Mimicking Intravasation–Extravasation with a 3D Glass Nanofluidic Model for the Chemotaxis-Free Migration of Cancer Cells in Confined Spaces

Abstract

A new 3D nanofluidic biochip for the study of cancer cell migration and invasion is proposed. In this design, femtosecond laser-assisted etching is applied to create embedded microfluidic channels, with a base thickness of less than 100 µm for high-resolution imaging using inverted microscopes. The glass deformation is thermally controlled during fabrication to create pillar-like formations separated by narrow constricted channels with widths of less than 1 µm spanning lengths of more than tens of microns, mimicking the 3D intravasation–extravasation configuration. Time-lapse microscopy is used to observe the behavior of prostate cancer (PC3) cells in chemoattractant-free media over long time intervals as the cells invade the narrow spaces. The PC3 cells are observed to be capable of breaching the fabricated submicrometric intravasation-like barriers while retaining their viability and proliferation activity. The cells are further able to penetrate the extravasation-like confining spaces, confirming their dynamic adaptability as they pass through constricted channels with volumes much less than that of the cell nucleus.