Tethered plasmonic switches as single-molecule, continuous monitoring biosensors
Single-molecule sensing with plasmonic nanorods has been demonstrated recently to be an effective means for detecting large proteins. This detection platform exploits the local refractive index change around the nanorod induced by the presence of the protein. The refractive index change is monitored by optically probing the plasmon resonance shift. However, this technique is not capable of small-molecule detection. To achieve both single-and small-molecule detection, a new plasmonic sensor design is needed. Here we present the construction and application of a plasmonic switch biosensor, comprised of a gold nanosphere tethered to a gold film, capable of detecting single, small molecules. Upon binding of a small molecule target to the tether (a DNA receptor sequence), the distance between the nanosphere and the film is modulated. Due to the plasmon coupling between the nanosphere and film, the distal change correlates with a large shift in the nanosphere’s plasmon resonance. The two states – analyte bound vs. unbound – are characterized by their nanosphere-film distance and are therefore distinguishable by the scattering intensity of the nanospheres at 637nm. We demonstrate the effectiveness of this sensor system by monitoring the opening and closing of a DNA hairpin tether. Due to the large shift in the plasmon resonance as a function of distance, intensity changes of ~40% are observed upon continuous opening and closing of the hairpin. For future applications, exchanging the DNA hairpin tether with alternative receptor molecules provides the opportunity to detect a variety of small-molecule analytes. Additionally, the single-molecule sensitivity gives access to measuring low concentrations and the reversibility of this plasmonic switching sensor enables real-time continuous monitoring.
Dr. Armstrong, Postdoctoral Researcher at Eindhoven University of TechnologyDr. Armstrong is a Postdoctoral Researcher at Eindhoven University of Technology. She currently works in the Molecular Biosensing for Medical Diagnostics group, embedded within the Institute for Complex Molecular Systems as well as the Applied Physics department. Dr. Armstrong obtained her Ph.D in Inorganic Chemistry at Florida State University where her research focused on nanoparticle-based energy transfer assays to study biomolecular conformations. Building upon that work, she moved to Eindhoven in 2017 and focuses her research on utilizing plasmonic nanoparticles tethered to biomolecules for single-molecule sensing applications. The primary goal of this work is to create plasmonic nanoparticle-based sensors for real-time, single-molecule, continuous monitoring in biological matrices.
RE Armstrong, P Zijlstra, M Horacek, EINDHOVEN, Netherlands