Abstract
Chirality is a fundamental property of molecules with far-reaching implications in biology and medicine, where misidentification or mischaracterization can lead to toxic outcomes. Due to the mismatch between the molecular twist of chiral molecules and the helical pitch of circularly polarized light, traditional techniques, such as optical rotatory dispersion and circular dichroism have had low detection sensitivity. Plasmonic nanoparticles, when interacting with circularly polarized light, undergo localized surface plasmon resonance, result in the generation of a super chiral field, dramatically boosting the detection sensitivity of molecular chirality. Since most chemically synthesized plasmonic nanostructures are inherently heterogeneous, ensemble circular dichroism measurements average out fine structure–property relationships. As a result, it is necessary to use single-particle measurements to resolve the sample heterogeneity and quantify chirality of plasmonic nanostructures. However, existing single-particle dark-field spectroscopy methods suffer from substantial artifacts from linear dichroism, caused by imperfect retardance of the broadband quarter waveplate resulting in measurement uncertainties of ±10%. This thesis develops an artifact-free single-particle chiral dark-field scattering spectromicroscopy to identify and eliminate artifacts of linear dichroism in the chiral measurements. Unpolarized white light excitation eliminates polarization distortions from high numerical aperture optics, while a quarter waveplate and Wollaston prism in the detection path simultaneously decode left-handed and right-handed circularly polarized scattering. Hyperspectral imaging collects spectra from hundreds of nanoparticles in four minutes. Linear dichroism artifacts are eliminated by dual measurements at quarter waveplate fast-axis orientations of +45° and −45° relative to the Wollaston prism. Stokes–Mueller calculus verifies that this method eliminates orientation-dependent artifacts from achiral gold nanorods while maintaining authentic chiral signals from chiral nanostructures. This method provides accurate chiral measurements without complicated modifications to the dark-field scattering microscope.