阅读说明：本技术 自动取样器及流体色谱仪 (Automatic sampler and fluid chromatograph ) 是由 柳林润 中谷友祐 于 2017-07-04 设计创作，主要内容包括：自动取样器是在向样品环填充试样时使注入阀成为试样填充状态,在试样的填充结束之后将注入阀切换成中间状态而先仅将样品环的一端与送液流路及分析流路连接。然后,将注入阀切换成试样注入状态,使样品环夹隔在送液流路与分析流路之间,由此将试样向分析流路注入。(The automatic sampler is configured such that the injection valve is set to a sample filling state when the sample ring is filled with the sample, and the injection valve is switched to an intermediate state after the completion of the filling of the sample, and only one end of the sample ring is connected to the liquid feeding channel and the analysis channel. Then, the injection valve is switched to a sample injection state, and the sample ring is sandwiched between the liquid feeding channel and the analysis channel, whereby the sample is injected into the analysis channel.)

1. An autosampler, comprising:

a sample collection unit for sucking a sample from a sample container and collecting the sample;

a sample ring that holds the sample collected by the sample collection unit; and

an injection valve having a plurality of connection ports and a rotor including a flow path for communicating the connection ports, the connection ports being switched between communication states by rotating the rotor, wherein the plurality of connection ports include at least a pump port to which a liquid feed flow path including a liquid feed pump for feeding a mobile phase is connected, a column port to which an analysis flow path leading to an analysis column is connected, a first ring port connected to one end of the sample ring, and a second ring port connected to the other end of the sample ring; and is

The injection valve is configured to be selectively switched to any one of a sample filling state in which the pump port is communicated with the column port and neither of the first ring port and the second ring port is communicated with the pump port and the column port, an intermediate state in which the pump port is communicated with the column port while the first ring port is communicated with the pump port and the column port and the second ring port is closed, and a sample injection state in which the pump port is communicated with one of the first ring port and the second ring port while the column port is communicated with the other of the first ring port and the second ring port.

2. The autosampler of claim 1,

the injection valve is configured to switch from the sample-filled state to the intermediate state while communicating the pump port and the column port via the flow path of the rotor.

3. The autosampler of claim 1 or 2,

the injection valve is configured to switch from the intermediate state to the sample injection state while maintaining communication between the pump port or the column port and the first annular port.

4. An autosampler according to any of claims 1 to 3, comprising:

a drive mechanism that drives the rotor; and

a control unit configured to control an operation of the drive mechanism; and is

The control unit includes a pressure fluctuation relaxation operation unit configured to control a speed at which the rotor is driven by the drive mechanism so that a time required for switching from the sample filling state to the intermediate state is longer than a time required for switching from the intermediate state to the sample injection state.

5. An autosampler according to any of claims 1 to 4, comprising:

a drive mechanism that drives the rotor; and

a control unit configured to control an operation of the drive mechanism; and is

The control unit includes a pressure recovery operation unit configured to control the operation of the drive mechanism so as to stop temporarily after the injection valve is switched from the sample filling state to the intermediate state, and then switch from the intermediate state to the sample injection state.

6. A fluid chromatograph comprising:

a liquid feeding flow path including a liquid feeding pump for feeding a mobile phase;

an analysis flow path including an analysis column for separating a sample into components and a detector for detecting the components of the sample separated by the analysis column; and

the autosampler according to any one of claims 1 to 5, comprising a sample ring for holding a sample, and comprising an injection valve which is selectively switched to any one of a sample filling state in which the liquid feeding flow path and the analysis flow path are connected without passing through the sample ring, a sample injection state in which the liquid feeding flow path and the analysis flow path are connected with passing through the sample ring, and an intermediate state in which only one end of the sample ring is connected to the liquid feeding flow path and the analysis flow path while the liquid feeding flow path and the analysis flow path are connected, and the other end of the sample ring is closed.

7. The fluid chromatograph of claim 6, wherein,

the liquid feeding pump is configured to increase a liquid feeding flow rate when the injection valve of the auto-sampler is switched from the sample filling state to the intermediate state or when the injection valve of the auto-sampler is in the intermediate state, compared to when the injection valve is in another state.

Technical Field

The present invention relates to an autosampler (autosampler) for automatically injecting a sample into an analysis flow path of a Fluid Chromatograph such as a Liquid Chromatograph (LC) or a Supercritical Fluid Chromatograph (SFC), and a Fluid Chromatograph (Chromatograph) using the autosampler.

Background

In an automatic sampler for a High Performance Liquid Chromatograph (HPLC), a rotary type switching valve (valve) is generally used as an "injection valve". The injection valve includes a stator (stator) having a plurality of connection ports (ports), and a rotor (rotor) having a flow path for communicating the connection ports. Then, the combination of the connection ports to be communicated is switched by rotating the rotor.

A liquid feeding channel for feeding a mobile phase by a liquid feeding pump (pump) is connected to a connection port of the injection valve, and an analysis channel leading to an analysis column (column) and a sample loop (sample loop) for temporarily holding a sample are connected thereto. The injection valve is configured to selectively switch between a sample filling state in which the liquid feeding channel and the analysis channel are connected without a sample ring and a sample injection state in which the liquid feeding channel and the analysis channel are connected with a sample ring.

The operation of injecting the sample into the analysis channel is performed by the following procedure (step). First, the injection valve is set to a sample-filled state. Thus, the mobile phase from the liquid feed pump flows directly to the analytical column without passing through the sample ring. At this time, the sample ring is filled with the test specimen. Thereafter, the injection valve is switched to a sample injection state, whereby the sample filled in the sample ring is introduced into the analytical column together with the mobile phase.

Disclosure of Invention

[ problems to be solved by the invention ]

In a state in which the injection valve is in the middle of switching from the sample filling state to the sample injection state, the communication between the liquid feeding channel and the analysis channel is temporarily blocked, and the pressure in the liquid feeding channel further increases and the pressure in the analysis channel decreases. In this way, the communication between the liquid feeding channel and the analysis channel is temporarily blocked in the middle of switching the injection valve from the sample filling state to the sample injection state, and pressure fluctuations occur in the liquid feeding channel and the analysis channel.

