Automated cell culture and high throughput screening
Effective drug discovery and development rely heavily on the availability of predictive preclinical models. For decades, target-based drug discovery has focused on immortalized cells to identify and optimize inhibitory or activating molecules. Testing on more complex biological systems takes place only during late stages in the drug development pipeline. Bringing the most relevant biology into the pipeline earlier would help to mitigate late-stage failures due to safety or efficacy concerns. However, complex biological systems are rarely available in the scale required for high throughput screening. Recent developments in human induced pluripotent stem cell (hiPSC) technologies hold great promise to overcome these limitations.
hiPSCs retain patient-specific genetic background information, differentiate into functional cell types, and closely mimic human pathophysiology. Ncardia has developed a system for scaled expansion and differentiation of hiPSCs, generating large batches of cells that can be cryopreserved until use. This enables the same batch of hiPSC-derived cells to be used for both hit identification and lead optimization.
Successful drug efficacy screening and validation studies require not only a physiologically relevant cell model, but also validated high throughput screening (HTS) protocols to test the effects of drug candidates. To achieve this, Ncardia has automated its cell culture processes in a 384-well microplate format, as well as its assay readouts and data handling.
This article outlines how the Fluent workstation was used to automate cell culture for Ncardia’s beating, hiPSC-derived cardiomyocytes. It also describes the use of these cultured cells to screen >3,500 small molecules in a chemically induced hypertrophy disease model, using a validated phenotypic assay.