Centrifugal partition chromatography Operating conditions, modeling and scale-up

Centrifugal Partition Chromatography (CPC) is a multi-stage separation technique using compact columns consisting of a cascade of chambers or partition cells linked by channels and subjected to a centrifugal acceleration field. The separation mechanism is based on the difference in compound distribution between two immiscible liquid phases. In the CPC column, one of the liquids is kept stationary by the rotation of the column, without the need for a solid support, while the mobile phase passes through the stationary phase at a flow rate dictated by a pump. The CPC chain and its range of applications are similar to those of a preparative HPLC (high-performance liquid chromatography) chain.

The main developments in CPC took place in the 1990s and 2000s with the emergence of new equipment manufacturers, bringing the technology to a level of maturity that makes it industrializable (columns are available in different materials, for volumes ranging from 30 mL to 25 L). The absence of a solid support for capture or fractionation operations means that complex feedstocks can be processed, as is often the case with natural substances (complex secondary metabolites, for example) or biotechnology-derived substances, without the risk of overloading or clogging the support (resin, silica). This operating flexibility, the low cost of the stationary phase and the reduced consumption of solvents mean that CPC can be used to extend the range of applications for liquid chromatography and reduce the number of purification stages. The purification of high value-added natural substances (peptides, alkaloids) was initially used as a case study. Although scale-up has long been considered a linear transposition, it is shown here that CPC is controlled by :

• phase hydrodynamics and material transfer ;

• column geometry, according to non-linear rules.

The CPC column modeling and engineering tools presented in this article can be used to size columns for a desired application and productivity, or to transpose a separation from R&D equipment to production equipment.

Like all processes based on the transfer of matter between two fluids, the performance of a CPC column (efficiency, resolution, productivity) results from the hydrodynamics of the phases, which are presented first.

The models developed can be used to describe and predict chromatograms in both elution and displacement modes. The models therefore incorporate the transport, transfer and, where applicable, reaction terms of the species involved in the separation. Phase hydrodynamics are taken into account in the models. via changes in phase ratio, phase velocity...