In order to suppress such pressure fluctuations, it has been proposed to provide a flow path for allowing the liquid feeding flow path and the analysis flow path to communicate with each other even in the middle of switching the injection valve from the sample filling state to the sample injection state in the stator (see patent document 1). In this way, even in the middle of switching the injection valve from the sample filling state to the sample injection state, the communication between the liquid feeding channel and the analysis channel is not blocked, and therefore, the pressure fluctuation caused by this is suppressed. However, the provision of such a flow path in the stator is not easy from the design point of view, and also leads to an increase in cost (cost).

In addition, the filling valve is generally designed to: when the sample filling state is switched to the sample injection state, the connection between the liquid feeding channel and one end of the sample ring and the connection between the analysis channel and the other end of the sample ring are performed simultaneously or with a slight time difference. However, depending on the machining and assembling error of the stator or rotor of the injection valve or the degree of abrasion of the rotor, both ends of the sample ring may not be connected to the liquid feeding flow path and the analyzing flow path as designed. That is, when the injection valve is switched from the sample filling state to the sample injecting state, there are cases where the pressure is first applied from one end side of the sample ring and where the pressure is first applied from the other end side, and this becomes an uncertain factor.

If the sample ring is pressurized from one end side, the sample filled in the sample ring moves to the other end side, and therefore, if such an indeterminate factor exists, the analysis result varies, and reproducibility is impaired.

The sample ring filled with the sample was set to atmospheric pressure. Therefore, when the injection valve is switched from the sample filling state and the liquid feeding channel and the analysis channel are connected to the sample ring, the pressure in the liquid feeding channel and the pressure in the analysis channel are instantaneously reduced. Such a pressure drop is commonly referred to as "pressure shock".

If the pressure in the liquid feeding flow path is instantaneously lowered due to the pressure shock, there is a problem as follows: the flow rate of the mobile phase or the composition of the mobile phase varies, and the analytical reproducibility is impaired. Particularly in the case of SFC, rapid pressure fluctuations of the mobile phase in the supercritical state cause fluctuations in the solubility of the sample in the mobile phase, which causes problems such as precipitation of sample components. Further, if the pressure in the analysis flow path instantaneously drops due to the pressure shock, there is also a problem that: the mobile phase flows back in the analytical column, which adversely affects the lifetime of the analytical column. These problems cannot be prevented by the technique disclosed in patent document 1.

Therefore, patent document 2 discloses the following technique: such pressure shock is suppressed by performing the sample injection operation in synchronization with the constant pressure control operation of the liquid sending pump. However, it is difficult to completely suppress the pressure shock in the technique. At the moment of pressure impact, a flow rate defect of several uL typically occurs in a short time of several ms. Therefore, in order to completely suppress the pressure shock, the liquid sending pump must instantaneously increase the flow rate of the few uL/ms to the few mL/s to the few tens mL/min. This would greatly exceed the capacity of a typical liquid delivery pump with a maximum flow rate of several mL/min. This results in an uninhibited pressure shock.

Patent documents 3 to 6 disclose the following techniques: the sample ring is pressurized in advance to suppress pressure shock before the sample injection operation by operating a pressurizing member provided outside or inside the sample ring. However, these techniques require, for example, a pressurizing means capable of pressurizing the sample ring in advance to, for example, a pressure exceeding 100MPa at the maximum. Such a pressing member is expensive, and a new problem arises in ensuring reliability of a driving mechanism of the pressing member, a high pressure seal (seal), and the like.

Therefore, an object of the present invention is to suppress pressure fluctuations in the flow path that occur when the injection valve is switched, and to reduce the influence of uncertainty factors on the analysis result when the injection valve is switched. Further, the object is to alleviate the pressure shock caused by the sample ring connected to the atmospheric pressure, thereby improving the analytical reproducibility and the column life.

[ means for solving problems ]

An automatic sampler of the present invention includes a sample collection unit that sucks a sample from a sample container and collects the sample, a sample ring that holds the sample collected by the sample collection unit, and an injection valve that has a plurality of connection ports and a rotor, and switches a communication state between the connection ports by rotating the rotor, wherein the plurality of connection ports include at least a pump port, a column port, a first ring port, and a second ring port, the pump port is connected to a liquid feed flow path including a liquid feed pump that feeds a mobile phase, the column port is connected to an analysis flow path leading to an analysis column, the first ring port is connected to one end of the sample ring, the second ring port is connected to the other end of the sample ring, and the rotor has a flow path for communicating the connection ports. The injection valve is configured to be selectively switched to any one of a sample filling state in which the pump port is communicated with the column port and neither of the first ring port and the second ring port is communicated with the pump port and the column port, an intermediate state in which the pump port is communicated with the column port while the first ring port is communicated with the pump port and the column port and the second ring port is closed, and a sample injection state in which the pump port is communicated with one of the first ring port and the second ring port while the column port is communicated with the other of the first ring port and the second ring port.

That is, in the automatic sampler of the present invention, the injection valve is set to the sample filling state when the sample ring is filled with the sample, and after the filling of the sample is completed, the injection valve is switched to the intermediate state, and only one end of the sample ring is connected to the liquid feeding channel and the analyzing channel. Then, the injection valve is switched to a sample injection state, and the sample ring is sandwiched between the liquid feeding channel and the analysis channel, whereby the sample is injected into the analysis channel. In this way, the injection valve is not directly switched from the sample filling state to the sample injection state, but is switched from the sample filling state to the intermediate state and from the intermediate state to the sample injection state in stages, so that one end of the sample loop is connected to the liquid feeding channel and the analysis channel and pressurized before the other end. This eliminates the uncertainty factor concerning which end of the sample ring is connected to the liquid feeding channel and the analysis channel first when the injection valve is switched from the sample filling state to the sample injection state, thereby improving the reproducibility of the analysis result.

Further, since the injection valve maintains the communication between the pump port and the column port when the sample filling state is switched to the intermediate state, the pressure fluctuation caused by the communication between them being temporarily blocked is suppressed.

Here, the auto-sampler of the present invention includes both the full injection method and the ring injection method. In the ring injection type automatic sampler, both one end and the other end of the sample ring are always connected to the connection ports of the injection valve 14. On the other hand, in the case of the full-volume injection method, a sample ring is provided on the proximal end side of a needle (needle) for sucking and discharging a sample, and one end of the sample ring is always connected to a connection port of an injection valve, but the other end of the sample ring is connected to the connection port of the injection valve when the tip of the needle is inserted into and connected to an injection port (injection port). Therefore, the "first loop port" and the "second loop port" in the present invention include not only a connection port that always connects one end or the other end of the sample loop, but also a connection port that connects one end or the other end of the sample loop when a needle is inserted into the sample inlet to connect.

