Fast, label-free tracking of single viruses and weakly scattering nanoparticles in a nano-fluidic optical fiber

TL;DR

This paper introduces a high-speed, label-free optical fiber-based method for tracking single viruses and nanoparticles at thousands of frames per second, overcoming limitations of fluorescence-based techniques.

Contribution

The authors develop a novel elastic light scattering technique within a nano-fluidic optical fiber for long-duration, high-speed tracking of unlabeled nanoscale particles and viruses.

Findings

Tracks particles as small as 20 nm and viruses like CCMV at over 2 kHz.

Enables long-duration measurements of nanoparticle dynamics.

Integrates easily with standard optical microscopes.

Abstract

High-speed tracking of single particles is a gateway to understanding physical, chemical, and biological processes at the nanoscale. It is also a major experimental challenge, particularly for small, nanometer-scale particles. Although methods such as confocal or fluorescence microscopy offer both high spatial resolution and high signal-to-background ratios, the fluorescence emission lifetime limits the measurement speed, while photobleaching and thermal diffusion limit the duration of measurements. Here we present a tracking method based on elastic light scattering that enables long-duration measurements of nanoparticle dynamics at rates of thousands of frames per second. We contain the particles within a single-mode silica fiber containing a sub-wavelength, nano-fluidic channel and illuminate them using the fiber's strongly confined optical mode. The diffusing particles in this cylinderical geometry are continuously illuminated inside the collection focal plane. We show that the method can track unlabeled dielectric particles as small as 20 nm as well as individual cowpea chlorotic mottle virus (CCMV) virions - 4.6 megadaltons in size - at rates of over 2 kHz for durations of tens of seconds. Our setup is easily incorporated into common optical microscopes and extends their detection range to nanometer-scale particles and macromolecules. The ease-of-use and performance of this technique support its potential for widespread applications in medical diagnostics and micro total analysis systems.