Fully automated high-throughput cardiac toxicity screening platform using interlocking-structured 192 SU-8 cantilever arrays

Abstract

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 IC50. However, Quinidine only increased the half-value duration (HaVD) by approximately 22%, even though it did not affect the contractile force at IC50. 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.