FLEXcyte 96 transforms traditionally limited cardiac contractility approaches of the Langendorff Heart into a cutting-edge modern high-throughput technique. Unique flexible substrates of the FLEXcyte recording plates mimic in vivo - like environments. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC- CMs) grown in such physiological conditions display positive inotropic responses without additional stimulation.
The FLEXcyte 96 brings in vitro contraction force measurements of cardiac cells to a new dimension. By using a well-defined, flexible substrate for cardiac cells, the system leverages maturity and mature responses of stem cell-derived cardiomyocytes to pharmacological compounds in a higher throughput format. In the 96-well plate, the cells adhere as monolayers on the flexible substrates and the contractility of the synchronized cell layers is recorded. This unique technology allows for recordings in a native-like environment close to the mechanical conditions of the heart. The FLEXcyte 96 is a turn-key system for structural and functional contraction force recordings in cardiotoxicity, safety and efficacy screening, and basic research.
With less than 10 μm in thickness and sophisticated surface modification, the polydimethylsiloxane (PDMS) membranes of the FLEXcyte 96 disposable plates offer physiological elasticity of native human heart tissue and strong mechanical support. While being deflected by the weight of the culture medium, rhythmic contraction of the cardiomyocytes lifts the membranes in the 96-well upwards. By measuring the changes in deflection, mechanical stress can be calculated.
The system has been validated with stem cell-derived cardiomyocytes from several providers (Ncardia, FUJIFILM Cellular Dynamics, Inc. (FCDI), Axol and NEXEL). Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC- CMs) display positive inotropic responses, no additional stimulation of “cell maturation” is necessary. Cardiac contraction force can also be measured on patient-derived cells.
No subtleties of cytotoxic responses are missed, and measuring contractile forces (mN/mm2) on heart muscle cells for safety, efficacy, and toxicity investigations in both chronic and acute time frames are performed reliably. The FLEXcyte 96 is a fully automated device, records from 96 wells in parallel.
Flexibility is key for a pro-maturation effect on cultured human iPSC-derived cardiomyocytes. An increase in the cell‘s contractile force over time, as well as a decreasing beat rate, are both well known parameters for an adult cardiac phenotype. The FLEXcyte 96 system provides both basic prerequisites needed to record mature cardiac force.