It’s the million-dollar question in optical microscopy: how to image biological events occurring in the nanometer range? For years, attempts to access such events have been frustrated by the diffraction limit. High spatial frequency information is carried by evanescent waves that decay too quickly to be captured by conventional optical lenses, which collect only propagating waves that do not contain any information about events taking place on the nanoscale. Led by Xiang Zhang, a group at the University of California, Berkeley, has spent much of the past decade working to break the diffraction limit. In the March 23, 2007, issue of Science they reported a device that brought them a step closer to this goal. The “hyperlens” uses an anisotropic medium to transform scattered evanescent waves into propagating waves and projects the high-resolution image onto a far-field plane up to 1 m away. Thus it could allow researchers to probe the behavior of individual molecules in real time.One developer of the hyperlens has described recent progress. The researchers are working to improve the achievable resolution, for example, and to test new materials for use in the hyperlens – including bulk meta-materials that exhibit negative refraction at visible frequencies. Shown here is a schematic of negative refraction into the metamaterials (left). The composite is composed of silver nanowires embedded in an alumina matrix (top right). The bottom right panel shows scanning electron microscopy images of the top and side views of the nanowires. Scale bars = 500 nm. Reprinted with permission of Science. The Science paper generated a great deal of excitement. However, as recently noted by Zhaowei Liu, then a postdoctoral researcher in Zhang’s lab and now an assistant professor at the University of California, San Diego, in La Jolla: As important as the advances are, the study was still only a proof of concept. Much work remains before the hyperlens can be applied to imaging of biological events on the nanoscale. The good news is that the researchers have not let up in pursuing that objective.The continued development has followed several distinct paths, Liu said. For example, he and colleagues have been pushing to see what the maximum resolution they can attain is. In the Science paper, they experimentally demonstrated a 2.5× enhancement in resolution with respect to conventional microscopes. Now, at least from a theoretical perspective, they believe that they can achieve an enhancement of up to one order of magnitude.Separately, they have been working to develop different materials – including so-called “metamaterials” – for possible use in the hyperlens. Metamaterials are man-made composites that possess extraordinary optical properties that cannot be found in natural materials. Some have a negative refractive index or support negative refraction, for example, which could help to advance the hyperlens.In the Aug. 15, 2008, issue of Science, they reported a study in which they observed negative refraction in bulk meta-materials consisting of silver nanowires with a separation distance much smaller than the diffraction limit. Compared with traditional nanomaterials with similar functionality, Liu said, this composite “has much less loss and also significant potential to work at broadband frequencies of light. In that sense, the nanowire metamaterials represent a [significant advance] and will provide new opportunities for better hyperlens design.”He added, however, that further work is needed to make such a flat geometry curved, the geometry that facilitates magnification in the hyperlens.