JP2006003203A - Gradient mixer for liquid chromatography - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a gradient mixer for liquid chromatography having a plurality of solvent systems. <P>SOLUTION: The gradient mixer for liquid chromatography has a first end part in which a plurality of solvents flow, a second end part from which a plurality of solvents flow out, the mixing chamber extending to the space between the first and second end parts and the stirring member put in the mixing chamber. The stirring member is formed so that the solvents flow through the inside and outside of the member. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to a gradient mixer for liquid chromatography having a plurality of solvent systems.

  A liquid chromatography apparatus is widely used as a means for performing separation and quantitative analysis of various compounds regardless of whether they are of synthetic origin or natural origin. In addition, the liquid chromatography method has excellent characteristics as a means for establishing separation and reproducibility of the target substance by variously changing the column, solvent, detector, etc. according to the target substance. is doing.

  In a test object containing many kinds of compounds, a gradient method using a plurality of solvents is frequently used. In this case, it is assumed that the test object includes compounds with different physicochemical properties (for example, hydrophilicity or hydrophobicity), and separation and analysis are performed by liquid chromatography using a single solvent. Difficult to do. Therefore, by adopting a liquid chromatography system using a plurality of solvents, sending a plurality of solvents on-line of the system, and variously changing the composition of the solvent in the system, the target compound / component is more It becomes possible to examine in detail.

  In the gradient method, it is necessary to accurately control the composition of multiple solvents in order to establish the desired separation and reproducibility, and a gradient mixer that mixes multiple solvents sent from multiple pumps is used. Yes. Each of the plurality of pumps delivers a constant flow rate of solvent over the system according to a predetermined time schedule, and a desired solvent composition ratio is achieved downstream of the system.

Patent Document 1 discloses a gradient mixer, and FIG. 2 shows a schematic diagram of a prior art gradient mixer. The gradient mixer 20 in the prior art has an inlet 22 through which a solvent flows, a mixing chamber 26 into which the solvent flows in, and an outlet 24 through which the mixed solvent flows out. Further, the mixing chamber 26 is filled with a porous resin 28, and a plurality of solvents are introduced into the gradient mixer 20 and mixed by the porous resin 28 in the mixing chamber 26.
JP-A-6-324026

  However, there has been a problem that the solvent mixing property of the gradient mixer in the prior art is not sufficient.

  The present invention has been made in view of the above circumstances, and is solved by a gradient mixer having the following configuration.

  That is, according to the first aspect of the present invention, the first end portion into which a plurality of solvents flows; the second end portion from which the plurality of solvents flow out; between the first end portion and the second end portion A gradient mixer for liquid chromatography having a mixing chamber extending to the mixing chamber; and a stirring member filled in the mixing chamber, wherein the stirring member is formed so that the solvent flows inside and outside the member. A gradient mixer for liquid chromatography is provided. This makes it possible to achieve the desired solvent composition on-line of the system.

  The stirring member is preferably formed so that a plurality of solvents used for liquid chromatography flow inside and outside, and examples thereof include a hollow member.

  Moreover, it is preferable to form with the material inactive with respect to the solvent used for a liquid chromatography, for example, a Teflon (trademark) resin can be mentioned. Thereby, in addition to the above, it is possible to achieve the desired composition ratio of the solvent on-line without affecting the separability and reproducibility of the object to be examined.

  Moreover, it is preferable that the full length of the said stirring member exists in the range of 1-5 mm. Thereby, in addition to the above, it becomes possible to achieve various composition ratios along the time schedule with good follow-up.

  Further, by adopting the gradient mixer according to any one of claims 1 to 5 of the present invention in a desired liquid chromatography system, it is possible to faithfully reproduce the originally intended eluent profile. Become.

  It is possible to provide a gradient mixer for liquid chromatography capable of mixing a plurality of solvents with good followability.

  Referring to FIG. 1, a gradient mixer 10 according to the present invention is shown. The gradient mixer 10 includes a first end portion 12 into which a plurality of solvents flow, a second end portion 14 from which a plurality of solvents flow out, and a mixing chamber 16 in which the plurality of solvents are mixed. Has a structure filled with a stirring member 18.

  A flow path A 120 and a flow path B 122 are connected to the first end portion 12, and each is further connected to a pump. During the control, a desired solvent is fed into the mixing chamber 16 through the first end 12 by a pump. The sent solvent passes through the gap between the stirring members 18 inside the mixing chamber 16 and is further sent to the downstream of the system via the second end portion 14. In FIG. 1, two flow paths (120 and 122) are shown connected to the first end 12, but two or more flow paths are connected to the first end 12. It may be. Moreover, the dimension of each element which comprises the gradient mixer 10 in this invention is not specifically limited, Although the dimension of the mixing chamber 16 may be variously changed according to desired application, for example, typically Has an inner diameter of 1.0 to 5.0 mm and extends to a length of 3 to 10 cm.

