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. 2023 Jan 12;3(2):143–156. doi: 10.1021/acsphyschemau.2c00061

Figure 2.

Figure 2

Examples of single-molecule direct assays. (a) Left: Schematic of the optical setup for monitoring stochastic protein interactions using plasmon sensing. Middle: Illustration of detection principle; gold nanorods are functionalized with receptors (depicted in red), whereas the sides are blocked with tetra ethylene glycol (depicted in green). The binding of individual antibodies results in a red shift of the plasmon resonance. Right: Time trace of the normalized scattered intensity of a single gold nanorod. Stepwise changes in the signal indicate stochastic binding of single antibodies. The distribution of waiting times between events is used to determine the antibody concentration. Reproduced with permission from (23). Copyright 2015 American Chemical Society. (b) Left: Experimental design of a Whispering Gallery Mode (WGM) based sensing platform showing detection of single virus particles. Middle: The resonance is identified at a specific wavelength from a dip in the transmission spectrum acquired with a tunable laser. A resonance shift associated with molecular binding; Δλr is indicated by the dashed arrow. Bottom panel: Binding of analyte is identified from a shift Δλr of resonance wavelength. Reproduced with permission from (28). Copyright 2008 Proceedings of the National Academy of Sciences. (c) Left: Concept of interferometric scattering mass spectrometry (iSCAMS) and working principle of label-free DNA detection employing iSCAMS. Individual DNA molecules diffusing in solution bind to an appropriately charged glass surface. Middle: Binding events cause changes to the reflectivity of the interface, visualized by a contrast-enhanced interferometric scattering microscope through the interference between scattered and reflected light. Right: Statistics of the image contrast provide a single-molecule readout of molecular mass. Adapted with permission from ref (33). Copyright 2020 Oxford University Press. Adapted with permission from (36). Copyright 2018 American Association for the Advancement of Science.