can be used. In addition, commercially available solid-phase cartridges can also be used. For example, Flash-SPE, Presh-SPE, Smash-SPE and AiSTI-SPE manufactured by Aisti Science Co., Ltd. can be mentioned. The elution solvent can be appropriately selected according to the components of the sample A and the properties of the solid phase of the solid phase cartridge.

Further, a solid-phase cartridge supporting sample A can be obtained, for example, based on the methods described in WO2016/024575 and WO2017/115841. In the methods described in these patent documents, a sample is supported on a solid-phase cartridge and processed until it becomes a state in which it is not eluted with the preparation solvent but can be eluted with the elution solvent.

The mixed solvent feeding pump 12 feeds a mixed solvent to be mixed with the sample A so that a predetermined mixing ratio is achieved. Also, the mixed solvent liquid feeding pump 12 is connected to the port (1) of the flow path switching valve 17 via the flow path 22 as will be described later. In the example shown in FIG. 1, the pump 12 is a syringe pump, but is not limited to this. The pump 12 is also connected to a mixed solvent container 20 that stores the mixed solvent via a three-way valve 21 so that the mixed solvent can be supplied into the pump 12 when necessary.

The sample loop 13 temporarily holds a mixture of the sample A and the mixed solvent. One end 13a is connected to the port (3) of the channel switching valve 17, and the other end 13b is connected to the port (6), as will be described later. The sample loop 13 may be provided with a vibration imparting mechanism that promotes mixing of the sample A and the mixed solvent from the viewpoint of mixing the sample A and the mixed solution more uniformly. Such a vibration imparting mechanism is not particularly limited as long as it can vibrate the mixed liquid in the sample loop 13 by vibrating the sample loop 13 and promote the mixing of the sample A and the mixed solvent. . For example, the sample loop is vibrated by irradiating the sample loop with vibrations generated by an ultrasonic transducer, and the sample loop 13 is vibrated by plucking the sample loop 13 . Among them, a device equipped with an ultrasonic transducer is preferable from the viewpoint of mixing efficiency and the like.

The analysis column 14 separates the sample A into components, and the detector 15 detects the components separated by the analysis column 14 . The mobile phase pump 16 delivers the mobile phase stored in the mobile phase storage container 23 to the analysis column 14 . The analysis column 14 is connected to the port (4) of the flow path switching valve 17 via the flow path 24 on its upstream side, and is connected to the detector 15 on its downstream side. The mobile phase feed pump 16 is connected to the port (4) of the flow path switching valve 17 through the flow path 25 on its downstream side.

The channel switching valve 17 has ports (1) to (7) in this example. Port (1) is the mixed solvent feeding pump 12, port (2) is the sample receiving part 11, port (3) is one end 13a of the sample loop 13, port (4) is the analysis column 14, port ( 5) is connected to the mobile phase pump 15, and the port (6) is connected to the other end 13b of the sample loop 13. Also, in this example, the port (7) is connected to the waste liquid container 26 and serves as a waste liquid port. In the example shown in FIG. 1, the ports (1) to (7) are arranged on the same circle clockwise in that order. Moreover, the interval on the circumference of each port is not particularly limited as long as flow paths are formed at the load position and the injection position, which will be described later. In the example shown in FIG. 1, each port is provided by selecting 7 of the 8 equally spaced circles that are adjacent to each other at equal intervals.

The flow path switching valve 17 has a load position for temporarily holding the mixture of the sample A and the mixed solvent in the sample loop 13 and an injection position for feeding the mixture held in the sample loop 13 to the analysis column 14. and can be switched to any position. In the load position, there are formed a channel a in which the ports (1) to (3) communicate, a channel b in which the ports (4) and (5) communicate, and a channel c in which the ports (6) and (7) communicate. (See FIG. 1). At the injection position, the flow path d communicates the ports (1) and (2), the flow path e communicates the ports (3) and (4), and the flow path f communicates the ports (5) and (6). is formed (see FIG. 4). At this time, port (7) is in an isolated state without communicating with other ports.

