Development of a Next-Generation Biosensing Platform for Simultaneous Detection of Mechano- and Electrophysiology of the Drug-Induced Cardiomyocytes

ACS Sens. 2019 Oct 25;4(10):2623-2630. doi: 10.1021/acssensors.9b00852. Epub 2019 Sep 19.

Abstract

Detection of adverse effects of cardiac toxicity at an early stage by in vitro methods is crucial for the preclinical drug screening. Over the years, several kinds of biosensing platforms have been proposed by the scientific society for the detection of cardiac toxicity. However, the proposed tissue platforms have been optimized to measure either mechanophysiology or electrophysiology of the cardiomyocytes but not both. Herein, we demonstrate in detail our successful attempt toward developing a novel "multifunctional microphysiological system" also known as "organs-on-chips" to measure simultaneously the mechanical and electrical characteristics of cardiomyocytes in vitro. The proposed device can rapidly recognize drug-induced cardiovascular toxicity in real time, which is one of the most significant factors for drug discovery and postmarketing surveillance. We confirm that the proposed sensor delivers the direct relationship between the contraction force and cell impedance of cardiomyocytes under the influence of different cardiovascular drugs such as verapamil, astemizole, and lidocaine. The obtained assay results provide a great potential for a deep understanding of the drug effects on the cardiomyocytes in vitro.

Keywords: SU-8 cantilever; astemizole; cardiac drug toxicity; contraction force; electrical impedance spectra; lidocaine; verapamil.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astemizole / pharmacology
  • Biosensing Techniques*
  • Cardiotoxicity
  • Cardiotoxins / pharmacology*
  • Cells, Cultured
  • Drug Evaluation, Preclinical / methods*
  • Electric Impedance
  • Electrophysiological Phenomena
  • Lidocaine / pharmacology
  • Microelectrodes
  • Myocytes, Cardiac / drug effects*
  • Myocytes, Cardiac / physiology
  • Rats
  • Verapamil / pharmacology

Substances

  • Cardiotoxins
  • Astemizole
  • Lidocaine
  • Verapamil