Advances in steady-state continuous-flow purification by small-scale free-flow electrophoresis

• Requirements for steady-state purification by free-flow electrophoresis.
• Solutions for removal of bubbles formed by electrolysis.
• Control of pH gradient occurring due to electrolysis.
• Methods to mitigate negative aspects of Joule heating.

This year marks the 150th anniversary of the first continuous-flow chemistry (CFC) technique, developed by Ernest Solvay, which revolutionized industrial level synthesis. CFC is defined by multi-stage processes in which mixing and reacting of chemicals occur without interruption. A significant challenge of CFC lies in post-reaction purification. Free-flow electrophoresis (FFE) could be integrated with CFC. FFE separates chemicals by an electric field that is directed orthogonally to a pressure driven hydrodynamic flow. Although there are problems with FFE, both macro-scale and small-scale FFE are feasible for CFC integration, and realizing long-term steady-state continuous-flow purification can have significant benefits. In this review, we discuss (i) the progress of CFC, (ii) existing continuous-flow purification techniques, (iii) small-scale FFE limitations associated with steady-state continuous-flow purification, and (iv) advances in FFE performance.