Dispersed mobile-phase countercurrent chromatography

Patent metadata

Field	Value
Publication number	US-10675558-B2
Application number	US-201715487845-A
Country	US
Kind code	B2
Filing date	Apr 14, 2017
Priority date	Apr 20, 2016
Publication date	Jun 9, 2020
Grant date	Jun 9, 2020

Abstract

A dispersed mobile-phase countercurrent chromatography system is described in which solutes are carried by a stream of dispersed mobile phase solvent through a column, or array of serially-connected columns, of stationary phase solvent with which the mobile phase solvent is immiscible. Solutes carried along by the stream of dispersed mobile-phase solvent will be equilibrated between the mobile-phase solvent and the stationary-phase solvent. Because the mobile-phase is dispersed into mini-droplets much smaller in diameter than the column of stationary phase, the enhanced surface/volume ratio of the droplets expedites countercurrent equilibration of different solutes between the mobile-phase solvent and the stationary-phase solvent in accordance with the distribution-coefficients of the solutes between the two solvents. As a result, a solute with a distribution coefficient that favors its dissolving in the stationary phase will be retarded in its migration through the columns compared to a solute with a distribution coefficient that favors its dissolving in the mobile phase. The different migration rates of different solutes bring about their chromatographic separation on the columns, effectively combining the advantages of countercurrent distribution (e.g., elimination of any solid chromatographic matrix, and therefore losses of solutes due to adsorption to the solid matrix and contamination of separated solutes by impurities leached from the solid matrix) and liquid column chromatography (e.g., continuous mode of operation, and scalable from analytical to large industrial separations without any centrifugal or discontinuous mechanical steps).

First claim

What is claimed is:

1. A method of separating a mixture of solutes using a dispersed-mobile phase countercurrent chromatography (DMCC) system, the method comprising:
introducing a liquid mobile phase through an inlet port into a first end portion of a column of a DMCC system, the DMCC system comprised of:
each of a series of chromatographic separation columns containing a liquid stationary phase and a device for dispersing the inflow of liquid mobile phase into droplets travelling through the liquid stationary phase, the device comprising a rotor- or magnet-driven device or an ultrasound device close to the inlet port through which the liquid mobile phase enters the column of liquid stationary phase, the liquid stationary phase having a density sufficient to retain the liquid stationary phase within the column during separation and being immiscible with the liquid mobile phase, and
the liquid mobile phase flowing from an outlet port at a second end portion of the first of the series of chromatographic separation columns to an inlet port of a first end portion of a second of the series of chromatographic separation columns and then from an outlet port at a second end portion of the second of the series of chromatographic separation columns to an inlet port at a first end portion of an adjacent separation column of the series, and continuing to flow through the series of chromatographic separation columns during separation;
introducing a mixture of solutes into the first end portion of the first of the series of chromatographic separation columns, wherein each of the solutes within the mixture travels within the series of chromatographic separation columns with the flow of dispersed liquid mobile phase at a rate determined by the distribution coefficient of the solute between the liquid mobile and liquid stationary phases;
eluting a solute in the liquid mobile phase from the series of chromatographic separation columns to separate the solute from the mixture of solutes; and
optionally removing the slower-migrating solutes from the series of chromatographic columns after the remainder of the solutes in the mixture have been eluted to complete the chromatographic run before the slower-migrating solutes are eluted from the last of the series of chromatographic separation columns, wherein each of the series of chromatographic separation columns is not segmented into a cascade of chambers.

2. The method of claim 1 , where the mobile phase is enriched in organic solvent(s), and the stationary phase is enriched in aqueous solvent(s).

3. The method of claim 1 , where the mobile phase is enriched in aqueous solvent(s), and the stationary phase is enriched in organic solvent(s).

4. The method of claim 1 , where different separated solutes are collected from the liquid mobile phase eluate exiting the series of chromatographic separation columns in accordance to their respective times of emergence in the eluate from the columns.

5. The method of claim 1 , where different separated solutes are collected from drainage of the liquid stationary phase from one or more of the series of chromatographic separation columns in accordance to the varied locations of different solutes on different columns at the end of a chromatographic run.

6. The method of claim 1 , further comprising dispersing the liquid mobile phase into droplets having an average diameter smaller than 30% of the internal diameter of the column of stationary phase through which it travels in order to provide a surface/volume ratio of the droplets sufficient for achieving a desired rate of equilibration of solutes between the dispersed liquid mobile phase and the liquid stationary phase.

7. The method of claim 1 , wherein the droplets of the liquid mobile phase travel upward through each of the columns, such that the first end portions are bottom portions, and the second end portions are top portions.

8. The method of claim 1 , wherein the droplets of the liquid mobile phase travel downward through each of the columns, such that the first end portions are top portions, and the second end portions are bottom portions.

9. The method of claim 1 , wherein the DMCC system further comprises an equilibration column connected in series with the series of chromatographic separation columns,
the equilibration column containing a liquid stationary phase and a device for dispersing the inflow of liquid mobile phase into droplets travelling through the liquid stationary phase, the liquid stationary phase having a density sufficient to retain the liquid stationary phase within the column during separation and being immiscible with the liquid mobile phase, and
the liquid mobile phase flowing from an outlet at a second end portion of the equilibration column to an inlet of a first end portion of a first of the series of chromatographic separation columns and continuing to flow through the series of chromatographic separation columns during separation; and
the liquid mobile phase is passed through the equilibration column, wherein it is equilibrated with the liquid stationary phase, before its entry into the first of the series of chromatographic separation columns.

10. The method of claim 1 , wherein the mixture of solutes to be separated is introduced into the first of the series of chromatographic separation columns dissolved in a pulse of liquid mobile phase.

11. The method of claim 1 , wherein the mixture of solutes to be separated is introduced into the first of the series of chromatographic separation columns dissolved in a pulse of liquid stationary phase.

12. The method of claim 1 , wherein the liquid mobile phase is introduced into the DMCC columns by pumping.

13. The method of claim 1 , wherein the mixture of solutes is introduced into the DMCC columns by pumping.

Assignees

• Ho Yiu Cheong
• Wong Jeffrey Tze Fei
• Xue Hong
• Univ Hong Kong Sci & Tech

Inventors

• Ho Yiu Cheong
• Wong Jeffrey Tze Fei
• Xue Hong

Classifications

• B01D11/0438 Primary

  comprising vibrating mechanisms, electromagnetic radiations · CPC title

• G01N30/42 Primary

  using counter-current · CPC title

• G01N2030/027

  Liquid chromatography · CPC title

• G01N30/6039

  in series · CPC title

• B01D11/0492

  Applications, solvents used · CPC title