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High-throughput biomimetic 3D gel-island chip for investigating cancer cell heterogeneity

Considerable evidence showing that ECM is an important regulator of cellular behavior including adhesion, metastasis, proliferation, and differentiation. Although hydrogel has been used in the cell culture, previous works focus on the collective cell behaviors rather than single cell heterogeneity. This paper reports a novel gel-islands microfluidic platform enabling single cells tracking in biomimetic three-dimensional (3D) microenvironment. The platform has the advantages of (1) reliable single cell encapsulation in 3D gel-islands, (2) high-throughput single-cell drug screening assays, and (3) automatic single cell lineage tracking. Combining gel-based 3D culture and single cell resolution, the presented platform can monitor cellular behaviors of hundreds of individual cells in 3D ECM microenvironment using small amount of matrix reagents and drugs.