Sperm are robotically allocated into wells (~10,000 cells/well) in a 384-well plate (top left); each well contains a different small molecule at a concentration of ~6 μM. The insets show KF-4939, an anti-platelet agent, binding to sperm cells. After incubation with the small molecules, sperm motility is imaged and assessed (middle left). Subsequently, the same sperm are mixed with two tags, peanut agglutinin (PNA; green) and propidium iodide (Pi; red), that emit fluorescence when attached to cells. Sperm were analyzed with a technique called flow cytometry (top right): PNA binding to a sperm cell indicates that the cell has undergone the acrosome reaction, while Pi only binds to dead cells. Most sperm cells do not bind to PNA or Pi, some bind to one but not the other, and some bind to both (bottom right).