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

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 Added by Sanli Faez
 Publication date 2015
  fields Physics
and research's language is English




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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 fibers 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.



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Detection and characterization of individual nano-scale particles, virions, and pathogens are of paramount importance to human health, homeland security, diagnostic and environmental monitoring[1]. There is a strong demand for high-resolution, portable, and cost-effective systems to make label-free detection and measurement of individual nanoparticles, molecules, and viruses [2-6]. Here, we report an easily accessible, real-time and label-free detection method with single nanoparticle resolution that surpasses detection limit of existing micro- and nano-photonic devices. This is achieved by using an ultra-narrow linewidth whispering gallery microlaser, whose lasing line undergoes frequency splitting upon the binding of individual nano-objects. We demonstrate detection of polystyrene and gold nanoparticles as small as 15 nm and 10 nm in radius, respectively, and Influenza A virions by monitoring changes in self-heterodyning beat note of the split lasing modes. Experiments are performed in both air and aqueous environment. The built-in self-heterodyne interferometric method achieved in a microlaser provides a self-reference scheme with extraordinary sensitivity [7,8], and paves the way for detection and spectroscopy of nano-scale objects using micro- and nano-lasers.
A nanoparticle detection scheme with single particle resolution is presented. The sensor contains only a taper fiber thus offering the advantages of compactness and installation flexibility. Sensing method is based on monitoring the transmitted light power which shows abrupt jumps with each particle binding to the taper surface. The experimental validation of the sensor is demonstrated with polystyrene nanoparticles of radii 120 nm and 175 nm in the 1550 nm wavelength band.
The dynamics of nanosystems in solution contain a wealth of information with relevance for diverse fields ranging from materials science to biology and biomedical applications. When nanosystems are marked with fluorophores or strong scatterers, it is possible to track their position and reveal internal motion with high spatial and temporal resolution. However, markers can be toxic, expensive, or change the objects intrinsic properties. Here, we simultaneously measure dispersive frequency shifts of three transverse modes of a high-finesse microcavity to obtain the three-dimensional path of unlabeled SiO$_2$ nanospheres with $300$$mathrm{mu}$s temporal and down to $8$nm spatial resolution. This allows us to quantitatively determine properties such as the polarizability, hydrodynamic radius, and effective refractive index. The fiber-based cavity is integrated in a direct-laser-written microfluidic device that enables the precise control of the fluid with ultra-small sample volumes. Our approach enables quantitative nanomaterial characterization and the analysis of biomolecular motion at high bandwidth.
Chip-based Evanescent Light Scattering (cELS) utilizes the multiple modes of a high-index contrast optical waveguide to provide a near-field illumination for unlabeled samples. The scattered light off the sample is engineered to have random phase differences within the integration time of the camera to mitigate the coherent speckle noise, thus enabling label-free superior-contrast imaging of weakly scattering nanosized specimens such as extra-cellular vesicles (EVs) and liposomes, dynamics of living HeLa cells etc. The article explains and validates experimentally the physics behind cELS, by demonstrating a wide highly multi-moded straight waveguide as a partially coherent light source. Next, to circumvent the diffraction-limit in cELS, intensity-fluctuation based algorithms are employed with spatially incoherent light engineered via multiple-arms waveguide chip. The proof-of-concept results are demonstrated on 100 nm polystyrene beads. We believe cELS will further propel the nascent field of label-free super-resolution microscopy finding applications in cell biology.
358 - Jun Yang , H. Dong , C.P. Sun 2008
In this letter, we investigate the coherent tunneling process of photons between a defected circular resonator and a waveguide based on the recently developed discrete coordinate scattering methods (L. Zhou et al., Phys. Rev. Lett. 101, 100501 (2008)). We show the detailed microscopic mechanism of the tunneling and present a simple model for defect coupling in the resonator. The Finite-Difference Time-Domain(FDTD) numerical results is explored to illustrate the analysis results.
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