Dual-angle interferometric scattering microscopy for optical multiparametric particle characterization

TL;DR

DAISY is a novel microscopy technique that simultaneously measures size and polarizability of individual nanoparticles without prior knowledge of the environment, enabling detailed particle characterization in complex samples.

Contribution

Introduces DAISY, a dual-angle interferometric scattering microscopy method that quantifies nanoparticle size, polarizability, and morphology in complex media without needing prior environmental information.

Findings

Differentiates biomolecular fractal aggregates from spherical particles.

Quantifies size and polarizability of nanoparticles in serum.

Provides morphological insights from scattering data.

Abstract

Traditional single-nanoparticle sizing using optical microscopy techniques assesses size via the diffusion constant, which requires suspended particles in a medium of known viscosity. However, these assumptions are typically not fulfilled in complex natural sample environments. Here, we introduce dual-angle interferometric scattering microscopy (DAISY), enabling optical quantification of both size and polarizability of individual nanoparticles without requiring a priori information regarding the surrounding media or super-resolution imaging. DAISY achieves this by combining the information contained in concurrently measured forward and backward scattering images through twilight off-axis holography and interferometric scattering (iSCAT). Going beyond particle size and polarizability, single-particle morphology can be deduced from the fact that hydrodynamic radius relates to the outer particle radius while the scattering-based size estimate depends on the internal mass distribution of the particles. We demonstrate this by optically differentiating biomolecular fractal aggregates from spherical particles in fetal bovine serum at the single particle level.