A cell culture system is presented for separation of cells from perfusate in a cell culture. Perfusate and cells suspended by the perfusate are directed through a nested-cone separator having an outer cone and an inner cone defining an annulus which forms an expanding cross-sectional area of flow whereby the velocity of perfusate within the annulus diminishes with distance from the suspended cell culture. The superficial velocity of the perfusate is thereby reduced. A Boycott effect and diminished superficial velocity within the annulus allow cells which are to be returned to the suspended cell culture to thereby settle across the path of perfusate flow in the annulus and to return to the cell culture. Perfusate is separated thereby from cells and is removed from the cell culture while allowing highly reliable and cost-effective control of cell cultures for prolonged periods of time.