Abstract

Organ-on-chip (OOC) is becoming the alternative tool to conventional in vitro screening. Heart-on-chip devices including microstructures for mechanical and electrical stimulation have been demonstrated to be advantageous to study structural organization and maturation of heart cells. This paper presents the development of metal and polymeric strain gauges for in situ monitoring of mechanical strain in the Cytostretch platform for heart-on-chip application. Specifically, the optimization of the fabrication process of metal titanium (Ti) strain gauges and the investigation on an alternative material to improve the robustness and performance of the devices are presented. The transduction behavior and functionality of the devices are successfully proven using a custom-made set-up. The devices showed resistance changes for the pressure range (0–3 kPa) used to stretch the membranes on which heart cells can be cultured. Relative resistance changes of approximately 0.008% and 1.2% for titanium and polymeric strain gauges are respectively reported for membrane deformations up to 5%. The results demonstrate that both conventional IC metals and polymeric materials can be implemented for sensing mechanical strain using robust microfabricated organ-on-chip devices.

Highlights

  • Organ-on-chip (OOC) aims to become the alternative tool for in vitro screening

  • The fabrication processes presented in this paper enabled the development of both metallic and polymeric strain gauges as a potential transduction mechanism for in situ monitoring of strain on PDMS membranes for OOC applications

  • A complete view of cell responses can be obtained if mechanical strain and other relevant cues could be quantitatively measured in situ and in a spatio-temporal manner

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Summary

Introduction

Organ-on-chip (OOC) aims to become the alternative tool for in vitro screening. Researchers are still facing biological and technological challenges that impede this cutting-edge technology to be adopted as a routine tool in drug development. The limited scalability of current fabrication processes and the lack of self-integrated monitoring are among the technical limitations hindering its adoption [1]. Monolithically microfabricated OOC devices have been developed aiming to overcome such limitations. The so-called Cytostretch [2,3], has been developed as a heart on chip with integrated microelectrodes. This platform enables the access of data related to the action potential generated by iPSC-derived cardiomyocytes with the possibility to precisely stimulate electrically the cell culture

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