MEMS piezoresistive cantilever for the direct measurement of cardiomyocyte contractile force

Abstract

This paper reports on a method to directly measure the contractile forces of cardiomyocytes using MEMS (micro electro mechanical systems)-based force sensors. The fabricated sensor chip consists of piezoresistive cantilevers that can measure contractile forces with high frequency (several tens of kHz) and high sensing resolution (less than 0.1 nN). Moreover, the proposed method does not require a complex observation system or image processing, which are necessary in conventional optical-based methods. This paper describes the design, fabrication, and evaluation of the proposed device and demonstrates the direct measurements of contractile forces of cardiomyocytes using the fabricated device.

MEMS-Based Pulse Wave Sensor Utilizing a Piezoresistive Cantilever

“…Two electrodes were placed at the roots of the two hinges and the resistance of the cantilever is defined as the resistance between the two electrodes. The fabrication process of the cantilever can be found in previous studies [24][25][26][27][28][29]. A photograph of the fabricated sensor chip attached and wire-bonded to a flexible substrate and a photograph of the cantilever are shown in Figure 2a.…”

“…A differential pressure in the range of ±10 Pa was applied to the cantilever using a pressure generator. The fractional resistance change of the cantilever was measured using the setup reported in previous studies [24][25][26][27][28][29][30][31][32], which consists of the Wheatstone bridge circuit and an amplifying circuit whose output is recorded using a ScopeCorder (Yokogawa Test & Measurement Co., Tokyo, Japan, DL850). The calibration result in Figure 2c shows the linear relationship between the differential pressure and the fractional resistance change of the cantilever.…”

Generation of spatial-patterned early-developing cardiac organoids using human pluripotent stem cells

“…EB-mediated cardiac differentiation suffers from variability of EB size, organoid heterogeneity, and poor spatial organization 26 . For example, in the biowire platform 27 , microfluidic-based devices 28 , and cantilever systems 29 , cardiomyocytes were first differentiated from hiPSCs/hESCs in conventional tissue culture plates and then seeded as single cells or tissue clusters into the fabricated devices to form adult-like aligned cardiac muscle 23,30 . The advantages of these engineered cardiac tissue models are not only the structural mimicry of adult heart tissue, but also their capability of electromechanical measurements and stimulations 31,32 .…”

Biomechanical Characterization at the Cell Scale: Present and Prospects

“…The design flexibility of MEMS translates into the possibility of force measurements along multiple axes, coupled to unprecedented measurable force range (10 −12 ÷ 10 −3 N; Sun and Nelson, 2007 ). Notable examples of MEMS devices for cell biomechanical characterization are represented by the work of Matsudaira et al (2017) who developed a silicon piezoresistive cantilever platform for measuring the beating contraction force of iPS-derived cardiomyocytes, and that of Takahashi et al, 2016 who designed a MEMS force plate to measure single cell horizontal and vertical traction forces. Although the majority of these devices are passive, approaches to single-cell mechanical actuation using MEMS have to be acknowledged ( Scuor et al, 2006 ; Antoniolli et al, 2014 ), also integrating force sensing capabilities besides actuation ones ( Fior et al, 2011 ; Zhang and Dong, 2012 ).…”