Groundbreaking 3D 2-photon microscope technology published by scientists at UCL

Scientists from the Department of Neuroscience, Physiology & Pharmacology at UCL have recently published details of their groundbreaking 3D 2-photon microscope technology, which has many potential applications in biology.

Many important biological processes, such as electrical signalling in neural circuits, occur rapidly (1–100 ms) and are distributed in 3D space. Such processes are difficult to measure with conventional optical microscopes.

Dr Paul Kirkby, Dr K. M. Naga Srinivas Nadella and Prof. R. Angus Silver have developed a new type of 2-photon microscope that uses an acousto-optic lens (AOL), allowing high-speed imaging and optical measurements of biological processes in 3D space.

Conventional optical microscopes, including 2-photon laser scanning microscopes, are designed for imaging in a single focal plane (X-Y). Focusing is slow because it involves physically moving the objective lens.

To overcome this limitation, researchers at UCL have developed a novel AOL that uses four acousto-optic deflectors (AODs) to both focus and scan the laser beam. As this is achieved by ultrasonic sound waves crossing the AOD crystals and does not involve moving a mass, focusing is 300-fold faster than current piezoelectric-based methods. The design and performance of a prototype acousto-optic lens 2-photon microscope are described for the first time in Optics Express (Vol. 18, Issue 13, pp. 13720-13744, 2010).

This new generic technology, which allows rapid interrogation of any series of points within a 3D volume, or rapid raster scanning in any plane in XYZ, has the potential for use in a wide range of applications.

Professor Silver and his team intend to use this technology to investigate brain function at synaptic, neuronal and network levels. Other applications potentially include laser photolysis of caged compounds, optical tweezers, data storage and high-speed 3D 2-photon lithography.

Prof. Silver, who is leading the technology development, said: “This new imaging technology will allow us to measure rapid physiological processes distributed in 3D space with unprecedented spatio-temporal resolution. We are keen to use this new technology to investigate how networks of neurons in the brain encode and process information, an area of neuroscience that is currently poorly understood. We are grateful to the MRC, EPSRC, UCL-CIF, UCLB and the Wellcome Trust for providing the support to reach this stage.”

UCLB considers this to be a significant advance in the field of 2-photon microscopy and has made a substantial investment, with several patent filings and a large Proof of Concept (PoC) award.

Chris Williams, Business Manager on the project, said: “We are very excited by the interest we have had in this technology and we are working to identify suitable partners to realise and deliver its benefits to the research community.”

Links

•  Optics Express: ‘A compact acousto-optic lens for 2D and 3D femtosecond based 2-photon microscopy’