In this talk, I will introduce “Convex Lens-induced Confinement (CLiC)” imaging, which works by mechanically confining single-molecules to an optical microscope’s field of view, isolating them in nanofabricated features, and eliminates the complexity and potential biases inherent to tethering molecules. I will discuss applications of our single-molecule platform to study structure-mediated DNA interactions in out-of-equilibrium conditions (Shaheen et. al., Nucl. Acid Research 2022), and how CLiC is helping develop emerging classes of genetic medicines by studying their interactions with nucleic acids. Finally, I will highlight current and future applications to connect our observations from single molecule to single cells.

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Sabrina Leslie, "Single-molecule, high-speed microscopy of DNA, RNA and lipid nanoparticle interactions to understand and advance therapeutics (Conference Presentation)," Proc. SPIE PC12390, High-Speed Biomedical Imaging and Spectroscopy VIII, PC123900E (Presented at SPIE BiOS: January 29, 2023; Published: 16 March 2023); https://doi.org/10.1117/12.2657450.6321659310112.