The "first annular port" and the "second annular port" are different in that a connection port connected to the pump port and the column port when the injection valve is in the intermediate state is the "first annular port".

In the intermediate state of the injection valve, the term "seal the second port" means that the second port does not communicate with any other connection port, or the second port communicates with another connection port, but a flow path for flowing a fluid is not connected to the other connection port that communicates with the second port or a flow path that is sealed is connected to the other connection port, whereby the other end side of the sample ring is sealed. When the injection valve is in the intermediate state and the first ring port communicates with the pump port and the winding port, the other end side of the sample ring is sealed, whereby the pressure in the sample ring can be increased to the same level as that in the liquid feeding channel and the analyzing channel.

The sample ring filled with the sample was set to atmospheric pressure. Therefore, when the injection valve is switched from the sample filling state and the liquid feeding channel and the analysis channel are connected to the sample ring, the pressure in the liquid feeding channel and the pressure in the analysis channel are instantaneously reduced. This pressure drop is commonly referred to as "pressure shock".

If the pressure in the liquid feeding flow path is instantaneously lowered due to the pressure shock, there is a problem as follows: the flow rate of the mobile phase or the composition of the mobile phase varies, and the analytical reproducibility is impaired. Particularly in the case of SFC, rapid pressure fluctuations of the mobile phase in the supercritical state cause fluctuations in the solubility of the sample in the mobile phase, which causes problems such as precipitation of sample components. Further, if the pressure in the analysis flow path instantaneously drops due to the pressure shock, there is also a problem that: the mobile phase flows back in the analytical column, which adversely affects the lifetime of the analytical column. These problems cannot be prevented by the technique disclosed in patent document 1.

Therefore, the autosampler according to the present invention preferably includes a drive mechanism that drives the rotor, and a control unit that controls an operation of the drive mechanism, and the control unit includes a pressure fluctuation relaxation operation unit that controls a speed at which the rotor is driven by the drive mechanism so that a time required for switching from the sample filling state to the intermediate state is longer than a time required for switching from the intermediate state to the sample injecting state. In this case, the time during which the flow path resistance of the connection portion toward the first annular port increases when the injection valve is switched from the sample-filled state to the intermediate state is increased, and thus the rapid inflow of the flow in the liquid-feeding flow path and the analysis flow path into the sample loop is suppressed. This alleviates the pressure shock when the injection valve is switched from the sample-filled state to the intermediate state.

In addition, the auto-sampler of the present invention preferably includes a drive mechanism that drives the rotor, and a control unit configured to control an operation of the drive mechanism, and the control unit includes a pressure recovery operation unit configured to control the operation of the drive mechanism so that the injection valve is temporarily stopped after switching from the sample filling state to the intermediate state, and then switches from the intermediate state to the sample injection state. If the state is maintained for a certain time after the injection valve is switched to the intermediate state, the flow rate of the liquid to be sent and the composition of the mobile phase when the sample loop is connected to the liquid sending channel and the analysis channel by switching the injection valve to the intermediate state can be converged to some extent during this time. This makes it possible to inject the sample into the analysis channel in a state where the liquid feeding flow rate and the composition of the mobile phase are stable, and thus, the reproducibility of the analysis result is improved.

The fluid chromatograph of the present invention includes a liquid feeding flow path including a liquid feeding pump for feeding a mobile phase, an analysis flow path including an analysis column for separating a sample into components and a detector for detecting components of the sample separated by the analysis column, and the automatic sampler including a sample ring for holding the sample and an injection valve selectively switched to any one of a sample filling state in which the liquid feeding flow path and the analysis flow path are connected via the sample ring, a sample injection state in which the liquid feeding flow path and the analysis flow path are connected via the sample ring, and an intermediate state in which the liquid feeding flow path and the analysis flow path are connected while the liquid feeding flow path and the analysis flow path are connected, one end of the sample loop is connected to the liquid feeding channel and the analysis channel, and the other end of the sample loop is closed.

The fluid chromatograph is a liquid chromatograph or a supercritical fluid chromatograph.

In a preferred embodiment of the fluid chromatograph according to the present invention, the liquid-sending pump is configured to make a liquid-sending flow rate larger than that when the injection valve is set to another state when the injection of the auto-sampler is switched from a sample-filled state to an intermediate state or when the injection is set to the intermediate state. Thus, the time required for the pressure in the liquid delivery passage, which has been temporarily lowered by switching the injection valve to the intermediate state, to return to the original liquid delivery pressure is shortened, and the analysis cycle (cycle) can be increased.

[ Effect of the invention ]

In the automatic sampler of the present invention, the injection valve is switched from the sample filling state to the intermediate state and from the intermediate state to the sample injection state in stages, and one end of the sample ring is connected to the liquid feeding flow path and the analysis flow path before the other end of the sample ring is pressurized, so that when the injection valve is switched from the sample filling state to the sample injection state, the uncertainty factor of which end of the sample ring is connected to the liquid feeding flow path and the analysis flow path first disappears, and the reproducibility of the analysis result is improved. Further, since the communication between the pump port and the column port is maintained when the injection valve is switched from the sample filling state to the intermediate state, the pressure fluctuation caused by the communication between them being temporarily blocked is suppressed.

Since the fluid chromatograph of the present invention includes the automatic sampler, it is possible to suppress pressure fluctuations in the flow path and improve the reproducibility of the analysis result. In addition, the pressure impact generated by the sample ring connected to the atmospheric pressure can be relaxed, and the analysis reproducibility and the column life can be improved.

Drawings

Fig. 1 is a diagram showing a flow path configuration when an injection valve of an auto-sampler is in a sample-filled state in an embodiment of a fluid chromatograph.

Fig. 2 is a view showing a flow path structure when the rotor of the injection valve of the automatic sampler is rotated 22.5 degrees in the above embodiment.

Fig. 3 is a diagram showing a flow path structure of the injection valve of the automatic sampler immediately before the injection valve is brought into an intermediate state in the above embodiment.

FIG. 4 is a view showing a flow path structure in the case where the injection valve of the automatic sampler is in an intermediate state in the above embodiment.

FIG. 5 is a view showing a flow path structure in the case where the injection valve of the automatic sampler is in a sample injection state in the above embodiment.

