Reverse-flow diafiltration for continuous in situ product recovery

In situ product recovery (ISPR) is a major challenge in downstream processing. ISPR is particularly advantageous for product-inhibited fermentation processes since it removes the product from the vicinity of the producing cell right after it is formed, thereby eliminating the inhibition of the reaction. This work presents a novel ISPR process named reverse-flow diafiltration. This process is characterized by submerged hollow-fiber membranes which are integrated in the bioreactor. The process handles two liquid streams which are exchanged alternatingly over the same membrane in a reverse-flow operation mode: One supplies the nutrient solution, the second one extracts product solution. As a result no net flux over the membrane occurs and cake-layer formation is kept low. Short emptying intervals in-between the two steps are applied, using air or permeate, respectively, for emptying the inside of the hollow-fiber lumen to improve product recovery values. Experiments with yeast suspensions of different concentrations showed that stable filtration performance could be ensured over a period of about one week. At the same time constant product recovery values of up to 100% could be achieved. The reverse-flow diafiltration process is very promising for future ISPR applications towards continuous fermentation processes. It is promising especially for more complex fermentation suspensions such as fungi suspensions, characterized by high viscosity and filamentous organisms, since it enables stable filtration performance and product recovery values over longer time periods than conventional processes.