Blood separation systems and methods are provided for controlling the interface between separated blood components. The system includes a blood separation chamber configured to separate blood into first and second blood components and an outlet line for removing at least a portion of the first blood component from the blood separation chamber. A primary optical sensor assembly is associated with the blood separation chamber to directly monitor the interior of the blood separation chamber. A secondary optical sensor assembly is associated with the outlet line to monitor the first blood component in the outlet line. The system also includes a controller programmed to select between the primary optical sensor assembly and the secondary optical sensor assembly for monitoring contamination of the first blood component. The system is particularly advantageous for preventing contamination of separated plasma which is lipemic or hemolytic.