Engineering tumor vasculature on an injection-molded plastic array 3D culture (IMPACT) platform.

ABSTRACT

Recent advances in microfluidic organ-on-a-chip technology have enabled the growth of 3D microphysiological systems for diverse biological studies. Fabrication and usage limitations inherent to conventional soft lithographic polydimethylsiloxane (PDMS) based microfluidic platforms drive demands for more accessible, standardized, and mass producible platforms for wider applications. Here, we introduce a novel injection-molded plastic array 3D culture (IMPACT) platform, a microfluidic system designed for easy and diverse patterning of 3D cellular hydrogel. The flexibility of the IMPACT platform enabled simultaneous high-content morphological profiling of the effect of nine different types of tumor cells on vascular formation. Moreover, screening of three different known anti-tumor drugs (5-FU, axitinib and cetuximab) was done at various delivered dosages. We observed distinct and expected molecular mechanism dependent response on both tumor and vasculature in response to treatment, confirming the applicability of the IMPACT as high-content drug testing tool. Therefore, we propose IMPACT as the next generation of 3D microfluidic co-culture platform compatible with any biological, clinical, and pharmaceutical investigations requiring robust high-throughput and high-content assays.