Circular Dichroism Measurement of Single Metal Nanoparticles Using Photothermal Imaging

Abstract

Circular dichroism (CD) spectroscopy is a powerful optical technique for the study of chiral materials and molecules. It gives access to an enantioselective signal based on the differential absorption of right and left circularly polarized light, usually obtained through polarization analysis of the light transmitted through a sample of interest. CD is routinely used to determine the secondary structure of proteins and their conformational state. However, CD signals are weak, limiting the use of this powerful technique to ensembles of many molecules. Here, we experimentally realize the concept of photothermal circular dichroism, a technique that combines the enantioselective signal from circular dichroism with the high sensitivity of photothermal microscopy, achieving a superior signal-to-noise ratio to detect chiral nano-objects. As a proof of principle, we studied the chiral response of single plasmonic nanostructures with CD in the visible range, demonstrating a signal-to-noise ratio better than 40 with only 30 ms integration time for these nanostructures. The high signal-to-noise ratio allows us to quantify the CD signal for individual nanoparticles. We show that we can distinguish relative absorption differences for right circularly and left circularly polarized light as small as gmin = 4 × 10–3 for a 30 ms integration time with our current experimental settings. The enhanced sensitivity of our technique extends CD studies to individual nano-objects and opens CD spectroscopy to numbers of molecules much lower than those in conventional experiments.

Photothermal Microscopy: Imaging the Optical Absorption of Single Nanoparticles and Single Molecules

“…By separating polarization and resolution requirements on the heating and probe beams, photothermal microscopy combines excellent polarization control with a high spatial resolution. 101 …”

“…Due to the modulation of polarization at high frequency, shot-noise-limited detection of photothermal CD can be achieved. As a proof of principle of the method, Spaeth et al ( 101 ) measured circular dichroism signals of single metallic chiral plasmonic nanostructures with a signal-to-noise ratio of more than 40 with only 30 ms integration time. The high sensitivity of the method promises widespread application toward detecting very weak CD signals of chiral materials down to numbers of molecules much smaller than in conventional CD measurements.…”

“…As the nanostructure is chiral, the absorbed powers for LCP and RCP are different. Reprinted from ref ( 101 ). Copyright 2019 American Chemical Society.…”

“…However, most biomolecules absorb in the UV range rather than in the visible range. The photothermal CD microscope demonstrated by Spaeth et al ( 101 ) needs to be upgraded for use in the UV wavelength range. 181 Being a pump–probe-based technique, PT CD will still allow high spatial resolution without the need of special UV optics.…”

Cancer Nanopharmaceuticals: Physicochemical Characterization and In Vitro/In Vivo Applications

“…Spaeth et al (2019) [ 78 ] have recently introduced the concept of photothermal circular dichroism, allowing one to achieve a superior signal-to-noise ratio for the detection of chiral nano-object. The chiral response of single plasmonic nanostructures with CD in the visible range was demonstrated for the first time, extending CD studies to individual NPs and significantly improving the conventional CD spectroscopy.…”