Use of ultrasound to monitor the packing of large-scale columns, the monitoring of media compression and the passage of molecules, such as monoclonal antibodies, through the column bed during chromatography

The novel use of ultrasound as a detector in pilot- and production-scale chromatography is described. The difficulties in packing production scale chromatography columns using an integral packing valve are reviewed. Results are presented from the packing of 400- and 600-mm diameter columns with various medias. From these results it is proposed that when packing large columns using a packing valve, for a given medium and column size, there is an ideal rate and pattern (or control “corridor”) by which the bed builds in order to give optimum performance. Ultrasound was shown to be able to monitor the building of such a column bed as the medium was pumped into the column. It was found that the ultrasound detector was sensitive to bed compression, mobile phase composition and components such as acetone, albumin, casein and monoclonal antibodies while on the chromatography bed. This enabled the visualisation, by ultrasound, of these components as they were chromatographed through the column.