Fast, Label-Free Tracking of Single Viruses and Weakly Scattering Nanoparticles in a Nanofluidic Optical Fiber.
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 having a subwavelength, nanofluidic channel and illuminate them using the fiber's strongly confined optical mode. The diffusing particles in this cylindrical 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-26 nm in size and 4.6 megadaltons in mass-at rates of over 3 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.
Huygens-Kamerlingh Onnes Laboratory, Leiden University , P.O. Box 9504, 2300 RA Leiden, The Netherlands.
Sanli
S
Faez
Department of Physics, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.
Yoav
Y
Lahini
Heraeus Quarzglas GmbH & Co. KG , 63450 Hanau, Germany.|Leibniz Institute of Photonic Technology , Albert-Einstein-Str. 9, 07754 Jena, Germany.
Stefan
S
Weidlich
Rees F
RF
Garmann
Leibniz Institute of Photonic Technology , Albert-Einstein-Str. 9, 07754 Jena, Germany.
Katrin
K
Wondraczek
Leibniz Institute of Photonic Technology , Albert-Einstein-Str. 9, 07754 Jena, Germany.
Matthias
M
Zeisberger
Leibniz Institute of Photonic Technology , Albert-Einstein-Str. 9, 07754 Jena, Germany.|Otto Schott Institute of Material Research , Fraunhoferstr. 6, 07743 Jena, Germany.
Markus A
MA
Schmidt
Huygens-Kamerlingh Onnes Laboratory, Leiden University , P.O. Box 9504, 2300 RA Leiden, The Netherlands.
Michel
M
Orrit
Vinothan N
VN
Manoharan
D046210:Microfluidic Analytical Techniques / Q000295:instrumentation*; D057139:Nanofibers / Q000737:chemistry*; D053758:Nanoparticles / Q000032:analysis*; D036103:Nanotechnology / Q000295:instrumentation*; D055100:Optical Fibers; D014773:Virology / Q000295:instrumentation / Q000379:methods; D014780:Viruses / Q000737:chemistry / Q000302:isolation & purification*
biosensing; label-free; nanofluidics; self-diffusion; single particle tracking; virus detection