Centrifugal microfluidic platform for single-cell level cardiomyocyte-based drug profiling and screening

Abstract

Drug screening and profiling is an important phase in drug discovery, development, and marketing. However, some profiling tests are not routinely done because of the needed additional technical skills and costly maintenance, which leads to cases of unexpected side effects or adverse drug reactions (ADRs). This study presents the design and operation of a microfluidic chip for single-cell level drug screening and profiling as an alternative platform for this purpose. Centrifugation was utilized to trap isolated single and groups of primary cultured neonatal rat cardiomyocytes in the same chip. In the off-spin operation of the chip, the cells can be observed under a microscope and movies of the beat motion can be recorded. The beat profiles of the cells were generated by image correlation analysis of the recorded video to study the contractile characteristics (beating rate, beating strength, and inter-beat duration). By utilizing this non-invasive tool, long term continuous monitoring, right after trapping, was made possible and cell growth and dynamics were successfully observed in the chip. Media and liquid replacement does not require further centrifugation but instead utilizes capillary flow only. The effect of carbachol (100 μM) and isoproterenol (4 μg mL⁻¹) on single cells and groups of cells was demonstrated and the feature for immunostaining (β-actin) applicability of the chip was revealed. Furthermore, these findings can be helpful for the headway of non-invasive profiling of cardiomyocytes and for future chip design and operation of high-throughput lab-on-a-chip devices.