Biosensor devices can constitute an advanced tool for monitoring and study complex dynamic biolog ical processes, as for example cellular adhesion. Cellular adhesion is a multipart process with crucial implications in physiology (i.e. immune response, tissue nature, architecture maintenance, or behavior and expansion of tumor cells). This work focuses on offering a controlled methodology in order to fabricate a flexible plasmo-nanomechanical biosensor placed within a microfluidic channel as a new tool for future cell adhesion studies. We designed, fabricated, and optically and mechanically characterized this novel optical biosensor. As a proof-of-concept of its functionality, the biosensor was employed to observe fibroblasts adhesion in a cell culture. The device is configured by an hexagonal array of flexible rigid/soft polymeric nanopillars capped with plasmonic gold nanodisks integrated inside a microfluidic channel. The fabrication employs low-cost and large-scale replica molding techniques using two different polymers materials (EPOTECK OG142 and 310M). By using those materials the spring constant of the polymer nanopillars (k) can be fabricated from 1.19E-02 [N/m] to 5.35E +00 [N/m] indicating different mechanical sensitivities to shear stress. Therefore, the biosensor has the feasibility to mimic soft and rigid tissues important for the description of cellular nanoscale behaviours. The biosensor exhibits a suitable bulk sensitivity of 164 nm or 206 nm/refractive index unit respectively, depending on the base material. The range of calculated forces goes from ≈1.98 nN to ≈.942 µN. This supports that the plasmo-nanomechanical biosensors could be employed as novel tool to study living cells behavior.