Fig. 6 is a flowchart (flowchart) for explaining an example of the analysis operation by the one-stage injection in the embodiment.

Fig. 7 is a flowchart for explaining an example of the analysis operation by the two-stage injection according to the embodiment.

Fig. 8 is a flowchart for explaining an example of the analysis operation by the three-stage injection according to the embodiment.

Fig. 9(a) and 9(B) are diagrams showing pressure waveforms of the respective channels when an analysis operation using one-stage injection is performed, and fig. 9(B) is an enlarged diagram showing a pressure waveform of a time period for switching the injection valve from the sample-filled state to the intermediate state in fig. 9 (a).

Fig. 10(a) and 10(B) are diagrams showing pressure waveforms of the respective channels when an analysis operation using two-stage injection is performed, and fig. 10(B) is an enlarged diagram showing a pressure waveform of a time period for switching the injection valve from the sample-filled state to the intermediate state in fig. 10 (a).

Fig. 11(a) and 11(B) are diagrams showing pressure waveforms of the respective channels when an analysis operation by three-stage injection is performed, and fig. 11(B) is an enlarged diagram showing a pressure waveform of a time period for switching the injection valve from the sample-filled state to the intermediate state in fig. 11 (a).

Fig. 12(a) and 12(B) are diagrams showing pressure waveforms of the respective flow paths when the analysis operation by the three-stage injection is performed and the rotor rotation in the second stage is performed at a lower speed than the three-stage injection in fig. 11(a) and 11(B), and fig. 12(B) is an enlarged diagram showing a pressure waveform of a time period for switching the injection valve from the sample-filled state to the intermediate state in fig. 12 (a).

Fig. 13 is a diagram showing a flow path configuration when an injection valve of an auto-sampler is in a sample-filled state in another embodiment of a fluid chromatograph.

FIG. 14 is a view showing a flow path structure in the case where the injection valve of the automatic sampler is in the intermediate state in the above embodiment.

FIG. 15 is a view showing a flow path structure in the case where the injection valve of the automatic sampler is in a sample injection state in the above embodiment.

Fig. 16 is a diagram showing a flow path configuration when an injection valve of an auto-sampler is in a sample-filled state in still another embodiment of a fluid chromatograph.

FIG. 17 is a view showing a flow path structure in the case where the injection valve of the automatic sampler is in the intermediate state in the above embodiment.

FIG. 18 is a view showing a flow path structure in the case where the injection valve of the automatic sampler is in a sample injection state in the above embodiment.

Fig. 19 is a diagram showing a flow path configuration when an injection valve of an auto-sampler is in a sample-filled state in still another embodiment of a fluid chromatograph.

FIG. 20 is a view showing a flow path structure in the case where the injection valve of the automatic sampler is in the intermediate state in the above embodiment.

FIG. 21 is a view showing a flow path structure in the case where the injection valve of the automatic sampler is in a sample injection state in the above embodiment.

Detailed Description

Hereinafter, an embodiment of an autosampler and a fluid chromatograph according to the present invention will be described with reference to the drawings.

First, the configuration of an embodiment of an automatic sampler and a fluid chromatograph will be described with reference to fig. 1. In the following examples, a liquid chromatograph is described as an example of a fluid chromatograph.

The liquid chromatograph of the embodiment includes an autosampler 2, and the autosampler 2 includes an injection valve 14. The injection valve 14 is a rotary switching valve and has a plurality of connection ports a to F. A rotor (not shown) of the injection valve 14 is provided with a flow path X, a flow path Y, and a flow path Z for communicating these connection ports, and the flow path structure of the fluid chromatograph is switched by rotating the rotor.

The automatic sampler 2 includes a sampling (sampling) flow path 16 including a needle 20 at a distal end thereof and a sample ring 18 at a proximal end side of the needle 20, and a driving mechanism (not shown) for driving the needle 20 in a vertical direction and an in-horizontal direction, in addition to the injection valve 14. These are sample collection units for collecting the sample stored in the sample container 22 by sucking it from the tip of the needle 20.

The ports a to E of the injection valve 14 of the automatic sampler 2 are arranged in this order counterclockwise on the same circumference, and the port F is arranged at the center. Intervals corresponding to the rotation angle of the rotor of 90 degrees are provided between the connection port a and the connection port B, between the connection port C and the connection port D, and between the connection port a and the connection port E, respectively, and intervals corresponding to the rotation angle of the rotor of 45 degrees are provided between the connection port B and the connection port C, and between the connection port D and the connection port E, respectively.

The proximal end of the sampling channel 16 is connected to the connection port a of the injection valve 14, the injection (syring) channel 26 is connected to the connection port B, a channel leading to the drain (drain) is connected to the connection port C, the sample inlet 24 is connected to the connection port D, the solvent feed channel 4 for feeding the solvent by the liquid feed pumps 6a and 6B is connected to the connection port E, and the analysis channel 8 leading to the analysis column 10 is connected to the connection port F.

A detector 12 is provided downstream of the analytical column 10 in the analytical flow path 8, and the detector 12 detects the sample component separated in the analytical column 10. The injection flow path 26 is connected to a suction-discharge port of an injection pump 30 via a three-way valve 28. A container for storing the cleaning liquid is also connected to the three-way valve 28, and the cleaning liquid can be sucked by a syringe pump 30 and supplied through the injection flow path 26.

In the above embodiment, the connection port E to which the liquid feeding channel 4 is connected serves as a pump port, and the connection port F to which the analysis channel 8 is connected serves as a column port. When the needle 20 is inserted into the sample inlet 24 and connected thereto, the connection port D to which the sample inlet 24 is connected to one end of the sample loop 18. The connection port a to which the base end of the sampling channel 16 is connected to the other end of the sample ring 18. Therefore, one of the connection port a and the connection port D is a "first ring port", and the other connection port is a "second ring port". In the above embodiment, since the connection port D is connected to the pump port E and the column port F when the injection valve 14 is in the intermediate state, the connection port D is the "first ring port", and the connection port a is the "second ring port".

The flow path X of the rotor provided in the injection valve 14 has a substantially L-shaped shape including an arc provided on the same circumference as the circumference on which the connection ports a to E are provided and having a length corresponding to the rotation angle of the rotor of 45 degrees, and a straight line extending in the radial direction so as to connect one end of the arc (the end on the flow path Z side) to the connection port F at the center. The flow path Y and the flow path Z are circular arc-shaped flow paths, and are provided on the same circumference as the circumference on which the connection ports a to E are provided, and have a length corresponding to the rotation angle of the rotor of 90 degrees. The flow paths X, Y, and Z have intervals corresponding to the rotation angle of the rotor of 45 degrees.

