It sounds like something out of a comic book or a science fiction movie
– a living laser – but that is exactly what two
investigators at the Wellman Center for Photomedicine at Massachusetts
General Hospital have developed. In a report that will appear in
the journal Nature Photonics and is receiving advance online release,
Wellman researchers Malte Gather, PhD, and Seok Hyun Yun, PhD, describe
how a single cell genetically engineered to express green fluorescent
protein (GFP) can be used to amplify the light particles called photons
into nanosecond-long pulses of laser light.
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| Microscope image of a single-cell living laser in action. |
"Since they were first developed some 50 years ago, lasers have used
synthetic materials such as crystals, dyes and purified gases as
optical gain media, within which photon pulses are amplified as they
bounces back and forth between two mirrors," says Yun, corresponding
author of the report. "Ours is the first report of a successful
biological laser based on a single, living cell."
Adds Gather, a research fellow and the paper's lead author, "Part of
the motivation of this project was basic scientific curiosity. 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 investigators 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 researcher 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 GFP solution could amplify input energy into
brief pulses of laser light, the researchers estimated the concentration of GFP
required to produce the laser effect.
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 millionths of a meter – in a microcavity
consisting of two highly reflective mirrors spaced 20 millionths of a meter
apart. Not only did the cell-based device produce pulses of laser light as in
the GFP solution experiment, the researchers 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 were able
to continue 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," says 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."
Gather adds, "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. 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 the next milestone in
this research." The study was supported by grants from the National Science
Foundation and the Korea National Research Foundation.
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