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Dai, Y.,Oyunbaatar, N.-E.,Lee, B.-K.,Kim, E.-S.,Lee, D.-W. Elsevier 2018 Sensors and actuators. B Chemical Vol.255 No.3
<P><B>Abstract</B></P> <P>In this paper, a spiral-shaped SU-8 cantilever with biocompatibility was proposed to monitor the changes of cardiac contraction in response to injection of drug in real time. The cantilever comprises a thick quadrate body and a filmy spiral cantilever with micro-grooves and gold patterns on the top of its surface. The longitudinally patterned micro-grooves facilitate the aligned growth of cardiomyocytes in order to increase the contraction force. In addition, the spiral shape increases the cantilever’s effective length and decreases its spring constant, which means its bending displacement can be increased for the same force as compared to that observed in a conventional rectangular cantilever. The bending displacement of the spiral SU-8 cantilever induced by the contraction of cardiomyocytes can be precisely measured at the nanoscale using a homemade laser-based measurement system. The displacement in the spiral SU-8 cantilever without micro-grooves was much greater than that in the case of traditional rectangular SU-8 cantilevers. The displacement produced by the spiral cantilever with grooves is 240% greater than that without grooves. Following preliminary experiments, cardiac drugs including Verapamil, Quinidine, Lidocaine, E-4031, and Bay K 8644 were used to evaluate their side effects on cardiomyocytes. Quantitative analysis of measurements shows that not only Verapamil and Quinidine but also Lidocaine and E-4031 treatment can decrease the cell beating frequency, and both the Verapamil and Lidocaine treatment can decrease the cell contraction force. Furthermore, Bay K 8644 assay results indicate that it can decrease the contraction force and increase the beating frequency of cardiomyocytes.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Spiral cantilever integrated with micro-grooves is proposed for a real time monitoring of cardiac contractibility. </LI> <LI> Home-made measurement system is developed to precisely measure the contractibility of cardiomyocytes at the nanoscale. </LI> <LI> Five different kind of drugs have been employed for the preliminary study of drug-induced cardiac toxicity. </LI> <LI> Spiral cantilever arrays are expected to be applied as a new method to support for the drawbacks of conventional methods. </LI> </UL> </P>
Kim, Jong Yun,Oyunbaatar, Nomin-E.,Lee, Dong-Weon Elsevier 2019 Sensors and actuators. B Chemical Vol.285 No.-
<P><B>Abstract</B></P> <P>This paper proposes a high-throughput drug-screening platform integrated with 48 well plates containing 192 SU-8 cantilevers that assess cardiac toxicity levels by measuring changes in the contractile force of cardiomyocytes in vitro environment. To improve the reliability and reproducibility of the measured data, four interlocking-structured cantilevers were employed in each well and the displacement changes were measured at the nanometer scale using a laser-based sensor. The use of the mean value of the cantilever displacement in each well greatly improved the accuracy of the drug toxicity results. In addition, microgrooves patterned onto the SU-8 cantilevers greatly enhanced the alignment of cardiomyocytes, resulting in an increase in the contraction force by approximately 2.4 times. After the preliminary experiment, the contractile behaviors of cardiomyocytes on the surface-patterned SU-8 cantilevers were measured under various drugs, namely, Bay K8644, Verapamil, Isoproterenol, Quinidine, Lidocaine, E-4031, and Astemizole. In the case of Bay K8644, Verapamil, and Isoproterenol, the contractile force of cardiomyocytes was increased or decreased by 30%, 50%, and 20%, respectively, at the value of IC<SUB>50</SUB>. However, Quinidine only increased the half-value duration (HaVD) by approximately 22%, even though it did not affect the contractile force at IC<SUB>50</SUB>. Potassium-channel inhibitors E-4031 and Astemizole also showed no change in contractile force at low concentrations. However, the HaVD increased by approximately 3.4 times and abnormal peaks were observed at higher drug concentrations. The fully automated high-throughput screening capability of the proposed platform has immense potential as a preliminary drug-screening system in the next generation.</P> <P><B>Highlights</B></P> <P> <UL> <LI> 192 SU-8 cantilever arrays integrated with a 48-well plate is proposed for high-throughput screening in drug-induced cardiac toxicity. </LI> <LI> Changes in cantilever displacement and beating frequency of cardiomyocytes treated with various drugs were systematically analyzed. </LI> <LI> The fully automated high-throughput screening approach has great potential to further improve the accuracy of drug discovery studies. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>The manuscript introduced a novel method of fully automated high-throughput cardiac toxicity screening system platform. This system can precisely and continuously measure the displacement of 192 cantilever arrays using a laser vibrometer and a motorized XY-stage for the purposed of high-throughput drug screening.</P> <P>[DISPLAY OMISSION]</P>