Label-Free Imaging of Single-Cell Adhesion Using Phase Angle-Responsive Light-Addressable Electrochemical Sensors

Cell adhesion to the extracellular matrix (ECM) regulates essential biological processes and plays a critical role in disease progression. Current adhesion assays often rely on labeling or lack single-cell resolution. Here, we present a phase angle-responsive light-addressable electrochemical sensor (LAES) for label-free, single-cell imaging of cell-substrate adhesion. By analyzing the phase angle, which is the temporal offset between voltage and photocurrent, we achieve robust detection of interfacial dielectric changes, overcoming limitations of conventional amplitude-based LAES. This platform enables the quantitative assessment of cell adhesion across diverse cell types and semiconductor substrates. Dynamic modulation of adhesion using ECM coatings and trypsin treatment further confirms the sensitivity of phase angle imaging to adhesion strength. A point-contact electrical equivalent circuit model supports the observed correlation between phase angle shifts and cell-substrate junction resistance. This work establishes phase angle-based LAES as a powerful tool for single-cell adhesion mapping with strong potential for mechanobiology and adhesion-targeting therapeutic screening.