Widespread application of the cone-jet electrospray has been hampered by the low flow rate at which the spray is dispersed, despite the unique ability of this device to disperse quasi-monodispersed particles over a phenomenal size range. Compact multiplexing, that is, with a high number of sources per unit area, is indispensable for dramatically increasing the throughput and reducing the cost per electrospray source. We demonstrate the successful operation of multiplexed electrospray systems with an unprecedented packing density of up to 11,547 sources/cm(2). The devices were fabricated and operated by implementing three criteria: (a) the extractor electrode configuration should be used to localize the electric field: (b) the viscous pressure drop acting on the liquid should dominate with respect to the electrostatic pulling force by the electric field; and (c) the electric field "driving" the droplets between the extractor electrode and the collector should be sufficiently intense to avoid reversal of the droplet motion near the extractor (satellite trapping). All devices showed excellent droplet size uniformity across the entire spray region, which indicates effective decoupling of the electrospray sources even for closely packed nozzles. The experimental results show that these design criteria provide effective and reliable guidelines for the successful design and operation of multiplexed devices from first principles, that is, based only on knowledge of the suitability of a liquid for electrospray dispersion and of the critical liquid properties such as surface tension, viscosity and electric conductivity. As a result, the design of these devices for a given application is achievable without costly trial-and-error microfabrication trials. This development opens the door for applications requiring flows from multiplexing 10(6)-10(7) individual electrospray sources from industry-standard 12-in silicon wafers. (C) 2009 Elsevier Ltd. All rights reserved.