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

摘要

High-speed tracking of single particles is a gateway to understandingphysical, chemical, and biological processes at the nanoscale. It is also amajor experimental challenge, particularly for small, nanometer-scaleparticles. Although methods such as confocal or fluorescence microscopy offerboth high spatial resolution and high signal-to-background ratios, thefluorescence emission lifetime limits the measurement speed, whilephotobleaching and thermal diffusion limit the duration of measurements. Herewe present a tracking method based on elastic light scattering that enableslong-duration measurements of nanoparticle dynamics at rates of thousands offrames per second. We contain the particles within a single-mode silica fibercontaining a sub-wavelength, nano-fluidic channel and illuminate them using thefiber's strongly confined optical mode. The diffusing particles in thiscylinderical geometry are continuously illuminated inside the collection focalplane. We show that the method can track unlabeled dielectric particles assmall 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 oftens of seconds. Our setup is easily incorporated into common opticalmicroscopes and extends their detection range to nanometer-scale particles andmacromolecules. The ease-of-use and performance of this technique support itspotential for widespread applications in medical diagnostics and micro totalanalysis systems.