Sample separation apparatus and method for multiple channel high throughput purification

• US 20020185442A1
• Filed: 07/30/2002
• Published: 12/12/2002
• Est. Priority Date: 10/30/1998
• Status: Abandoned Application

• Current Assignee: Jonathan Krakover, Romaine R. Maiefski
• Original Assignee: Jonathan Krakover, Romaine R. Maiefski
• Inventors: Maiefski, Romaine R., Krakover, Jonathan
• Application Number:
  US10/209,367
• Publication Number:
  US 20020185442A1
• Time in Patent Office: Days
• US Class Current: 210/656
• CPC Class Codes: B01D 15/08 Selective adsorption, e.g. chromatography
• CPC Class Codes: B01D 15/14 relating to the introduction of the feed to the apparatus
• CPC Class Codes: B01D 15/40 using supercritical fluid as mobile phase or eluent
• CPC Class Codes: B01J 2219/00452 Means for the recovery of reactants or products
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/00587 High throughput processes
• CPC Class Codes: B01J 2219/00759 Purification of compounds synthesised
• CPC Class Codes: G01N 1/405 by adsorption or absorption
• CPC Class Codes: G01N 2030/8804 automated systems
• CPC Class Codes: G01N 2030/8881 Modular construction, specially adapted therefor
• CPC Class Codes: G01N 30/02 Column chromatography
• CPC Class Codes: G01N 30/20 using a sampling valve
• CPC Class Codes: G01N 30/24 Automatic injection systems
• CPC Class Codes: G01N 30/466 with separation columns in parallel
• CPC Class Codes: G01N 30/6004 end pieces
• CPC Class Codes: G01N 30/6052 body
• CPC Class Codes: G01N 30/74 Optical detectors measurement of intensity, velocity, spectral content, polarisation, or phase of infrared, visible or ultraviolet light G01J
• CPC Class Codes: G01N 30/82 Automatic means therefor
• CPC Class Codes: G01N 30/88 Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86
• CPC Class Codes: G01N 35/00 Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
• CPC Class Codes: G05D 16/202 : actuated by an electric motor

Abstract

A high throughput liquid chromotagraphy column assembly for separating a large sample with a selected mass weight and fluid volume. The assembly includes a loading column with a loading chamber with a first inner diameter and a first length. The loading chamber contains a removable cartridge containing a bed packing material on to which sample is loaded and spatially distributed. The cartridge'"'"'s volume is sufficient to fully load the sample therein but the length of the loading chamber is insufficient to achieve the selected chromatographic separation. A separation column is in fluid communication with the loading column. The separation column has a separation chamber with a diameter smaller than the loading cartridge'"'"'s inner diameter and a length greater than the cartridge'"'"'s length. In one embodiment, the cartridge has an inner diameter two or more times greater than the separation chamber'"'"'s diameter, and the cartridge has a length one-half or less than the length of the separation chamber. The separation chamber'"'"'s diameter is such that the separation chamber has a volume over the same length as the cartridge'"'"'s length insufficient to act as a loading area for the entire selected sample for the given mass and volume of the sample.

Claims

1. A high throughput liquid chromatography column assembly configured to receive a selected sample for chromatographic separation, comprising:

a loading column having a loading chamber;

a cartridge removably retained in the loading chamber, the cartridge containing a first packing material with a vertical absorptive profile and a selected volume to spatially distribute the sample within the cartridge to load the sample prior to chromatographic separation of the sample, the cartridge having a first diameter and a first length, the first length of the cartridge being insufficient to achieve the selected chromatographic separation of the sample as the sample passes through the first packing material; and

a separation column having a separation chamber and a second packing material therein in fluid connection with the loading chamber and being positioned to receive the sample from the loading column, the separation chamber having a second length greater that the first length, sufficient to achieve the selected chromatographic separation of the sample as the sample passes therethrough.

2. The chromatography column assembly of claim 1 wherein the cartridge is a disposable cartridge.

3. The chromatography column assembly of claim 1 wherein the cartridge is a disposable cartridge, and the separation column is a disposable separation column releasably connected to the loading column.

4. The chromatography column assembly of claim 1 wherein the cartridge includes an outer container extending between two porous frits, and the first packing material is filly contained in the container between the porous frits.

5. The chromatography column assembly of claim 1 wherein the loading column includes an upper portion above the cartridge defining dilution chamber in fluid connection with the cartridge, the dilution chamber being sized to receive the sample therein before the sample enters the cartridge.