In this way, in the load position, the mixed solvent is fed from the upstream side in the flow path a of the flow path switching valve, and the sample A is mixed with the mixed solvent and fed downstream while being mixed. , the total amount of the sample A or a necessary amount can be used to temporarily hold a mixed solution in which the sample A and the mixed solvent are well mixed in the sample loop 13 . Then, by switching to the injection position, the mixed liquid in the sample loop 13 can be pushed out toward the analytical column 14 by the mobile phase, and the mixed liquid can be introduced into the analytical column 14 . Since the polarity of this mixed solution is adjusted by the mixed solvent in consideration of the polarity of the analytical column 14, the measurement can be performed with good sensitivity. For example, if acetonitrile is used as the elution solution and water is used as the mixed solvent, the mixed solution containing sample A will have a polarity opposite to that of the analytical column. Therefore, each component in the sample A contained in the liquid mixture that is sequentially sent from the sample loop 13 is concentrated at the inlet portion of the analysis column 14 at a reduced moving speed. Then, while being separated into each component in a concentrated state, it is moved to the outlet part of the analysis column 14 by the mobile phase and detected by the detector 15, so that the peak of each component becomes sharp and the sensitivity is improved. improves.

The channel switching valve 17 is, for example, a rotary valve having a stator provided with ports (1) to (7) and a rotor having three channel grooves for forming the channels a to f. Can be configured. By rotating the rotor, it is possible to switch between the load position and the injection position.

The example shown in FIG. 1 further has a connecting portion 27 . The connecting part 27 is connected to an elution solvent feeding pump (hereinafter simply referred to as "elution solvent feeding pump") 18 as a sample liquid feeding pump. The connecting part 27 and the elution solvent feeding pump 18 are connected via a channel 28 . Moreover, the connecting part 27 has a structure that can be detachably connected to the solid phase cartridge 19 . The solid phase cartridge 19 and the connecting portion 27 can be connected so as to maintain a liquid-tight state. The connecting part 27 has a nozzle 27a detachable from the solid-phase cartridge, and a main body 27b connected from the nozzle 27a. As will be described later, the body portion 27b becomes a portion that can be integrated with the drive mechanism D (see FIG. 12) when the drive mechanism D is provided.

The example shown in FIG. 1 further includes a solvent switching valve 29 in the channel 28 between the elution solvent feeding pump 18 and the connecting portion 27 . The solvent switching valve 29 has ports (8) to (11). Port (8) is connected to the preparation liquid delivery pump 30, port (9) is connected to the connection part 27, port (10) is connected to the elution solvent delivery pump 18, and port (11) is connected to the waste liquid container 31. connected to Also, the port (9) is connected to the connecting part 27 via the channel 28a, and the port (10) is connected to the elution solvent feeding pump 18 via the channel 28b. The preparation liquid is a solution that does not elute the sample A supported on the solid phase cartridge 19 . Such a preparation liquid can be appropriately selected according to the properties of the solid phase that captures the sample A in the solid phase cartridge 19 .

The solvent switching valve 29 forms an eluate position in which a channel g is formed in which the port (9) and the port (10) communicate, and a channel i in which the port (9) and the port (8) communicate. It is possible to switch between the prepared liquid position and the prepared liquid position. In the example shown in FIG. 1, along with the flow path g, a flow path h communicating between the port (8) and the port (11) is formed at the same time, and along with the flow path i, the port (10) communicates with the port (11). It is configured such that a flow path j for both is formed at the same time. Note that FIG. 1 shows a state in which the flow path i and the flow path j are formed at the same time.

The solvent switching valve 29 is, for example, a rotary valve having a stator provided with ports (8) to (11) and a rotor provided with two channel grooves for forming the channels g to j. Can be configured. By rotating the rotor, it is possible to switch between the eluate position and the prep liquid position.

The elution solvent delivery pump 18 and the preparation liquid delivery pump 30 are both syringe pumps in the example shown in FIG. 1, but are not limited to this. The elution solvent feeding pump 18 is connected via a three-way valve 33 to an elution solvent container 32 in which the elution solvent is stored, so that the elution solvent can be supplied into the pump 18 as necessary. 30 is similarly connected via a three-way valve 34 to a preparation liquid container 35 in which the preparation liquid is stored, so that the preparation liquid can be supplied into the pump 30 as necessary. As will be described later, the elution solvent and preparatory liquid are also used as a cleaning liquid for cleaning the inside of the channel.

In the example shown in FIG. 1, a connection adapter 36 that can be detachably installed in the sample receiving portion and the connection portion instead of the solid phase cartridge 19 is prepared in advance. As will be described later, after the mixed liquid in the sample loop 13 is sent to the analysis column 14, the flow path switching column 17 is set to the load position, and the elution solvent or the preparation liquid is introduced into the predetermined flow path. is installed as described above in place of the solid phase cartridge 19 when feeding as a washing liquid.

