JP4433757B2 - Channel switching valve and liquid chromatograph - Google Patents

Description

  The present invention relates to a flow path switching valve that can be suitably used when automatically injecting a large volume of sample into an analysis column, and a liquid chromatograph including the flow path switching valve.

  The “loop method” that is common in sample injection devices for liquid chromatographs is a high-pressure type that can be switched between two positions: the “load position” where the sample is stored in the loop and the “inject position” where the stored sample is introduced into the column. A valve is used. A method of introducing a sample into an analytical column by connecting a loop larger than the volume to be injected in advance, filling the sample with the loop, and switching a valve is employed.

  As an improved method of the above injection method, there is a combination of a 6-port switching valve and a 4-port switching valve (see, for example, Patent Document 1). The 6-port switching valve in Patent Document 1 is composed of a stator having six ports arranged on the circumference and a rotor having three flow channel grooves for switching and connecting the ports. One of the rotor channel grooves is the same as the length between the stator ports, and the length of the remaining two channel grooves is 1.5 times the length between the stator ports. This makes it possible to take an intermediate position while being a two-position switching valve. This intermediate position is used for processes such as releasing the residual pressure in the loop. This method is effective for accurately injecting a small amount of sample. However, in order to inject a large amount of sample, it is necessary to prepare a loop suitable for the volume, and the equipment for measuring the sample amount is large. In addition, since the operation is complicated, it is difficult to use, and it is not intended to inject a large volume of several tens to several hundred mL, and it has been desired to improve the injection of a large volume of sample.

  In addition, as a valve for switching the fluid flow path in two directions, there is a system in which the stator and the rotor are brought into close contact with each other, a liquid contact portion is formed therebetween, and the direction is switched on the stator portion side according to the rotation angle of the rotor seal portion (For example, refer to Patent Document 2). In this patent document 2, an increase in pressure at the time of channel switching is suppressed with respect to a fluid channel switching valve under a pressurized condition to avoid an adverse effect on the entire apparatus. There has been a demand for a valve capable of switching the flow path with a more stable operation under a milder condition and with as little pressure load on the apparatus as possible, and a separation apparatus using the same.

JP 2001-255316 A

JP-A-8-159310

  The “loop method” described in the background art is a method suitable for injecting a sample of a small volume of several tens to several hundreds μL, which is effective for normal qualitative analysis and quantitative analysis. However, in order to inject a large volume sample, it is necessary to prepare a loop suitable for the volume, and the injection apparatus becomes large and the operation becomes complicated.

  On the other hand, when purifying, concentrating, desalting, and fractionating a protein, it is necessary to inject a sample of a large volume of several tens to several hundred mL, and it is difficult to use the loop method.

  On the other hand, a method of directly sucking a sample with a pump for feeding an eluent and loading the sample onto an analytical column is simple. In this method, first, the sample is loaded on the analytical column by inserting the suction pipe of the pump into the bottle containing the sample and starting the liquid feeding. After loading the target volume, the liquid feeding is stopped once, the pump suction pipe is inserted into the eluent bottle, and the liquid feeding is started again to perform separation.

  In this method, it is necessary to stop the liquid feeding once during the injection operation, and automation is difficult. In addition, since one suction pipe is inserted into both the sample and the eluent, the eluent may be contaminated by the sample.

  In automating this method, it is conceivable to switch the sample and the eluent using a switching valve. However, stable operation is difficult with a known switching valve. As shown in FIG. 4, in the known switching valve, the length between the ports arranged on the circumference and the length of the flow channel are all the same. Therefore, at the intermediate position where switching is performed between the first position where the eluent is connected to the suction side of the liquid feeding section and the second position where the suction side of the liquid feeding section is connected to the sample, the suction of the liquid feeding section is performed. The side is not connected anywhere and there is a time to be completely sealed. In such a state, the pump for feeding liquid becomes negative pressure, causing troubles such as sucking up air, and it becomes impossible to feed the sample and eluent accurately.

  Therefore, the object of the present invention is suitable for automatically injecting a large volume of several tens to several hundred mL into an analytical column with a pump, ensuring a stable switching operation and preventing contamination of the eluent. Another object of the present invention is to provide a flow path switching valve and a flow path switching valve that can suppress the occurrence of factors that hinder the separation operation of bubbles and the like when the sample and / or eluent is fed by suction. Moreover, it is providing the liquid chromatograph provided with such a flow-path switching valve.

