Methods for separating particulate substrates from solution while minimizing particle loss

The present invention provides a method for separation of a particulate matrix from a solution while reducing loss of particles during separation steps. Methods are also disclosed for isolation of molecules of interest using affinity particles or beads, wherein at least one step of the isolation is conducted in the presence of a detergent. The presence of detergent reduces the loss of matrix particles and enhances reproducibility and yield of the molecule of interest. The invention makes possible the manual and automated processing of affinity beads, especially magnetic beads, in multi-well as well as single-well vessels with significantly reduced bead loss, as compared with similar processes conducted in the absence of detergent.