The injection valve 14 is selectively switched to any one of a sample filling state (state of fig. 1) in which the connection port E and the connection port F are communicated with each other via the flow path X and the connection port a and the connection port B are communicated with each other via the flow path Y, an intermediate state (state of fig. 4) in which the connection port E and the connection port D and the connection port F are communicated with each other via the flow path X and the connection port a is not communicated with any other port, and a sample injection state (state of fig. 5) in which the connection port a and the connection port E are communicated with each other via the flow path Y and the connection port D and the connection port F are communicated with each other via the flow path X.

When the injection valve 14 is in the sample-filled state, the liquid feeding channel 4 communicates with the analysis channel 8 and the sampling channel 16 communicates with the injection channel 26, as shown in fig. 1. Thus, the mobile phase fed by the liquid feeding pump 6 flows directly to the analysis channel 8 without passing through the sample ring 18. At this time, since the proximal end of the sampling channel 16 communicates with the injection channel 26, the sample can be sucked from the distal end of the needle 20 by driving the syringe pump 30. The sample ring 18 is filled with a sample sucked from the tip of the needle 20.

When the injection valve 14 is in the intermediate state, the sample inlet 24 communicates with the liquid feeding channel 4 and the analyzing channel 8 as shown in fig. 4. At this time, the tip of the needle 20 is inserted into the sample inlet 24 and connected thereto, and the sampling channel 16 is pressurized from the tip side connected to the liquid feeding channel 4 and the analysis channel 8.

When the injection valve 14 is in the sample injection state, as shown in fig. 5, the liquid feeding channel 4 communicates with the base end of the sampling channel 16, and the sample inlet 24 communicates with the analysis channel 8. At this time, the tip of the needle 20 is inserted into the sample inlet 24 and connected, and the liquid feeding channel 4 and the analysis channel 8 are sandwiched by the sample ring 18. In this state, the sample filled in the sample ring 18 is transported to the analysis channel 8 by the mobile phase from the liquid feeding channel 4, and introduced into the analysis column 10. The sample introduced into the analytical column 10 is separated into components, and the components of the sample are detected by the detector 12.

The intermediate state (state of fig. 4) of the fill valve 14 is a state in which the rotor is rotated by 45 degrees in the clockwise direction from the sample filling state (state of fig. 1). While the injection valve 14 is switched from the sample-filled state to the intermediate state, the connection port E and the connection port F are maintained in a state of communication via the flow path X. Since the communication between the liquid feeding channel 4 and the analysis channel 8 is not blocked while the injection valve 14 is switched from the sample filling state to the intermediate state, the pressure fluctuations in the liquid feeding channel 4 and the analysis channel 8 are suppressed.

The sample injection state (state of fig. 5) of the injection valve 14 is a state in which the rotor is further rotated by 45 degrees clockwise from the intermediate state (state of fig. 4). While the injection valve 14 is switched from the intermediate state to the sample injection state, the connection port D and the connection port F are maintained in a state of being communicated with each other via the flow path X. On the other hand, the connection port a and the connection port E are initially connected to each other by the injection valve 14 in the sample injection state. That is, in the above embodiment, the injection valve 14 is switched in the order of the sample filling state, the intermediate state, and the sample injection state, so that the direction in which the sample ring 18 is pressurized after the sample filling is always fixed.

As shown in fig. 1, the operation of a drive mechanism (not shown) that drives the rotor of the injection valve 14 is controlled by a control unit 32. The control unit 32 is realized by a computer (computer) dedicated to the auto-sampler 2, a computer dedicated to the liquid chromatograph, or a general-purpose personal computer (personal computer). The control unit 32 is configured to appropriately switch the injection valve 14 to a desired state to execute each step of analysis by the liquid chromatograph.

A normal analyzing operation by the liquid chromatograph will be described with reference to the flowchart of fig. 6, first, the injection valve 14 is brought into a sample filling state (the state of fig. 1) (step S1), and a sample is sucked from the tip of the needle 20 and filled in the sample ring 18 (step S2). Thereafter, the rotor of the injection valve 14 is rotated 90 degrees at a normal speed (high speed) in the clockwise direction, and the injection valve 14 is switched to the sample injection state (the state of fig. 5) (step S3). When the injection valve 14 is in the sample injection state, the sample filled in the sample ring 18 is introduced into the analysis channel 8, and the sample is analyzed (step S4).

In this manner, the case where the injection valve 14 is switched from the sample filling state (the state of fig. 1) to the sample injection state (the state of fig. 5) at a normal speed (high speed) to inject the sample into the analysis channel 8 is referred to as "one-stage injection" herein. Since the intermediate state is passed through immediately when the injection valve 14 is switched from the sample filling state to the sample injection state, the pressure in the sample ring 18 rises to some extent until the injection valve 14 is in the sample injection state, and the direction in which the pressure in the sample ring 18 is applied can be fixed at all times.

Fig. 9(a) is a pressure waveform of each channel when analysis is performed by the one-stage injection as described above, and fig. 9(B) is an enlarged view of a time period in which the injection valve 14 is switched to connect one end of the sample loop 18 between the liquid feeding channel 4 and the analysis channel 8 in fig. 9 (a). As can be seen from these figures, at the moment when the rotor of the injection valve 14 rotates and the injection valve 14 is in the intermediate state, the pressure in the liquid feeding channel 4 and the analysis channel 8 decreases, and the pressure in the sample loop 18 increases.

As shown in fig. 1, the control portion 32 includes a pressure recovery operation portion 34 and a pressure variation relaxation operation portion 36 so that analysis using more stages of injection can be performed in addition to analysis using one stage of injection as described. The pressure recovery operation unit 34 and the pressure fluctuation relaxation operation unit 36 are functions of the control unit 32 obtained by executing a predetermined program (program) by an arithmetic element.

