Label-Free Probing of Molecule Binding Kinetics Using Single-Particle Interferometric Imaging

Probing molecular interactions is critical for screening drugs, detecting pollutants, and understanding biological processes at the molecular level, but these interactions are difficult to detect, especially for small molecules. A label-free optical imaging technology that can detect molecule binding kinetics is presented, in which free-moving particles are driven into oscillations with an alternating electrical field and the interferometric scattering patterns of the particles are imaged via an optical imaging method. By tracking the charge-sensitive variations in the oscillation amplitude with sub-nanometer precision, the small molecules and metal ions binding to the surface as well as protein–protein binding kinetics were measured. The capability of the label-free measurement of molecular interactions can provide a promising platform for screening small-molecule drugs, probing conformational changes in proteins, and detecting environmental pollutants.