Partitioning of biomolecules using an aqueous liquid-liquid extraction is a promising technology to move the industry from batch to continuous processing, a technological leap that has been extremely beneficial for other industries like steel production. However, there is still not a full understanding of the physical forces that govern the partitioning of the molecules between the different phases. Currently, studies are conducted by manually optimizing hundreds of small, batch experiments. This slow and costly approach is too inflexible to produce enough data to develop theories on the physical forces that govern the transport of the biomolecules from one phase to another. High throughput screening using liquid handling stations or microfluidic devices could help develop information quickly, thus providing enough data to begin to analyze the molecular driving forces that govern the partitioning. However, high throughput screening often requires significant volumes of high-titer candidate stocks and the microfluidics approach requires a plethora of experiments. A second, more powerful approach is development of predictive models for the biomolecule partition coefficient. Currently, models based on existing datasets, thermodynamic equations of state, and surface science are being published. Here we discuss examples of each approach, including the Collander Equation, ePC-SAFT, lattice cluster theory combined with density gradient theory, and two recently published interfacial energy models for application to designing aqueous liquid-liquid extractions for purification of bioparticles. We argue that the surface energy models, with contributions from contact angles between bioparticles and both phases and pH-dependent surface charges, will unlock the door to understand partitioning and creating continuous downstream processing using liquid-liquid extraction.

Development of interfacial energy models to predict the partitioning of biomolecules in aqueous liquid-liquid extraction

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.