Can oligonucleotide purification be simplified and scaled without solid-phase chromatography?

As demand for high-purity oligonucleotides continues to grow across therapeutic and research applications, downstream purification remains a critical bottleneck. Conventional ion-exchange and solid-phase chromatographic methods can be costly, difficult to scale, and often require multiple purification steps to achieve the desired purity and yield. Developing a simpler and more scalable alternative is increasingly important for efficient oligonucleotide manufacturing.

This application note explores the use of ion-exchange centrifugal partition chromatography (IEX-CPC) as a liquid–liquid purification approach that eliminates the need for expensive solid stationary phases. By leveraging tunable solvent systems and partition-based separation, CPC enables selective isolation of oligonucleotides while maintaining high loading capacity and cost efficiency. The technique also offers potential advantages in removing challenging impurities such as endotoxins through optimized biphasic solvent systems.

Through a practical case study, the note demonstrates how a single-step CPC process can achieve high purity and yield for a model oligonucleotide, while remaining scalable and compatible with industrial purification workflows.

Benefits of CPC