In the example shown in FIG. 1, the attachment and detachment of the sample receiving portion 11 and the solid phase cartridge 19 or the connection adapter 36 and the attachment and detachment of the solid phase cartridge 19 and the connection portion 27 or the connection adapter 36 may be performed manually, or the connection may be performed manually. It may be performed by automatic control using a drive mechanism D for moving the portion 27 . For example, the drive mechanism D can move the connecting portion 27 in the horizontal direction and the vertical direction. The connection part 27 and the drive mechanism D may be, for example, always integrated while the liquid clone 1 is operating, or may be connected to the body part of the connection part 27 while the liquid clone 1 is operating. 27b may be detachably gripped.

The liquid chromatography 1 may have valves 17, 29, pumps 12, 16, 18, 30, analysis column 14, and a controller 39 for controlling the operation of the drive mechanism D, which is an optional configuration. FIG. 12 is a block diagram showing an example of the electrical configuration of the liquid bath 1 shown in FIG.

The control unit 39 is, for example, a CPU (Central Processing Unit) that executes predetermined arithmetic processing.
), RAM (Random Access Memory) for temporarily storing data, non-volatile ROM (Read Only Memory) for storing predetermined control programs, etc., flash ROM, HDD (Hard Disk Drive), etc. It is composed of a circuit, these peripheral circuits, and the like. The control unit 39 controls the operations of the valves 17 and 29, the pumps 12, 16, 18 and 30, and the analysis column 14 by executing the control program described above, for example. Moreover, when the drive mechanism D which is an arbitrary structure is provided, the operation|movement is controlled. Also, arithmetic processing is performed based on the detection signal from the detection unit 15 . Further, when a vibration imparting mechanism having an arbitrary configuration is provided, its operation is controlled.

The control unit 39 functions as a mixture preparation unit 40 and an analysis unit 41 by executing the control program described above, for example. It also functions as a preparation/cleaning processing unit 42 when performing preparation processing and cleaning processing, which will be described later.

The operation of the liquid chromatography 1 will be described with reference to FIGS. FIG. 13 is a flow chart showing an example of the operation of the liquid clone 1 having the channel configuration shown in FIG.

In the stopped state shown in FIG. 1, the operation can be started after the solid phase cartridge 19, the connecting portion 27 and the sample receiving portion 11 are connected in a liquid-tight state. When the drive mechanism D is provided, the operation can be started after the solid phase cartridge 19 or the connection adapter 36 is placed on the preparation table B, for example. When the operation is started, the preparation/cleaning processing unit 42 operates the channel switching valve 17 to the load position, and operates the solvent switching valve 29 to the preparation liquid position (step S1). When the drive mechanism D is provided, the drive mechanism D is operated to connect the solid-phase cartridge 19, the connecting portion 27, and the sample receiving portion 11 in a liquid-tight state, and then the valves 17 and 29 are similarly moved to the positions described above. Let

Examples of the drive mechanism D include those that operate as follows. The solid phase cartridge 19 or the solid phase cartridge 19 and the connection adapter 36 are installed in advance on the preparation table B, and the connection part 27 is moved by the driving mechanism D integrated with the connection part 27, and the nozzle 27a of the connection part 27 and the solid phase are moved. The other end side of the cartridge 19 or the connection adapter 36 is fitted to connect them in a liquid-tight manner. In this state, the connecting portion 27 is moved by the driving mechanism D to fit the sample receiving portion 11 and one end side of the solid phase cartridge 19 or the connecting adapter 36, thereby liquid-tightly connecting them. Thereby, the sample receiving part 11, the solid phase cartridge 19 or the connection adapter 36, and the connection part 27 are connected in this order. In addition, the connection portion 27 is moved by the driving mechanism D to release the connection between the sample receiving portion 11 and one end of the solid phase cartridge 19 or the connection adapter 36, and the connection portion 27 and the solid phase cartridge 19 or the connection adapter 36 are released. disconnect from the

In FIG. 2, from the stopped state shown in FIG. This shows a state in which a preparatory process (step S2) is being carried out in which a predetermined liquid is sent to the flow paths formed and the air inside them is removed. In FIG. 2, the portions indicated by thick lines indicate that the liquid is passed through, and the arrows indicate the direction of flow of each liquid. These points are the same for FIGS. 3 to 11. FIG.

