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Multi-moded high-index contrast optical waveguide for super-contrast high-resolution label-free microscopy

Abstract

The article elucidates the physical mechanism behind the generation of superior-contrast and highresolution label-free images using an optical waveguide. Imaging is realized by employing a high index contrast multi-moded waveguide as a partially coherent light source. The modes provide near-field illumination of unlabeled samples, thereby repositioning the higher spatial frequencies of the sample into the far-field. These modes coherently scatter off the sample with different phases and are engineered to have random spatial distributions within the integration time of the camera. This mitigates the coherent speckle noise and enhances the contrast (2–10) × as opposed to other imaging techniques. Besides, the coherent scattering of the different modes gives rise to fluctuations in intensity. The technique demonstrated here is named chip-based Evanescent Light Scattering (cELS). The concepts introduced through this work are described mathematically and the high-contrast image generation process using a multi-moded waveguide as the light source is explained. The article then explores the feasibility of utilizing fluctuations in the captured images along with fluorescence-based techniques, like intensity-fluctuation algorithms, to mitigate poor-contrast and diffraction-limited resolution in the coherent imaging regime. Furthermore, a straight waveguide is demonstrated to have limited angular diversity between its multiple modes and therefore, for isotropic sample illumination, a multiple-arms waveguide geometry is used. The concepts introduced are validated experimentally via high-contrast label-free imaging of weakly scattering nanosized specimens such as extra-cellular vesicles (EVs), liposomes, nanobeads and biological cells such as fixed and live HeLa cells.
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Category

Academic article

Language

English

Author(s)

  • Nikhil Jayakumar
  • Firehun Tsige Dullo
  • Vishesh Kumar Dubey
  • Azeem Ahmad
  • Florian Ströhl
  • Jennifer Cauzzo
  • Eduarda Mazagao Guerreiro
  • Omri Snir
  • Natasa Skalko-Basnet
  • Krishna Agarwal
  • Balpreet Singh Ahluwalia

Affiliation

  • SINTEF Digital / Smart Sensors and Microsystems
  • Karolinska Institutet
  • UiT The Arctic University of Norway

Year

2022

Published in

Nanophotonics

ISSN

2192-8606

Volume

11

Issue

15

Page(s)

3421 - 3436

View this publication at Norwegian Research Information Repository