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Related Experiment Video

Updated: Aug 5, 2025

Correlative Light- and Electron Microscopy Using Quantum Dot Nanoparticles

Correlative Light- and Electron Microscopy Using Quantum Dot Nanoparticles

Published on: August 7, 2016

Correlative light-electron microscopy using small gold nanoparticles as single probes.

Iestyn Pope¹, Hugh Tanner^2,3, Francesco Masia¹

¹School of Biosciences, Cardiff University, Museum Avenue, Cardiff, CF10 3AX, UK.

Light, Science & Applications

|March 28, 2023

Summary

This summary is machine-generated.

This study introduces a new correlative light-electron microscopy (CLEM) method using gold nanoparticles and four-wave mixing (FWM) microscopy. This technique achieves high-precision imaging of cellular structures without fluorescence, offering a powerful alternative for biological research.

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Area of Science:

Biophysics
Cell Biology
Nanotechnology

Background:

Correlative light-electron microscopy (CLEM) demands probes visible in both light and electron microscopy.
Existing fluorescence-based methods have limitations in certain biological applications.

Purpose of the Study:

To develop and validate a novel CLEM approach utilizing gold nanoparticles as a single, versatile probe.
To demonstrate the efficacy of resonant four-wave mixing (FWM) microscopy for localizing these nanoparticles in live cells.

Main Methods:

Employing small gold nanoparticles (5-10 nm radius) as probes for epidermal growth factor protein in human cancer cells.
Utilizing resonant four-wave mixing (FWM) microscopy for background-free, nanometric localization in light microscopy.
Correlating FWM images with transmission electron microscopy (TEM) for high-accuracy mapping.

Main Results:

Achieved correlation accuracy below 60 nm over >10 µm areas without fiducial markers.
Improved correlation accuracy to below 40 nm by minimizing systematic errors.
Demonstrated localization precision below 10 nm and potential for multiplexing via nanoparticle shape recognition.

Conclusions:

Four-wave mixing CLEM (FWM-CLEM) with gold nanoparticles provides a robust, photostable alternative to fluorescence-based CLEM.
The method is applicable to living cells, expanding possibilities for dynamic cellular process imaging.
This technique offers high accuracy and precision for nanoscale imaging in biological systems.