Contactless micro-elastography of single cells using oscillating microbubbles as shear wave sources

The mechanical properties of cells play key roles in their physiology, function, physiological and pathological transformations. Micro-elastography has recently emerged as a promising tool to estimate cellular viscoelastic properties within a millisecond, without the need for mechanical modeling. Here, we report a fully contactless approach to single-cell micro-elastography, using acoustically oscillating gas microbubbles positioned near individual cells (20 µm diameter megakaryocytes) as localized shear wave sources. Using this approach, we successfully performed micro-elastography on cells up to five times smaller than those studied in previous works, establishing the smallest single-cell elastography measurements to date. Spherical or non-spherical bubble oscillations generated 15 kHz elastic waves, which we detected using a high-speed camera coupled to a standard bright-field microscope. Noise correlation elastography enabled the measurement of average and local shear-wave velocities within single cells. Our results demonstrate that this method is robust and reproducible across multiple cells from the same cell line, paving the way for real-time, label-free mechanical monitoring of single cells during fast biological processes. Significance Statement Cell mechanics are central to processes such as differentiation, migration, and disease progression, but current imaging tools are often slow or limited to unusually large cells. By harnessing acoustically oscillating microbubbles as localized wave sources, we achieve contactless micro-elastography of cells five times smaller than previously possible, with acquisition times under one millisecond. This advance enables real-time, label-free monitoring of fast biological processes in diverse cell types, offering powerful opportunities for cell biology, mechanopathology, and drug discovery.