High-throughput screening or HTS is a drug development technique used to rapidly evaluate the biological activity of a large number of compounds and targets. It is an essential part of discovering potential therepeutic compounds, known as lead candidates.

Virtual screening utilizes computer simulations to model compound interactions with a target, saving time and cost in the early stages of drug discovery where a subset of potential compounds must be identified for further validation in biological assays. HTS, on the other hand, requires more resources and time to physically test interactions between compounds and targets, but provides tangible data about compound activity. Virtual screening can be used to enhance HTS by narrowing down the scale of the actual campaign.

Microplates or microtiter plates are commonly used in HTS. While 384-well and 1536-well plates are ideal for greater throughput due to a higher density, 96-well plates are also amenable for smaller screening operations. Microfluidics systems are also used when small volumes of fluids and efficient reagent use are required.

A high-throughput screening campaign usually consists of these main steps: target identification, assay development, compound screening, analysis of results and hit selection.

Depending on the capabilities of the screening facilities, readiness of the bioassay, and the size of the compound library, HTS can take less than a week (for a small library with thousands of compounds) or a few months (for a large library with hundreds of thousands to millions of compounds). The overall HTS campaign duration, however, will vary significantly depending on the scope of the project.