Thermoplastic elastomer based microfluidic gradient generator for cell culture and drug testing

Abstract

Microfluidic systems are increasingly utilized in preclinical research, however, developing platforms that are compatible with large-scale manufacturing remains a critical challenge. In this regard, we show that thermoplastic elastomer (TPE)-based microfluidic chips could be a viable alternative to traditional poly(dimethylsiloxane) (PDMS) devices for drug testing applications. Microfluidic concentration gradient generators are essential components in these systems, enabling local spatial and temporal control of biochemical stimuli for applications such as cellular response studies and drug screening. TPEs offer key advantages, especially, optical transparency, flexibility, and compatibility with high-throughput fabrication processes compared to PDMS, thereby enhancing commercialization potential. This study demonstrates the design and fabrication of TPE-based microfluidic devices incorporating concentration gradient generators that allow precise control over solute distributions. Gradient formation was validated through numerical modeling and co-flow experiments using fluorescent dyes. The platform supported the co-culture of human lung fibroblast cells and human colon adenocarcinoma cells (HT-29), which exhibited coordinated responses to gradients of fetal bovine serum (FBS) and sepantronimum bromide (YM-155). Performance benchmarks against PDMS chips demonstrated comparable functionality, underscoring the potential of TPE-based devices for future scalable and cost-effective drug testing and cellular assays.