  The mixing chamber 16 is filled with a stirring member 18 which is a feature of the present invention. FIG. 3 is a schematic view relating to one preferred embodiment of the stirring member filled in the gradient mixer according to the present invention. The stirring member 18 is preferably formed so that a plurality of solvents used for liquid chromatography flow inside and outside. The stirring member 18 may be a substantially cylindrical shape, a substantially spherical shape, or a substantially rectangular shape, and the stirring member 18 may have an internal structure portion having any diameter and any cross-sectional shape. For example, a specific example of the stirring member 18 may include a hollow member having an outer diameter and an inner diameter and having a structure extending in a substantially longitudinal direction with respect to the cross section. If there is, it is not limited to this.

By adopting such a configuration, each solvent of liquid chromatography flows from the first end portion 12 of the gradient mixer 10 through the flow path A120 and the flow path B122 at the time of control, and mixing of the gradient mixer 10 is performed. It flows further into the chamber 16. The inside of the mixing chamber 16 is filled with a stirring member 18, and the sent solvent passes, for example, outside the stirring member 18 or through the inside of the stirring member 18 along the vicinity of the stirring member 18. While flowing in various directions. Eventually, the solvent passes through the mixing chamber 16 and is sent downstream of the liquid chromatography through the second end 14 of the gradient mixer 10.
The stirring member 18 is preferably formed of a material that is inert to the solvent, and for example, a Teflon (registered trademark) resin is preferable.

  The stirring member 18 may have any orientation with respect to the structure of the mixing chamber 16. Further, the number of the stirring members 18 filled in the mixing chamber 16 is not limited, but it is preferable that the mixing chamber 16 is filled so as not to cause a dead space. It is preferable that the stirring member 18, particularly its total length, is 5 mm or less. It is necessary to fill a sufficient amount of the stirring member 18 with respect to the size of the conventional mixing chamber 16, for example, when the dimension of the extending mixing chamber 16 is 10 cm, at least several hundred stirring members 18 are filled. It is preferable that

  Using a liquid chromatography system having a gradient mixer in the present invention, the solvent composition was changed over time, and the programmed solvent profile was compared with the actually detected solvent profile.

The outline of the liquid chromatography system used is
A first pump A for feeding a first solvent A;
A second pump B for feeding the second solvent B;
A system controller that controls solvent delivery of pumps A and B;
A gradient mixer provided downstream of pumps A and B;
Sampler that supplies samples on-line in the system;
A column for separating the sample; and a detector for detecting a component in the separated sample;
have.

Example 1
Solvent A is methanol, solvent B is methanol + 0.05% acetone, and according to the time schedule shown in Table 1 below, the gradient mixer in the present invention shown in FIG. , L = 3 mm), using the above-mentioned liquid chromatography system, the solvent was fed and the UV absorption at 254 nm derived from acetone was monitored. The obtained results are shown in FIG. The Y1 axis (left) indicates the absorbance (mAbs) at 254 nm, and the Y2 axis (right) indicates the ratio of the solvent B to the total solvent amount shown in Table 1 below. Moreover, the dotted line shows the time schedule of the solvents A and B scheduled in Table 1, and the solid line shows the solvent profile obtained by monitoring at 254 nm.

(Comparative Example 1)
Examination was performed in the same manner as in Example 1 except that the gradient mixer in the present invention in Example 1 was changed to the gradient mixer in the prior art shown in FIG. 2, and the obtained results are shown in FIG. The axes and other references are the same as in FIG.

  Table 1. Time schedule of solvent A and solvent B

It is a section schematic diagram of a gradient mixer in the present invention. It is the schematic of the gradient mixer in a prior art. It is the schematic regarding one suitable Example of the stirring member with which the gradient mixer in this invention is filled. It is a graph which shows the response characteristic at the time of changing a solvent composition with time in the liquid chromatography system using the gradient mixer in a prior art. It is a graph which shows the response characteristic at the time of changing a solvent composition with time in the liquid chromatography system using the gradient mixer in this invention.

Explanation of symbols

DESCRIPTION OF SYMBOLS 10 Gradient mixer 12 1st end part 14 2nd end part 16 Mixing chamber 18 Stirring member 120 Flow path A
122 Channel B
20 Gradient Mixer 22 Inlet 24 Outlet 26 Mixing Chamber 28 Porous Resin

Claims (6)

A first end into which a plurality of solvents flow;
A second end through which the plurality of solvents flow out;
A mixing chamber extending between the first end and the second end; and a stirring member filled in the mixing chamber;
A liquid chromatography gradient mixer comprising:
The gradient mixer for liquid chromatography, wherein the stirring member is formed so that the solvent flows inside and outside the member.   The gradient mixer according to claim 1, wherein the stirring member is a hollow member.   The gradient mixer according to claim 1, wherein the stirring member is made of a material that is inert to the solvent.   The gradient mixer according to claim 3, wherein the stirring member is Teflon (registered trademark) resin.   The gradient mixer according to any one of claims 1 to 4, wherein the total length of the stirring member is about 3 mm.   A liquid chromatography system comprising the gradient mixer according to any one of claims 1 to 5.

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