Automated System and Method for Monitoring Chromatography Column Performance, and Applications Thereof

Abstract

The present invention provides automated systems and methods for monitoring column performance in process chromatography, and applications thereof. In an embodiment, column performance is monitored by generating a plurality of process values such as, for example, conductivity values or pH values with a detector during a chromatography step transition between a first mobile phase liquid and a second mobile phase liquid. The process values are transformed to form transformed process values in which noise present in the process values is suppressed. Column performance parameters are calculated based on the transformed process values and displayed during movement of the second mobile phase liquid through the chromatography column. The displayed performance parameters enable an operator to make a determination, for example, regarding the quality of the chromatography column packing and whether to continue the chromatography process or stop the chromatography process until the chromatography column can be repacked or replaced.

What is claimed is: 
     
         1 . A method for monitoring or controlling chromatography column performance, comprising:
 (1) generating a plurality of process values with a detector during a chromatography step transition between a first mobile phase liquid and a second mobile phase liquid;   (2) transforming the plurality of process values to form a plurality of transformed process values, wherein the transforming suppresses noise present in the plurality of process values by reducing or filtering out spike noise;   (3) calculating performance parameters based on the plurality of transformed process values;   (4) displaying the performance parameters calculated in (3) during movement of the second mobile phase liquid through the chromatography column; and   (5) making a determination that the quality of the chromatography column packing is acceptable if a performance parameter displayed in (4) is inside a specified range of values.   
     
     
         2 . The method of  claim 1 , wherein (1) comprises generating a plurality of values selected from the group consisting of:
 a) conductivity values;   b) pH values;   c) salt concentration values;   d) light absorption values;   e) fluorescence values after excitation with light of a suitable wavelength;   f) refractive index values;   g) electrochemical response values; and   h) mass spectrometry values.   
     
     
         3 . The method of  claim 1 , wherein (2) further comprises smoothing the plurality of transformed process values. 
     
     
         4 . The method of  claim 1 , wherein (2) further comprises calculating a moving average for the plurality of transformed process values. 
     
     
         5 . The method of  claim 1 , wherein (3) comprises calculating one of a plate number (N) value, a height equivalent to a theoretical plate (HETP) value, and an asymmetry (As) value. 
     
     
         6 . The method of  claim 1 , wherein (5) comprises making a determination that the quality of the chromatography column packing is unacceptable if a performance parameter displayed in (4) is outside a specified range of values. 
     
     
         7 . The method of  claim 7 , wherein said determination triggers an automated alert system to notify users of said determination. 
     
     
         8 . The method of  claim 1 , wherein transforming the plurality of process values comprises applying a filter that operates by:
 (a) comparing a process value (C i ) with a corresponding process value before (C i−1 ), and a corresponding process value after (C i+1 ), and   (b) replacing C i  with C i+1  if C i+1  and C i−1  are identical or maintaining C i  if C i+1  and C i−1  are not identical.   
     
     
         9 . The method of  claim 1 , wherein transforming the plurality of process values comprises applying a filter that operates by:
 (a) comparing a process value (C i ) with a corresponding process value before (C i−2 ), and a corresponding process value after (C i+2 ), and   (b) replacing C i  with C i+2  if C i+2  and C i−2  are identical or maintaining C i  if C i+2  and C i−2  are not identical.   
     
     
         10 . The method of  claim 1 , wherein transforming the plurality of process values comprises applying a filter that operates by:
 (a) comparing a process value (C i ) with a corresponding process value before (C i−2 ), and a corresponding process value after (C i+1 ), and   (b) replacing C i  with C i+1  if C i−2  and C i+1  are identical or maintaining C i  if C i+1  and C i−2  are not identical.   
     
     
         11 . The method of  claim 1 , wherein transforming the plurality of process values comprises applying a filter that operates by:
 (a) comparing a process value (C i ) with a corresponding process value before (C i−1 ), and a corresponding process value after (C i+2 ), and   (b) replacing C i  with C i+2  if C 1 ., and C i+2  are identical or maintaining C i  if C i+2  and C i−1  are not identical.   
     
     
         12 . The method of  claim 1 , wherein transforming the plurality of process values comprises applying one or more filters as defined in any of  claims 12 - 15  several times and in an alternating fashion. 
     
     
         13 . The method of  claim 1 , wherein transforming the plurality of process values comprises applying a filter that operates by:
 (a) comparing the sum of the process data values (ΣΔC) and the sum of the absolute process data values (Σ abs(ΔC)) on each side of the maximum process sample value to identify the presence of noise, and   (b) replacing a process value (C i ) that includes noise with the minimum corresponding process value selected from the group consisting of C i−3 , C i−2 , C i−1 , C i+1 , C i+2  and C i+3 .   
     
     
         14 . The method of  claim 1 , wherein transforming the plurality of process values comprises applying a filter that normalizes the filtered process values.