We propose a novel cantilever device integrated with a polydimethylsiloxane (PDMS)encapsulated crack sensor that directly measures the cardiac contractility. The crack sensor was chemically bonded to a PDMS thin layer to form a sandwiched structure which allows to be operated very stably in culture media. The reliability of the proposed crack sensor has improved dramatically -2-compared to no encapsulation layer. After evaluating the durability of the crack sensor bonded with the PDMS layer, cardiomyocytes were cultured on the nano-patterned cantilever for real-time measurement of cardiac contractile forces. The highly sensitive crack sensor continuously measured the cardiac contractility without changing its gauge factor for up to 26 days (>5 million heartbeats). In addition, changes in contractile force induced by drugs were monitored using the crack sensorintegrated cantilever. Finally, experimental results were compared with those obtained via conventional electrophysiological methods to verify the feasibility of building a contraction-based drug-toxicity testing system.
This paper describes the surface-patterned polydimethylsiloxane (PDMS) pillar arrays for enhancing cell alignment and contraction force in cardiomyocytes. The PDMS micropillar (μpillar) arrays with microgrooves (μgrooves) were fabricated using a unique micro-mold made using SU-8 double layer processes. The spring constant of the μpillar arrays was experimentally confirmed using atomic force microscopy (AFM). After culturing cardiac cells on the two different types of μpillar arrays, with and without grooves on the top of μpillar, the characteristics of the cardiomyocytes were analyzed using a custom-made image analysis system. The alignment of the cardiomyocytes on the μgrooves of the μpillars was clearly observed using a DAPI staining process. The mechanical force generated by the contraction force of the cardiomyocytes was derived from the displacement of the μpillar arrays. The contraction force of the cardiomyocytes aligned on the μgrooves was 20% higher than that of the μpillar arrays without μgrooves. The experimental results prove that applied geometrical stimulus is an effective method for aligning and improving the contraction force of cardiomyocytes.
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.
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