Microscale cell stretcher to generate spatially uniform equi-biaxial strain using an elastomeric membrane with a contoured thickness profile

Cellular response to mechanical signals is an intriguing research topic that is central to numerous fundamental questions in cell biology and has attracted extraordinary research interests. Delivering in-plane equi-biaxial strain towards adherent cells is a critical step for studying cellular mechanical responses. Mechanical straining is often performed by pushing a circular elastomeric membrane against a post or an O-ring or applying in-plane strain via through perforations on the membrane. Such methods, however, are not well compatible with miniaturization because the difficulties of device assembly and operation increase dramatically as the dimension of the membrane reduces. In this paper, we report a post-less elastomeric membrane with a contoured thickness profile for delivering in-plane equi-biaxial strain with significantly improved spatial uniformity. The easy assembly and operation allow for miniaturization of individual cellular mechanical stimulation sites to support parallel operation. The improvement of the spatial uniformity of the in-plane strain was experimentally validated with different membrane deformations. Cell reorientation and reorganization of actin filaments in fibroblasts under dynamic loading were examined using such elastomeric membranes. This work is expected to hasten the next-generation high throughput cellular mechanical stimulators for a broad range of cellular mechanobiological studies.