A ultrasound technique from the University of Nottingham will allow the production of sharper images inside live cells without causing damage at resolutions that were previously unattainable.
The project, from the Faculty of Engineering's Optics and Photonics research group, explores a way to look deep inside tiny structures, such as single cells, that regular light-based microscopes cannot, and without harming them.
This technique has been used to measure the stiffness of cancer cells at a single-cell level, which could allow for new methods of early cancer diagnosis to be developed.
The new technique uses sound waves, travelling through materials, to create detailed images.
To achieve this, the research team, led by Dr Mengting Yao, a research associate at the University of Nottingham, developed upon the technique called "phonon microscopy," which relies on tiny sound waves (in the gigahertz range, 10^9 Hz, 1000 times the frequency of normal medical ultrasound) generated by ultrafast lasers.
These sound waves do not naturally focus, which limits the clarity of the images they are able to obtain. To address this, special opto-acoustic lenses are being developed that can focus these sound waves in 3D.
These lenses, some of which have features as small as ~100 nm, have the potential to produce sharper images at resolutions that were previously unattainable - all without causing damage.
Dr Yao said of the research: "Acoustics holds great promise for achieving high-resolution imaging at the microscopic and even nanoscopic scale. However, generating and detecting acoustic waves with wavelengths comparable to light, and thus achieving equivalent resolution, has posed significant technical challenges.
"Scanning Acoustic Microscopy (SAM), pioneered at Stanford 40 years ago and widely adopted across various fields, demonstrated the potential of acoustics for high-resolution imaging, including proof-of-concept studies on biological cells. However, it required cryogenic freezing of samples, limiting its application to living systems.
Our technique, combined with newly developed optoacoustic lenses, enables 3D imaging of subcellular components in living cells, overcoming these barriers."
This breakthrough will also allow biologists to dynamically monitor processes like the cell cycle, cancer cell progression, and the intracellular effects of various drugs in real time.
By offering insights into cellular behaviour at the single-cell level, this technique has the potential to advance research in cancer biology, drug development, and regenerative medicine.
Sal La Cavera III, Research Fellow in the Faculty of Engineering, said: "Developing an 'acoustic microscope' that matches or exceeds the performance of an optical microscope is a holy grail of microscopy.
"Extremely high resolution optical microscopes typically require potentially toxic fluorescent labels and chemical stains, and/or harmful wavelengths of light (e.g., ultraviolet). Acoustics avoids these problems, significantly reducing harm to the specimen (acoustic waves deliver 100,000 times less energy to the specimen than visible optical waves), and even more, provides access to quantitative mechanical information about the specimen.
Dr Yao's opto-acoustic lens technology is the first solution that can actually deliver on these benefits in a practically feasible way.
"The ability to detect mechanical properties in biology at the nano-scale is a huge bonus, since recent scientific breakthroughs have shown that many diseases are driven by changes in mechanics at the cellular scale."
The full research is available online here.
