Refractometric biosensing based on optical phase flips in sparse and short-range-ordered nanoplasmonic layers

Noble metal nanoparticles support localized surface plasmon resonances (LSPRs) that are extremely sensitive to the local dielectric properties of the environment within distances up to 10–100 nm from the metal surface. The significant overlap between the sensing volume of the nanoparticles and the size of biological macromolecules has made LSPR biosensing a key field for the application of plasmonics. Recent advancements in evaluating plasmonic refractometric sensors have suggested that the phase detection of light can surpass the sensitivity of standard intensity-based detection techniques. Here, we experimentally confirm that the phase of light can be used to precisely track local refractive index changes induced by biomolecular reactions, even for dilute and layers of short-range-ordered plasmonic nanoparticles. In particular, we demonstrate that the sensitivity can be enhanced by tuning in to a zero reflection condition, in which an abrupt phase flip of the reflected light is achieved. Using a cost-effective interference fringe tracking technique, we demonstrate that phase measurements yield an approximately one order of magnitude larger relative shift compared with traditional LSPR measurements for the model system of NeutrAvidin binding to biotinylated nanodisks. Sensitive phase-based biosensing has been achieved using plasmonic metamaterial layers made of sparse, non-periodic gold-nanodisk arrays. Mikael Svedendahl and colleagues at Chalmers University of Technology in Göteborg, Sweden, realized a relative phase shift that is an order of magnitude larger than that of conventional localized surface plasmon resonance techniques using a model system of Neutravidin bound to biotinylated nanodisks. They attained this enhanced sensitivity by tuning to obtain zero reflection, since under these conditions an abrupt flip in the phase of the reflected light occurs. The set-up used is simple and inexpensive. The authors claim that this is the first time that biosensing has been carried out using the zero-reflection phase flip from purely localized plasmonic resonances. This work demonstrates that the sensitivity of phase-based detection can surpass that of standard intensity-based schemes.