You can’t literally be a proverbial fly on the wall to spy on confidential conversations, but you can at least get inside a fly’s head – thanks to an ultramicroscope from the Vienna University of Technology. The instrument can image in 3-D the tiniest features of biological tissues, such as the smallest blood vessels and the thin branches of nerve tracts or even the neuron network of a mouse brain. In one test, its developers created a finely detailed image of the interior of a fly’s head. The standard light-sheet ultramicroscope setup was developed in the bioelectronics department by professor Hans Ulrich Dodt; new designs to improve and modify the ultramicroscope system were made by Dr. Saiedeh Saghafi, an optical physicist. Saghafi initially used various optical strategies to convert a round laser beam into an elliptical one, which she then transformed into a thin sheet of light. Stimulated by the laser light, an extremely thin layer of the sample begins to fluoresce – and this light can be picked up with a camera to produce images layer by layer. The images are used to construct a complete 3-D model of the sample on the computer. This 3-D image of the inside of a fly’s head was captured using a newly developed ultramicroscope that allows high-resolution 3-D image capture on a very small scale. Courtesy of TU Vienna. “If we didn’t shine the laser surface through the sample, it would be a case of having to cut the sample into thin layers and then put these under a microscope one at a time,” she said. “Of course, this approach could never match the accuracy we achieve with our ultramicroscope.” For laser beams to penetrate deep into a biological sample and represent its internal structure, the sample must be clarified – any water contained in the sample must be replaced by a liquid with different optical properties. “Compared with a standard light-sheet microscope, we have achieved a marked improvement in the optical characteristics of the light sheet,” Saghafi said. “For example, the beam width at the focus is only about 1.5 μm thick, with improved uniform intensity distribution along the light sheet, and we even expect further improvement with our new project.” For her work in light surface technology, Saghafi received an award in Edmund Optics’ 2012 Higher Education Global Grant Program. A winner among 750 entries, she was granted €3000 in Edmund Optics’ products to support her research activities. The New Jersey-based optics manufacturer’s program recognizes outstanding optics work in science, technology, engineering and mathematics in nonprofit colleges and universities worldwide. The ultramicroscope has applications in medical research, including the investigation and 3-D representation of human tumors from a pathology perspective.