  In order to solve such a problem, the present inventors have intensively studied to find a switching valve that can inject a large amount of sample with respect to the conventional loop method and that can stably switch the flow path between the sample and the eluent. As a result, a sample such as liquid chromatography and / or an eluent are continuously injected into a separation means such as an analytical column, and in a system for separating the target sample, the eluent is fed after the sample is injected. When separating the target sample, a large amount of sample can be injected by switching the sample and the eluent with the switching valve without going through the sample loop. The structure and position of the holes and grooves provided in the valve so that it can be connected has been devised, and a liquid chromatograph that can be switched through this switching valve while aspirating the sample and / or eluent with the liquid feed pump is constructed The present invention has been completed by suppressing the occurrence of obstacles in sample separation such as the generation of water bubbles. It came to that. Hereinafter, the present invention will be described in detail.

  The flow path switching valve according to the present invention is a valve for switching the flow path of the sample and / or eluent that is continuously injected, and the first input port into which the eluent is injected, the sample being injected. A stator having a second input port and an output port for delivering the injected sample and / or eluent, and a sample and / or eluent in contact with the stator and continuously injected from the input port And a rotor or a slider having a channel groove that can always feed liquid from the output port when the channel is switched. The stator further includes a port for sucking a sample in addition to the first input port, the second input port, and the output port, and the rotor or slider has a second input port and a port for sucking the sample, It is also possible to have a sub-channel groove that enables connection.

  The flow path switching valve according to the present invention is a combination of a part having a plurality of holes (ports) usually called a stator and a part having a groove capable of communicating a gap corresponding to the holes of the stator called a rotor or a slider. Device.

  In the flow path switching valve according to the present invention, the first input port, the second input port, and the one output port provided in the stator each have one end on the sliding surface of the stator and the rotor or slider. The other end can be connected to the first liquid input pipe, the second liquid input pipe and the liquid output pipe, respectively. These liquid input pipes and liquid output pipes can be connected. Various eluents and sample solutions for the step gradient elution of liquid chromatography can be connected to these liquid input pipes. The liquid output pipe is usually connected with liquid feeding means including a suction liquid feeding pump and an analytical column.

  In the present invention, the stator may be of a commonly used 6-hole type, but at least a first input port into which an eluent is injected, a second input port into which a sample is injected, and an injected It is preferable to use three ports of the output port for sending the sample and / or the eluent, and in addition to the first input port, the second input port and the output port, further for sucking the sample It is preferable to use four ports. For example, when a 6-hole type is used, the remaining ports using 3 or 4 ports may not be used, and a stator having 3 or 4 ports from the beginning can be used. The number of ports in these stators can be appropriately increased or decreased according to the purpose.

  In the present invention, the rotor is in contact with the stator, and has a flow channel groove that allows the sample and / or eluent continuously injected from the input port to be always sent from the output port. The flow path groove is a groove provided to connect one or both of the first input port and the second input port of the stator to the output port. Further, when a port for sucking a sample is provided in the stator, a sub flow channel for connecting to the second input port is provided.

  In the present invention, the slider has the same function as the above rotor.

  The shape of the sliding surface between the stator and the rotor or slider is not particularly limited as long as the flow path can be switched between the first input port and the second input port with respect to the output port. It may be a part of a plane and a cylinder side surface.

  Typically, a rotary valve in which a disk-shaped stator and a rotor are brought into close contact with each other with a plane of rotation can be exemplified. The stator has three or four ports (ports A, B, C, and a sample at intervals of 60 ° on the circumference). It is even more desirable to have a port D) for suction. More preferably, the sub-channel groove of the rotor has a length of 60 ° on the circumference, and the channel groove has a length of 120 ° (twice the sub-channel groove).

  In addition, a slide type valve in which a rectangular parallelepiped stator and a rotor are brought into close contact with each other with a plane of rotation can be exemplified. The stator has three or four ports (ports A, B, C and ports for sucking a sample at regular intervals). It is more desirable to have D). It is more desirable that the sub flow channel of the rotor has a length between two adjacent ports, and the flow channel has a length between three adjacent ports (twice the sub flow channel).

  As will be described later, more specifically, if a flow path switching valve composed of the above-mentioned stator and a rotor or a slider is shown, the rotary valve in each switching position of FIGS. 3 to 5 or the same rotary type, The rotor (12) and the stator (13) taking the positions as shown in FIG. 13 or its D cross-section shown in FIG. 13 and FIG. -Various shapes such as those in which the rotor (12) and the slider (24) taking the positions as shown in FIG. You can use them accordingly. For example, in the case of the rotary valve of FIGS. 3 to 5, the adhesion between the rotor and the stator is good, and liquid leakage during operation can be suppressed as much as possible, and the cylindrical shape of FIGS. -If it is a slider type of FIG. 19, it is mentioned that it is excellent in workability.