The pressure recovery operation unit 34 is configured to perform a pressure recovery operation on the injection valve 14 to recover a pressure drop between the liquid feeding channel 4 and the analysis channel 8 caused by the switching operation of the injection valve 14. The so-called pressure recovery operation is the following operation: when the injection valve 14 is switched from the sample filling state (the state of fig. 1) to the sample injection state (the state of fig. 5), the intermediate state (the state of fig. 4) is temporarily stopped, and then the state is switched to the sample injection state (the state of fig. 5). While the injection valve 14 is stopped in the intermediate state, the pressure in the liquid feeding channel 4 and the analysis channel 8, which is lowered when one end of the sample ring 18 is connected between the liquid feeding channel 4 and the analysis channel 8, can be restored.

The pressure fluctuation relaxation operation unit 36 is configured to relax the pressure fluctuation during the switching operation of the injection valve 14 by performing the pressure fluctuation relaxation operation of the injection valve 14. The pressure fluctuation alleviating operation is as follows: the time required to switch the injection valve 14 from the sample filling state (the state of fig. 1) to the intermediate state (the state of fig. 4) is longer than the time required to switch from the intermediate state (the state of fig. 4) to the sample injection state (the state of fig. 5), and thus the state immediately before the injection valve 14 becomes the intermediate state as shown in fig. 3 is longer than the time required to switch the same. The state immediately before the injection valve 14 is in the intermediate state is as follows: the connection port D (first ring port) to which one end of the sample ring 18 is connected is slightly connected to the flow path X, so that the flow path resistance at the connection portion of the connection port D and the flow path X is larger than the flow path resistance at the connection portion of the connection port E (pump port) and the flow path X and the flow path resistance at the connection portion of the connection port F (column port) and the flow path X. By making such a state longer than the case where the time required for switching is the same, the inflow of the flow-facing sample ring 18 becomes slow, and the pressure fluctuation when one end of the sample ring 18 is connected between the liquid feeding channel 4 and the analyzing channel 8 can be alleviated, and the pressure shock can be alleviated. Such an operation is realized by setting the driving speed of the rotor to a low speed slower than the normal speed for the entire time or the latter half of the time of switching from the sample-filled state (the state of fig. 1) to the intermediate state (the state of fig. 4). Here, the normal speed is a driving speed of the rotor when the injection valve 14 is switched from the intermediate state (the state of fig. 4) to the sample injection state (the state of fig. 5).

The analysis by the two-stage injection combined with the pressure recovery operation will be described with reference to the flowchart of fig. 7.

First, in the same manner as the analysis by the one-stage injection, the injection valve 14 is brought into the sample filling state (the state of fig. 1) to fill the sample into the sample ring 18 with the sample (step S11, step S12), and then the rotor of the injection valve 14 is rotated clockwise at a normal speed (high speed) by 45 degrees to be brought into the intermediate state (the state of fig. 4) (step S13). After the injection valve 14 is stopped in the intermediate state for a predetermined time (for example, 3 seconds) (step S14), the rotor is further rotated clockwise at a normal speed (high speed) by 45 degrees to bring the injection valve 14 into the sample injection state (the state of fig. 5) (step S15), and the sample is analyzed (step S16).

In the analysis using the two-stage injection, while the injection valve 14 is stopped in the intermediate state, the pressures in the liquid feeding channel 4 and the analysis channel 8, which are lowered when the injection valve 14 is switched from the sample-filled state to the intermediate state, can be restored. Then, by starting the analysis with the injection valve 14 in the sample injection state, the analysis can be started in a state in which the influence of the flow rate of the mobile phase and the composition fluctuation of the mobile phase due to the switching of the inflow valve 14 is suppressed, and the reproducibility of the analysis result can be further improved compared to the analysis using the one-stage injection.

Fig. 10(a) is a pressure waveform of each channel when analysis by the above-described two-stage injection is performed, and fig. 10(B) is an enlarged view of a time period during which the injection valve 14 is switched to connect one end of the sample loop 18 between the liquid feeding channel 4 and the analysis channel 8 in fig. 10 (a). As is clear from these figures, although the pressures in the liquid feeding channel 4 and the analysis channel 8 decrease at the moment when the injection valve 14 is in the intermediate state, the pressures in the liquid feeding channel 4 and the analysis channel 8 are restored to some extent by maintaining the injection valve 14 in the intermediate state for a certain period of time, and thereafter, the pressures in these channels are stable after the injection valve 14 is switched to the sample injection state.

Further, the flow rate of the mobile phase to be fed by the liquid feeding pump 6 may be increased when the injection valve 14 is switched from the sample filling state to the intermediate state and while the injection valve 14 is stopped in the intermediate state. This increases the speed of recovery of the pressure in the liquid feeding channel 4 and the analysis channel 8, and makes it possible to shorten the time for which the injection valve 14 is stopped in the intermediate state, thereby increasing the analysis cycle. The liquid feeding flow rate may be increased by constant pressure control using the pressure before the sample injection operation as a target value, or by increasing the predetermined flow rate for a predetermined time.

The analysis by the three-stage injection in which the pressure recovery operation and the pressure fluctuation relaxation operation are combined will be described with reference to the flowchart of fig. 8.

First, similarly to the analysis by the one-stage injection and the analysis by the two-stage injection, the injection valve 14 is brought into the sample filling state (the state of fig. 1) to fill the sample into the sample ring 18 with the sample (step S21, step S22), and then the rotor of the injection valve 14 is rotated clockwise at the normal speed (high speed) by 22.5 degrees as shown in fig. 2 (step S23). From the state of fig. 2, the rotor of the inlet valve 14 is further rotated clockwise by 22.5 degrees at a low speed slower than the normal speed, and the inlet valve 14 is brought into an intermediate state (the state of fig. 4) (step S24). As a result, as shown in fig. 3, the state of the injection valve 14 immediately before the intermediate state is maintained longer than the case where the rotor is rotated at the normal speed, and the pressure shock is alleviated. After the injection valve 14 is stopped in the intermediate state for a predetermined time (for example, 3 seconds) (step S25), the rotor is further rotated clockwise at a normal speed (high speed) by 45 degrees to bring the injection valve 14 into the sample injection state (the state of fig. 5) (step S26), and the sample is analyzed (step S27).

In the analysis by the three-stage injection, in addition to the effect of the two-stage injection, since the state immediately before the injection valve 14 is switched from the sample-filled state (the state of fig. 1) to the intermediate state (the state of fig. 4), that is, the state in which the flow path resistance of the connection portion between the connection port D and the flow path X is larger than the flow path resistance of the connection portion between the connection port E (the pump port) and the flow path X and the flow path resistance of the connection portion between the connection port F (the column port) and the flow path X are maintained longer than the case of rotating the rotor at the normal speed, the pressure shock when one end of the sample ring 18 is connected between the liquid-feeding flow path 4 and the analysis flow path 8 is alleviated.

