Supercritical fluid chromatography system

Abstract

Provided is a supercritical fluid chromatography system, and components comprising such a system, including one or more of a supercritical fluid chiller, a supercritical fluid pressure-equalizing vessel, and a supercritical fluid cyclonic separator. The supercritical fluid chiller and the use of the chiller allow efficient and consistent pumping of liquid-phase gases employing off-the-shelf HPLC pumps in the supercritical chromatography system using liquid-phase gas mobile phase. The pressure equalizing vessel allows the use of off the shelf HPLC column cartridges in the supercritical chromatography system. The cyclonic separator efficiently and effectively allows for separation of sample molecules from a liquid phase or gas phase stream of a supercritical fluid.

What is claimed is: 
     
         1 . A method of separating components of a sample using supercritical fluid in a chromatography system, said method comprising:
 pumping carbon dioxide from a source in gaseous phase through a single, chilled pump head, to cool and compress the carbon dioxide to behave as a compressed fluid in supercritical phase, said supercritical phase carbon dioxide able to flow at a flow rate that is repeatable and proportionate to pumping speed without cavitation effects after passing from the source through the single, chilled pump head;   mixing a portion of the supercritical phase carbon dioxide with a sample designated for component separation, said mixing performed to create a sample mixture suitable for chromatographic separation of the sample into components;   pumping the sample mixture into a removable, cylindrical inner chromatography column containing stationary phase media; and   pumping an unmixed portion of the supercritical phase carbon dioxide into an outer chamber that surrounds the cylindrical walls of the inner chromatography column to balance the pressures on the inside and outside of the inner chromatography column so that no part of the cylindrical walls of the inner chromatography column is exposed to a pressure differential between the interior and exterior of the inner chromatography column that is greater than about 200 psi (about 14 bar).   
     
     
         2 . The method of  claim 1 , wherein the supercritical phase carbon dioxide is pressurized to a pressure in the range of about 500 psi (about 35 bar) to about 20,000 psi (about 1380 bar). 
     
     
         3 . The method of  claim 1 , wherein the supercritical phase carbon dioxide is pressurized to a pressure of at least about 1000 psi (about 69 bar). 
     
     
         4 . The method of  claim 1 , wherein the supercritical phase carbon dioxide is pressurized to a pressure of at least about 5076 psi (at least about 350 bar). 
     
     
         5 . The method of  claim 1 , wherein the inner chromatography column comprises an inlet end and an outlet end and the pressure at the inlet end is substantially the same as the pressure at the outlet end. 
     
     
         6 . The method of  claim 1 , wherein the inner chromatography column comprises a capacity size in the range of from about 4 grams to about 350 grams stationary phase media. 
     
     
         7 . The method of  claim 1 , wherein the inner chromatography column comprises a diameter in the range of about 0.5 inches to about 3.5 inches, and a column length in the range from about 3.5 inches to about 11 inches. 
     
     
         8 . The method of  claim 1 , wherein the stationary phase media comprises an average particle size in the range of about 10 to about 100 microns. 
     
     
         9 . The method of  claim 1 , wherein the outer chamber comprises an adaptor configured to fit and lock with a connector on the removable, cylindrical inner chromatography column. 
     
     
         10 . The method of  claim 9 , wherein the connector is a slip connector. 
     
     
         11 . The method of  claim 9 , wherein the connector is a luer-lock connector. 
     
     
         12 . The method of  claim 9 , wherein the adaptor comprises an O-ring that seals around the connector. 
     
     
         13 . The method of  claim 1 , wherein the inner chromatography column comprises an inlet end and an outlet end, wherein neither the inlet end nor the outlet end of the inner column comprises a perforated stopper. 
     
     
         14 . The method of  claim 1 , wherein the outer chamber contains a single inlet and no outlet or vent. 
     
     
         15 . The method of  claim 1 , wherein the system further pumps a co-solvent. 
     
     
         16 . The method of  claim 1 , wherein the stationary phase media comprises a silica gel.