In step S2, the following preparatory processing is performed. (i) The preparation liquid is sent to the solid-phase cartridge 19 by the pump 30 via the flow paths i, 28a, and the connecting portion 27, and the waste liquid is discharged from the solid-phase cartridge 19 via the flow path a, the sample loop 13, and the flow path c. Drain into container 26 . At the same time, the mixed solvent is sent by the pump 12, mixed with the preparation liquid in the flow path a, and discharged to the waste liquid container 26 in the same manner. (ii) The mobile phase is sent to the analysis column 14 via the flow path b by the pump 16 and discharged. (iii) The elution solvent is sent to the channel j by the pump 18 and discharged to the waste solution 31 . At this time, the sample A is maintained in a state supported by the solid-phase cartridge 19 . Further, each liquid is sent at a preset flow rate.

After the preparation process (step S2) is performed for a predetermined period of time, for example, the process of preparing the mixture is performed (step S3: mixture preparation step). In step S3, the liquid mixture preparation unit 40 sets the valves 17 and 29 to predetermined positions, operates the pumps 12, 16, 18, and 30 to send a predetermined liquid to the solid phase cartridge 19 and the formed channel. Then, the sample A is eluted from the solid phase cartridge 19 and the mixture of the sample A and the mixed solvent is held in the sample loop 13 . FIG. 3 shows the state at this time. Incidentally, in this example, the mixed liquid is composed of the sample A, the elution solvent, and the mixed solvent.

In step S3, for example, a process of preparing the following mixed solution is performed. (i) Valve 17 is maintained at the load position and valve 29 is switched to the eluate position to form channels g and h. Then, the eluate is sent to the solid phase cartridge 19 through the channels g, 28 a and b by the pump 18 to elute the sample A from the solid phase cartridge 19 . (ii) At the port (2) of the channel a, the mixed solution is obtained by merging the sample A together with the eluate and the mixed solvent so that a predetermined mixing ratio is obtained. (iii) The resulting mixed solution is sent from one end of the sample loop 13 to the other end to retain the mixed solution in the sample loop. (iv) In parallel with the processing of (i) to (iii), the preparation liquid is sent by the pump 30 through the flow path h, discharged to the waste liquid container 31, and the mobile phase is transferred by the pump 16 to the flow path b. to the analysis column 14 and discharged. Further, if necessary, the sample loop 13 may be vibrated by operating the vibration imparting mechanism in order to more uniformly mix the sample A and the mixed solvent of the mixed liquid sent to the sample loop 13 . The operation may be intermittent or continuous, and the operation period can be appropriately determined, for example, within the period in which the liquid mixture exists in the sample loop 13 .

After performing the process of preparing the mixture (step S3) for a predetermined time, for example, the process of setting the valve 17 to the injection position is performed (step S4). The processing time of step S3 can be appropriately determined in consideration of the capacity of the sample loop, the mixing ratio of the liquid mixture, the flow rate, and the like. In step S4, the analysis unit 41 operates the valve 17 to the injection position to form the flow paths d, e, and f. At this time, the pumps 12, 18, 30 are stopped. Pump 16 continues to operate.

After step S4, the analysis unit 41 feeds the mobile phase from the other end of the sample loop 13 through the flow channel f to the one end of the sample loop 13, and the mixed liquid held in the sample loop 13 is transferred to the flow channel. Analysis process 1 is performed in which the solution is sent to the analysis column 14 through e (step S5). At this time, the mixed liquid is pushed out of the sample loop 13 by the mobile phase, and the mixed liquid is introduced into the analysis column.

Further, in step S5, the solid phase cartridge 19 in which the sample A has been eluted is removed, and the connection adapter 36 previously placed on the preparation table B is connected to the connection portion 27, and then the connection adapter 36 is connected to the sample receiving portion 11. , and connect the connection portion 27, the connection adapter 36, and the sample receiving portion 11 in a liquid-tight state. When the driving mechanism D is provided, the solid phase cartridge 19 and the connection adapter 36 are exchanged by operating the driving mechanism D by the analysis unit 41 to move the connection unit 27 . FIG. 4 is a diagram showing a state when the connection adapter 36 is connected to the connection portion 27 in step S5.

Step S5 is started, the connecting portion 27, the connecting adapter 36 and the sample receiving portion 11 are connected in a liquid-tight state, and after a predetermined time has passed, the valve 17 is set to the load position (step S6). In step S6, the analysis unit 41 operates the valve 17 to the injection position to form the flow paths a, b, and c.

After step S6, the analysis unit 41 performs analysis processing 2 in which the mobile phase is sent via the channel b and the mixture is continuously sent to the analysis column (step S7). In step S<b>7 , the analysis column 14 separates the components for each component, and arithmetic processing is performed in the analysis unit 41 based on the signals detected by the detector 15 . Further, after all of the mixed liquid has passed through the analysis column 14 and the signal based on the component is no longer detected by the detector 15, the mobile phase is continued to be sent for cleaning the analysis column 14 and the inside of the flow path. is preferred.

