High Def 3D Nanoscale Ultrasound Imaging Of Live Cells

A breakthrough technique that uses sound instead of than light to see inside live cells, has been developed by researchers at The University of Nottingham. The method has the potential for applications in stem cell transplants and cancer diagnosis.

The new nanoscale ultrasound technique uses shorter-than-optical wavelengths of sound and could even rival super-resolved fluorescence microscopy, the optical techniques which won the 2014 Nobel Prize for Chemistry.

This new sub-optical phonon imaging enables the capture of invaluable information about the structure, mechanical properties and behavior of individual living cells at a scale not achieved before.

Looking Inside Single Cells

In conventional optical microscopy, which uses light photons, the size of the smallest object you can see, or the resolution, is limited by the wavelength.

“People are most familiar with ultrasound as a way of looking inside the body. In the simplest terms we’ve engineered it to the point where it can look inside an individual cell. Nottingham is currently the only place in the world with this capability,”

said Professor Matt Clark, who contributed to the study.

For biological specimens, the wavelength cannot go smaller than that of blue light because the energy carried on photons of light in the ultraviolet (and shorter wavelengths) is so high it can destroy the bonds that hold biological molecules together damaging the cells.

Optical super-resolution imaging also has distinct limitations in biological studies. This is because the fluorescent dyes it uses are often toxic and it requires huge amounts of light and time to observe and reconstruct an image which is damaging to cells.

Acanthamoeba

Acanthamoeba, an amoeba that can cause eye infections in contact lens wearers. Credit: University of Nottingham

Unlike light, sound does not have a high-energy payload. This has enabled the Nottingham researchers to use smaller wavelengths and see smaller things and get to higher resolutions without damaging the cell biology.

“A great thing is that, like ultrasound on the body, ultrasound in the cells causes no damage and requires no toxic chemicals to work. Because of this we can see inside cells that one day might be put back into the body, for instance as stem-cell transplants,” adds Professor Clark.

The work was supported by grants from the Engineering and Physical Sciences Research Council.

Pérez-Cota, F. et al.
High resolution 3D imaging of living cells with sub-optical wavelength phonons
Sci. Rep. 6, 39326; doi: 10.1038/srep39326 (2016)

Top Image: Stem cells becoming fat cells. University of Nottingham

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