Label-free, in situ monitoring of viscoelastic properties of cellular monolayers via elastohydrodynamic phenomena

Recent advances recognize that the viscoelastic properties of epithelial structures play important roles in biology and disease modeling. However, accessing the viscoelastic properties of multicellular structures in mechanistic or drug-screening applications face challenges in repeatability, accuracy, and practical implementation. Here, we present a microfluidic platform that leverages elastohydrodynamic phenomena, sensed by graphene strain sensors, to measure the viscoelasticity of cellular monolayer in situ, without using labels or specialized equipment. We demonstrate platform utility with two systems: cell dissociation following trypsinization, where viscoelastic properties change over minutes, and an epithelial-to-mesenchymal transition, where changes occur over days. These cellular events could only be resolved with our platforms higher signal-to-noise ratio: relaxation times of 14.5 plus or minus 0.4 s-1 for intact epithelial monolayers versus 13.4 plus or minus 15.0 s-1 in other platforms. By rapidly assessing combined contributions from cell stiffness and intercellular interactions, we anticipate that the platform will hasten translation of new mechanical biomarkers.