Abstract: An external-loop perfusion bioreactor for cultivating microbial, plant, animal or insect cells to produce valuable metabolites has a riser conduit; a cell culture medium inlet in the riser conduit; an inlet for an oxygen containing gas in the riser conduit; a downcomer conduit, having an upper portion and a lower portion, the upper portion of the downcomer conduit being in the shape of a truncated cone; an upper and lower transfer conduit connecting the riser conduit and the downcomer conduit; a spent medium outlet port defining a liquid level surface in the upper portion of the downcomer conduit; and a baffle means having a fluid impermeable wall for creating a settling zone in the upper portion of the downcomer conduit. A series of conical lamellar settling surfaces can be arranged in the settling zone to enhance particle separation from the aqueous medium.