Description
Quantitative phase imaging (QPI) provides nanometric phase sensitivity for label-free mapping of biological samples, but its intrinsic contrast mechanism lacks molecular specificity. Here, we present an interferometric imaging approach that overcomes this limitation through plasmon-assisted photothermal labeling. Gold nanoparticles excited by time-modulated illumination at their plasmonic absorption peak generate localized heating, modulating the refractive index of the surrounding medium and producing measurable phase shifts that are detected by wide-field interferometric phase microscopy without lateral scanning. By analyzing the temporal phase response over the entire field of view, spatial maps of nanoparticle locations are obtained, thereby introducing molecular contrast into quantitative phase measurements. This approach constitutes one of the first demonstrations of wide-field interferometric photothermal imaging at the subcellular level without scanning, enabling molecularly specific quantitative phase imaging across extended fields of view. Furthermore, by establishing the relationship between nanoparticle geometry, optical absorption, thermal diffusion, and the resulting phase signatures, the photothermal response can be predicted and optimized for enhanced detection sensitivity and molecular labeling performance.
Unlike scanning-based photothermal microscopy techniques, the proposed interferometric method simultaneously interrogates the entire field of view, enabling high-throughput molecular-specific imaging while preserving the quantitative information provided by QPI. Beyond molecular specificity, the detection and localization of individual plasmonic labels provide a pathway toward super-resolved phase imaging beyond the diffraction limit, opening new opportunities for quantitative molecular imaging, nanoscale sensing, and biological investigation.
| I am the presenting author | Yes |
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