In parallel with step S7, a cleaning process is performed (step S8). In step S8, the following cleaning processes 1 and 2 are performed. In the cleaning process 1, the preparation/cleaning processing unit 42 (i) operates the pump 18 to supply the eluate as the cleaning liquid to the flow path g of the valve 29, the flow paths 28a and 28b, the flow path a, the sample loop 13, the flow path (ii) operate the pump 12 to discharge the mixed solvent as the washing liquid through the flow path a, the sample loop 13, and the flow path c into the waste liquid container 26; (iii) ) The pump 30 is operated to discharge the preparation liquid as the cleaning liquid to the waste liquid container 26 through the flow path h of the valve 29 . By performing the processes (i) and (ii) at the same time, both cleaning liquids merge at the port (2) of the valve 17. FIG.

In the cleaning process 2, the preparation/cleaning processing unit 42 maintains the valve 17 in the load position, switches the valve 29 to the preparation liquid position, and operates the pump 30 to supply the preparation liquid as the cleaning liquid to the flow path i. After the liquid is sent to the flow path 28a through the flow path j, it is finally discharged to the waste liquid container 26 in the same manner as in the cleaning process 1, and the pump 18 is operated to transfer the eluate as the washing liquid to the waste liquid container through the flow path j. 31 to discharge.

FIG. 5 shows the state when cleaning process 1 and analysis process 2 are being performed, and FIG. 6 shows the state when cleaning process 2 and analysis process 2 are being performed. Note that the processing of steps S4 to S7 corresponds to the analysis step.

Then, analysis processing 2 and cleaning processing 2 are performed for a predetermined period of time, the pump 16 is stopped by the analysis unit 41, and the pumps 12, 18, and 30 are stopped by the preparation/cleaning processing unit 42, and a series of processing ends. Incidentally, after the pumps 12, 18 and 30 are stopped, the connection adapter 36 may be removed and placed on the preparation table B, if necessary. In addition, when the drive mechanism D is provided, after the pumps 12, 18, and 30 are stopped by the preparation/cleaning processing unit 42, the connection unit 11 is moved by operating the drive mechanism D to move the sample from the sample receiving unit 11. After removing the connection adapter 36, the connection adapter 36 can be removed from the connection portion 27 and placed on the preparation table B. FIG.

(Modification of Embodiment 1)
FIG. 7 shows a modification of the liquid chromatography 1 shown in FIG. The liquid chromatograph 2 (hereinafter sometimes referred to as "liquid chromatograph 2") shown in FIG. A waste port is further provided to allow the effluent or preparatory liquid to be discharged to the waste container via d. By providing such a port, analysis processing and cleaning processing can be performed in parallel without switching the channel switching valve to the load position again. Except for the provision of this waste liquid port, it has the same configuration as the liquid clone 1 and can form the same flow path. Therefore, in FIG. 7, the same reference numerals are assigned to the same configurations as those of the liquid crystal 1, and the different configurations will be described below.

The liquid bath 2 shown in FIG. 7 has a channel switching valve 17a. The channel switching valve 17a is the same as the switching valve 17 of the liquid channel 1 shown in FIG. That is, the flow path switching valve 17a has ports (1) to (8), and in this example, the ports (1) to (8) are arranged clockwise in that order on the same circumference at regular intervals. there is At the load position, the same flow paths a, b, and c as those of the switching valve 17 are formed. On the other hand, at the injection position, a flow channel d through which the ports (1) and (2) communicate and a flow channel k through which the ports (1) and (8) communicate are formed. That is, a channel dk is formed through which the ports (1), (2), and (8) communicate. Flow path dk allows the effluent or prep liquid and mixed solvent to exit port ( 8 ) into waste container 26 .

The flow path switching valve 17a is, for example, a rotary valve having a stator provided with ports (1) to (8) and a rotor having three flow grooves for forming flow paths a to d and k. Although it can be constituted by a valve, the channel groove formed in the rotor is the same as the switching valve 17 shown in FIG.

The operation of liquid claw 2 will be described with reference to FIGS. 1 will be briefly described with reference to FIGS. 1 to 6 as necessary. FIG. 14 is a flow chart showing an example of the operation of the liquid clone 2 having the channel configuration shown in FIG.

