A Miniaturized EHT Platform for Accurate Measurements of Tissue Contractile Properties

A Miniaturized EHT Platform for Accurate Measurements of Tissue Contractile Properties
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DOI:
10.1109/jmems.2020.3011196
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发表时间:
2020-10-01
影响因子:
2.7
通讯作者:
Sarro, Pasqualina M.
Sarro, Pasqualina M.
中科院分区:
工程技术3区
文献类型:
--
作者:
Dostanic, Milica;Windt, Laura M.;Sarro, Pasqualina M.

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我们提出了一个晶圆级制造的,基于PDMS的平台,用于培养小型化的工程心脏组织(EHTs),它允许高度准确地测量这些组织的收缩特性。该平台的设计是Heart-Dyno系统的各向异性缩小版本,由椭圆形微孔内的两个弹性微柱组成,体积范围为3至1 μ L,支持EHT形成。尺寸缩小有利于平台的制造,并使其与准确和高度可重复的批量晶片规模处理兼容;此外,缩小降低了细胞培养的成本并增加了测定通量。在制造之后,通过纳米压痕来表征装置以评估柱的机械性质,并转移到96孔板中用于细胞接种。无论平台的大小如何,细胞接种导致EHT的成功形成,并且所有组织都具有功能活性(即显示出周期性收缩)。微柱刚度的精确表征使得能够通过微柱位移的光学跟踪来准确测量心脏组织施加的收缩力。本文描述的微型EHT平台代表了培养和研究EHT的合适微环境。[2020- 01 - 30]
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 1 mu L 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. [2020-0130]