Mechanism of Action and Toxicity Profiling

Explore cytotoxicity beyond cell death

In vitro toxicity assays are crucial for evaluating potential health hazards of drug candidates and other compounds like environmental pollutants.

Cytotoxicity is typically measured by looking at cell health or death after exposure. But traditional assays only capture a single snapshot in time which shows how toxic a compound is, not its specific mechanism of action (MoA). Pixel™ changes that with real-time, multiparametric readouts that reveal how compounds affect cell shape, behavior, function, and more over time.

Drug discovery powered by microchips

Pixel’s unique semiconductor-to-live-cell-interface integrates microchips at the bottom of each well in a standard 96- or 384-well Pixel plate. It captures longitudinal data on over 20 cell properties, including attachment, motility, tissue barrier, and growth. With this ultra-high-density electrode configuration, Pixel generates high-resolution cellular insights that let you distinguish unique mechanisms of action between compounds.

“FDA’s New Alternative Methods Program is intending to spur the adoption of alternative methods for regulatory use that can replace, reduce, and refine animal testing, help prevent products with increased toxicological risk from reaching the market, and improve predictivity of nonclinical testing to streamline the development of FDA-regulated products.”

FDA, Implementing Alternative Methods

Rich insights to accelerate targeted drug development

Track real-time changes in cell viability and death

While most cytotoxicity assays capture one endpoint readout to quantify cell health or death, Pixel provides longitudinal data on how cells respond to different compounds. This experiment highlights how drug responses can vary widely — Carmofur triggers immediate and continuous cell death compared to treatment with Doxorubicin where cells exhibit a 12-hour lag time before dying off.

Effect of different compounds on cell culture confluence over time.

Identify mechanisms of action using multiparametric drug response data

Confluence measurements can show how drugs impact cell growth and death, but they don’t provide the nuance necessary to determine a drug’s MoA. By capturing high-dimensional data on cell morphology, behavior, and function, Pixel enables a comprehensive understanding of cellular responses to different compounds, allowing for elucidation of distinct MoAs.

High-dimensional analysis reveals clustering of 904 compounds by mechanism of action.

Compare responses to drugs with different MoAs across cell lines

Drugs acting on different cellular pathways can have markedly distinct responses on different cell lines. Pixel provides insights that both help identify a drug’s MoA and reveal which cells are most responsive. This experiment shows how commonly-used cancer cell lines used in in vitro assays respond to compounds that act on different pathways, highlighting their unique drug sensitivities.