HCS and HCA systems, which involve automated microscopy and image analysis, were first introduced over twenty years ago. Although the equipment has since evolved, the screening process typically remains universal amongst the scientific community.

Traditional screening and imaging methods limit quantitative results to clusters of thousands of cells. HCS allows a combination of morphological and functional information to be recorded for individual cells. HCS uses automation, fluorescence imaging and detection, and specialized algorithms to provide visualization and quantification for large-scale applications.

These visualizations make it useful in a variety of fields that require live cell imaging, such as drug discovery, cell behavior/mechanisms, and in vitro toxicology studies. HCS systems are also ideal for studying 3D cell culture models.

Like high-throughput screening (HTS), high-content imaging enables a more efficient workflow by automating the imaging process and removing possible investigator bias by providing highly quantitative rather than subjective results.

However, the two techniques have their differences. While HTS binds its targets in larger dimensions, HCS focuses on cell-based target responses, including the change in phenotype of the whole cell. In other words, HCS sacrifices some throughput capabilities for more comprehensive data.

Since its introduction, high-content screening systems have continually evolved. This evolution includes developments to the automated microscope hardware—cameras and confocal optics, for instance—as well as substantial software enhancements, improving image acquisition, analysis, evaluation, and data storage.

HCS improvements have supported the growing high-content screening requirements for higher-throughput, phenotypic screening and assays involving complex disease models, such as live cells, primary cells, stem cells and 3D spheroids.