Preparative chromatography column

Abstract

A chromatography column design and a packing device, as well as a method for obtaining a column with a very compact and uniform bed are provided. The bed remains compact and uniform during operation of the column and during sanitization, storage and transportation of the column. The amount of hardware, particularly the hardware parts in contact with product, is minimized, especially with the implementation of an internal liner. With this internal liner, the packed bed can be separated from the column in intact form, or even prepared separately from, and outside of, the column.

What is claimed is: 
     
         1 . A method of packing a chromatography column, said method comprising:
 (a) placing a tube of flexible, water-impermeable material in a rigid column shell, said tube being open at a first end and closed at a second end with a bottom plate comprising a layer of porous material over a rigid and liquid-impermeable base, said layer of porous material facing said first end of said tube and said rigid and liquid-impermeable bottom plate base having a bottom plate port therein for discharge of liquid;   (b) placing a slurry of separation medium particles in said tube within said rigid column shell and placing a piston in said tube over said slurry, said piston having a layer of porous material facing said slurry and a piston port for supply of liquid over said layer of porous material;   (c) exerting a downward circulation of liquid between the said piston and the said bottom plate to settle and compact the said slurry; and   (d) lowering said piston over said slurry to compact said particles into a packed bed.   
     
     
         2 . The method of  claim 1 , wherein the piston or the rigid column shell further comprises a releasable seal between the tube and the piston. 
     
     
         3 . The method of  claim 2 , wherein the seal is selected from the group consisting of an O-ring, a lobe joint, and a scraper seal. 
     
     
         4 . The method of  claim 1 , wherein the flexible, water-impermeable material is elastic. 
     
     
         5 . The method of  claim 1 , wherein the chromatography column further comprises a slurry injection port, and wherein the placing comprises injecting the slurry of separation medium particles through the slurry injection port. 
     
     
         6 . The method of  claim 1 , comprising assisting packing of the slurry with percussive tapping from under the rigid and liquid-impermeable bottom plate base. 
     
     
         7 . The method of  claim 6 , wherein the percussive tapping comprises a periodic projecting of a hammer upwards against a projection plate positioned under the rigid and liquid-impermeable bottom plate base. 
     
     
         8 . The method of  claim 8 , wherein impulses from the percussive tapping are dampened by one or more shock absorbers. 
     
     
         9 . The method of  claim 8 , wherein the one or more shock absorbers comprises an elastic block. 
     
     
         10 . The method of  claim 8 , wherein the one or more shock absorbers comprises a spring. 
     
     
         11 . The method of  claim 6 , wherein the frequency of the percussive tapping is between 0.1 and 300 Hz. 
     
     
         12 . The method of  claim 6 , wherein the amplitude of the percussive tapping is less than 15 mm. 
     
     
         13 . The method of  claim 1  further comprising attaching a column shell extension to said rigid column shell to extend the height of said rigid column shell prior to placing said tube of flexible, water-impermeable material in said rigid column shell, and wherein:
 step (a) comprises placing said tube of flexible, water-impermeable material in both said rigid column shell and said column shell extension; 
 step (b) comprises placing a sufficient quantity of said slurry within said tube to extend into both said rigid column shell and said column shell extension; 
 step (c) comprises compacting all of said particles into a portion of said tube within said rigid column shell; 
 
       said method further comprising:
 (e) removing said column shell extension after step (c) to leave said rigid column shell containing said packed bed. 
 
     
     
         14 . The method of  claim 13 , wherein step (e) further comprises compressing the tube at a position below the column shell extension and above the rigid column shell and the piston. 
     
     
         15 . The method of  claim 14 , wherein the compressing comprises the pressing of pins against the wall of the tube. 
     
     
         16 . The method of  claim 15 , wherein the pressing comprises the piercing of the tube. 
     
     
         17 . The method of  claim 13 , comprising assisting packing of the slurry with percussive tapping from under the rigid and liquid-impermeable bottom plate base. 
     
     
         18 . The method of  claim 17 , wherein the column shell extension and the piston are isolated from the rigid and liquid-impermeable bottom plate base, such that column shell extension and the piston are subjected to a reduced force associated with the percussive tapping. 
     
     
         19 . The method of  claim 13  further comprising closing the top of said column shell extension with a cap that supports said piston, and for securing said first end of said tube of flexible, water-impermeable material to said cap, prior to step (c). 
     
     
         20 . The method of  claim 13  further comprising:
 (f) severing said tube of flexible, water-impermeable material above said packed bed to leave a shortened length of said tube encircling said packed bed