Combining Top‐Down and Bottom‐Up: An Open Microfluidic Microtumor Model for Investigating Tumor Cell‐ECM Interaction and Anti‐Metastasis

Abstract Using a combined top‐down (i.e., operator‐directed) and bottom‐up (i.e., cell‐directed) strategy, an Under‐oil Open Microfluidic System (UOMS)‐based microtumor model is presented for investigating tumor cell migration and anti‐metastasis drug test. Compared to the mainstream closed microfluidics‐based microtumor models, the UOMS microtumor model features: i) micrometer‐scale lateral resolution of surface patterning with open microfluidic design for flexible spatiotemporal sample manipulation (i.e., top‐down); ii) self‐organized extracellular matrix (ECM) structures and tumor cell‐ECM spontaneous remodeling (i.e., bottom‐up); and iii) free physical access to the samples on a device with minimized system disturbance. The UOMS microtumor model – allowing a controlled but also self‐organized, cell‐directed tumor‐ECM microenvironment in an open microfluidic configuration – is used to test an anti‐metastasis drug (incyclinide, aka CMT‐3) with a triple‐negative breast cancer cell line (MDA‐MB‐231). The in vitro results show a suppression of tumor cell migration and ECM remodeling echoing the in vivo mice metastasis results.