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

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.