A human embryonic kidney cell genetically engineered to include a light-emitting jellyfish protein forms a living laser capable of producing visible nanosecond pulses of light. Lasers have used synthetic gain medium materials to amplify light since their invention in the 1960s, but professor Seok-Hyun Yun and colleague Malte Gather of the Wellman Center for Photomedicine at Massachusetts General Hospital are instead using green fluorescent protein (GFP) as their gain material. Microscope image of a single-cell living laser in action. The irregular internal structure of the green fluorescent protein-expressing cell causes the apparently random pattern of laser light emission. (Images: Nature Photonics and Malte Gather, Wellman Center for Photomedicine, Massachusetts General Hospital) "Part of the motivation of this project was basic scientific curiosity," said Gather, co-author of the report that appeared in Nature Photonics. "In addition to realizing that biological substances had not played a major role in lasers, we wondered whether there was a fundamental reason why laser light, as far as we know, does not occur in nature or if we could find a way to achieve lasing in biological substances or living organisms." The researchers chose GFP for their exploration of those questions because the protein — originally found in a species of jellyfish — can be induced to emit light without the application of additional enzymes. Its properties are well understood, and there are established techniques to genetically program many organisms to express GFP. To determine the protein's potential for generating laser light, the researchers first assembled a device consisting of an inch-long cylinder, with mirrors at each end, filled with a solution of GFP in water. After first confirming that the solution could amplify input energy into brief pulses of laser light, they estimated the concentration of GFP required to produce the laser effect. Schematic of a living laser. When a single biological cell genetically programmed to produce green fluorescent protein is placed inside an optical resonator consisting of two parallel mirrors separated by 20 µm (0.02 mm), the cell can generate green laser light. Using that information, their next step was to develop a line of mammalian cells expressing GFP at the required levels. The cellular laser was assembled by placing a single GFP-expressing cell — with a diameter of from 15 to 20 µm — in a microcavity consisting of two highly reflective mirrors spaced 20 µm apart. Not only did the cell-based device produce pulses of laser light as in the GFP solution experiment, the investigators also found that the spherical shape of the cell itself acted as a lens, refocusing the light and inducing emission of laser light at lower energy levels than required for the solution-based device. The cells used in the device survived the lasing process and continued producing hundreds of pulses of laser light. "While the individual laser pulses last for only a few nanoseconds, they are bright enough to be readily detected and appear to carry very useful information that may give us new ways to analyze the properties of large numbers of cells almost instantaneously," said Yun, who is an associate professor of dermatology at Harvard Medical School. "And the ability to generate laser light from a biocompatible source placed inside a patient could be useful for photodynamic therapies, in which drugs are activated by the application of light, or novel forms of imaging." "One of our long-term goals will be finding ways to bring optical communications and computing, currently done with inanimate electronic devices, into the realm of biotechnology," Gather said. "That could be particularly useful in projects requiring the interfacing of electronics with biological organisms. We also hope to be able to implant a structure equivalent to the mirrored chamber right into a cell, which would be the next milestone in this research." The study was supported by grants from the National Science Foundation and the Korea National Research Foundation. For more information, visit: www.partners.org