Composite‐Scattering Plasmonic Nanoprobes for Label‐Free, Quantitative Biomolecular Sensing

Biosensing based on localized surface plasmon resonance (LSPR) relies on concentrating light to a nanometeric spot and leads to a highly enhanced electromagnetic field near the metal nanostructure. Here, a design of plasmonic nanostructures based on rationally structured metal–dielectric combinations is presented, called composite scattering probes (CSPs), to generate an integrated multimodal biosensing platform featuring LSPR and surface‐enhanced Raman spectroscopy (SERS). Specifically, CSP configurations are proposed, which have several prominent resonance peaks enabling higher tunability and sensitivity for self‐referenced multiplexed analyte sensing. Using electron‐beam evaporation and thermal dewetting, large‐area, uniform, and tunable CSPs are fabricated, which are suitable for label‐free LSPR and SERS measurements. The CSP prototypes are used to demonstrate refractive index sensing and molecular analysis using albumin as a model analyte. By using partial least squares on recorded absorption profiles, differentiation of subtle changes in refractive index (as low as 0.001) in the CSP milieu is demonstrated. Additionally, CSPs facilitate complementary untargeted plasmon‐enhanced Raman measurements from the sample's compositional contributors. With further refinement, it is envisioned that the method may lead to a sensitive, versatile, and tunable platform for quantitative concentration determination and molecular fingerprinting, particularly where limited a priori information of the sample is available. The ability of metal nanoparticles to concentrate and enhance near‐field enhancement can be harnessed for sensing the local biological environment. Here, a plasmonic nanostructure design based on rationally tailored metal–dielectric combinations is presented to generate an integrated multimodal, label‐free molecular fingerprinting and quantification platform featuring localized surface plasmon resonance and surface‐enhanced Raman scattering measurements.