WO2020144865A1

WO2020144865A1 - Mixer used in liquid chromatograph, and liquid chromatograph

Info

Publication number: WO2020144865A1
Application number: PCT/JP2019/000768
Authority: WO
Inventors: 悠佑長井
Original assignee: 株式会社島津製作所
Priority date: 2019-01-11
Filing date: 2019-01-11
Publication date: 2020-07-16
Also published as: JP7207435B2; WO2020144878A1; JP7259870B2; JPWO2020144865A1; JPWO2020144878A1

Abstract

This mixer, which is used in a liquid chromatograph, comprises: an inflow opening through which a plurality of types of eluting solutions flow in; a mixing part that mixes the plurality of types of eluting solutions flowing in from the inflow opening; an outflow opening through which the plurality of types of eluting solutions that were mixed by the mixing part flow out, the outflow opening being connected to a flow path that extends to a separation column; and a mixer filter that is provided to both the inflow opening and the outflow opening, or to only the outflow opening. The mixer filter is configured from a sintered compact of a metal material in which no binder is used.

Description

Mixers and liquid chromatographs used in liquid chromatographs

The present invention relates to a mixer and a liquid chromatograph used for a liquid chromatograph.

-For reasons such as improving the elution efficiency in the separation column, two or more different eluents may be used in the liquid chromatograph. For example, when two kinds of eluents are used, the two kinds of eluents supplied via the pump are mixed in the mixer. A ball mixer, for example, is used as the mixer. The ball mixer is filled with ceramic particles, and the two kinds of eluents are mixed while passing between the ceramic particles. The following Patent Document 1 discloses a mixer used in a liquid chromatograph.

In a ball mixer, a filter is used to prevent the outflow of ceramic particles or to remove contaminants in the eluent. As the filter, a sintered body of a metal material having excellent corrosion resistance and heat resistance is used. In the process of manufacturing a filter of a metal sintered body, a sintering aid called a binder is used in order to improve adhesion between metal materials. Patent Document 2 below discloses a filter of a metal sintered body obtained by sintering a mixture of metal powder and an organic binder. As the binder, for example, an organic material such as polyethylene or polypropylene is used. Alternatively, an inorganic material is used as the binder.
JP, 10-185893, A JP, 2011-179077, A

The binder is removed during the manufacturing process of the sintered metal filter. However, it is difficult to completely remove the binder, and the unremoved binder remains in the filter of the metal sintered body. Therefore, when a metal sintered body filter is used in the mixer of the liquid chromatograph, the binder remaining in the filter is gradually eluted from the mixer. Then, the binder eluted from the filter may reach the detector at the subsequent stage.

As a liquid chromatograph detector, for example, an absorbance detector having a quartz flow cell is used. When a quartz flow cell is used for the detector, the inflowing binder contaminates the quartz flow cell. Contamination of quartz flow cells causes baseline drift in the chromatogram. Alternatively, contamination of the quartz flow cell causes ghosts in the chromatogram.

The object of the present invention is to prevent the binder from flowing into the detector in the mixer used for the liquid chromatograph.

(1) A mixer used in a liquid chromatograph according to one aspect of the present invention includes an inflow port into which a plurality of types of eluents flow, a mixing unit that mixes a plurality of eluents that flow in from the inflow port, and a mixing unit. A plurality of kinds of eluents mixed out in the outlet, the outlet being connected to the flow path leading to the separation column, both the inlet and the outlet, or the mixer provided at the outlet. And a mixer, and the mixer filter is composed of a sintered body of a metal material that does not use a binder.

The mixer used in this liquid chromatograph has a mixer filter formed by sintering a metal material without using a binder. Since the binder does not elute from the mixer, it is possible to prevent the binder from flowing into the detector. This can prevent the occurrence of baseline drift or ghost in the chromatogram.

(2) The metal material may include spherical particles of metal. By using the spherical particles, the metal material can be packed in a close-packed structure or a structure close to the close-packed structure, and the spherical particles are closely arranged. As a result, even if the binder is not used, the degree of adhesion of the sintered body of the metal material can be increased. Moreover, by using spherical particles, voids are secured between the spherical particles in the mixer filter. As a result, the pressure loss in the mixer can be reduced.

(3) The metal material may include metal fibers. By using the metal fiber, the manufacturing cost of the mixer filter can be reduced.

