Review of Optical Detection of Single Molecules Beyond the Diffraction and Diffusion Limit Using Plasmonic Nanostructures

Single-molecule detection has become a unique and indispensable tool for the study of molecular motions and interactions at the single-molecule level. Unlike ensemble measurement where the information is averaged, single-molecule analysis yields invaluable information on both the individual molecular properties and their microenvironment. Among the various technologies for the detection of single molecules, the detection with optical methods has many advantages in terms of its high sensitivity, electrical passiveness, and robustness. The recent advances in the engineering of either the excitation light or the solution of the molecules have paved the way for enhanced single-molecule detection. We present recent developments and future perspectives for single-molecule detection in the following three regimes: on a dry surface, in solutions at ultralow concentrations, and in solutions at native physiological concentrations