An electrowetting on dielectric (EWOD) device includes an EWOD device array that applies electrowetting forces and contains a non-polar fluid. A barrier droplet configuration is formed using electrowetting forces to obstruct migration of a species from a first area of the EWOD device array to a protected area of the EWOD device array. A method of operating the EWOD device includes the steps of: dispensing a source droplet into a first area of the EWOD device array, the source droplet containing a migrating species, wherein the EWOD device array includes a second area to be protected from the migrating species; and forming a barrier droplet configuration positioned between the first area and the second area of the EWOD device array that obstructs a migration pathway of the migrating species between the first area and the second area. The barrier droplet configuration includes at least one aqueous or polar barrier droplet, and the migrating species exhibits a preference for either the polar or aqueous environment of the barrier or the non-polar environment of the oil to obstruct migration.