<p>Quantitative characterization of dynamic cell–substrate interactions at high spatiotemporal resolution remains a key challenge for bio-integrated microsystems, particularly under rapid external perturbations. Existing approaches are limited by labeling requirements, low temporal resolution, or endpoint measurements, preventing real-time access to early cellular responses. Here, we develop an integrated nanophotonic surface plasmon resonance microscopy (SPRM) microsystem for real-time, label-free quantification of single-cell interfacial dynamics. The system establishes a multi-parameter sensing framework by jointly extracting SPR intensity, cell–substrate axial position, and adhesion area, enabling continuous and quantitative mapping of cell–interface coupling with high spatiotemporal resolution. After validating system performance under controlled perturbations, we apply the platform to monitor rapid cellular responses using photodynamic therapy (PDT) as a model system. The microsystem resolves an ultrafast weakening of cell–substrate adhesion within ~25 s of stimulation onset and enables quantitative discrimination of treatment efficacy across different conditions. Notably, these early biophysical changes precede alterations in adhesion-related biomarkers measured by conventional immunofluorescence and flow cytometry. This work establishes SPRM as an integrated sensing microsystem that converts nanophotonic signals into quantitative descriptors of cellular mechanics, providing a generalizable platform for real-time, non-invasive analysis of cellular responses. The proposed framework offers broad potential for drug screening, cell–material interaction studies, and bio-integrated sensing applications.</p><p></p>

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An integrated nanophotonic SPRM microsystem for real-time, label-free quantification of single-cell adhesion dynamics

  • Songfeng Huang,
  • Yue Jiao,
  • Yuye Wang,
  • Xiaoqi Dai,
  • Junkang Deng,
  • Jiali Tai,
  • Xiaorui Liu,
  • Hailong Ni,
  • Feiran Xie,
  • Jiajie Chen,
  • Junle Qu,
  • Gaixia Xu,
  • Yonghong Shao

摘要

Quantitative characterization of dynamic cell–substrate interactions at high spatiotemporal resolution remains a key challenge for bio-integrated microsystems, particularly under rapid external perturbations. Existing approaches are limited by labeling requirements, low temporal resolution, or endpoint measurements, preventing real-time access to early cellular responses. Here, we develop an integrated nanophotonic surface plasmon resonance microscopy (SPRM) microsystem for real-time, label-free quantification of single-cell interfacial dynamics. The system establishes a multi-parameter sensing framework by jointly extracting SPR intensity, cell–substrate axial position, and adhesion area, enabling continuous and quantitative mapping of cell–interface coupling with high spatiotemporal resolution. After validating system performance under controlled perturbations, we apply the platform to monitor rapid cellular responses using photodynamic therapy (PDT) as a model system. The microsystem resolves an ultrafast weakening of cell–substrate adhesion within ~25 s of stimulation onset and enables quantitative discrimination of treatment efficacy across different conditions. Notably, these early biophysical changes precede alterations in adhesion-related biomarkers measured by conventional immunofluorescence and flow cytometry. This work establishes SPRM as an integrated sensing microsystem that converts nanophotonic signals into quantitative descriptors of cellular mechanics, providing a generalizable platform for real-time, non-invasive analysis of cellular responses. The proposed framework offers broad potential for drug screening, cell–material interaction studies, and bio-integrated sensing applications.