Experimentally Derived Design Rules for Engineering Scattering in Plasmonic Nanomaterials for Optical Coherence Tomography (OCT)

Rational engineering of plasmonic nanomaterials for scattering-based optical technologies requires experimentally validated structure−property relationships that connect nanoparticle design to optical performance. Here, we establish an experimentally derived engineering framework that systematically relates nanoparticle concentration, size, composition, geometry, surface chemistry, and biological environment to diffuse reflectance and scattering-based optical behavior. Using gold, silver, and titanium dioxide nanomaterials with diverse sizes and morphologies, we evaluate how concentration, size, composition, geometry, surface chemistry, and surrounding environment influence PS-normalized relative diffuse reflectance. The measurements reveal nonlinear, concentration-dependent responses; composition-dependent optical performance; and geometry-dependent spectral tuning into the near-infrared. Increasing particle diameter from 60 to 80 nm was associated with substantially stronger relative diffuse reflectance under the tested conditions. Hybrid lipid membrane coatings largely preserved characteristic optical responses during assembly and subsequent exposure to physiologically relevant ionic strength, pH, and tissue-mimicking environments. OCT phantom imaging produced contrast trends consistent with reflectance-based screening, supporting diffuse reflectance spectroscopy as a practical tool for formulation selection. Together, these findings provide an integrated, application-oriented framework for developing scattering-based OCT contrast agents, with numerical relationships and material rankings restricted to the formulations and measurement conditions evaluated.