Accurate single-nanoparticle sizing down to 3 nm with an optofluidic microcavity

TL;DR

The paper presents a dispersive, label-free method for sizing single nanoparticles down to $3 nm$ using a locked, high-finesse optofluidic fiber Fabry-Perot cavity. By modeling the diffusion-induced autocorrelation function in a standing-wave cavity field and carefully processing transient single-particle events, the authors extract translational diffusion constants and hydrodynamic radii without ensemble averaging, achieving quantitative sizes that agree with DLS and TEM. The approach offers high measurement bandwidth and minimal sample volume, enabling future studies of fast dynamics such as rotation and conformational changes in nanoscale particles. This opens new avenues for analyzing unlabeled nanomaterials and dynamic processes in native-like environments.

Abstract

Nanoparticles are ubiquitous, and methods that reveal insights into single-particle properties are highly desired to enable their advanced characterization. Techniques that achieve label-free single-nanoparticle detection often lack bandwidth or do not provide quantitative information. Here, we present a cavity-based dispersive sensing method that achieves a high bandwidth to capture all relevant timescales of translational diffusion, and a sensitivity to detect and size single particles with diameters down to 3 nm. We develop an analytical model describing the autocorrelation function for particle diffusion in a standing-wave sensing geometry and propose a method to address the challenges posed by the transient nature of single-particle signals. With this, we achieve quantitative particle sizing with high precision and accuracy, and provide an important tool to analyze single-particle diffusion.

Figures (4)

• Figure 1: (a) Illustration of gold nanospheres diffusing through an optofluidic fiber Fabry-Perot microcavity. (b) The optoelectronic setup for active cavity stabilization. The two cavity fibers are inserted into a glass ferrule with a lateral microfluidic channel. Piezoelectric transducers (PZT) driven by an arbitrary function generator (AFG) and proportional-integral-derivative (PID) feedback controller allow to tune the cavity mirror separation and to actively stabilize the cavity on the slope of a resonance respectively. For a detailed description, see Methods. (c) Detection of dispersive resonance shifts induced by nanoparticles via changes in transmission of a locked cavity.
• Figure 2: (a) Example of the transmission of a locked cavity disturbed by the diffusion of a 20 nm nanosphere through the optical mode. (b) The autocorrelation of the nanoparticle signal and its fit to the analytical ACF developed in this work, along with the relatively flat background autocorrelation. (c)--(d) Time traces (top panel), correlation amplitudes $G(\delta\tau)$ (middle panel), and autocorrelograms (bottom panel) of 20 nm and 10 nm nanosphere events respectively. (e) Each nanoparticle can be mapped onto the two-dimensional space of nanoparticle diameter and autocorrelation amplitude contrast $\Delta G(\delta\tau)$.
• Figure 3: (a) Calculated normalized intensity of the cavity mode field. (b) The standing wave is modeled as a series of Gaussian functions with separation $\lambda/2$. The dashed line shows the deviation from the standing wave weighted with the normalized intensity. (c) The analytical ACF for diffusion through an optical field with varying numbers of Gaussians. The case of a single Gaussian corresponds to the ACF used in FCS.
• Figure 4: (a)--(c) Autocorrelations of single particle events with nanoparticles having nominal diameters 20 nm, 15 nm and 10 nm respectively. The averaged curves are shown darker, and the theoretical ACFs with the mean measured sizes are shown dotted. (d)--(h) Particle sizes measured with nanoparticles having nominal diameters diameters 20 nm, 15 nm, 10 nm, 5 nm and 3 nm respectively. For comparison, the size distributions obtained from a commercial DLS device are shown as dashed lines. (i) Comparison of nanoparticle sizing methods: the microcavity, DLS and TEM (10 nm and 20 nm only). Note that for clarity, the data points for different measurement methods are slightly horizontally offset.