As in the case of the liquid clone 1 shown in FIG. 1, the liquid clone 2 performs the processing from step S1 to step S3 in the same stopped state as shown in FIG. 1 and in the same manner as shown in FIGS. . After the process of preparing the mixture (step S3: mixture preparation step) is performed for a predetermined period of time, for example, the valve 17a is set to the injection position (step S4a). In step S4a, the analysis unit 41 operates the valve 17a to the injection position to form the flow paths d, e, f, and k. Also, the pumps 12, 16, 18, 30 continue to operate. FIG. 7 shows the state at this time. As shown in FIG. 7, the analysis unit 41 operates the pumps 12 and 18 to transfer the mixed solvent from the port (1) to the port (8) through the channel g, and the elution solvent to the channels k, 28a, and b. , from the port (2) to the port (8) through the channel dk, and discharged to the waste liquid container 26.

After step S4a, the analysis unit 41 feeds the mobile phase from the other end of the sample loop 13 through the flow channel f to the one end of the sample loop 13, and the mixed liquid held in the sample loop 13 is transferred to the flow channel. Analysis processing is performed by sending the liquid to the analysis column 14 through e (step S9). In step S9, the sample A sent from the sample loop 13 is separated into components by the analysis column 14, and arithmetic processing is performed in the analysis section 41 based on the signals detected by the detector 15, respectively. In addition, after all of the mixed liquid has passed through the analysis column 14 and the signal based on the component is no longer detected by the detector 15, the mobile phase is continued to be sent for cleaning the analysis column 14 and the inside of the flow channel. may

In parallel with step S9, a cleaning process is performed (step S10). In step S10, the pumps 12, 18, and 30 are operated by the preparation/cleaning processing unit 42, and the following cleaning processing can be performed, for example. (i) The washing process is performed with the channel configuration shown in FIG. (iii) After the signal based on the components of sample A is no longer detected by the detector 15 in step S9, the channel switching valve 17a is switched from the injection position to the load position. Then, after performing the cleaning process for a predetermined time with the channel configuration shown in FIG. 5, the cleaning process is performed with the channel configuration shown in FIG. Then, the analysis process and the cleaning process are performed for a predetermined period of time, the pump 16 is stopped by the analysis unit 41, and the pumps 12, 18, and 30 are stopped by the preparation/cleaning processing unit 42, thereby completing a series of processes. In the above cases (i) and (ii), the flow path switching valve 17a may be switched from the injection position to the load position after the cleaning process. In the cases of (i) to (iii) above, the process of placing the connection adapter 36 on the preparation table B as described above may be performed as necessary.

(Embodiment 2)
8 to 11 show an example of the flow path configuration of a liquid chromatograph 3 (hereinafter sometimes referred to as "liquid chromatograph 3") according to Embodiment 2. FIG. Embodiment 2 is an example in which the sample is not carried on a solid-phase cartridge as in Embodiment 1, but is a liquid enclosed in a sample container 43 . The examples shown in FIGS. 8 to 11 do not use the configuration for feeding the elution solvent as in the example shown in FIG. It has the same configuration as the example shown in FIG. Therefore, in FIGS. 8 to 11, the same reference numerals are assigned to the same configurations as those of the liquid crystal 1, and the different configurations will be described below.

FIG. 8 shows the flow channel configuration of the liquid clone 3 in a state where preparation processing is being performed. In the liquid clone 3, the sample receiving part 11 has a structure in which the needle 37a of the connecting part 37 can be attached and detached in a liquid-tight manner. The sample receiving unit 11 receives a sample A2 that is sent by a preparation liquid sending pump 30 as a sample sending pump. The pump 30 is connected to the connecting portion 37 via the flow path 38 . The connecting portion 37 has a needle 37a and a main body 37b connected from the needle 37a. As in the case of the first embodiment, the body portion 27b becomes a portion that can be integrated with the drive mechanism D (see FIG. 12) when the drive mechanism D is provided. A sample container 39 containing the sample A2 is placed on the preparation table B2.

The operation of the liquid claw 3 will be described with reference to FIGS. 1 will be briefly described with reference to FIGS. 1 to 6 as necessary. An example of the electrical configuration of the liquid chromatography 3 has the same electrical configuration as in the block diagram shown in FIG. Therefore, description will be made with reference to FIG.

