Microdevice Platform for Continuous Measurement of Contractility, Beating Rate, and Beating Rhythm of Human-Induced Pluripotent Stem Cell-Cardiomyocytes inside a Controlled Incubator Environment

Abstract

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 (CM) monolayers. Here, we report a microdevice array that is capable of performing continuous, long-term (14 days) measurement of contractility, beating rate, and beating rhythm in a monolayer of human-induced pluripotent stem cell-CMs (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 the hiPSC-CMs and quantify the cell responses to different concentrations of agonists and antagonists, which altered the average contractile stress to the range of 1.15 ± 0.13 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 in the beating rhythm of hiPSC-CMs under different drug treatments.

Optimized CNT-PDMS Flexible Composite for Attachable Health-Care Device

“…The CNT-PDMS composites with a weight ratio from 8 to 10 wt% were similar to the gel without fluidity. By using the fabrication process of screen printing and casting, CNT-PDMS composites (weight ratio 8%~10%) can be used as flexible strain sensors [ 15 , 38 , 44 , 52 ].…”

“…The CNT-PDMS composite material exhibits excellent electromechanical, mechanical [ 12 ], electrical, and biocompatible properties [ 13 , 14 , 15 ]; thus, types of sensors including piezoresistive sensors, capacitive sensors [ 16 ], and piezoelectric sensors made from the CNT-PDMS composite are widely applied in medical diagnosis [ 17 , 18 ], health examination [ 19 , 20 , 21 ], and energy storage [ 22 ]. Among them, CNT-PDMS composite based piezoresistive sensors utilize the principle that the resistance of CNT-PDMS would change when the strain/deflection impacts the CNT-PDMS device.…”

Fabrication and Biomedical Applications of Heart-on-a-chip

“…After a period of incubation, the cell begun to contract and the contraction force causes the change of electrical resistance of CNT ( Figure 3Ci ). This platform can continuously measure the contraction force and beating rate of CMs in a long term (14 days)[ 68 ]. Another choice is to use the piezoelectric material to measure the contraction force[ 69 - 71 ].…”

Advances in Multidimensional Cardiac Biosensing Technologies: From Electrophysiology to Mechanical Motion and Contractile Force

“…Because of the excellent mechanical properties, CNT-based strain sensors were first introduced into the fabrication of the microdevice platform for continuous and long-term measurement of mechanical characteristics of hiPSC-CMs. [217] Hou et al created CNTs-wrapped spider silks to detect cell growth and simultaneously record potential signals from cardiomyocytes. [218] Remarkably, Zhao's group developed graphene hybrid anisotropic structural color films [219] and anisotropic hydrogel structural color particles, [220] providing an excellent visible method for dynamic cardiomyocytes monitoring and sensing, which also further enrich the development and application of cardiomyocyte-actuated bioinspired soft robotics.…”

“…Because of the excellent mechanical properties, CNT‐based strain sensors were first introduced into the fabrication of the microdevice platform for continuous and long‐term measurement of mechanical characteristics of hiPSC‐CMs. [ 217 ] Hou et al. created CNTs‐wrapped spider silks to detect cell growth and simultaneously record potential signals from cardiomyocytes.…”