(4) When the metal material is spherical particles of metal, the particle size of the spherical particles may be smaller than 20 μm. By making the particle diameter of the spherical particles smaller than 20 μm, even when the material forming the mixing portion is small, the material forming the mixing portion is prevented from flowing out, and the contaminants contained in the eluent are prevented from flowing out. Can be prevented.

(5) The particle size of the spherical particles may be smaller than 10 μm. The accuracy of the filter can be further improved.

(6) The mixer further includes a flow path pipe through which a plurality of types of eluents or mixed eluents flow, and a flow path pipe filter provided in the flow path pipe. The flow path pipe filter uses a binder. It may be composed of a sintered body of a non-metallic material. It is possible to more effectively prevent the binder from being eluted from the mixer.

(7) A liquid chromatograph comprising the mixer according to any one of (1) to (6), further comprising a plurality of eluent tanks containing a plurality of eluents and a plurality of eluents. A plurality of pumps for feeding the sample to the mixer, and an autosampler for injecting a sample into the mixed eluent flowing out of the mixer, and a plurality of flow paths from the plurality of eluent tanks to the plurality of pumps, a plurality of pumps and The filter included in any of the autosamplers may be composed of a sintered body of a metal material that does not use a binder.

It is possible to prevent the binder from eluting from units other than the mixer that the liquid chromatograph has. This makes it possible to more effectively prevent the occurrence of baseline drift or ghost in the chromatogram.

According to the present invention, it is possible to prevent the binder from flowing into the detector in the mixer used for the liquid chromatograph.

FIG. 1 is an overall view of a liquid chromatograph according to this embodiment. FIG. 2 is a diagram comparing the chromatogram obtained by using the mixer of the present embodiment and the chromatogram obtained by using the mixer of the comparative example.

[1] First Embodiment Next, the configuration of a liquid chromatograph according to an embodiment of the present invention will be described with reference to the accompanying drawings.

(1) Overall Configuration of Liquid Chromatograph FIG. 1 is an overall configuration diagram of a liquid chromatograph 10 according to the present embodiment. The liquid chromatograph 10 includes an eluent tank 1A, an eluent tank 1B, a pump 2A, a pump 2B, a mixer 3, an autosampler 4, a separation column 5 and a detector 6.

Eluent 11A is stored in the eluent tank 1A. The eluent 11B is stored in the eluent tank 1B. The liquid chromatograph 10 of the present embodiment is capable of performing gradient elution, in which two kinds of

eluents

11A and 11B are supplied to the separation column 5 while adjusting the mixing ratio thereof.

One end of a flow path pipe 71A is connected to the eluent tank 1A. The other end of the flow path pipe 71A is connected to the pump 2A. By driving the pump 2A, the eluent 11A in the eluent tank 1A is sent to the flow passage pipe 72A downstream of the pump 2A via the flow passage pipe 71A. One end of a flow path pipe 71B is connected to the eluent tank 1B. The other end of the flow path pipe 71B is connected to the pump 2B. By driving the pump 2B, the eluent 11B in the eluent tank 1B is sent to the flow path pipe 72B downstream of the pump 2B via the flow path pipe 71B.

As described above, the liquid chromatograph 10 of the present embodiment can perform gradient elution. When performing gradient elution, the liquid feed patterns of the

pumps

2A and 2B (for example, pump pressure or liquid feed flow rate) are adjusted to adjust the liquid feed amounts of the

eluents

11A and 11B. As a result, the mixed eluent can be supplied to the separation column 5 while changing the mixing ratio of the eluent 11A and the eluent 11B flowing into the mixer 3 with time.

For example, the eluent 11A and the eluent 11B are eluents containing water, acetonitrile, methanol and the like. However, the eluent 11A and the eluent 11B have different mixing ratios of water, acetonitrile, and methanol. Therefore, the mixing ratio of the eluent 11A and the eluent 11B is changed by adjusting the liquid sending pattern (for example, the pump pressure or the liquid sending flow rate) of the pump 2A and the pump 2B, so that the eluent is contained in the mixed eluent. The proportion of each component can be changed over time.

The mixer 3 has an inflow port 32. Flow

path pipes

72A and 72B are connected to the inflow port 32. By driving the

pumps

2A and 2B, the

eluents

11A and 11B sent through the

flow path pipes

72A and 72B flow into the mixer 3 from the inflow port 32. The

eluents

11A and 11B flowing into the mixer 3 from the inflow port 32 pass through the mixing section 31 in the mixer 3 via the inflow port filter 32F. In the present embodiment, mixing section 31 is formed of an aggregate of ceramic particles. The

eluents

11A and 11B that have passed through the mixing section 31 flow out of the mixer 3 from the outlet 33 through the outlet filter 33F.

