Group leader Vinothan Manoharan holds a prop that he uses to explain how viruses assemble. Credit: Eliza Grinnell / Harvard University School of Engineering
Understanding how viruses assemble inside their hosts may provide valuable information that could help researchers develop new ways to stop viral infections, fabricate novel nanomaterials and deliver genetic material into cells. A research team led by Vinothan Manoharan at Harvard University School of Engineering (HSEAS, USA), reports a new optofluidic fiber platform based on elastic light scattering that can track unlabeled and freely moving individual viruses and nanoparticles with subwavelength precision and microsecond time resolution (ACS Nano, doi: 10.1021/acsnano.5b05646).
Confocal fluorescence microscopy methods for tracking nanoparticles are limited by fluorescence emission lifetime (speed) and photobleaching (duration). After discussions with collaborators at the Otto Schott Institute of Material Research and Heraeus Quarzglas GmbH & Co. in Germany, Manoharan says, the co-first author of the study, Sanli Faez, proposed using a special optical fiber to overcome these limitations in speed and measurement duration.
The optofluidic fiber platform consists of a single-mode, step-index optical fiber with a central subwavelength nanofluidic channel. Nanoparticles suspended in a liquid are placed in the nanochannel and are illuminated with the fiber’s confined optical mode. Because the nanochannel is smaller than the wavelength of light, part of the optical mode overlaps with the nanochannel cross section. Light that scatters off the nanoparticles travels through the fiber cladding and is collected by a microscope positioned perpendicular to the fiber. HSEAS produced a video illustrating the platform concept:
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The researchers tested the platform with 19-nm latex nanoparticles and 26-nm cowpea chlorotic mottle virus particles. Their data show that the fast, label-free tracking method can capture long-duration measurements of nanoparticle dynamics at frame rates up to 3.5 kHz.
According to the study’s authors, three key features allow their setup to conduct high-speed measurements over long time scales. First, the microscope’s perpendicular orientation to the fiber separates illumination from detection, creating a high signal-to-background ratio. Second, the fiber physically keeps the nanoparticles in focus under the microscope’s lens. And, third, the elastically scattered light’s coherence allows for interferometric measurement of the distance between nanoparticles.
The authors say that their tracking technique could be easily incorporated into existing microscope systems, extending their detection range to the nanoscale and could have “widespread applications in medical diagnostics and micro total analysis systems.”