Imaging turns a corner

Scientists have developed a new microscope which enables a dramatically improved view of biological cells.

The researchers, at the University of St Andrews, have found a way to see far more detail thanks to an unusually curved beam of light. The innovative development, using curved surfaces (sheets) of light, provides essential information over a ten times larger volume.

It is hoped that the development will lead to improved understanding of biological development, cancer, and diseases such as Alzheimer’s, Parkinson, and Huntington that affect the human brain.

The new form of ‘light sheet imaging’, has been developed by an interdisciplinary team at St Andrews led by physicists Professor Kishan Dholakia and Dr Tom Vettenburg.

Professor Dholakia said: “There has never been a more important time to improve and enhance our visualisation of the biological world. Light plays an ever more important role in our understanding of how events at the cellular level can alter the course of the development of an organism, or the onset and evolution of disease.”

“Our novel methodology allows the University of St Andrews to emerge as a world leading institute for biomedical imaging, something we could not have envisaged even a few years ago.”

A light sheet microscope creates 3D images of cells by seeing how a sample lights up slice-by-slice when moved through a sheet of light. This sheet would ideally be as thin as a razor’s edge to be able to probe the inner workings of all cells, yet gentle as light to avoid cell damage. Unfortunately, the laws of optics show that when the light sheet is squeezed in one place it tends to spread elsewhere; we thus see the inner detail of only a handful of cells at the time near the squeezed region (the beam focus) – the ‘optical’ razorblade is not as thin as we’d like across our whole sample.

Dr Vettenburg noted: “The big picture can only emerge when we are able to see how events within each and every cell affect the organism as a whole.”

Professor Dholakia added: “Crucially, low intensity, single photon, excitation should be used efficiently to avoid harming the biology.”

The St Andrews group achieved this by exploiting a beam of light that moves on a peculiarly curved trajectory. The beam, known as the Airy beam (after the British astronomer Sir George Airy), is shaped in such a way that high resolution can be obtained without it being thin. Using this method, the light is used more efficiently to see the inner details of hundreds of cells with clarity creating an image equivalent to that which would be taken from an extended ultra-thin ‘blade’ of light.

Professor Dholakia continued: “The peculiar curved light sheet formed by the Airy beam is not a single sheet but consists of multiple parallel sheets of varying thickness, far from what may appear to be the best candidate for imaging. However, this pattern remains intact as it moves in space without spreading and the form of the beam actually results in dramatic improvements in imaging.”

Dr Vettenburg, added: “This is an exciting example of how innovative photonics can challenge and improve the way we see the biomedical world. We have been able to image large biological objects and cancer cell spheroids with subcellular detail.

“This Airy mode is set to change the way we perform light sheet imaging, a method poised to impact our understanding of the development of complex organs such as the brain in model organisms.”

Partners are sought for the commercialization of the technology. The work was funded by a UK EPSRC Programme Grant and carried out with St Andrews colleagues Dr Heather Dalgarno and Jonathan Nylk (School of Physics & Astronomy), Dr David Ferrier and Clara Coll-Lladó (Scottish Oceans Institute), Dr Tomáš Cižmár (School of Medicine), and Professor Frank Gunn-Moore (School of Biology).

The research is published in the May issue of Nature Methods.

ENDS

Notes to news editors

The research will be published at doi:10.1038/nmeth.2922

The researchers are available for interview:

Professor Dholakia: +44 1334 46 3184, [email protected]
Dr Vettenburg: +44 1334 46 3124, [email protected]