Manifolds and methods of operating manifolds are provided. An example manifold for controlling multi-lumen devices is provided that includes a substance supply mechanism. The substance supply mechanism independently provides a substance to, or remove a substance from, each of a plurality of lumens. The example manifold also includes a lumen selection mechanism. The lumen selection mechanism selectively opens and closes a connection between the substance supply mechanism and at least one of the plurality of lumens. A corresponding method of operation is also provided. An example embodiment also includes a manifold for use with a vessel seclusion device.