Fig. 11(a) is a pressure waveform of each channel when analysis is performed by the three-stage injection, and fig. 11(B) is an enlarged view of the time period in which the injection valve 14 is switched to connect one end of the sample loop 18 between the liquid feeding channel 4 and the analysis channel 8 in fig. 11 (a). From these figures, it was confirmed that the pressure fluctuations in the liquid feeding channel 4 and the analysis channel 8 at the moment when one end of the sample ring 18 was connected between the liquid feeding channel 4 and the analysis channel 8 were further alleviated than those in fig. 10(a) and 10 (B). This alleviates the pressure shock, suppresses the disturbance of the flow rate of the mobile phase and the composition of the mobile phase, and improves the life of the analytical column 10.

Fig. 12(a) and 12(B) are pressure waveforms of the respective flow paths when the driving speed of the rotor in the pressure fluctuation reducing operation in the three-stage injection is set to a speed further lower than that in fig. 11(a) and 11 (B). From the above-described graph, it was confirmed that the pressure fluctuation in the analysis channel 8 was more gradual than in the case of fig. 11(a) and 11 (B). From this, it is understood that the effect of mitigating the pressure shock is greater as the driving speed of the rotor for performing the pressure fluctuation mitigating operation is slower, and the effect of improving the life of the analytical column 10 is greater. Accordingly, by appropriately adjusting the rotation speed of the rotor, it is possible to balance (balance) the effects of speeding up the analysis cycle and improving the life of the column.

As a further advantage (merit) of such a pressure fluctuation mitigating operation, a combination with the above-described operation of increasing the liquid delivery flow rate by the liquid delivery pump can be cited. That is, since the pressure in the liquid feeding channel 4 and the analyzing channel 8 takes a longer time to fluctuate by the pressure fluctuation alleviating operation, the increase width of the liquid feeding flow rate for eliminating the fluctuation is suppressed to be small. Therefore, it becomes easy to eliminate the pressure fluctuation in the liquid sending capability of the liquid sending pump.

In order to suppress pressure shock caused by switching of the injection valve 14, it is preferable to switch the switching valve 14 at a high speed in a general conceivable method. In contrast, the present inventors have found that the pressure shock generated by switching the injection valve 14 is alleviated as the rotation speed of the rotor at the moment when the pressure shock is generated, that is, at the stage when the sample ring 18 starts to be connected to the liquid feeding channel 4 and the analyzing channel 8, is made slower.

Next, another embodiment of the automatic sampler and the liquid chromatograph will be described with reference to fig. 13 to 15. In fig. 13 to 15, the constituent elements that exhibit the same functions as those shown in fig. 1 to 5 are denoted by the same reference numerals, and detailed description thereof is omitted.

The injection valve 14a of the auto-sampler 2a according to the above-described embodiment is also configured to be selectively switched to any one of a sample filling state (the state of fig. 13), an intermediate state (the state of fig. 14), and a sample injection state (the state of fig. 15), as in the auto-sampler 2 according to the embodiment described with reference to fig. 1 to 5.

The connection ports a to E of the injection valve 14a are arranged in this order in the counterclockwise direction on the same circumference, and the connection port F is arranged at the center. Intervals corresponding to the rotation angle of the rotor of 90 degrees are provided between the connection port a and the connection port B, between the connection port C and the connection port D, and between the connection port D and the connection port E, respectively, and intervals corresponding to the rotation angle of the rotor of 45 degrees are provided between the connection port B and the connection port C, and between the connection port a and the connection port E, respectively.

The proximal end of the sampling channel 16 is connected to the connection port a of the injection valve 14a, the injection channel 26 is connected to the connection port B, a channel leading to the drain is connected to the connection port C, the sample inlet 24 is connected to the connection port D, the analysis channel 8 is connected to the connection port E, and the liquid feeding channel 4 is connected to the connection port F.

The connection port E serves as a column port, and the connection port F serves as a pump port. In the above-described embodiment, contrary to the embodiment shown in fig. 1 to 5, the connection port a is connected to the pump port E and the column port F when the injection valve 14a is in the intermediate state (the state of fig. 14). Therefore, the connection port a becomes the "first ring port", and the connection port D becomes the "second ring port".

The flow path X of the rotor provided in the injection valve 14a has a substantially L-shaped shape including an arc provided on the same circumference as the circumference on which the connection ports a to E are provided and having a length corresponding to the rotation angle of the rotor of 45 degrees, and a straight line extending in the radial direction so as to connect one end of the arc (the end on the flow path Y side) to the connection port F at the center. The flow path Y and the flow path Z are circular arc-shaped flow paths, and are provided on the same circumference as the circumference on which the connection ports a to E are provided, and have a length corresponding to the rotation angle of the rotor of 90 degrees. The flow paths X, Y, and Z have intervals corresponding to the rotation angle of the rotor of 45 degrees.

In the above embodiment, the rotor of the injection valve 14a is rotated 45 degrees in the counterclockwise direction from the sample filling state (the state of fig. 13) to be in the intermediate state (the state of fig. 14), and is further rotated 45 degrees in the counterclockwise direction to be in the sample injection state (the state of fig. 15).

In contrast to the embodiment shown in fig. 1 to 5, in the above embodiment, when the injection valve 14a is in the intermediate state, as shown in fig. 14, the base end of the sampling channel 16 communicates with the liquid feeding channel 4 and the analyzing channel 8. At this time, the distal end of the needle 20 is inserted into the sample inlet 24 and connected, and the sampling channel 16 is pressurized from the proximal end side.

The flow path structure of the injection valve 14a in the sample filling state and the sample injection state is the same as that of the embodiment of fig. 1 to 5. In the above-described embodiment, analysis using multi-stage injection in which the pressure recovery operation and the pressure fluctuation relaxation operation are combined as shown in the flowcharts of fig. 7 and 8 may be performed. By performing the analysis using such multi-stage injection, the pressure fluctuations in the liquid feeding channel 4 and the analysis channel 8 caused by switching of the injection valve 14a can be suppressed, and the reproducibility of the analysis result and the life of the analysis column 10 can be improved.

