Unified 2D and 3D cell-based high-throughput screening platform using a micropillar/microwell chip

A unified high-throughput screening (HTS) platform is proposed for both 2D and 3D cell culture models in a single chip platform. Comparison studies between well-established 2D models and in vivo-like 3D models are important to understand the underlying mechanisms of chemotherapeutic drugs. In the present unified platform, cells were seeded on top of micropillars and cultured with 2D or 3D cell culture protocols. Through a simple assembly of a micropillar/microwell chip, the cells on the micropillars were dipped into a microwell array, thus providing a one-step quick media exchange without additional washing steps. To demonstrate the utility of the proposed platform, drug-response assays for human lung cancer cells (A375) in both 2D and 3D models were done with 12 different compounds. Most of the IC₅₀ values of the drugs in the 3D model were higher than those in the 2D case; however, cancer cells exposed to a hypoxia-activated drug (TPZ) showed higher resistance in the 2D model. The proposed unified platform represents an opportunity to achieve effective and reliable cell assessment standards by linking various model-based studies with biochemical and pharmaceutical applications.