The mixed liquid of the eluent 11A and the eluent 11B flowing out from the mixer 3 (hereinafter referred to as the mixed eluent) is supplied to the autosampler 4 via the flow path pipe 73. In the auto sampler 4, the injector 41 drops the sample into the mixed eluent. The mixed eluent on which the sample is dropped in the autosampler 4 is sent to the separation column 5 via the flow path pipe 74.

The separation column 5 is supplied with the mixed eluent in which the sample is injected. In the separation column 5, the sample is separated while the mixed eluent passes through the stationary phase in the separation column 5. The mixed eluent in which the sample flowing out from the separation column 5 is dissolved is sent to the detector 6 via the flow path pipe 75.

The detector 6 is supplied with the mixed eluent obtained by separating the sample in the separation column 5. In this embodiment, an absorbance detector is used as the detector 6. The detector 6 includes a quartz flow cell, and when the mixed eluent containing the sample passes through the flow cell having quartz in the liquid contact portion, the quartz flow cell is irradiated with light having a predetermined wavelength. Then, the sample is detected by measuring the intensity change of light before and after the quartz flow cell.

(2) Configuration of Mixer As described above, the mixer 3 includes the mixing unit 31. As described above, the mixing section 31 is composed of an aggregate of ceramic particles in the present embodiment. The ceramic particles are housed in the case 35 of the mixer 3 in a freely movable state. The inflow filter 32F and the outflow filter 33F prevent the ceramic particles from flowing out of the mixer 3. The eluent 11A and the eluent 11B are mixed while moving between the ceramic particles.

As described above, the mixer 3 includes the inflow filter 32F and the outflow filter 33F. Both the inlet filter 32F and the outlet filter 33F are made of a sintered body of a metal material. In the present embodiment, both the inlet filter 32F and the outlet filter 33F are made of a sintered body of metallic spherical particles.

The inflow filter 32F and the outflow filter 33F are filters obtained by sintering spherical metal particles without using a binder. When the metal material is not spherical particles but has an irregular shape, a binder is used in the process of manufacturing a sintered body of the metal material in order to improve the adhesion of the metal material. Since the inlet filter 32F and the outlet filter 33F of the present embodiment use spherical particles as the metal material, a sintered body is formed without using a binder.

Specifically, in the inlet filter 32F and the outlet filter 33F, the spherical particles are closely arranged by being filled with the metallic material of the spherical particles in a close-packed structure or a structure close to the close-packed structure. Therefore, a sintered body is formed without using a binder. The closest packing structure may be a face centered cubic lattice or a hexagonal closest packing structure.

In the present embodiment, the inflow filter 32F and the outflow filter 33F are made of a sintered body of spherical particles of stainless steel. Specifically, SUS316L spherical particles are used as the metal material. The metal material used for the sintered body forming the inflow filter 32F and the outflow filter 33F is not particularly limited. Besides, for example, compounds such as iron and nickel are used. Alternatively, a compound of a plurality of metal alloys is used as the metal material.

As described above, the mixer 3 of this embodiment includes the inflow filter 32F and the outflow filter 33F. The inlet filter 32F and the outlet filter 33F are made of a metal material that is sintered without using a binder. As a result, the binder does not elute from the mixer 3, so that the binder can be prevented from flowing into the detector 6. Therefore, it is possible to prevent the flow cell having quartz in the liquid contact portion, which is included in the detector 6, from being contaminated with the binder. It is possible to prevent the occurrence of baseline drift or ghost in the chromatogram obtained from the detection result of the detector 6.

In liquid chromatographs, filters are used in units other than mixers. Of the filters used in each unit, the capacity of the filter used in the mixer is generally the largest. Therefore, when a binder is used for the filter used in the mixer, the influence of the binder elution on the detector is larger than that of other units. In the liquid chromatograph 10 of the present embodiment, in the mixer 3 that is greatly affected by the elution of the binder, the inlet filter 32F and the outlet filter 33F that do not use the binder are used. This can effectively prevent the occurrence of baseline drift or ghost in the detector 6.

