Preparative column chromatography system

Abstract

A chromatography system comprising a mixing circuit or a mixing chamber, a bubble trap, a concentration detector and one or more pumps, characterized in that the bubble trap has a permanent opening at its highest point is described herein. Furthermore, a chromatography system is described, characterized in that it contains two concentration detectors the first of which is located in the mixing circuit or the mixing chamber and the second is located downstream of the main pump.

1 - 16 . (canceled) 
     
     
         17 : A chromatography system comprising:
 a mixing circuit or mixing chamber;   a main pump located downstream of the mixing circuit or mixing chamber;   a chromatography column located downstream of the main pump;   a first concentration detector located in the mixing circuit or the mixing chamber; and   a second concentration detector located downstream of the main pump.   
     
     
         18 : The chromatography system of  claim 17 , further comprising a bubble trap comprising a permanent opening at the highest point. 
     
     
         19 : The chromatography system of  claim 18 , wherein the bubble trap is located outside or downstream of the mixing circuit or the mixing chamber. 
     
     
         20 : The chromatography system of  claim 18 , further comprising a first valve between the mixing circuit or mixing chamber and the bubble trap configured to regulate the volume flow into the bubble trap. 
     
     
         21 : The chromatography system of  claim 20 , wherein the first valve is an adjustable valve. 
     
     
         22 : The chromatography system of  claim 18 , wherein the bubble trap comprises a second valve configured to regulate the volume flow through the permanent opening. 
     
     
         23 : The chromatography system of  claim 22 , wherein the second valve is an adjustable valve. 
     
     
         24 : The chromatography system of  claim 17 , further comprising a bypass route around the chromatography column. 
     
     
         25 : A method of checking the efficiency of a chromatography system,
 wherein the chromatography system comprises:
 one or more buffer supplies; 
 a mixing circuit or mixing chamber located downstream of the one or more buffer supplies; 
 a main pump located downstream of the mixing circuit or mixing chamber; 
 a chromatography column located downstream of the main pump; 
 a first concentration detector located in the mixing circuit or the mixing chamber; and 
 a second concentration detector located downstream of the main pump, 
   
       the method comprising:
 operating the chromatography system such that a buffer composition is directed from the one or more buffer supplies through at least a portion of the chromatography system; 
 measuring a signal of the buffer composition at the first concentration detector and a signal of the buffer composition at the second concentration detector; 
 comparing the signal of the buffer composition at the first concentration detector with the signal of the buffer composition at the second concentration using a time correction to account for the buffer composition traveling from the first concentration detector to the second concentration detector to check the efficiency of the chromatography system,
 wherein a deviation of the signal of the buffer composition at the first concentration detector with the signal of the buffer composition at the second concentration using the time correction is indicative of an inefficiency in the chromatography system. 
 
 
     
     
         26 : The method of  claim 25 , wherein the buffer composition is based on a predetermined gradient. 
     
     
         27 : The method of  claim 25 , wherein the chromatography system further comprises a bypass route around the chromatography column. 
     
     
         28 : The method of  claim 27 , wherein the method comprises directing the buffer composition through the bypass route around the chromatography column. 
     
     
         29 : The method of  claim 25 , wherein the chromatography system further comprises a bubble trap comprising a permanent opening at the highest point. 
     
     
         30 : The method of  claim 29 , wherein the bubble trap is located outside or downstream of the mixing circuit or the mixing chamber. 
     
     
         31 : The method of  claim 29 , wherein the chromatography system further comprises a first valve between the mixing circuit or mixing chamber and the bubble trap configured to regulate the volume flow of the buffer composition into the bubble trap, wherein the first valve is an adjustable valve, and wherein the method further comprises adjusting the first valve to adjust the flow of the buffer composition into the bubble trap. 
     
     
         32 : The method of  claim 29 , wherein the bubble trap comprises a second valve configured to regulate the volume flow through the permanent opening, wherein the second valve is an adjustable valve, and wherein the method further comprises adjusting the second valve to adjust the flow of the buffer composition exiting the permanent opening at the highest point. 
     
