A Micro Device Platform for Continuous Measurement of Contractility, Beating Rate, and Beating Rhythm of hiPSC-Cardiomyocytes inside a Controlled Incubator Environment.

The heart completes a complex set of tasks, including the initiation or propagation of an electrical signal with regularity (proper heart rate and rhythm), and generating sufficient force of contraction (contractility). Probing mechanisms of heart diseases and quantifying drug efficacies demand a platform that is capable of continuous operation inside a cell incubator for long-term measurement of cardiomyocyte monolayers. Here we report a micro device array that is capable of performing continuous, long-term (14 days) measurement of contractility, beating rate, and beating rhythm in a monolayer of hiPS-Cardiomyocytes (hiPSC-CMs). The device consists of a deformable membrane with embedded carbon nanotube (CNT)-based strain sensors. Contraction of the hiPSC-CMs seeded on the membrane induces electrical resistance change of the CNT strain sensor. Continuously reading the sensor signals revealed that hiPSC-CMs started to beat from Day 2, and plateaued on Day 5. Average contractile stress generated by a monolayer of hiPSC-CMs was determined to be 2.34 ± 0.041 kPa with a beating rate of 1.17 ± 0.068 Hz. The device arrays were also used to perform comprehensive measurement of the beating rate, rhythm, and contractility of hiPSC-CMs and quantify cell responses to different concentrations of agonists and antagonists, which altered the average contractile stress to the range of 1.15 ± 0.13 kPa to 3.96 ± 0.53 kPa. The continuous measurement capability of the device arrays also enabled the generation of Poincaré plots for revealing subtle changes of the beating rhythm of hiPSC-CMs under different drug treatments.