JP5505249B2 - Online sample introduction device - Google Patents

Description

  The present invention relates to a sample introduction apparatus for introducing a sample online from a manufacturing process or the like into an analysis flow path of a liquid chromatograph.

  In order to introduce a sample into the analysis channel of a liquid chromatograph, there is an on-line sample introduction device that uses a syringe pump to hold the sample in a sample loop and introduces the sample held in the sample loop into the analysis channel ( (See Patent Document 1).

  An example of the configuration of the online sample introduction apparatus will be described with reference to FIGS. 6 and 7 are diagrams showing an example of a flow channel configuration of a liquid chromatograph system including a conventional sample introduction device. FIG. 6 shows a sample suction time, and FIG. 7 shows a sample introduction time.

  The sample introduction apparatus of this example is configured to perform suction of the sample and introduction of the sample into the analysis flow path of the liquid chromatograph by the syringe pump 8. The syringe pump 8 is connected to one end of the first pump connection channel 2c or the cleaning liquid suction channel 2d by the switching valve 12. The other end of the first pump connection flow path 2 c is connected to one port of the 6-way valve 20, and the other end of the cleaning liquid suction flow path 2 d is connected to the cleaning liquid container 21.

  The analysis mobile phase supply flow path 6a and the analysis flow path 6b are connected to the other two ports of the six-way valve 20, and both ends of the sample loop 22 as injection ports of the analysis flow path are connected to the other two ports. Is connected. The remaining one port of the six-way valve 20 is connected to an online sample introduction channel 2b that is connected to the sample channel 2a or the drain 36 by switching. The six-way valve 20 connects the first pump connection channel 2c and the online sample introduction channel 2b via the sample loop 22 and directly connects the analysis mobile phase supply channel 6a and the analysis channel 6b. The sample loop 22 connects the first pump connection flow path 2c and the online sample introduction flow path 2b directly, and the analysis mobile phase supply flow path 6a and the analysis flow path 6b. It is possible to switch to a position to be connected via the position (position in FIG. 7).

  As shown in FIG. 6, when drawing the sample, the flow path is configured so that the syringe pump 8 is connected to the sample flow path 2 a via the sample loop 22, and the sample is sucked by the syringe pump 8. The sample loop 22 holds the sample. Then, as shown in FIG. 7, by switching so that the sample loop 22 is connected between the analysis mobile phase supply flow path 6a and the analysis flow path 6b, the sample held in the sample loop 22 is changed. It is introduced into the analysis flow path 6b by the mobile phases 24a and 24b fed by the pumps 26a and 26b of the analysis mobile phase supply flow path 6a, and is guided to the analysis column 28 and the detector 30 for separation and analysis.

Japanese Patent No. 3815322

  The conventional online sample introduction apparatus as described above simply introduces the sample sucked by the syringe pump 8 and held in the sample loop 22 into the analysis flow path 6b as it is, and diluted before being introduced into the analysis flow path 6b. However, it is not configured to assume that a small amount of sample smaller than the amount held in the sample loop 22 is introduced. For example, when a mixer for diluting a sample is provided, a high liquid feeding pressure is required to feed the sample into the mixer, and a syringe pump with a low pressure resistance causes problems such as liquid leakage. When the sample channel 2a has a long channel length, a syringe pump 8 having a large cylinder capacity of, for example, about 3 mL is used. Such a large-capacity syringe pump cannot accurately inject a small amount of sample such as several μL to several tens of μL into the analysis channel.

From the above, it has been difficult for the conventional on-line sample introduction apparatus to perform processing such as sample dilution or micro-quantization at the stage before introduction into the liquid chromatograph.
SUMMARY OF THE INVENTION Accordingly, an object of the present invention is to provide a sample introduction apparatus capable of performing processing such as dilution and microinjection on a sample at a stage before introducing the sample into an analysis flow path of a liquid chromatograph. is there.

  An on-line sample introduction apparatus according to the present invention includes a first sample loop that holds a sample from an on-line sample introduction flow path for sucking a circulating sample, and a sample to the first sample loop via the online sample introduction flow path. A first pump comprising a syringe pump for suction, a second pump for extruding a sample held in the first sample loop with a solvent, both ends of the first sample loop, an on-line sample introduction channel, a first pump, a second pump, and A port having a port connected to each of the sample transport channels, a position for connecting the first sample loop between the online sample introduction channel and the first pump, and a first sample loop connected to the second pump and the sample transport channel A first flow path switching valve for switching between a position connected to the first and a second position for holding a sample to be injected into the liquid chromatograph A sample loop, two ends of the second sample loop, a mobile phase supply channel for analysis of a liquid chromatograph, a channel connected to a column of a liquid chromatograph, a port connected to a sample transport channel and a discharge channel, Between a position where the second sample loop is connected between the sample transport channel and the discharge channel, and a position where the second sample loop is connected between the mobile phase supply channel for analysis and the channel connected to the column. A second flow path switching valve for switching is provided.