     
         33 : A method of checking the integrity of a chromatography column located in a chromatography system,
 wherein the chromatography system comprises:
 one or more buffer supplies; 
 a mixing circuit or mixing chamber located downstream of the one or more buffer supplies; 
 a main pump located downstream of the mixing circuit or mixing chamber; 
 a chromatography column located downstream of the main pump; 
 a first concentration detector located in the mixing circuit or the mixing chamber; and 
 a second concentration detector located downstream of the chromatography column, 
   
       the method comprising:
 operating the chromatography system such that a buffer composition is directed from the one or more buffer supplies through at least a portion of the chromatography system including the chromatography column; 
 measuring a signal of the buffer composition at the first concentration detector and a signal of the buffer composition at the second concentration detector; 
 comparing the signal of the buffer composition at the first concentration detector with the signal of the buffer composition at the second concentration using a time correction to account for the buffer traveling from the first concentration detector to the second concentration detector to check the integrity of the chromatography column,
 wherein a deviation of the signal of the buffer composition at the first concentration detector with the signal of the buffer composition at the second concentration using the time correction is indicative of an integrity issue in the chromatography column. 
 
 
     
     
         34 : A method of using a ratio of the signal of a buffer composition of a first concentration detector and the signal of the buffer composition at a second concentration detector to control a chromatography system,
 wherein the chromatography system comprises:
 one or more buffer supplies; 
 a mixing circuit or mixing chamber located downstream of the one or more buffer supplies; 
 a main pump located downstream of the mixing circuit or mixing chamber; 
 a chromatography column located downstream of the main pump; 
 a first concentration detector located in the mixing circuit or the mixing chamber; and 
 a second concentration detector located downstream of the main pump, 
   
       the method comprising:
 operating the chromatography system such that a buffer composition is directed from the one or more buffer supplies through at least a portion of the chromatography system; 
 measuring a signal of the buffer composition at the first concentration detector and a signal of the buffer composition at the second concentration detector; 
 determining a ratio of the signal of the buffer composition at the first concentration detector with the signal of the buffer composition at the second concentration using a time correction to account for the buffer traveling from the first concentration detector to the second concentration detector; and 
 adjusting an operating parameter based on the determined ratio to control the chromatography system. 
 
     
     
         35 : The method of  claim 34 , wherein the operating parameter is a flow rate from at least one of the one or more buffer supplies. 
     
     
         36 : The method of  claim 34 , wherein the buffer composition is based on a predetermined gradient. 
     
     
         37 : The method of  claim 34 , wherein the second concentration detector is located downstream of the chromatography column. 
     
     
         38 : The method of  claim 37 , wherein the method comprises directing the buffer composition through the chromatography column. 
     
     
         39 : The method of  claim 34 , wherein the chromatography system further comprises a bypass route around the chromatography column. 
     
     
         40 : The method of  claim 39 , wherein the method comprises directing the buffer composition through the bypass route around the chromatography column. 
     
     
         41 : The method of claim  47 , wherein the operating parameter is a circulation rate in the mixing circuit or the mixing chamber based on an assessment of the signal of the buffer composition at the first concentration detector in view of a predetermined input buffer composition. 
     
     
         42 : The method of  claim 34 , wherein the chromatography system further comprises a bubble trap comprising a permanent opening at the highest point. 
     
     
         43 : The method of  claim 42 , wherein the chromatography system further comprises a first valve between the mixing circuit or mixing chamber and the bubble trap configured to regulate the volume flow into the bubble trap, wherein the first valve is an adjustable valve, and wherein the operating parameter is adjusting the first valve to adjust the flow of the buffer composition to the bubble trap. 
     
     
         44 : The method of  claim 42 , wherein the bubble trap is located within the mixing circuit or the mixing chamber. 
     
     
         45 : The method of  claim 42 , wherein the bubble trap comprises a second valve configured to regulate the volume flow through the permanent opening, wherein the second valve is an adjustable valve, and wherein the operating parameter is adjusting the second valve to adjust the flow of the buffer composition exiting the permanent opening at the highest point. 
     
     
         46 : The method of  claim 34 , wherein the operating parameter is the chromatography column, and wherein the method comprises substituting the chromatography column for a second chromatography column.