6. The chromatography column assembly of claim 1 wherein the separation column is releasably connected to the loading column.

7. The chromatography column assembly of claim 1 wherein the separation column is threadably connected to the loading column.

8. The chromatography column assembly of claim 1 wherein the first length is one half or less than the second length.

9. The chromatography column assembly of claim 1 wherein the separation chamber has an inner second diameter, and wherein the first diameter of the cartridge is at least two times greater than the second diameter of the separation chamber.

10. The chromatography column assembly of claim 1 wherein the loading column includes a dilution chamber in fluid communication with the loading chamber.

11. The chromatography column assembly of claim 10 wherein the dilution chamber contains inert packing material.

12. The chromatography column assembly of claim 1 wherein the loading column and the separation column are modularly connected to each other.

13. The chromatography column assembly of claim 12 wherein a frit is sandwiched between the loading column and the separation column.

14. The chromatography column assembly of claim 1 wherein the separation chamber has a substantially constant cross sectional area along the second length.

15. The chromatography column assembly of claim 1 wherein the separation chamber has first and second end portions, the first end portion being closest to the loading column, the second diameter being at the first end portion, and the separation chamber having a third diameter at the second end portion smaller than the second diameter.

16. The chromatography column assembly of claim 1 wherein the separation chamber has a truncated conical shape.

17. A high throughput liquid chromatography column assembly configured to receive a selected sample for flow therethrough to achieve a selected chromatographic separation of the sample, the sample having a mass weight and a fluid volume, comprising:

a loading column having a loading chamber;

a cartridge removably retained in the loading column, the cartridge containing a bed of first packing material with a vertical absorptive profile, the bed of first packing material having a first length, a first cross sectional area, and a first volume configured to spatially distribute the sample within the cartridge to load the sample prior to chromatographic separation of the sample, the first length of the bed of first packing material being insufficient to achieve the selected chromatographic separation of the sample as the sample passes through the loading chamber; and

a separation column having a second packing material and a separation chamber therein in fluid connection with the loading chamber and being positioned to receive the sample from the loading column, the separation chamber having a second cross-sectional area smaller than the first cross-sectional area and having the second length greater that the first length, the separation chamber being sized to retain a second packing material, the second length of the separation chamber begin sufficient to achieve the selected chromatographic separation of the sample as the sample passes therethrough.

18. The chromatography column assembly of claim 17 wherein the separation chamber has a second volume of the second packing material over a same length as the first length that is insufficient to act as a loading region for the entire selected sample.

19. The chromatography column assembly of claim 17 wherein the loading column and separation column are modularly coupled to each other.

20. A chromatographic column, comprising first and second column portions, the first column portion having a loading chamber with a first inner diameter and first length, the loading chamber sized to accept a removably retained cartridge containing a bed of first packing material with a vertical absorptive profile, the second column portion having a separating chamber with a second inner diameter and second length, the first inner diameter being approximately two times greater than the second inner diameter and the first length being approximately ½

or less than the second length.

21. The column of claim 20 wherein the first length is approximately equal to or less than one-half of the second length.

22. The column of claim 20 wherein the cartridge contains a solid phase material.

23. The column of claim 20 wherein the first column contains a dilution chamber, the dilution chamber being in fluid communication with the loading chamber.

24. The column of claim 22 wherein the separation chamber is a tapered chamber that tapers inwardly as the second column portion extends away from the first column portion.

25. A method for high throughput purification of a selected sample in a chromatographic column having a loading column and a separation column, the sample having a mass weight and a fluid volume, comprising;

placing a removably retained cartridge in a loading chamber of the loading column, the cartridge containing a first packing material with a vertical absorptive profile and a selected volume to spatially distribute the sample within the cartridge to load the sample prior to chromatographic separation of the sample, the cartridge having a first diameter and a first length, the first length of the cartridge being insufficient to achieve the selected chromatographic separation of the sample as the sample passes through the first packing material; and

separating chromatographically the selected sample in the separation column, the separation column having a separation chamber and a second packing material therein in fluid connection with the loading chamber and being positioned to receive the sample from the loading column, the separation chamber having a second length greater than the first length, sufficient to achieve the selected chromatographic separation of the sample as the sample passes therethrough.

26. The method of claim 25, further comprising removing the cartridge from the loading chamber and replacing the first removably retained cartridge with a second removably retained cartridge in the loading chamber.

27. The method for high throughput purification of a selected sample in a chromatographic column of claim 25, further comprising replacing a first separator column with a second separation column.