  According to the above configuration, in the online sample introduction device according to the present invention, the position of the first flow path switching valve is switched to a position where the first sample loop is connected between the online sample introduction flow path and the first pump. The sample is sucked from the online sample introduction channel by the first pump, and the sample is held in the first sample loop. Thereafter, the position of the first flow path switching valve is switched to a position where the first sample loop is connected between the second pump and the sample transport flow path, and the position of the second flow path switching valve is changed by the second sample loop. At a position connected between the sample transport channel and the discharge channel, the sample held in the first sample loop is transported to the second sample loop by the solvent fed by the second pump, and is liquid chromatographed. Hold the sample to be injected. The sample held in the second sample loop is obtained by switching the position of the second flow path switching valve to a position where the second sample loop is connected between the mobile phase supply flow path for analysis and the flow path connected to the column. The analysis is conducted by introducing it to the column together with the mobile phase for analysis.

  As described above, in the on-line sample introduction apparatus of the present invention, the sample is introduced into the liquid chromatograph through the holding of the sample twice by the first sample loop and the second sample loop. The sample can be processed at the stage of sending the sample to the second sample loop. The sample is transported from the first sample loop to the second sample loop using a second pump that is different from the first pump that sucks the sample through the online sample introduction flow path. A pump can be used.

  When dilution is performed as processing into the above-described sample, a pump for feeding higher pressure than the first pump is used as the second pump, a mixer is provided in the sample transport channel, and the diluent is sampled through the mixer. It is preferable to provide a diluent supply channel that supplies the transport channel. If a mixer is provided in the sample transport flow path, a high liquid pressure is required when sending a sample from the first sample loop to the second sample loop, so a high back pressure is applied to the second pump. Since a pump for high-pressure liquid feeding is used rather than the first pump, occurrence of liquid leakage or the like can be prevented.

  In addition, when a smaller amount of sample than the sample held in the first sample loop is injected into the liquid chromatograph, it is preferable to use a syringe pump having a smaller capacity than the first pump as the second pump. Since the syringe pump having a smaller capacity than the first pump has higher resolution than the first pump, a small amount of sample that cannot be accurately delivered by the first pump can be delivered with high accuracy.

  According to the present invention, since the sample is introduced into the liquid chromatograph through the holding of the sample twice by the first sample loop and the second sample loop, the first sample loop to the second sample loop. At the stage of sending the sample, it is possible to process the sample such as diluting or reducing the amount of the sample. And since it is configured to use different pumps for sucking and holding the sample in the first sample loop and for sending the sample from the first sample loop to the second sample loop, it is possible to process the sample. A suitable pump can be used.

It is a flow-path figure at the time of sample drawing which shows an example of the flow-path structure of the liquid chromatograph system containing an online sample introduction apparatus. It is a flow path figure at the time of the sample introduction to the injection port in the Example. It is a flow path figure at the time of the sample introduction to the injection port in the Example. It is a flow path figure at the time of the sample introduction | transduction to the analysis flow path in the Example. It is a flow-path figure which shows the other example of the flow-path structure of the liquid chromatograph system containing an online sample introduction apparatus. It is a channel diagram at the time of sample aspiration showing an example of a channel configuration of a liquid chromatograph system including a conventional sample introduction device. FIG. 7 is a flow chart when a sample is introduced into an analysis flow path in the same example as in FIG. 6.

  One embodiment of an on-line sample introduction apparatus for introducing a sample into an analysis flow path of a liquid chromatograph will be described with reference to FIGS. 1 to 4 are flow charts showing an example of the flow path configuration of a liquid chromatograph system including an on-line sample introduction device. FIG. 1 is a drawing of a sample, and FIGS. 2 and 3 are a drawing of a sample to an injection port. FIG. 4 shows the channel configuration when the sample is introduced into the analysis channel.

First, the flow channel configuration of the liquid chromatograph system of this embodiment will be described with reference to FIG.
The liquid chromatograph includes an analysis mobile phase supply channel 6a and an analysis channel 6b. The analysis mobile phase supply flow path 6a is a flow path for feeding the mobile phases 24a and 24b by the liquid feed pumps 26a and 26b, and the downstream end is one of the six-way valve 20 (second flow path switching valve). Connected to the port. The analysis flow path 6 b includes an analysis column 28 and a detector 30, and an upstream end is connected to one port of the 6-way valve 20.

