# Meta-amplified dark-field interferometric scattering microscopy

**Authors:** Hongki Lee, Junxiang Zhao, Pan Hu, Zhaoyu Nie, Ming Lei, Guanghao Chen, Soojeong Baek, Qianyi Wu, Li Chen, Ang Li, Mojie Luo, Shizhen Emily Wang, Sui Yang, Wei Wu, Zhaowei Liu

PMC · DOI: 10.1038/s41467-026-68697-6 · Nature Communications · 2026-01-23

## TL;DR

A new microscopy technique called MAD-iSCAT improves the detection of tiny bioparticles by using a plasmonic metasurface to boost signal strength and image contrast.

## Contribution

The novel use of a plasmonic metasurface to amplify scattering signals and enhance contrast in interferometric scattering microscopy.

## Key findings

- MAD-iSCAT significantly improves the detection sensitivity and image contrast for small bioparticles.
- The metasurface generates bright radiation modes in the presence of nanoparticles and minimal background in their absence.
- The method successfully detects dielectric nanoparticles, exosomes, and proteins with enhanced signal-to-noise ratio.

## Abstract

Label-free optical detection of nanometer-scale bioparticles is highly desirable for noninvasive biological studies but challenging due to the weak scattering signals that are difficult to distinguish from the illumination background. Interferometric scattering microscopy (iSCAT) has enabled high-sensitivity imaging by detecting the interference between the particle’s scattered light and a reference beam. However, enhancing the detection sensitivity and the image contrast for small particles continues to be a challenge in iSCAT. Here, we introduce meta-amplified dark-field interferometric scattering microscopy (MAD-iSCAT), which leverages a plasmonic metasurface to drastically enhance nanoparticle detection sensitivity in iSCAT. By employing a metasurface comprising sub-diffraction plasmonic meta-atom arrays, MAD-iSCAT generates bright radiation modes that intensely scatter light toward the far field in the presence of a detection nanoparticle, substantially amplifying the sensitivity. In the absence of a nanoparticle, the metasurface produces minimal background due to the dark collective mode, resulting in improved image contrast. We present a theoretical analysis of amplified interferometric imaging using designed metasurfaces and experimentally demonstrate enhancements in contrast and signal-to-noise ratio for detecting dielectric nanoparticles, exosomes, and proteins. Our approach offers broad applications in label-free biosensing and optical mass spectrometry, enabling significantly improved throughput and sensitivity.

We introduce meta-amplified dark-field interferometric scattering microscopy, which uses a plasmonic metasurface to enhance sensitivity and contrast by converting nanoparticle-induced phase perturbations into strong far-field scattering signals.

## Full-text entities

- **Diseases:** breast cancer (MESH:D001943)
- **Chemicals:** silver (MESH:D012834), water (MESH:D014867), Es (MESH:D004540), PMMA (MESH:D019904), MAD (MESH:C110804), SiO2 (MESH:D012822), PAH (MESH:C063994), silicon (MESH:D012825), DMEM (-), halogen (MESH:D006219), Er (MESH:D004871), PS (MESH:D011137)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** HTB-26 — Mus musculus (Mouse), Hybridoma (CVCL_A8FQ), MDA-MB-231 — Homo sapiens (Human), Breast adenocarcinoma, Cancer cell line (CVCL_0062)

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12932657/full.md

## References

4 references — full list in the complete paper: https://tomesphere.com/paper/PMC12932657/full.md

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Source: https://tomesphere.com/paper/PMC12932657