Methods for chromatography resin slurry determination

Patent metadata

Field	Value
Publication number	US-12372502-B2
Application number	US-201816160179-A
Country	US
Kind code	B2
Filing date	Oct 15, 2018
Priority date	Oct 17, 2017
Publication date	Jul 29, 2025
Grant date	Jul 29, 2025

Abstract

The present invention relates to methods for determining a slurry concentration for a slurry of a chromatography resin during a column packing. The present invention provides a more accurate and consistent method for determining a slurry concentration for packing a chromatography column. The method of the present invention utilizes an automated pump to provide a controlled flow rate to consolidate a resin sample. Based on the consolidated resin, a slurry concentration can be determined. The determined slurry concentration can be utilized to pack the resin in a chromatography column with highly accurate bed heights.

First claim

What is claimed is:

1. A method of determining a slurry concentration, comprising:
adding a slurry comprising a resin to a first chromatography column;
pumping a volume of liquid through the first chromatography column at a flow rate;
controlling the flow rate to match a consolidation rate employed by a second chromatography column to form a consolidated resin in the first chromatography column, wherein the volume of liquid is pumped through the first chromatography column by an automated pump system, wherein the automated pump system is programed to cycle on and off for a predetermined period of time or for multiple periods of time;
upon completion of the pumping step, measuring a bed height of the consolidated resin in the first chromatography column;
determining a slurry concentration in the first chromatography column; and
packing the second chromatography column with the determined slurry concentration in the first chromatography column, wherein the second chromatography column has a packing factor within 5% of an ideal packing factor.

2. The method of claim 1 , wherein the liquid is deionized water, distilled water, purified water, a saline solution, or an organic solvent.

3. The method of claim 1 , wherein the step of adding the slurry further comprises adding water to the first chromatography column and allowing the slurry to settle for about five minutes to about one hour prior to pumping.

4. The method of claim 1 , wherein the second chromatography column comprises a consolidation rate and wherein the flow rate of the first chromatography column is equivalent to the consolidation rate of the second chromatography column.

5. The method of claim 1 , wherein the automated pump system comprises a syringe operatively coupled to a pump.

6. The method of claim 1 , wherein the packed second chromatography column has a bed height within 1 cm of a target bed height.

7. A method for determining a slurry concentration for a slurry of a chromatography resin during column packing, comprising:
adding a slurry comprising a resin to a first chromatography column;
setting an automated pump to run at a constant flow rate for a period of time;
pumping a volume of liquid through the first chromatography column at the flow rate that matches a consolidation rate employed by a second chromatography column to form a consolidated resin in the first chromatography column, wherein the volume of liquid is pumped through the first chromatography column by the automated pump, wherein the automated pump is programed to cycle on and off for a predetermined period of time or for multiple periods of time;
upon completion of the pumping step, measuring a bed height of the consolidated resin of the first chromatography column;
determining a slurry concentration from the measured bed height in the first chromatography column; and
packing the second chromatography column with the determined slurry concentration in the first chromatography column, wherein the second chromatography column has a packing factor within 5% of an ideal packing factor.

8. The method of claim 7 , further comprising, pausing the automated pump to stop the flow of liquid through the first chromatography column and allowing the resin to settle, and restarting the pump to flow liquid through the first chromatography column before completion of the pumping step.

9. The method of claim 8 , wherein the pumping is paused for more than one time period.

10. The method of claim 8 , wherein the pumping is paused for a time period of 1 to 60 minutes.

11. The method of claim 7 , wherein the step of setting the automated pump further comprises providing a flow rate based on which type of resin is utilized in the slurry and the consolidation rate employed by the second chromatography column.

12. The method of claim 11 , wherein the flow rate is within a range of about 20 cm/hr to about 1500 cm/hr.

13. The method of claim 7 , further comprising mixing the slurry prior to adding the slurry to the first chromatography column.

14. The method of claim 7 , wherein the liquid is deionized water, distilled water, purified water, a saline solution, or an organic solvent.

15. The method of claim 7 , wherein the packed second chromatography column has a bed height within 1 cm of a target bed height.

16. A method for determining a slurry concentration for a slurry of a chromatography resin during a column packing, comprising:
providing a slurry comprising a resin;
mixing the slurry to uniformly distribute the resin;
adding the slurry to a first chromatography column;
providing an automated pump system comprising a pump having a controller and, wherein the automated pump system is configured to pump a volume of water through the first chromatography column and the controller is configured to control a flow rate of the volume of water to match a consolidation rate employed by a second chromatography column, wherein the flow of the volume of water will pack the resin in the first chromatography column;
pumping the volume of water through the first chromatography column at a constant flow rate to form a consolidated resin, wherein the automated syringe pump system is programed to cycle on and off for a predetermined period of time or for multiple periods of time;
upon completion of the pumping step, measuring a bed height of the consolidated resin of the first chromatography column;
determining a slurry concentration from the measured bed height of the first chromatography column;
inputting the determined slurry concentration into the automated pump system;
and packing the resin in the second chromatography column using the determined slurry concentration in the first chromatography column, wherein the second chromatography column has a packing factor within 5% of an ideal packing factor.

17. The method of claim 16 , wherein the flow rate is within a range of about 30 cm/hr to about 60 cm/hr.

18. The method of claim 16 , wherein the second chromatography column comprises a consolidation rate and the flow rate of the first chromatography column is equivalent to the consolidation rate of the second chromatography column.

19. The method of claim 16 , wherein the packed second chromatography column has a bed height within 1 cm of a target bed height.

Assignees

• Regeneron Pharma

Inventors

• Mao Nathan
• Shierly Eric
• Gallea Joseph
• Feng Raymond
• Dissanayake Tikiri
• Schilling Bernhard
• Carver Scott

Classifications

• B01D15/206 Primary

  Packing or coating · CPC title

• G01N2030/565

  slurry packing · CPC title

• G01N2030/326

  pumps · CPC title

• G01N2030/324

  speed, flow rate · CPC title

• G01N2030/8804

  automated systems · CPC title