Too big to bind? Will the purification of large and complex therapeutic targets spell the beginning of the end for column chromatography?

Abstract

Progress in some areas of medical research is leading to larger and more complex therapeutic products -for example, cellular or gene therapies. For decades, the bioprocessing industry has relied upon column chromatography as the mainstay of purification processes. Whilst highly effective for the purification of proteins and smaller molecules, chromatographic techniques are not necessarily well suited to purification of these newer, larger targets. This article considers the approaches adopted in the purification of large, complex targets and emphasises the need for more focused development of purification techniques more suited to the target's size and complexity.

Evaluation of a Novel Non-Destructive Catch and Release Technology for Harvesting Autologous Adult Stem Cells

“…Previously the use of beads in this size range has not been considered favourable for isolation of mammalian cells due to an expectation that binding kinetics would be too slow [29], the cell loading capacity of the beads would be too low due to a lack of surface area [29] or there would simply be a lack of interaction between cells and beads of this size [30]. A previous report on an end-over-end mixed batch adsorption process using large beads (mean diameter 61 µm) did not perform well and this was attributed to poor suspension of the beads, a lack of contact of cells with the beads and the possibility of mechanical disruption of the cells on the bead surface [31]–[32].…”