For example, the pumps 12, 16, and 30 are stopped, and the connection portion 37 is not connected to the sample receiving portion 11, and the needle 37a of the connection portion 37 and the sample receiving portion 11 are in a liquid-tight state. After connecting with , the operation can be started. When the operation is started, the preparation/cleaning processing unit 42 operates the channel switching valve 17 to the load position (step S1). When the drive mechanism D is provided, the operation can be started from the above-described stopped state. When the operation is started, the driving mechanism D is operated to connect the connection portion 37 and the sample receiving portion 11 in a liquid-tight state, and then the valve 17 is set to the load position (step S1).

After step S1, the preparation/cleaning processing unit 42 operates the pumps 12, 16, and 30 to perform preparation processing (step S2). In step S2, the pumps 12 and 30 are operated to send the preparation liquid to the channel 38, the channel a, the sample loop 13, and the channel c. Also, the pump 16 is operated to send the mobile phase to the flow path b and the analysis column 14 . Until step S2, the sample container 39 containing the sample A2 is placed on the preparation table B2.

After step S2, a mixed solution preparing step for preparing a mixed solution is performed (step S3). In step S3, the following processing is performed. (i) The mixed liquid preparing section 40 operates the pump 16 while stopping the pumps 12 and 30, disconnecting the connecting section 37 from the sample receiving section 11, and inserting the needle 37a of the connecting section 37 into the sample container 39. (ii) after a predetermined amount of the sample A2 is sucked, the pump 30 is stopped, and the needle 37a and the sample receiving portion 11 are again brought into contact with each other; (iii) After that, the pumps 12 and 30 are operated again to mix the sample A2 and the mixed solvent in the channel a, and the resulting mixed solution is held in the sample loop 13 (see FIG. 10). ). Details are the same as in the case of the first embodiment.

After performing step S3 for a predetermined period of time, for example, the valve 17 is moved to the injection position (step S4). In step S4, the analysis unit 41 operates the valve 17 to the injection position to form the flow paths d, e, and f. At this time, the pumps 12, 18, 30 are stopped. Pump 16 continues to operate.

After step S4, the analysis unit 41 performs analysis processing 1 in the same manner as in the example shown in FIG. 1 (step S5). However, unlike the example shown in FIG. 1, the connection adapter 36 is not replaced. FIG. 11 shows the state at this time.

After a lapse of a predetermined time from the start of step S5, processing is performed to set the valve 17 to the load position (step S6). Then, in the same manner as in the example shown in FIG. 1, the analysis unit 41 performs analysis processing 2 in which the mobile phase is sent through the flow path b and the mixed solution is continuously sent to the analysis column. (step S7). In step S7, after all of the mixture has passed through the analysis column 14 and the signal based on the component is no longer detected by the detector 15, the mobile phase is stopped to wash the inside of the analysis column 14 and the channel. It is preferable to continue.

In parallel with step S7, a cleaning process is performed (step S8). In step 8, the following processing is performed. The preparation/washing processing unit 42 (i) operates the pump 30 to discharge the preparation liquid as the washing liquid to the waste liquid container 26 through the flow path 38, the flow path a, the sample loop 13, and the flow path c, and (ii) ) The pump 12 is operated to discharge the mixed solvent as the washing liquid through the flow path a, the sample loop 13 and the flow path c into the waste liquid container 26 . By performing the processes (i) and (ii) at the same time, both cleaning liquids merge at the port (2) of the valve 17. FIG. It should be noted that FIG. 10 also shows a situation in which steps S6 to S8 are substantially performed.

Then, the analysis process and the cleaning process are performed for a predetermined period of time, the pump 16 is stopped by the analysis unit 41, and the pumps 12, 18, and 30 are stopped by the preparation/cleaning processing unit 42, thereby completing a series of processes. The needle 37a of the connecting portion 37 may be removed from the sample receiving portion 11 as necessary. When the drive mechanism D is provided, after the pumps 12 and 30 are stopped by the preparation/cleaning processing unit 42, the connection adapter 36 is removed from the sample receiving unit 11 by moving the connection unit 37 by operating the drive mechanism D. May be removed.

Also in the second embodiment, as in the case of the first embodiment, the channel switching valve 17a shown in FIG. 7 can be used.

