An optical “antenna-in-a-box” capable of detecting and sensing individual molecules at high concentrations could provide a better understanding of biological and biochemical reactions to detect early stages of disease. One ultimate goal of molecular biology is being able to observe single-molecule dynamics under physiological conditions. Detecting one molecule amongst millions of neighboring molecules has been technically challenging — until now. The novel antenna-in-a-box designed by researchers at the Institute for Photonic Sciences (ICFO) in Barcelona and the Fresnel Institute in Marseille, France, is capable of detecting and sensing individual biomolecules at concentrations similar to those found in a cellular context. The device consists of a tiny dimer antenna made out of two gold semi-spheres, separated by a gap as small as 15 nm. Light sent to the antenna is amplified only in the gap area, so only molecules present in this tiny region are detected. Researchers at the Fresnel Institute and ICFO have designed and fabricated a dimer antenna inside a nanobox for single-biomolecule analysis at high concentrations. Courtesy of ICFO. To reinforce the design, the researchers embedded the dimer antennas inside nanosized boxes, screening “out the unwanted ‘noise’ of millions of other surrounding molecules, reducing the background and improving as a whole the detection of individual biomolecules,” said Jerome Wenger of the Fresnel Institute. When tested under different sample concentrations, the platform allowed for 1100-fold fluorescence brightness enhancement, together with detection volumes down to 58 zeptoliters (1 zL = 10−21 L), the smallest observation volume in the world. The antenna-in-a-box offers a highly efficient platform for nanoscale biochemical assays with single-molecule sensitivity under physiological conditions, and for ultrasensitive detection of minute amounts of molecules, providing an early diagnostic tool for biosensing of many disease markers. “It can also be used as an ultrabright optical nanosource to illuminate molecular processes in living cells and ultimately visualize how individual biomolecules interact with each other,” said professor Maria Garcia-Parajo of ICFO. “This brings us closer to the long-awaited dream of biologists.” The findings were published in Nature Nanotechnology (doi:10.1038/nnano.2013.98). For more information, visit: www.icfo.es