  In the present specification, the eluent is a mobile phase for sample injection or a so-called mobile phase for injecting a sample to the analytical column so that the state held in the column can be substantially maintained by the principle of adsorption or the like. In addition to what is used as a medium for initializing the column, it also includes an eluent for eluting the sample retained in the analytical column from the analytical column, but the eluent for performing the elution operation is particularly eluted. Sometimes called liquid. For example, when a sample is separated using a column packed with an ion exchange gel, the eluent has a composition that can substantially maintain the state where the sample is held in the ion exchange column, more specifically 20 mmol. / L phosphate buffer (pH 6.5) and other low ionic strength buffers are used, and this low ionic strength buffer is used as the eluent used when eluting the sample held in the analytical column. A liquid in which salt is added to increase ionic strength so as to be 1.0 mol / L sodium chloride is used. Alternatively, in the case of separation by affinity chromatography, any composition may be used as long as the sample can be bound to the column for affinity chromatography as the eluent, and the eluent may be a composition capable of eluting the target sample held in the column, for example, affinity. Any composition may be used as long as a substance similar to the ligand is added. In addition to the column for anion exchange or cation exchange, the column for affinity chromatography, the analytical column according to the present invention has the principle of elution after holding the target sample in a column such as hydrophobic chromatography. The column system used is not particularly limited.

  The flow path switching valve according to the present invention is a valve for switching the flow path of the sample and / or eluent that is continuously injected, and the valve can be switched by rotating operation. The first input port into which the eluent is injected, the output port for feeding the injected sample and / or the eluent, and the second into which the sample is injected are arranged on the circumference from the center of rotation. A stator in which input ports are arranged in a circumferential order, and a flow channel groove that is in contact with the stator and allows the output port to be switched between the first input port and the second input port. And a rotor having. Furthermore, the flow path groove may be an arc-shaped flow path groove having at least a length from the first input port through the output port to the second input port, and the stator may be the first input port, the second input port, and the second input port. In addition to the input port and the output port, a port for sucking the sample is also provided, and the rotor also has an arc-shaped sub-channel groove that enables the rotor to connect the second input port and the port for sucking the sample It may be.

  When the flow path is switched by the rotation operation as in the rotary valve described above, the first input port, the output port and the second input port, and further a port for sucking the sample provided as necessary, A flow path switching valve having a stator arranged in order around the circumference and a rotor having a flow path groove capable of switching the flow path is preferably used. The flow path groove extends from the first input port to the output port. It is sufficient that the groove has an arcuate flow channel having at least a length to reach the second input port through the above-described configuration. By adopting such a configuration, it is possible to obtain a large amount of sample as an object of the present invention and to ensure a stable switching operation. There is an effect. Further, when the stator is provided with a port for sucking the sample, a sub-flow channel for connecting to the second input port is provided.

  The flow path switching valve according to the present invention is a valve for switching the flow path of the sample and / or eluent to be continuously injected, and the valve can be switched by a linear reciprocating operation. On the operation straight line, there are a first input port into which the eluent is injected, an output port for sending the injected sample and / or the eluent, and a second input port into which the sample is injected. A stator disposed in order, and a slider having a channel groove that is in contact with the stator and allows the output port to be switched between the first input port and the second input port. Provided flow path switching valve. Further, the flow channel groove may be a linear flow channel groove having at least a length from the first input port through the output port to the second input port, and the stator may be the first input port, the first input port, In addition to the two input ports and the output port, there is also a port for sucking the sample, and a linear sub-channel groove that allows the slider to connect the second input port and the port for sucking the sample You may have.

  When the flow path is switched by a linear reciprocating operation, a first input port, an output port, a second input port, and a port for sucking a sample provided as necessary are arranged in order. A flow path switching valve including a rotor having a flow path groove that enables flow path switching is preferably used, and the flow path groove extends from the first input port to the second input port through the output port. A linear channel groove having at least a thickness may be used, and by adopting such a configuration, excellent effects such as mass injection of a sample and securing a stable switching operation, which are the objects of the present invention, can be achieved. Further, when the stator is provided with a port for sucking the sample, a sub-flow channel for connecting to the second input port is provided.

