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1536-well Screening Assays with iCell Cardiomyocytes2

15361536-well plates are the format of choice for high-throughput screening (HTS). The high density/low well volume necessitates minimal cell and reagent handling and has historically precluded the use of native cells. As such, HTS methodologies have traditionally been target-based efforts against heterologous cell lines expressing one, or at most, a few targets. iCell® Cardiomyocytes2 are changing this paradigm. The shortened workflow and in vivo biology of iCell Cardiomyocytes2 are bringing relevant phenotypic-based screens and the resultant advantages into HTS applications.

With a 4-day workflow and single media change, iCell Cardiomyocytes2 supply an optimal native cell type for cardiac-based discovery and toxicity screens. Easy to follow plating procedures produce an even monolayer of functional cardiomyocytes (Figure 1). In addition, dose response relations provide an excellent assay window (Figure 2) and show congruence with 96-well assays (Table 1).

Together, these qualities are enabling early screening on cells with native behavior and physiology. Contact CDI’s Technical Support for additional information on implementing iCell Cardiomyocytes2 in 1536-well plates.

Figure 1

Figure 1: iCell Cardiomyocytes2 Provide a Relevant Substrate for HTS
Eight representative wells of a 1536-well plate containing iCell Cardiomyocytes2 stained with calcein AM. Note the even distribution of cardiomyocytes.

Table 1

Table 1: Screening with iCell Cardiomyocytes2 Provides Congruent Data across Plate Formats
Cardiomyocyte viability was determined as in Figure 2 across 96- and 1536-well plate formats. The nearly identical values indicate minimal to no loss of sensitivity and relevance with miniaturization.

Figure 2

Figure 2: Screening in 1536 Wells with iCell Cardiomyocytes2 Enables Robust, Quantifiable Interrogations
iCell Cardiomyocytes2 were plated into 1536 wells and dosed with the indicated compounds. Cell viability was determined with the CellTiter-Glo 2.0 Assay (Promega Corp.). Note the robust dose-response relations to toxicant application, small error bars (Figure 2A), with an excellent assay window and z’ score (Figure 2B).