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Automated cell culture and high throughput screening of cardiomyocyte disease model

20 January, 2021

Effective drug discovery and development rely heavily on the availability of predictive preclinical models. Target-based drug discovery used to focus on immortalized cells, and only used more complex biological systems for testing later in the drug development pipeline. Bringing the most relevant biology earlier into the pipeline mitigates late-stage failures due to safety or efficacy concerns. However, large-scale manufacturing of these cells remains a challenge.

Recent developments in human induced pluripotent stem cell (hiPSC) technologies hold great promise to overcome these limitations. To provide hiPSC-derived disease models in large batches that can be used all the way from hit identification to lead optimization, we have developed a system for large-scaled hiPSC expansion and differentiation. Cell manufacturing is done using non-contact, liquid handling equipment to reduce variation across plates or assays, increasing the physiological relevance of our clients’ requested disease models.

Dr Stefan Braam, co-founder and CEO of Ncardia, explains:
“Our aim is to put ‘human’ testing at the forefront of drug discovery, by developing the best possible human cellular models. This is very attractive from an industry perspective, as it ensures only viable candidate drugs are progressed through the pipeline, while minimizing risks and ethical considerations associated with animal testing.”

Next to controlled large-scale manufacturing, we have also automated our assay readouts and data handling, ensuring a validated high-throughput screening process. Setting up such a complex workflow requires optimal labware and workdeck configurations, to avoid variation across microplates. Tecan’s Fluent Automation Workstation offers the speed and flexibility required to meet such process-specific liquid handling needs.

Schematic overview of automated phenotypic screening workflow using hiPSC-derived cardiomyocytes

Figure 1: Schematic overview of automated phenotypic screening workflow using hiPSC-derived cardiomyocytes

We described how we automated cell culturing for hiPSC-derived cardiomyocytes in a whitepaper, in collaboration with Tecan. The paper 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.

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