Article: Stochastic Protein Interactions Monitored by Hundreds of Single-Molecule Plasmonic Biosensors

Michael A. Beuwer , Menno W. J. Prins , and Peter Zijlstra

Molecular Biosensing for Medical Diagnostics, Faculty of Applied Physics and Faculty of Biomedical Engineering and Institute for Complex Molecular Systems, Eindhoven University of Technology, P.O. Box 513, 5600 MB, Eindhoven, The Netherlands


We present a plasmonic biosensor based on hundreds of individual gold nanorods with single-molecule sensitivity that are simultaneously monitored in real-time within a dark-field microscopy setup. The approach allows for the statistical analysis of single-molecule interactions without requiring any labeling of the analyte. We study an antibody–antigen interaction and find that the waiting-time distribution is concentration-dependent and obeys Poisson statistics. The ability to probe hundreds of nanoparticles simultaneously will provide a sensor with a dynamic range of 7 decades in concentration and will enable the study of heterogeneity in molecular interactions.