Simultaneous measurement of contractile force and field potential of dynamically beating human iPS cell-derived cardiac cell sheet-tissue with flexible electronics

Abstract

Human induced pluripotent stem (iPS) cell-derived cardiomyocytes are used for in vitro pharmacological and pathological studies worldwide. In particular, the functional assessment of cardiac tissues created from iPS cell-derived cardiomyocytes...

Tissue-embedded stretchable nanoelectronics reveal endothelial cell–mediated electrical maturation of human 3D cardiac microtissues

“…S4), which is consistent with previous reports of hPSC-CM electrophysiological recording (21,31,(38)(39)(40). In addition, the tissue-level flexibility and high stretchability of our mesh design enable seamlessly integrating electronics throughout the entire time course of hPSC-CM tissue development, providing long-term stable electrophysiological recordings, while other methods are typically limited in recording duration because of the limited device stretchability and flexibility so that the device typically contacts with tissue at only one surface plane and will lose contact with tissue due to the mechanical contraction and tissue development (table S1) (21,31,(38)(39)(40)(41)(42)(43). We next further investigated how the activation time delay across different channels changed over the time course of development for both hiPSC-CMs and hiPSC-CMs/hiPSC-ECs (fig.…”

A Carbon-Based Biosensing Platform for Simultaneously Measuring the Contraction and Electrophysiology of iPSC-Cardiomyocyte Monolayers

“…On the basis of the configurations of in vitro cardiac models, several types of biosensing approaches have been developed for in vitro measurement of contractile functional properties (mechanical motion, contractile force/stress) and electrophysiology (action potential, extracellular field potential, conduction velocity). ,,, However, mechanical and electrophysiological function are commonly collected separately using different experimental settings and conditions. − Separate testing increases the experimental workload and misses key information involved in coordinated electro-mechanical coupling during cardiomyocyte beating. Recent attempts to simultaneously collect contractility and electrophysiological measurements suffered from interference from an applied sweeping voltage on electrical signal recording and a reliance on external force probes creating a complex experimental setup. − The carbon-based biosensing platform that we have developed integrates a flexible thin-film cantilever embedded with a CB-PDMS strain sensor and four CNT electrodes on a single chip, to perform simultaneous and multiparameter measurements on iPSC-CM monolayers. The integration of in vitro cardiac models with advanced biosensing components on a single platform enabled continuous, facile measurement of electro-mechanical cardiac functions during drug testing and disease modeling.…”

“…Ohya et al integrated gold microelectrodes onto parylene thin films for field potential measurement and transferred the flexible electronic sheet onto an external apparatus for simultaneous force measurement. 37 However, film transfer after cell culture can damage the cell monolayer, and the complicated experimental setup is also a roadblock for routine use in drug testing. Biosensing platforms that integrate flexible bioelec-tronics are required for on-chip and simultaneous measurement of electrophysiological and contractility parameters.…”

“…Contractility measurement can be determined by optical tracking of cantilever deflections, integrating laser-reflecting plates to accurately measure deflection-induced laser vibration or integrating flexible strain gauges to obtain contractility readout from electrical resistance signals. , For simultaneous measurement of electro-mechanical function, platforms have been developed to combine MEAs and IDEs for recording field potential and contraction-induced impedance signals of a cell monolayer. , However, membrane potential and impedance signals need to be recorded alternately since the applied AC sweeping voltage on the IDEs can influence the recoding of field potential signals. Ohya et al integrated gold microelectrodes onto parylene thin films for field potential measurement and transferred the flexible electronic sheet onto an external apparatus for simultaneous force measurement . However, film transfer after cell culture can damage the cell monolayer, and the complicated experimental setup is also a roadblock for routine use in drug testing.…”

Cell sheet-based in vitro bone defect model for long term evaluation of bone repair materials

“…CST has advantages in clinical application, which can improve the effect of cell transplantation, promote tissue repair and regeneration, reduce immune rejection, and reduce surgical risks. Besides, CST has also been applied in building in vitro heart and muscle tissue [25][26][27][28][29]. Recently, we have reported a macromolecular crowding based-strategy for rapid fabrication of intact, robust cell sheets [30].…”