An international collaboration spearheaded by the Zepler Institute for Photonics and Nanoelectronics, the Department of Chemistry and the School of Biological Sciences at Southampton has yielded highly-detailed images of lab-grown neurons using Extreme Ultraviolet radiation that could enhance the analysis of Alzheimer’s and other neurodegenerative diseases.
The study, recently published in Science Advances, used coherent Extreme Ultraviolet (EUV) light from an ultrafast laser to create images of the neuron samples by collecting scattered light, without the need for a lens. The EUV technique processes multiple scatter patterns from a sample using a computer algorithm. The project compared EUV-produced images of lab-grown neurons originating from mice with traditional light microscope images, revealing its much finer details and higher resolution. Unlike hard x-ray microscopy, no damage was observed to the delicate neuron structure.
EUV microscopy provides many advantages over optical, hard x-ray or electron-based techniques, however the traditional sources and optics involved have (until now) required large associated scale and costs. This new approach has focused on nonlinear optical techniques and, in particular, from high harmonic generation (HHG) using intense femtosecond lasers. The combination of tomographic imaging techniques with these latest advances in laser technologies and coherent EUV sources also has the potential for high-resolution biological imaging in 3D.
These experiments from the Southampton-based scientists, in collaboration with Dr Richard Chapman’s team at the Central Laser Facility in Harwell and research partners in Germany and Italy, demonstrated how extra detail can be sampled without large, expensive facilities such as synchrotrons and free electron lasers.
Dr Bill Brocklesby of the Zepler Institute, one of the study’s authors, commented:
The ability to take detailed images of delicate biological structures like neurons without causing damage is very exciting, and to do it in the lab without using synchrotrons or other national facilities is a real innovation. Our way of imaging fills an important niche between imaging with light, which doesn’t provide the fine details we see, and things like electron microscopy, which require cryogenic cooling and careful sample preparation.
Professor Jeremy Frey, Head of Computational Systems Chemistry and another principle investigator, added:
It has been a long and sustained effort but highly rewarding. In April 2003, we started a journey with the award of an Engineering and Physical Sciences Research Council Basic Technology grant for New Technology for nanoscale X-ray sources: Towards single isolated molecule scattering.
Some 17 years later, almost to the day, our paper in Science Advances demonstrates that the effort was well worth the hard work of our interdisciplinary team, obtaining the first ultra-high resolution images of a real biological sample using coherent soft-x-ray microscopy (ptyography). We are looking forward to applying our microscope to many biological, chemical and material problems. We continue to pursue even higher resolution with the ultimate aim of singe molecule imaging, a goal that now seems very much in view.
With further work and regular scientific provision of the EUV technique, this small-scale study has potential for future applications to aid the medical field, including the study of Alzheimer’s disease (the primary cause of old-age dementia).
