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.