1, 2, 3 liquid chromatograph; 11 sample receiving part; 12 mixed solvent pump; 13 sample loop; one end of 13a sample loop; Liquid-sending pump; 17, 17a Channel switching valve; 18 Elution solvent liquid-sending pump; 19 Solid phase cartridge; 20 Mixed solvent container; 21, 33, 34 Three-way valve; Flow path; 23 Mobile phase storage container; 26, 31 Waste liquid container; 27, 37 Connecting part; 27a Nozzle; Preparation liquid container; 36 Connection adapter 37a Needle; 39 Control section; 40 Mixed liquid preparation section; 41 Analysis section; 42 Preparation/wash processing section; 43 Sample container;

Claims (11)

a sample receiving section for receiving a sample sent by a sample liquid sending pump;
a mixed solvent feeding pump for feeding a mixed solvent to be mixed with the sample at a predetermined mixing ratio;
a sample loop that temporarily holds a mixed solution of the sample and the mixed solvent and has one end and the other end;
an analysis column for separating the sample into components;
a detector that detects components separated by the analysis column;
a mobile phase pump for sending a mobile phase to the analysis column;
A channel switch capable of switching between a load position for temporarily holding the mixed solution in the sample loop and an injection position for sending the mixed solution held in the sample loop to the analysis column. a valve;
The switching valve has ports connected to the sample receiving unit, the mixed solvent pump, one end and the other end of the sample loop, the analysis column, and the mobile phase pump,
At the load position, a channel a in which a port connected to the mixed solvent feeding pump, the sample receiving unit and one end of the sample loop communicate, and each connected to the mobile phase feeding pump and the analysis column Forming a flow path b through which the port communicates,
At the injection position, a channel d in which the port connecting the sample receiving unit and the mixed solvent feeding pump communicates, a channel e in which the port connecting the one end of the sample loop and the analysis column communicate, and Forming a channel f in which the other end of the sample loop and a port connected to the mobile phase pump are in communication,
Liquid chromatograph. the channel switching valve has a waste liquid port connected to a waste liquid container for collecting the waste liquid;
At the load position, a channel c is formed in which the waste liquid port communicates with a port connected to the other end of the sample loop,
in the injection position, the waste port does not communicate with other ports;
The liquid chromatograph according to claim 1. a solid-phase cartridge preloaded with a sample, which is detachably installed in the sample receiving portion;
an elution solvent feeding pump as the sample liquid feeding pump for feeding an elution solvent for eluting the sample carried on the solid phase cartridge;
a connecting portion connected to the elution solvent feeding pump and detachably connected to the solid phase cartridge;
3. The liquid chromatograph according to claim 1 or 2. A solvent switching valve is provided in a channel between the elution solvent feeding pump and the connecting portion,
The solvent switching valve has respective ports connected to the connecting portion, the elution solvent feeding pump, and the preparation liquid feeding pump that feeds the preparation liquid that does not elute the sample supported on the solid phase cartridge. have
It is possible to switch to a channel g in which the elution solvent feeding pump and the connecting portion communicate, or a channel i in which the preparation liquid feeding pump and the connecting portion communicate.
The liquid chromatograph according to claim 3. It has a connection adapter that can be detachably installed in the sample receiving part and the connection part instead of the solid phase cartridge, and after the mixed solution in the sample loop is sent to the analysis column, the load position in which an elution solvent can be sent as a washing liquid through the connection adapter,
The liquid chromatograph according to claim 4 . 6. The liquid chromatograph according to claim 5, wherein said preparation liquid is further fed as a cleaning liquid. It has a connection adapter that can be detachably installed in the sample receiving part and the connection part instead of the solid phase cartridge, and after the mixed solution in the sample loop is sent to the analysis column, the load position in which the elution solvent is used as a washing solution through the connection adapter
can be pumped by
The liquid chromatograph according to claim 3. a sample container containing the sample;
a connecting portion having a needle detachably connected to the sample container and the sample receiving portion;
the sample liquid feeding pump for sucking and discharging the sample through the needle;
3. The liquid chromatograph according to claim 1 or 2. 9. The liquid chromatograph according to any one of claims 3 to 8 , further comprising a driving mechanism for moving said connecting portion. The flow path switching valve is set to the load position, and the sample injected by the sample liquid feeding pump and the mixed solvent injected by the mixed solvent liquid feeding pump are merged in the flow path a so as to have a predetermined mixing ratio. a mixed solution preparation step of feeding the mixed solution from one end of the sample loop to the other end and holding the mixed solution in the sample loop; The injection position is set, and the mobile phase is sent from the other end of the sample loop to the one end through the channel f by the mobile phase delivery pump, and the mixed solution held in the sample loop is delivered. 10. The liquid chromatograph according to any one of claims 1 to 9 , further comprising a controller configured to execute an analysis step of sending a liquid through said channel e to said analysis column. 11. The liquid chromatograph according to any one of claims 1 to 10 , wherein the sample loop is provided with a vibration imparting mechanism that promotes mixing of the sample and the mixed solvent.

Images