A Miniaturized EHT Platform for Accurate Measurements of Tissue Contractile Properties

Journal article (2020)

Authors

M. Dostanic Electronic Components, Technology and Materials - EEMCS
Jeroen Stein Leiden University Medical Center
Laura Windt Leiden University Medical Center
Berend J. van Meer Leiden University Medical Center
M. Bellin Leiden University Medical Center, Università degli Studi di Padova
Valeria Orlova Leiden University Medical Center
Massimo Mastrangeli Electronic Components, Technology and Materials - EEMCS
Christine Mummery Leiden University Medical Center
Pasqualina M Sarro Electronic Components, Technology and Materials - EEMCS
Research Group
Electronic Components, Technology and Materials (EEMCS) (TU Delft)
Copyright: © 2020 M. Dostanic, Jeroen Stein, Laura Windt, Berend van Meer, Milena Bellin, Valeria Orlova, Massimo Mastrangeli, Christine Mummery, Pasqualina M Sarro
DOI: https://doi.org/10.1109/JMEMS.2020.3011196
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Published Date

30-07-2020

Language

English

Faculty

Electrical Engineering, Mathematics and Computer Science

Department

Microelectronics

Research Group

Electronic Components, Technology and Materials

Abstract

We present a wafer-scale fabricated, PDMS-based platform for culturing miniaturized engineered heart tissues (EHTs) which allows highly accurate measurements of the contractile properties of these tissues. The design of the platform is an anisometrically downscaled version of the Heart-Dyno system, consisting of two elastic micropillars inside an elliptic microwell with volume ranging from 3 down to 1μL which supports EHT formation. Size downscaling facilitates fabrication of the platform and makes it compatible with accurate and highly reproducible batch wafer-scale processing; furthermore, downscaling reduces the cost of cell cultures and increases assay throughput. After fabrication, the devices were characterized by nanoindentation to assess the mechanical properties of the pillars and transferred to 96-well plates for cell seeding. Regardless the size of the platform, cell seeding resulted in successful formation of EHTs and all tissues were functionally active (i.e. showed cyclic contractions). The precise characterization of the stiffness of the micropillars enabled accurate measurements of the contractile forces exerted by the cardiac tissues through optical tracking of micropillar displacement. The miniature EHT platforms described in this paper represent a proper microenvironment for culturing and studying EHTs.