  As described above, the flow path switching valve according to the present invention connects the eluent with at least the eluent suction side of the liquid feed section provided with a pump or the like for feeding the liquid in the liquid chromatograph. And the second position where the sample is connected to the suction side of the liquid feeding section.

  In the first position, the output port is connected to the first input port via the flow channel, and the eluent is sent to the pump. During a short period of time from the first position to the second position, the output port is connected to the first input port and the second input port via the flow channel, and the eluent and the sample are connected to the pump. Is delivered. In the second position, the output port is connected to the second input port via the flow channel, and the sample is fed to the pump.

  In the process of switching between the first position and the second position, the pump is always connected to either or both of the eluent and the sample. Smooth and accurate pumping of the sample and eluent can be performed without causing any troubles such as the pump being pulled.

  A liquid chromatograph according to the present invention includes a flow path switching valve, an analysis column that separates a sample, and an eluent and / or a sample that is sucked through the flow path switching valve and sent to the analysis column. A liquid section, a detection section for detecting the sample separated by the analytical column, a pipe connecting these components, and a control section for controlling the operation of the liquid feeding section and the flow path switching valve. In the liquid chromatograph, the flow path switching valve is used as a sample injection switching valve when the eluent and / or the sample is sent to the analysis column.

  As described above, the liquid chromatograph according to the present invention uses the flow path switching valve as the sample injection switching valve, sucks the eluent and / or sample through the flow path switching valve, and sends the liquid to the analysis column. Take the configuration. Unlike the case of switching the valve under normal pressurization conditions, the flow path is switched under the suction pressure condition. For this reason, if pressure fluctuation occurs at the time of valve switching, an unfavorable situation occurs in terms of operation. There were new challenges. However, since the flow path switching valve of the present invention shows an operation in which the flow path switching valve is always connected to either or both of the eluent and the sample, there is substantially no such a situation of the suction pressure, and stable operation is possible. It becomes possible. Therefore, even when a large amount of sample is separated and purified, a chromatogram having excellent separation performance can be obtained by a stable operation.

  According to the present invention, a large amount of samples of several tens to several hundred mL can be loaded directly onto the analytical column with a pump without being stable and contaminated, ensuring a stable switching operation and preventing contamination of the eluent. It does not occur and is easy to automate. In addition, it is possible to suppress the occurrence of factors that obstruct the separation operation, such as bubbles, when the sample and / or eluent is fed by suction.

  Embodiments of a liquid chromatograph according to the present invention will be described below with reference to the drawings.

  FIG. 1 schematically shows a liquid chromatograph according to the present invention. Pump A (7) for feeding two types of eluent, pump B (8), mixer (9) for mixing the eluent, analysis column (10) for separating the sample, detector for measuring the separated components (11). The pump A (7) is for feeding the eluent (1) and the sample (3), and the pump B (8) is for feeding the eluent (2). The sample injection switching valve (4) is for switching the liquid-feeding fluid of the pump A (7) between the eluent (1) and the sample (3). In addition, a syringe unit (5) and a three-way solenoid valve (6) are connected to the sample injection switching valve (4) for sucking the sample (3) in advance to the port of the sample injection switching valve (4). ing. Sample feeding / discharging part (20) composed of a liquid feeding part (22) composed of pump A (7) and pump B (8), syringe unit (5) and three-way solenoid valve (6), and sample injection The switching valve (4) is controlled by the controller (21).

  FIG. 2 shows an outline of a liquid chromatograph according to the conventional “loop method” shown as a comparative example. The difference from FIG. 1 is that the flow path switching valve (4) provided with the sample loop (25) feeds two types of eluents, and the analysis for separating the sample from the pumps A (7) and B (8). It is arrange | positioned between columns (10), and the flow-path switching valve (4) receives the discharge pressure from a pump, and becomes a pressure higher than FIG.

  3 to 5 show the structure of the valve of the present invention, and FIGS. 9 to 11 schematically show the operation of the present invention. The sample injection switching valve (4) includes a rotor (12) and a stator (13). The stator (13) is provided with four ports (port A to port D) at intervals of 60 ° on the circumference from the center of rotation. The rotor (12) has a channel groove for switching and connecting port B (output port) to port A (first input port) or port C (second input port), and port D (suction sample) A sub-flow channel for connecting the port B to the port B. In the best mode, the flow channel is disposed in an arc extending over the length of the rotor rotation angle of 120 °, and the sub-channel groove is disposed over the length of the rotation angle of 60 °.

