The unperturbed picture: Label-free real-time optical monitoring of cells and extracellular vesicles for therapy

High-content screening (HCS) and high-throughput screening (HTS) are common processes used in biological research and drug discovery. They allow rapid examination of thousands of compounds tested at the same time for their activity in designed biological assays. After evolving in the 1990s, they quickly became pillars in the pharmaceutical industry, relying on the advances of process automation and adaptation of biochemical assays for small quantities, such as with multiple-well plates. The basic components of HTS and HCS are a miniaturized biological assay, automated transfers and liquid handling steps, and automated quantitative readouts of the assays. However, there has been an increased need for probing complex cellular and subcellular phenotypes as outputs, such as changes in morphology and metabolic activity. The more common approach of labeling is expensive, time-consuming, and prohibits any usage of labeled cells or their products. Novel label-free noninvasive optical imaging could provide tools for multiparametric evaluation at the scale of biopharmaceutical production as well as for personalized medicine.