A Novel Microfluidic Device to Study Cell to Cell Communication By Dynamic Sampling of Paracrine Factors

Breast cancer is the second leading cause of cancer related death in American women. Breast tumors are composed of a highly diverse cellular make up including cancer cells that interact with the surrounding tumor stroma to produce cancer associated adipocytes, fibroblasts, and macrophages. Secreted factors from these stromal cells modulates the tumor microenvironment (TME) to induce drug resistance and metastasis in cancer cells. There are no commercially available cell co-culture methods capable of the dynamic sampling of extracellular media during an experiment to investigate cell-to-cell communications. To address this, a novel microfluidic device was designed, fabricated, and tested to study intercellular communications during co-culture. The device consists of three parallel fluidic channels connected by an array of microchannels to facilitate the orthogonal diffusion of biomolecules. COMSOL Multiphysics was used to model the mass transfer in the device to optimize channel length and width. The final device design consisted of three parallel 1500 µm long with the two outermost channels for static cell culture and the center channel connected to a peristaltic pump. A proof-of-concept device was fabricated using a combination of soft lithography and polydimethylsiloxane (PDMS) replication. Initial data confirmed the ability to seed cells into the two outer cell culture channels. This microfluidic device will be used in the future to analyze the cell-to-cell communications between MDA-MB-231 breast cancer cells, a triple negative cell line, and adipose-derived stem cells (ASCs) to study how stromal cells enhance the proliferation and drug resistance of cancer cells.