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

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.