Microchip electrospray performance during gradient elution with bulk conductivity changes.

This work identifies dynamic changes in bulk conductivity during reversed-phase HPLC gradient elution as a major source for spray mode changes and instabilities observed in ESI-MS. A commercial microchip-HPLC/ESI-MS configuration was modified to enable electrospray diagnostics based on frequency analysis of the microchip emitter current combined with spray imaging. This approach facilitated detection of different spray modes together with their onset potentials. Water/acetonitrile mixtures containing formic acid were selected as the electrosprayed solutions to represent typical conditions in reversed-phase HPLC. Experimental data are complemented by computational fluid dynamics simulations, treating the electrosprayed solution as leaky dielectric fluid, to address the influence of bulk conductivity and applied potential difference on the developing cone-jet morphology and stability.