The vulnerability of vesicles to electroporation and rupture by externally applied electric fields, combined with the ability of dielectrophoresis and/or AC electroosmosis to manipulate suspended vesicles over micropatterned electrodes suggests new techniques to electrically trigger localized chemical reactions at predetermined positions in microfluidic devices. The electric field conditions needed to rupture giant unilamellar phospholipid vesicles were determined as a function of vesicle size in a simple coplanar microelectrode array geometry. Rupture results were interpreted in terms of the spatially varying electric field strength, calculated via the Poisson equation and accounting for frequency effects on electrode impedance, and the experimentally measured vesicle elevation. The vesicle transmembrane voltage scales linearly with the applied electric field strength according to the Schwan theory of electroporation, so that larger vesicles are usually more prone to electric field induced rupture than smaller ones in the uniform electric fields that are typically employed to cause electroporation and rupture. Yet, in the coplanar microelectrode arrangement, larger vesicles preferentially reside at larger elevations where the local field strengths are weaker. As a result, there is a sensitive range of vesicle radii that are most prone to electric field induced rupture over a micropatterned electrode array that leaves the largest vesicles resistant to rupture. (c) 2008 Elsevier Inc. All rights reserved.