Leveraging Partial Coherence to Enhance Nanoparticle Detection Sensitivity and Throughput in Interferometric...

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.