OSmini: A Microfluidic Platform for Multiplexed, Gradient-Based Drug Delivery on Intact Tumor Slices

Abstract

Traditional preclinical cancer models often fail to predict clinical outcomes, limiting drug development and personalized treatment strategies. Tumor slice cultures offer a physiologically relevant alternative by preserving native tissue architecture and the tumor microenvironment (TME). However, their use has been limited by difficulties in achieving spatially precise drug delivery and ensuring device reproducibility. To overcome these challenges, we developed the OSmini platform—a digitally manufactured microfluidic system for multiplexed, gradient-based drug delivery across intact tumor slices. Using precision CNC milling of poly(methyl methacrylate) (PMMA), we fabricated eight independent microchannels that enable spatially resolved compound delivery with high reproducibility, optical transparency, and chemical compatibility. Flow characterization confirmed uniform performance with less than 8% variability across device iterations. We evaluated lateral diffusion using fluorescein at different flow rates and established operational parameters that maintain spatial precision. Biological validation with fixed and fresh PY8119 murine tumor slices demonstrated successful multiplexed delivery of fluorescent dyes and Doxorubicin gradients. By enabling spatially controlled drug testing in a physiologically relevant ex vivo model, OSmini advances functional precision oncology through improved drug screening and tissue-level pharmacodynamic profiling.