Further, in the present embodiment, the sintered body forming the inflow filter 32F and the outflow filter 33F is formed of spherical particles of a metal material. By using the spherical particles, voids are secured between the spherical particles in the inlet filter 32F and the outlet filter 33F. As a result, the pressure loss in the mixer 3 can be reduced.

The particle size of the spherical particles of the metal material forming the sintered body is not particularly limited, but is preferably smaller than 20 μm. By making the particle diameter of the spherical particles smaller than 20 μm, even if the ceramic particles filled in the mixer 3 are small, the outflow of the ceramic particles is prevented and the contaminants contained in the

eluents

11A and 11B are prevented. It can prevent outflow. The particle diameter of the spherical particles of the metal material forming the sintered body is more preferably smaller than 10 μm. By making the particle size smaller than 10 μm, the accuracy of the filter can be further improved.

(3) Experimental Results FIG. 2 is a diagram comparing the chromatogram obtained by using the mixer 3 of the present embodiment and the chromatogram obtained by using the mixer of the comparative example. FIG. 2 shows experimental results based on Example 1, Example 2 and Comparative Example.

The baseline BL1 in FIG. 2 shows the baseline of the chromatogram according to the first embodiment. In Example 1, the filter including the binder-free sintered body according to the present embodiment was used. In the first embodiment, the inflow filter 32F and the outflow filter 33F are made of a sintered body of spherical particles of stainless steel (SUS316L) having a particle size of 1 μm.

The baseline BL2 in FIG. 2 shows the baseline of the chromatogram according to the second embodiment. In Example 2, the filter including the binder-free sintered body according to the present embodiment was used. In the second embodiment, the inflow filter 32F and the outflow filter 33F are made of a sintered body of spherical particles of stainless steel (SUS316L) having a particle diameter of 2 μm.

The baseline BL3 in FIG. 2 shows the baseline of the chromatogram according to the comparative example. In the comparative example, a filter made of a sintered body using a binder was used. In the comparative example, the inflow filter 32F and the outflow filter 33F are composed of a sintered body of spherical particles of stainless steel (SUS316L) that are adhered to each other using a binder.

In FIG. 2, it can be seen that the baseline BL1 of Example 1 having a particle size of 1 μm hardly causes the baseline drift. In FIG. 2, the baseline BL2 of Example 2 having a particle size of 2 μm has a slight drift as compared with Example 1. However, the drift amount of the baseline BL2 of the example 2 is much smaller than that of the baseline BL3 of the comparative example using the binder. As described above, it can be seen that Example 1 and Example 2 have a significant difference in the drift amount of the baseline as compared with the comparative example.

[2] Second Embodiment Next, a second embodiment of the present invention will be described. In the first embodiment, the mixer 3 included in the liquid chromatograph 10 uses a filter made of a sintered body that does not use a binder. The liquid chromatograph 10 also uses a plurality of filters in other units.

Specifically, the liquid chromatograph 10 includes the following filters. As described above, the

flow path pipes

71A and 71B are connected to the

eluent tanks

11A and 11B. A suction filter is used for the suction ports of the

flow path pipes

71A and 71B.

Further, in the

pumps

2A and 2B, a suction filter is used at the inflow port where the

eluents

11A and 11B flow into the

pumps

2A and 2B. Further, a line filter is used in the flow paths through which the

eluents

11A and 11B are sent in the

pumps

2A and 2B.

Also, in the auto sampler 4, a line filter is used in the flow path through which the mixed eluent is sent.

In the second embodiment, as the suction filter provided in the above-described

flow path pipes

71A and 71B, the suction filter and line filter provided in the

pumps

2A and 2B, and the line filter provided in the autosampler 4. , A filter that does not use a binder is used. That is, as these filters, similar to the inlet filter 32F and the outlet filter 33F used in the mixer 3 described in the first embodiment, a filter that does not use a binder is used. More specifically, as these filters, filters made of a sintered body of a metal material that does not use a binder are used. Alternatively, some of these filters are composed of a sintered body of a metal material that does not use a binder.

As described above, in the second embodiment, the filter provided in any of the

flow path pipes

71A and 71B from the

eluent tanks

1A and 1B to the

pumps

2A and 2B, the

pumps

2A and 2B, and the autosampler 4 is the binder. It is composed of a sintered body of a metal material that does not use. It is possible to prevent the binder from eluting from units other than the mixer 3 included in the liquid chromatograph 10. This can prevent the occurrence of baseline drift or ghost in the chromatogram.