  The remaining ports of the six-way valve 20 are connected to both ends of the sample loop 22 (second sample loop), the sample transport channel 4b, and the drain 38 (discharge channel). A mixer 32 is provided on the sample transport channel 4 b, and a diluent supply channel for supplying a diluent by a diaphragm pump 34 is connected to the mixer 32.

  The 6-way valve 20 connects the sample loop 22 between the sample transport channel 4b and the drain 38, and at the same time directly connects the analysis mobile phase supply channel 6a and the analysis channel 6b, and the sample transport channel. 4b and the drain 38 can be directly connected and simultaneously switched between positions for connecting the sample loop 22 between the analysis mobile phase supply flow path 6a and the analysis flow path 6b.

  The transfer mobile phase supply flow path 4a is connected to one port of the six-way valve 14 (first flow path switching valve). The transfer mobile phase supply channel 4a is a channel through which the solvent 19 is sent by the diaphragm pump 18 (second pump). The remaining ports of the six-way valve 14 are connected to both ends of the sample loop 16 (first sample loop), the online sample introduction channel 2b, and the first pump connection channel 2c.

  The online sample introduction channel 2 b is a channel that is switched and connected to the sample channel 2 a or the drain 36 via the switching mechanism 10. The sample channel 2a is a channel for sucking a sample from the tip.

  The first pump connection channel 2c is a channel connected to the syringe pump 8 (first pump) via the switching mechanism 12. The switching mechanism 12 also has a port connected to one end of the cleaning liquid suction flow path 2d, and the port connected to the syringe pump 8 can be switched and connected to the first pump connection flow path 2c or the cleaning liquid suction flow path 2d. . The other end of the cleaning liquid suction channel 2d is connected to a container containing the cleaning liquid 21.

  The 6-way valve 14 connects the sample loop 16 between the first pump connection channel 2c and the online sample introduction channel 2b, and at the same time, directly connects the transfer mobile phase supply channel 4a and the sample transfer channel 4b. A position to connect the sample loop 16 between the transfer mobile phase supply flow path 4a and the sample transfer flow path 4b at the same time as the first pump connection flow path 2c and the online sample introduction flow path 2b are directly connected. Can be switched between.

Next, the operation of the liquid chromatograph system of this embodiment will be described.
As shown in FIG. 1, the syringe pump 8-first pump connection channel 2c-sample loop 16-online sample introduction channel 2b-sample channel 2a is connected. The syringe pump 8 is driven to the suction side to draw the sample, and the sample is held by the sample loop 16.

  Next, as shown in FIG. 2, the transfer mobile phase supply flow path 4a-sample loop 16-sample transfer flow path 4b-sample loop 22-drain 38 is connected. The solvent 19 is fed by the diaphragm pump 18, and the sample held by the sample loop 16 is pushed out by the solvent 19 and conveyed to the sample loop 22. At this time, the diluent is supplied to the mixer 32 at a constant flow rate by the diaphragm pump 34, and the sample and the diluent are mixed at a constant ratio in the mixer 32, and the diluted sample is introduced into the sample loop 22 and held. Is done.

  At this time, the syringe pump 8 is connected to the first pump connection channel 2c, the on-line sample introduction channel 2b, and the drain 36, and the syringe pump 8 is driven in the discharge direction to discharge unnecessary samples to the drain 36. Can do. Further, as shown in FIG. 3, the switching mechanism 12 is switched to connect the syringe pump 8 to the cleaning liquid suction flow path 2d, the cleaning liquid is sucked by the syringe pump 8, and then the switching mechanism 12 is switched again to switch the syringe pump. 8-First pump connection channel 2 c-Online sample introduction channel 2 b-Drain 36 is connected, and the cleaning liquid is supplied into these channels from syringe pump 8, thereby cleaning the inside of the channel.

  After holding the sample in the sample loop 22, the six-way valve 20 is switched to connect the sample loop 22 between the analysis mobile phase supply flow path 6a and the analysis flow path 6b, whereby the analysis mobile phase supply flow path 6a. The sample held in the sample loop 22 by the solvents 24a and 24b fed from the liquid is guided to the analysis column 28 and the detector 30 in the analysis flow path 6b. At this time, the sample remaining in the sample loop 16 and the sample transport channel 4b is discharged to the drain 38 together with the solvent 19 fed by the diaphragm pump 18.

