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In this technical note, we demonstrate the hyphenation of production-scale free-flow electrophoresis (FFE) and sheathless electrospray ionization mass spectrometry (ESI-MS). In contrast to previous hyphenation approaches, we used a highly conductive background electrolyte (BGE) required for production-scale FFE. We found that this kind of BGE as well as a production-scale setup leads to significant electric interference between FFE and MS. This interference prevents steady-state FFE operation. We examine this interference in detail and discuss possible solutions to this issue. We demonstrate that the straightforward grounding of the transfer line removes the influence of ESI-MS on FFE, but creates a current leak from the ESI interface, which adversely affects the ESI spray. Furthermore, we show that only the electrical disconnection of the ESI probe from the FFE-MS transfer line suppresses this undesirable current. In order to facilitate the electrical disconnection we used a low conductivity, silica-based ESI probe with withdrawn inner capillary. This approach allowed the interference-free hyphenation of production-scale FFE (using a highly conductive BGE) with ESI-MS. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]