The invention relates to certain novel approaches to reducing or eliminating the movement of contaminants from one droplet to another on a droplet actuator via liquid filler fluid. In one application, a method of detecting an analyte is provided and includes providing in a detection window a droplet including a signal-producing substance indicative of the presence and/or quantity of an analyte and one or more magnetically responsive beads which may interfere with signal produced by the signal producing substance. The method further includes using a magnetic field for magnetically removing the magnetically responsive beads from the detection window and/or magnetically restricting the magnetically responsive beads from entering the detection window while transporting and/or retaining the droplet in the detection window. The method additionally includes detecting a signal produced by the signal-producing substance.