3D Biomimetic Chips for Cancer Cell Migration in Nanometer-Sized Spaces Using “Ship-in-a-Bottle” Femtosecond Laser Processing

Abstract

Cancer cells undergo dramatic morphology changes when migrating in confined spaces narrower than their diameter during metastasis, and thus it is necessary to understand the deformation mechanism and associated molecular events in order to study tumor progression. To this end, we propose a new biochip with three-dimensional (3D) polymer nanostructures in a closed glass microfluidic chip. "Ship-in-a-bottle" femtosecond laser processing is an exclusive technique to flexibly create 3D small details in biochips. The wavefront correction by the spatial light modulator significantly improves the fabrication resolution of this technique. The device could then accommodate defect-free 3D biomimetic nanoconfigurations for the evaluation of prostate cancer cell migration in confined spaces. Specifically, polymeric channels with widths of ∼900 nm, which is more than one order of magnitude smaller than the cell size, are integrated by femtosecond laser inside glass channels. The cells are responsive to an in-channel gradient of epidermal growth factor and can migrate a distance greater than 20 μm. After migration, the cells suffer partial cytokinesis, followed by fusion of the divided parts back into single cell bodies.