  In the sample introduction apparatus of this embodiment, since the mixer 32 for mixing the diluent is provided on the sample transport channel 4b, a high liquid feeding pressure is applied when the sample is transported from the sample loop 16 to the sample loop 22. Necessary. When only one syringe pump 8 is provided as a liquid-feeding pump as in the conventional sample introduction apparatus shown in FIGS. 6 and 7, the sample must be transported to the sample loop 22 using the syringe pump 8. However, since the mixer 32 is present, a high back pressure is applied to the syringe pump 8 and there is a possibility that problems such as liquid leakage may occur. However, in this embodiment, when the sample is transported from the sample loop 16 to the sample loop 22, the diaphragm pump 18 for high-pressure liquid feeding is used rather than the syringe pump 8, so that the sample is diluted into the sample loop 22 without any problem. Transport can be performed.

  In the above embodiment, the diaphragm pump 18 is used when the sample is introduced into the sample loop 22. However, as shown in FIG. 5, the capacity of the syringe pump 8 is larger than that of the diaphragm pump 18. A small syringe pump 18a can be used. In this case, the syringe pump 18a is switched and connected to either the transfer mobile phase supply flow path 4a or the solvent container 19 by a flow path switching mechanism.

  In order to transport the sample held in the sample loop 16 to the sample loop 22 in the liquid chromatograph system of FIG. 5, the solvent 19 is sucked into the syringe pump 18a, and then the syringe pump 18a-transporting mobile phase supply flow Connected to the channel 4a-sample loop 16-sample transport channel 4b-sample loop 22-drain 38, the amount of solvent required to introduce a predetermined amount of sample into the sample loop 22 from the syringe pump 18a is pushed out. Since the syringe pump 18 a has a higher resolution than the syringe pump 8, a small amount of sample that cannot be controlled with high accuracy using the syringe pump 8 can be accurately introduced into the sample loop 22.

  If the position where the sample exists is far and the length of the flow path 2a becomes long, a large amount of sample must be sucked in order to hold the sample by the sample loop 16, and it is necessary to use a syringe pump having a large cylinder capacity. There is. Since the syringe pump with a large cylinder capacity has a large cylinder inner diameter, the resolution of the suction amount and the discharge amount is low, and if a small amount of sample is sucked or discharged with such a syringe pump, the error becomes large. In the sample introduction device in the liquid chromatograph system shown in FIG. 5, the sample loop 16 is removed from the sample loop 16 using a syringe pump 18 a having a higher resolution than the syringe pump 8 different from the syringe pump 8 for sucking the sample into the sample loop 16. Since the sample is transported to the sample loop 22, an amount of sample that cannot be handled accurately by the syringe pump 8 can be accurately introduced into the sample loop 22.

2a Sample channel 2b Online sample introduction channel 2c Syringe pump connection channel 2d Cleaning liquid suction channel 4a Mobile phase supply channel for transfer 4b Sample transfer channel 6a Mobile phase supply channel for analysis 6b Analysis channel 8 Syringe pump 10 , 12 Channel switching mechanism 14, 20 6-way valve 16, 22 Sample loop 18, 26a, 26b, 34 Diaphragm pump 19, 24a, 24b, mobile phase 21 Washing liquid 28 Analytical column 30 Detector 32 Mixer 36, 38 Drain

Claims (1)

A first sample loop for holding a sample from an online sample introduction flow path for sucking a circulating sample;
A first pump comprising a syringe pump for sucking a sample into the first sample loop via the online sample introduction channel;
A pump for extruding the sample held in the first sample loop with a solvent, and a second pump for feeding higher pressure than the first pump ;
It has ports connected to both ends of the first sample loop, the online sample introduction flow path, the first pump, the second pump, and the sample transfer flow path, and the first sample loop is connected to the online sample introduction flow path and the first sample loop. A first flow path switching valve for switching between a position connected to the pump and a position connecting the first sample loop between the second pump and the sample transport flow path;
A mixer provided in the sample transport channel;
A flow path for supplying a dilution liquid to the sample transport flow path through the mixer, and comprising a third pump independent of the first pump and the second pump for supplying the dilution liquid A liquid supply channel;
A second sample loop holding a sample for injection into a liquid chromatograph;
And having ports connected to both ends of the second sample loop, a mobile phase supply channel for analysis of the liquid chromatograph, a channel connected to the column of the liquid chromatograph, the sample transport channel and the discharge channel, Position for connecting two sample loops between the sample transport channel and the discharge channel, and position for connecting the second sample loop between the mobile phase supply channel for analysis and a channel connected to the column A second flow path switching valve for switching between,
An online sample introduction device for diluting an online sample and injecting it into a liquid chromatograph .

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