In the context of Single-Dose Screening and Affinity Screening, a positive control sample corresponds to a Ligand sample that is a well-known or well-characterized interactor of the Target (sometimes also called tool compound). 

The major purpose of the positive control sample is to ensure target stability throughout the time course of the screening. We therefore recommend running a positive control sample at least twice on a 384-well plate in single-dose screens and once in affinity screens per plate. The positive control sample is also often used to establish assay conditions for the screening. It is therefore beneficial if the positive control sample is like the potential ligands that are supposed to be tested (e.g. use a small molecule positive control for a small molecule screening).