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Related Experiment Video

Updated: Sep 10, 2025

Implementation of a Reference Interferometer for Nanodetection
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Leveraging Partial Coherence to Enhance Nanoparticle Detection Sensitivity and Throughput in Interferometric

Chiara Lombardo1, Andrea Sottini1, Sarina Seiter1

  • 1Nanophotonic Systems Laboratory, Department of Mechanical and Process Engineering, ETH Zurich, Tannenstrasse 3, Zurich 8092, Switzerland.

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|August 27, 2025
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Summary

This study shows how partial coherence improves label-free microscopy for detecting single nanoparticles. Tuning partial coherence enhances sensitivity and throughput in techniques like interferometric scattering microscopy (iSCAT).

Keywords:
digital holographyiSCATinterferometric microscopylabel-free imagingnanophotonicspartial coherencesensing

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Area of Science:

  • Optical microscopy
  • Nanotechnology
  • Biotechnology

Background:

  • Interferometric microscopy offers label-free, real-time monitoring of nanoparticles and chemical reactions.
  • Coherent artifacts and low photon flux limit sensitivity and throughput in current methods.
  • Interferometric scattering microscopy (iSCAT) is a key technique in this field.

Purpose of the Study:

  • To investigate the impact of partial coherence on signal contrast and noise in inline holography microscopes.
  • To enhance the signal-to-noise ratio for detecting single nanoparticles (NPs) regardless of their properties or light source.
  • To improve sensitivity and throughput in label-free microscopy for complex biological and chemical systems.

Main Methods:

  • Systematic characterization of partial coherence effects in reflection-geometry inline holography.
  • Modification of lasers into partially coherent sources for enhanced photon flux.
  • Application of findings to synthetic and biological nanoparticles, and single-protein detection.

Main Results:

  • Partially coherent laser sources can match incoherent source performance with higher photon flux.
  • Tuning partial coherence significantly enhances detection sensitivity for various NPs.
  • Signal contrast is shown to vary with focus position based on partial coherence.
  • Principles confirmed for differential imaging modalities, achieving highest sensitivity.

Conclusions:

  • Partial coherence is a critical factor for improving label-free nanoparticle detection sensitivity and throughput.
  • This approach overcomes limitations of coherent artifacts and photon flux in advanced microscopy.
  • Findings pave the way for next-generation microscopes in biotechnology, nanotechnology, and biosensing.