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<p>Cell mechanics is essential for understanding cellular motion, function and disease, and relies on measuring forces ranging from piconewtons to micronewtons in liquid environments. Yet, despite extensive technological developments, precisely monitoring cellular forces without perturbing their natural motion remains challenging, requiring a highly adaptable force sensor with piconewton-level sensitivity. Microcantilever-based sensors hold great potential but face limitations, including complex feedback systems, electromagnetic interference and limited liquid compatibility. Here we report a cell stethoscope based on an optical microcantilever that demonstrates an ultrasensitive optical phase detection system within a miniaturized microfibre interferometric structure, achieving subpiconewton sensitivity and megahertz-level responses. The microfibre is encapsulated in a biocompatible film, providing excellent liquid compatibility and immunity to electromagnetic interference, as demonstrated by piconewton-resolution dynamic force sensing in liquid-phase physicochemical reactions. We establish the microcantilever as a versatile platform for cell mechanics analysis, achieving real-time quantitative analysis and acoustic monitoring of cardiomyocyte contractions under electrical stimulation, enabling non-invasive mechanical characterization of live cells. Meanwhile, the transparent microcantilever allows simultaneous optical observation and calcium fluorescence imaging of the underlying cell, facilitating multiparametric cellular analysis. These results showcase precise sensing of cellular mechanical dynamics across diverse environments, providing emerging opportunities in cellular mechanics and biomechanics.</p>

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Piconewton-sensitive cell stethoscope using an optical microcantilever

  • 期刊论文

  • 发表日期：

    2026年7月9日

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  • Xitao Tu,
  • Guoliang Hao,
  • Wenjing Tu,
  • Yuqi Zhen,
  • Gang Wang,
  • Pansi Huang,
  • Kaicheng Deng,
  • Tao Feng,
  • Bowen Cui,
  • Jianbin Zhang,
  • Yuanbiao Tong,
  • Pan Wang,
  • Xin Guo,
  • Dawei Di,
  • Yang Zhu,
  • Tiefeng Li,
  • Limin Tong,
  • Lei Zhang

摘要

Cell mechanics is essential for understanding cellular motion, function and disease, and relies on measuring forces ranging from piconewtons to micronewtons in liquid environments. Yet, despite extensive technological developments, precisely monitoring cellular forces without perturbing their natural motion remains challenging, requiring a highly adaptable force sensor with piconewton-level sensitivity. Microcantilever-based sensors hold great potential but face limitations, including complex feedback systems, electromagnetic interference and limited liquid compatibility. Here we report a cell stethoscope based on an optical microcantilever that demonstrates an ultrasensitive optical phase detection system within a miniaturized microfibre interferometric structure, achieving subpiconewton sensitivity and megahertz-level responses. The microfibre is encapsulated in a biocompatible film, providing excellent liquid compatibility and immunity to electromagnetic interference, as demonstrated by piconewton-resolution dynamic force sensing in liquid-phase physicochemical reactions. We establish the microcantilever as a versatile platform for cell mechanics analysis, achieving real-time quantitative analysis and acoustic monitoring of cardiomyocyte contractions under electrical stimulation, enabling non-invasive mechanical characterization of live cells. Meanwhile, the transparent microcantilever allows simultaneous optical observation and calcium fluorescence imaging of the underlying cell, facilitating multiparametric cellular analysis. These results showcase precise sensing of cellular mechanical dynamics across diverse environments, providing emerging opportunities in cellular mechanics and biomechanics.