Hepatocellular Carcinoma-on-a-Chip Based on Microfluidic Well Array for Personalized Drug Evaluation.

Abstract

The high interpatient variability in hepatocellular carcinoma (HCC) poses a critical challenge to drug therapy, underscoring the need for personalized platforms that can assess therapeutic efficacy while capturing tumor heterogeneity. Here, we present a stereo microfluidic well array-based hepatocellular carcinoma-on-a-chip for one-stop individualized drug evaluation. We design the device with two modules for tumor spheroid formation and drug concentration gradient generation in a single platform. Using projection micro-stereolithography, the chip template is fabricated in a one-step process and subsequently molded in polydimethylsiloxane (PDMS). Controlled microfluidic flow in the chip enables precise cell loading into microwells, producing uniform-sized and high-viability HCC spheroids (∼2200 per chip) under dynamic culture conditions. Based on these features, this tumor-on-a-chip further supports high-throughput drug screening across tunable and multiple concentration gradients, validated with patient-derived HCC samples. Thus, this platform is capable of high-throughput generation of three-dimensional spheroids and multi-dose drug gradient exposure; it has already completed proof-of-concept studies for a drug screening platform based on microfluidic spheroids, laying the groundwork for subsequent translational research incorporating clinical data.