Optical Label-Free Microscopy Characterization of Dielectric Nanoparticles: A tutorial on ArXiv

Propagation of scattered light through a scattering microscope, illustrating typical nanoparticles studied. (Image by B. García Rodriguez.)
Optical Label-Free Microscopy Characterization of Dielectric Nanoparticles: A tutorial
Berenice Garcia Rodriguez, Erik Olsén, Fredrik Skärberg, Giovanni Volpe, Fredrik Höök, Daniel Sundås Midtvedt
arXiv: 2409.11810

In order to relate nanoparticle properties to function, fast and detailed particle characterization, is needed. The ability to characterize nanoparticle samples using optical microscopy techniques has drastically improved over the past few decades; consequently, there are now numerous microscopy methods available for detailed characterization of particles with nanometric size. However, there is currently no “one size fits all” solution to the problem of nanoparticle characterization. Instead, since the available techniques have different detection limits and deliver related but different quantitative information, the measurement and analysis approaches need to be selected and adapted for the sample at hand. In this tutorial, we review the optical theory of single particle scattering and how it relates to the differences and similarities in the quantitative particle information obtained from commonly used microscopy techniques, with an emphasis on nanometric (submicron) sized dielectric particles. Particular emphasis is placed on how the optical signal relates to mass, size, structure, and material properties of the detected particles and to its combination with diffusivity-based particle sizing. We also discuss emerging opportunities in the wake of new technology development, with the ambition to guide the choice of measurement strategy based on various challenges related to different types of nanoparticle samples and associated analytical demands.

Berenice García Rodríguez presented her half-time seminar on 8 March 2024

Berenice García Rodríguez (right) and opponent Dr. Hana Jungová (left). (Photo by J. P. Ramírez)
Berenice García Rodríguez completed the first half of her doctoral studies, and she defended her half-time on the 8th of March 2024.

The presentation, “Quantitative Analysis of Nanoparticle Properties Using Optical Scattering Techniques,” was held in a hybrid format, with part of the audience in the Nexus room and the rest connected through Zoom. The half-time consisted of a presentation about her past and planned projects, followed by a discussion and questions proposed by her opponent, Dr. Hana Jungová.

The presentation started with a short background introduction to optical scattering techniques and nanoparticle characterization techniques, followed by an introduction and description of the first paper, “Dual-Angle Interferometric Scattering Microscopy for Optical Multiparametric Particle Characterization,” and, in the end, a brief description of the projects in which Berenice is involved.

In the last section, she outlined the proposed continuation of her PhD: quantification and characterization of biomolecular condensates and their evolution over time, monitoring lipid droplets during long timescales inside living cells, and parametrization for core-shell particles.

Dual-Angle Interferometric Scattering Microscopy for Optical Multiparametric Particle Characterization published in Nano Letters

Conceptual schematic of dual-angle interferometric scattering microscopy (DAISY). (Image by the Authors of the manuscript.)
Dual-Angle Interferometric Scattering Microscopy for Optical Multiparametric Particle Characterization
Erik Olsén, Berenice García Rodríguez, Fredrik Skärberg, Petteri Parkkila, Giovanni Volpe, Fredrik Höök, and Daniel Sundås Midtvedt
Nano Letters, 24(6), 1874-1881 (2024)
doi: 10.1021/acs.nanolett.3c03539
arXiv: 2309.07572

Traditional single-nanoparticle sizing using optical microscopy techniques assesses size via the diffusion constant, which requires suspended particles to be 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 (radius <170 nm) 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 the 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 differentiating biomolecular fractal aggregates from spherical particles in fetal bovine serum at the single-particle level.