  The flow path switching valve (4) connects the sample to the elution liquid suction side of the liquid delivery part shown in FIG. 9 and the first position for connecting the eluate, and the suction side of the liquid delivery part shown in FIG. Is switched to the second position. In the step of switching between the first position and the second position, the intermediate position shown in FIG. 10 is passed. As is apparent from the figure, since the sample and / or the eluent are connected to the pump side at any position, it can be seen that there is no pressure fluctuation at the valve due to the pump operation.

  On the other hand, in the conventional valve structure shown in FIGS. 6 to 8, the first position for connecting the eluent to the eluent suction side of the liquid feed section shown in FIG. Is switched between the suction side of the liquid-feeding portion and the second position where the sample is connected. In the step of switching between the first position and the second position, the intermediate position shown in FIG. 7 is passed. As is apparent from the figure, since the sample and / or the eluent are not connected to the pump side at the intermediate position shown in FIG. 7, it can be seen that a large pressure fluctuation occurs in the piping by the pump operation.

  From the first position to the middle position, the eluent suction side and the eluent are connected to the liquid feed section, and in the middle position, both the eluent and sample are connected to the eluent suction side of the liquid feed section. . From the middle position to the second position, the sample is connected to the eluent suction side of the liquid feeding section. The reverse is true when switching from the second position to the first position.

  FIG. 12 shows measurement results (chromatograms) depending on the injection method. The chromatogram shown in FIG. 12 a is a measurement by the conventional “loop injection” in the system configuration of FIG. 2, the volume of the sample loop is 0.3 mL, and the chromatogram shown in FIG. The measurement result by the injection method is shown. The analytical column is an ion exchange column BioAssistS (manufactured by Tosoh Corporation), the eluent is 20 mmol / L phosphate buffer (pH 6.5), the eluent is 20 mmol / L phosphate buffer (pH 6.5) +1.0 mol / L chloride. Ultraviolet detection was performed at 268 nm using sodium. The sample was α-chymotrypsinogen, ribonuclease, cytochrome C, lysozyme, and the flow rate was 3.0 mL / min, and separation was performed with a gradient of 30 minutes from 100% eluent to 100% eluent.

  The steps up to the sample injection in the present invention are as follows. First, the sample injection switching valve is set to the first position, the eluent is sent to the analysis column, and the analysis column is initialized. Next, the sample injection switching valve is in the first position, and the sample is sucked to the port (19) of the sample injection switching valve using the syringe unit and the three-way solenoid valve. Next, the sample injection switching valve is switched to the second position, and the sample is fed to the analysis column for a certain period of time with a pump. Next, the sample injection switching valve is switched to the first position, the eluent is sent by the pump, and the sample remaining in the pump is sent to the analysis column.

  The time until switching from the second position to the first position is the injection time. The chromatogram shown in FIG. 12b is obtained by introducing a sample into the analytical column for 10 minutes. The flow rate was 3 mL / min, and 30 mL of sample was introduced into the analytical column. The sample (protein) used this time does not move in the analysis column with the analysis column and eluent used, so all loaded samples are concentrated on the inlet side of the analysis column. Next, a gradient is started with the eluent and the eluent, and the sample loaded on the analytical column is separated.

  All the above processes are controlled by the control unit 21.

  Although it is clear when comparing the chromatograms shown in FIGS. 12a and 12b, the analysis results are different in the conventional loop injection measurement and the injection method of the present invention even though the sample load is different by about 100 times. As can be seen from the (chromatogram), no difference is seen in the resolution, and it can be seen that it can be used stably as in the conventional method. In the diagram showing the chromatogram in FIG. 12, the vertical axis (Y-axis) indicates the absorbance at 280 nm (the left side is the present invention, the right side is the conventional method), but the unit is arbitrary, but the absorbance according to the present invention is It is about 100 times the absorbance scale according to the conventional method (absorbance numbers indicate the relative relationship between the two).

