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

Area of Science:

• Optics and Photonics
• Biomedical Imaging
• Nanotechnology

Background:

• Label-free imaging techniques often struggle with poor contrast and limited resolution.
• Coherent imaging modalities can suffer from speckle noise, degrading image quality.
• Existing methods lack efficient ways to illuminate samples with diverse spatial frequencies.

Purpose of the Study:

• To elucidate the physical mechanism of generating superior-contrast, high-resolution label-free images using optical waveguides.
• To introduce and validate chip-based Evanescent Light Scattering (cELS) as a novel imaging technique.
• To explore methods for mitigating contrast and resolution limitations in coherent imaging.

Main Methods:

• Utilizing a high index contrast multi-moded waveguide as a partially coherent light source for near-field sample illumination.
• Engineering waveguide modes for coherent scattering with random spatial distributions to reduce speckle noise.
• Employing a multiple-arms waveguide geometry for isotropic sample illumination and enhanced angular diversity.

Main Results:

• Achieved (2-10)x enhanced contrast compared to other imaging techniques by mitigating speckle noise.
• Demonstrated high-contrast, label-free imaging of nanosized specimens (EVs, liposomes, nanobeads) and biological cells (HeLa).
• Validated the physical concepts mathematically and experimentally, showing superior image quality.

Conclusions:

• cELS offers a promising approach for high-quality, label-free imaging of biological samples.
• The technique effectively overcomes limitations of coherent imaging, including speckle noise and resolution.
• Further exploration of intensity-fluctuation algorithms could enhance coherent imaging further.