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Updated: Sep 11, 2025

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Biomolecular Imaging of Cellular Uptake of Nanoparticles using Multimodal Nonlinear Optical Microscopy
Published on: May 16, 2022
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Combined Super-Resolution Fluorescence and Coaxial 3D Scanning Microwave Microscopy: Proof-Of-Concept In-Liquid
Chia-Hung Lee1, Kamel Haddadi2, Peter J Burke3
1Department of Biomedical Engineering, University of California, Irvine, CA 92697, USA.
Summary
We developed a 3D scanning microwave microscope for live-cell imaging, combining electrical and super-resolution optical microscopy. This novel system enables precise in-liquid measurements for life science applications.
Area of Science:
- Biophysics
- Microscopy
- Nanotechnology
Background:
- Accurate nanoscale imaging of live cells is crucial for understanding biological processes.
- Existing microscopy techniques often lack the ability to simultaneously probe electrical properties at high resolution.
- Near-field scanning microwave microscopy (SMM) offers quantitative local microwave measurements but faces challenges with biological media.
Purpose of the Study:
- To present a proof-of-concept 3D scanning microwave microscope for in-liquid, live-cell imaging.
- To integrate electrical (GHz) and optical (super-resolution) imaging capabilities.
- To establish a foundation for nanoscale imaging across the electromagnetic spectrum.
Main Methods:
- A miniaturized coaxial probe was combined with high-resolution fluorescence microscopy.
- The system operates in-liquid, enabling live-cell imaging.
- A shielded tip design minimizes microwave absorption by biological media.
Main Results:
- Simultaneous electrical and optical imaging of live cells was achieved.
- The system demonstrated micrometric spatial resolution in the 0.01–6 GHz frequency range.
- A shielded probe design significantly improved signal integrity compared to unshielded tips.
Conclusions:
- The developed system provides a novel platform for in-liquid, multi-modal nanoscale imaging.
- This technology lays the groundwork for future nano-radar imaging systems for biological applications.
- Integration with super-resolution microscopy offers a comprehensive approach to probing biology from DC to lightwave.
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