[3] Correspondence between each constituent element of the claims and each element of the embodiment Hereinafter, an example of correspondence between each constituent element of the claim and each element of the embodiment will be described, but the present invention is as follows. Not limited to. In the above embodiment, ceramic particles are an example of the mixing section, and the inlet filter and the outlet filter are examples of the mixer filter.

As each constituent element of the claim, various elements having the configurations or functions described in the claim may be used.

[4] Other Embodiments In the above embodiment, the mixer 3 is provided with the filters at both the inlet 32 and the outlet 33. That is, the case where the mixer 3 includes the inflow filter 32F and the outflow filter 33F has been described as an example. As a configuration other than this, the mixer 3 may have a configuration in which the inlet 32 is not provided with a filter and the outlet 33 is provided with a filter. In this case, the filter provided at the outflow port 33 is composed of a sintered body of a metal material that does not use a binder. This can prevent the binder from being eluted from the mixer 3 and flowing into the detector 6.

Further, a filter for removing foreign matters that may block the flow path such as foreign matters and dust may be used in the flow path pipe in which the eluent 11A or the eluent 11B flows in the mixer 3. Alternatively, a filter that removes foreign matter may be used in the flow path pipe through which the eluent mixed in the mixer 3 flows. In this case, the filter provided in the flow path tube in the mixer 3 is made of a sintered body of a metal material that does not use a binder. This can prevent the binder from being eluted from the mixer 3 and flowing into the detector 6.

In the above embodiment, the case where the metal material is spherical particles has been described as an example. As another example, the metal material may be metal fiber. Similarly, the filter is made of a sintered body of metal fibers that does not use a binder. Then, a filter made of a sintered body of metal fibers is used as the inlet filter 32F and the outlet filter 33F of the mixer 3. If the mixer 3 does not include the inflow filter 32F, the outflow filter 33F is configured by a filter made of a sintered body of metal fibers. Even in this case, since the binder is not used for the sintered body of metal fibers, the binder does not elute from the mixer 3. Further, by using the metal fiber, the manufacturing cost of the filter used in the mixer 3 can be reduced.

In the above embodiment, the case where the mixer 3 is a ball mixer filled with ceramic particles has been described as an example. That is, the case where the ceramic particles are used in the mixing section for mixing the eluent has been described as an example, but this is an example. As the mixer 3, a mixer other than the ball mixer may be used. For example, a dynamic mixer that mixes an eluent by rotating a magnetic stirrer with a magnetic force may be used. That is, a magnetic stirrer may be used as the mixing unit.

The specific configuration of the present invention is not limited to the above-described embodiment, and various changes and modifications can be made without departing from the spirit of the invention.

Claims

An inlet into which multiple types of eluents flow,
A mixing section for mixing the plurality of types of eluents flowing in from the inflow port,
An outlet through which the plurality of types of eluents mixed in the mixing section flow out, and an outlet connected to a flow path leading to a separation column,
Both the inflow port and the outflow port, or a mixer filter provided in the outflow port,
Equipped with
A mixer used in a liquid chromatograph, wherein the mixer filter is composed of a sintered body of a metal material that does not use a binder.
The mixer used in the liquid chromatograph according to claim 1, wherein the metallic material includes spherical metal particles.
The mixer used in the liquid chromatograph according to claim 1, wherein the metal material includes metal fibers.
The mixer used in the liquid chromatograph according to claim 2, wherein the spherical particles have a particle size smaller than 20 μm.
The mixer used in the liquid chromatograph according to claim 2, wherein the spherical particles have a particle size smaller than 10 μm.
The mixer further comprises
A flow path tube through which the plural kinds of eluents or mixed eluents flow,
A flow channel filter provided in the flow channel,
Equipped with
The mixer used in the liquid chromatograph according to any one of claims 1 to 5, wherein the flow channel filter is composed of a sintered body of a metal material that does not use a binder.
A liquid chromatograph comprising the mixer according to claim 1, further comprising:
A plurality of eluent tanks containing the plurality of kinds of eluents;
A plurality of pumps for sending the plurality of types of eluents to the mixer;
An autosampler for injecting a sample into the mixed eluent flowing out from the mixer,
Equipped with
A plurality of flow paths from the plurality of eluent tanks to the plurality of pumps, a filter provided in any of the plurality of pumps and the autosampler, is composed of a sintered body of a metal material without using a binder. Chromatograph.