Improved devices, systems and methods for treating a tissue region provide straightforward, yet reliable ways for installing diverse functional components within the confined space of a catheter-based instrument. Methods include providing a manifold body sized to fit within a catheter tube, the manifold body including a single main fluid junction, multiple branch fluid junctions, and a fluid circuit formed within the manifold body to channel fluid flow between the single main fluid junction and the multiple branch fluid junctions, coupling the single main fluid junction to a fluid source or a fluid destination external to the catheter tube, coupling each of the multiple branch fluid junctions individually to a fluid-conveying port on the operative element, and mounting the manifold within the catheter tube.