Michel Orrit

University of Leiden, Leiden Institute of Technology
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“Seeing” Single Molecules and Nanoparticles

Various optical signals enable “seeing” single molecules and single nanoparticles: fluorescence or photoluminescence, dark-field or bright-field scattering, absorption through photothermal contrast, nonlinear susceptibilities, refractive effects leading to shifts of plasmon resonances, or plasmon-enhanced optical signals from weak emitters. For more than 30 years, fluorescence has been the workhorse of single-molecule optics and still provides novel insight into single chemical events, such as the turnovers of single redox proteins [1]. Enhanced by resonant local fields around plasmonic gold nanoparticles, fluorescence reveals very weak emitters or the anti-Stokes photoluminescence of gold nanoparticles, which provides their absolute temperature in a simple and direct way.
In recent years, absorption- and scattering-based techniques have reached single-molecule sensitivity. Photothermal microscopy can detect single photostable molecules, or even photosensitive ones such as single organic conjugated polymers. The differential absorption of circularly polarized light provides quantitative circular dichroism of single absorbing chiral nanoparticles, in particular magnetic ones [2]. Plasmonic gold nanoparticles can sense refractive index changes of their environment, enabling label-free detection of non-absorbing protein molecules [3]. The binding of single polymer molecules can be detected from changes in the rotational diffusion of single gold nanorods measured on-the-fly in a solution [4].
Figure 1: Scattering time trace of a single gold nanorod showing bursts upon free 3D rotational diffusion in the confocal volume. Burst statistics provide the diffusion constant quantitatively, and thereby insight about such events as the binding of single polymer molecules (from ref. [4]).

Figure 1: Scattering time trace of a single gold nanorod showing bursts upon free 3D rotational diffusion in the confocal volume. Burst statistics provide the diffusion constant quantitatively, and thereby insight about such events as the binding of single polymer molecules (from ref. [4]).

[1] Pradhan B. et al., Chem. Sci. 11, 763-771 (2020).
[2] Spaeth P. et al., Nanolett. 22, 3645-3650 (2022).
[3] Baaske M. D. et al., Sci. Adv. 8, eabl5776 (2022).
[4] Asgari N. et al., ACS Nano 7 12683-12692 (2023).