On-a-Chip-Based Sensitive Detection of Drug-Induced Apoptosis in Polarized Gastric Epithelial Cells

Abstract

Microfluidic devices for culturing cells have been successfully utilized for biomedical applications, including drug screening. Several cell lines could be cultivated in microengineered environments with promising results, but gastric cell lines have not yet been widely used or studied. Therefore, this study focuses on establishing a polarized gastric epithelial monolayer on-a-chip and describes a general-purpose methodology applicable for bonding any porous material to PDMS through an adhesive sublayer. The fully transparent microfluidic chip consists of two microfluidic channels separated by a collagen-coated porous membrane and lined by human polarized gastric epithelial (NCI-N87) cells. We present considerations on how to ensure continuous and stable flow through the channels. The continuous flow rate was achieved using a pressure-driven pump. Media flow at a constant rate (0.5 μL/min) rapidly led the gastric epithelial cells to develop into a polarized monolayer. The barrier integrity was assessed by the FITC-dextran test. The generation of a monolayer was faster than in the static Boyden chamber. Moreover, fluorescence microscopy was used to monitor the apoptotic cell death of gastric epithelial monolayers on-a-chip in response to camptothecin, a therapeutic gastric cancer drug.