It is a figure which shows the outline of the liquid chromatograph by this invention. It is a figure which shows the outline of the conventional liquid chromatograph. It is a figure which shows the 1st position among the structures of the valve | bulb of this invention. It is a figure which shows the middle position among the structures of the valve | bulb of this invention. It is a figure which shows the 2nd position among the structures of the valve | bulb of this invention. It is a figure which shows typically the operation | movement by the valve | bulb of the conventional format, and shows a 1st position. It is a figure which shows typically the operation | movement by the valve | bulb of the conventional type, and shows an intermediate position. It is a figure which shows typically the operation | movement by the valve | bulb of the conventional format, and shows a 2nd position. It is a figure which shows operation | movement of this invention typically, and shows a 1st position. It is a figure which shows operation | movement of this invention typically, and shows an intermediate position. It is a figure which shows operation | movement of this invention typically, and shows a 2nd position. It is the result (chromatogram) which measured the protein with the apparatus of this invention, a is a measurement result by the conventional loop injection, b is a measurement result by the injection method by this invention, and a vertical axis | shaft (Y-axis) in the figure Is the absorbance at 280 nm (unit is arbitrary, the left side is the present invention, the right side is according to the conventional method), the horizontal axis (X axis) is the retention time (Retention Time, the unit is minutes (min)) by the liquid chromatograph. It is a figure which shows typically the example which applied this invention to the cylindrical valve | bulb. It is an example which applied this invention to the cylindrical valve | bulb, and shows a 1st position (D section of FIG. 13). It is an example which applied this invention to the cylindrical valve | bulb, and shows a 1st intermediate position (D cross section of FIG. 13). It is an example which applied this invention to the cylindrical valve | bulb, and shows a 2nd position (D section of FIG. 13). This is an example in which the present invention is applied to a slider-like valve, and shows a first position. This is an example in which the present invention is applied to a slider-like valve, and shows an intermediate position. This is an example in which the present invention is applied to a slider-like valve, and shows the second position.

Explanation of symbols

1: Eluent 2: Eluent 3: Sample 4: Sample injection switching valve 5: Syringe unit 6: Three-way solenoid valve 7: Pump A
8: Pump B
9: Mixer 10: Analysis column 11: Detector 12: Rotor seal 13: Stator 14: Channel groove 15: Subchannel groove 16: Port A
17: Port B
18: Port C
19: Port D
20: Sample suction / discharge unit 21: Control unit 22: Liquid feeding unit 23: Sample injection valve 24: Slider 25: Sample loop

Claims (9)

A valve for switching a flow path of a sample and / or an eluent to be continuously injected, the first input port into which the eluent is injected, the second input port into which the sample is injected, and the injected A stator having an output port for feeding a sample and / or an eluent, and the output port in switching the flow path of the sample and / or eluent that is in contact with the stator and continuously injected from the input port A flow path switching valve provided with a rotor or a slider having a flow path groove that allows liquid to be fed more constantly. The stator has a port for sucking a sample in addition to the first input port, the second input port, and the output port, and the rotor or slider connects the second input port and the port for sucking the sample. 2. The flow path switching valve according to claim 1, further comprising a secondary flow path groove that enables the flow path. A valve for switching the flow path of the sample and / or eluent to be continuously injected, and the flow path can be switched by a rotating operation. The first input port into which the eluent is injected, the injected sample and / or the output port for delivering the eluent and the second input port into which the sample is injected are arranged in circumferential order A flow path comprising: a stator; and a rotor having a flow path groove in contact with the stator and capable of switching the flow path between the first input port and the second input port. Switching valve. 4. The flow path switching valve according to claim 3, wherein the flow path groove is an arc-shaped flow path groove having at least a length from the first input port through the output port to the second input port. The stator has a port for sucking a sample in addition to the first input port, the second input port and the output port, and the rotor can connect the second input port and the port for sucking the sample. The flow path switching valve according to claim 3 or 4, further comprising an arcuate sub flow path groove. A valve for switching the flow path of the sample and / or eluent that is continuously injected, and the flow path can be switched by a linear reciprocating operation. A stator in which a first input port into which the sample is injected, an output port for feeding the injected sample and / or eluent, and a second input port into which the sample is injected are arranged in order, and is in contact with the stator A flow path switching valve comprising: a slider having a flow path groove capable of switching the flow path between the first input port and the second input port of the output port. 7. The flow path switching valve according to claim 6, wherein the flow path groove is a linear flow path groove having at least a length from the first input port to the second input port via the output port. The stator has a port for sucking the sample in addition to the first input port, the second input port and the output port, and the slider can connect the second input port and the port for sucking the sample. The flow path switching valve according to claim 6 or 7, further comprising a linear sub flow path groove. 9. The flow path switching valve according to claim 1; an analysis column for separating a sample; A liquid section, a detection section for detecting the sample separated by the analytical column, a pipe connecting these components, and a control section for controlling the operation of the liquid feeding section and the flow path switching valve. A liquid chromatograph, wherein the flow path switching valve is used as a sample injection switching valve when the eluent and / or the sample is sent to the analysis column.

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