Dynamic Gap Structure for High-Throughput Measurement of Cellular Mechanical Properties

Abstract

Precise quantification of cellular mechanical properties (Young's modulus) is essential for understanding cellular physiology, disease progression, and therapeutic responses. In contrast to existing deformability cytometry approaches that rely on fixed static constrictions, extensional flows or hydrodynamic shear, we present an all-glass microfluidic platform incorporating a Dynamic Gap Structure (DGS) formed by an ultra-thin glass membrane integrated into a rigid microchannel. This design enables high-throughput mechanical characterization of suspended cells under well-defined compressive loading. The DGS allows large populations of cells to traverse a tunable constriction gap under precisely controlled pressure, thereby accommodating cell-to-cell mechanical heterogeneity while effectively preventing clogging. By quantitatively correlating the applied pressure with the resulting whole-cell deformation during passage through the gap, we estimate the population-averaged Young's modulus of A549, C6, and NIH3T3 cells.Compared with atomic force microscopy (AFM), the proposed method provides substantially higher throughput and improved measurement consistency, yielding markedly narrower modulus distributions. This label-free platform enables robust, quantitative mechanical phenotyping of cells and offers significant potential for applications in cancer diagnostics, drug screening, and mechanobiology research.