Fig. 16 to 18 show still another embodiment of an autosampler and a liquid chromatograph. In fig. 16 to 18, constituent elements that exhibit the same functions as those of the constituent elements shown in fig. 1 to 5 are given the same reference numerals, and detailed description thereof is omitted.

The injection valve 14b of the auto-sampler 2b according to the embodiment is also configured to be selectively switched to any one of a sample filling state (the state of fig. 16), an intermediate state (the state of fig. 17), and a sample injection state (the state of fig. 18) as in the auto-sampler 2 according to the embodiment described with reference to fig. 1 to 5.

In the injection valve 14b of the above embodiment, all the connection ports a to F are arranged in this order in the counterclockwise direction on the same circumference. An interval corresponding to 80 degrees in terms of the rotational angle of the rotor is provided between the connection port a and the connection port B and between the connection port C and the connection port D. The interval corresponding to 40 degrees in terms of the rotational angle of the rotor is provided between the connection port B and the connection port C, between the connection port D and the connection port E, and between the connection port E and the connection port F.

The rotor of the injection valve 14b is provided with three circular arc flow paths X, Y, and Z. The flow paths X, Y, and Z each have a length corresponding to 80 degrees in terms of the rotational angle of the rotor, and have an interval corresponding to 40 degrees in terms of the rotational angle of the rotor.

The proximal end of the sampling channel 16 is connected to the connection port a of the injection valve 14B, the injection channel 26 is connected to the connection port B, a channel leading to the drain is connected to the connection port C, the sample inlet 24 is connected to the connection port D, the analysis channel 8 is connected to the connection port E, and the liquid feeding channel 4 is connected to the connection port F.

The connection port E serves as a column port, and the connection port F serves as a pump port. In the above-described embodiment, similarly to the embodiment shown in fig. 1 to 5, the connection port D is configured to be connected to the column port E and the pump port F via the flow path X when the injection valve 14b is in the intermediate state (the state of fig. 17). Therefore, the connection port D becomes the "first ring port", and the connection port a becomes the "second ring port".

In the above-described embodiment, the rotor of the injection valve 14b is rotated 40 degrees clockwise from the sample filling state (the state of fig. 16) to be in the intermediate state (the state of fig. 17), and is further rotated 40 degrees clockwise to be in the sample injection state (the state of fig. 18).

In the above-described embodiment, analysis using multi-stage injection in which the pressure recovery operation and the pressure fluctuation relaxation operation are combined as shown in the flowcharts of fig. 7 and 8 may be performed. By performing the analysis using such multi-stage injection, the pressure fluctuations in the liquid feeding channel 4 and the analysis channel 8 caused by switching of the injection valve 14b can be suppressed, and the reproducibility of the analysis result and the life of the analysis column 10 can be improved.

Fig. 19 to 21 show still another embodiment of an autosampler and a liquid chromatograph. In fig. 19 to 21, the constituent elements that exhibit the same functions as those of the constituent elements shown in fig. 1 to 5 are given the same reference numerals, and detailed description thereof is omitted.

The injection valve 14c of the auto-sampler 2c according to the embodiment is also configured to be selectively switched to any one of a sample filling state (the state of fig. 19), an intermediate state (the state of fig. 20), and a sample injection state (the state of fig. 21) as in the auto-sampler 2 according to the embodiment described with reference to fig. 1 to 5.

In the injection valve 14c of the above-described embodiment, all the connection ports a to F are arranged in this order in the counterclockwise direction on the same circumference, similarly to the injection valve 14b of the auto-sampler 2b of the embodiment described with reference to fig. 16 to 18. Intervals corresponding to 80 degrees in terms of the rotational angle of the rotor are provided between the connection port a and the connection port B, between the connection port C and the connection port D, and between the connection port D and the connection port E, respectively. The distance corresponding to 40 degrees in terms of the rotational angle of the rotor is provided between the connection port B and the connection port C, between the connection port E and the connection port F, and between the connection port a and the connection port F.

The rotor of the injection valve 14b is provided with three circular arc flow paths X, Y, and Z. The flow paths X, Y, and Z each have a length corresponding to 80 degrees in terms of the rotational angle of the rotor, and have an interval corresponding to 40 degrees in terms of the rotational angle of the rotor.

The proximal end of the sampling channel 16 is connected to the connection port a of the injection valve 14B, the injection channel 26 is connected to the connection port B, a channel leading to the drain is connected to the connection port C, the sample inlet 24 is connected to the connection port D, the analysis channel 8 is connected to the connection port E, and the liquid feeding channel 4 is connected to the connection port F.

The connection port E serves as a column port, and the connection port F serves as a pump port. In the above-described embodiment, similarly to the embodiment shown in fig. 13 to 15, the connection port a is configured to be connected to the column port E and the pump port F via the flow path X when the injection valve 14c is in the intermediate state (the state of fig. 20). Therefore, the connection port a becomes the "first ring port", and the connection port D becomes the "second ring port".

In the above embodiment, the rotor of the injection valve 14c is rotated 40 degrees counterclockwise from the sample filling state (the state of fig. 19) to be in the intermediate state (the state of fig. 20), and is further rotated 40 degrees counterclockwise to be in the sample injection state (the state of fig. 21).

In the above-described embodiment, analysis using multi-stage injection in which the pressure recovery operation and the pressure fluctuation relaxation operation are combined as shown in the flowcharts of fig. 7 and 8 may be performed. By performing the analysis using such multi-stage injection, the pressure fluctuations in the liquid feeding channel 4 and the analysis channel 8 caused by switching of the injection valve 14c can be suppressed, and the reproducibility of the analysis result and the life of the analysis column 10 can be improved.

In the embodiment described above, the "full injection type" autosampler that injects the entire amount of the sample filled in the sample ring 18 into the analysis channel 8 is shown, but the present invention is not limited to this, and the present invention can be similarly applied to the "ring injection type" autosampler.

[ description of symbols ]

2. 2a, 2b, 2 c: automatic sampler

4: liquid feeding flow path

6: liquid feeding pump

8: analytical flow path

10: analytical column

12: detector

14: injection valve

16: sampling flow path

18: sample ring

20: needle

22: sample container

24: sample inlet

26: injection flow path

28: three-way valve

30: injection pump

32: control unit

34: pressure recovery operating part

36: a pressure fluctuation relaxation operation section.