Scientists have developed a laser in which the optical gain medium comprises a single cell expressing green fluorescent protein (GFP). Malte C. Gather, Ph.D., and Seok Hyun Yun, Ph.D., at the Massachusetts General Hospital’s Wellman Center for Photomedicine, placed a single GFP-expressing mammalian cell into a microcavity formed by the gap between two parallel dielectric mirrors placed just 20 μm apart.
When they used a customized microscope to expose the cell to 5 nanosecond pulses of blue light, cavity feedback in the system caused the stimulated emission of intense pulses of green light by the cell rather than just fluorescence. The researchers hope their achievement will pave the way for the development of new methods for intracellular sensing, cytometry, and imaging, or photochemical therapeutics. Writing in Nature Photonics, they describe their work in a paper titled “Single-cell biological lasers.”
Since their development some 50 years ago, lasers have used synthetic materials including crystals, dyes, and purified gases as the optical gain media in which photon pulses are amplified as they bounce between the two mirrors, Dr. Yun explains. The new research suggests that biological gain media can now be added to this list.
The researchers first demonstrated that GFP itself could act as a gain medium by constructing a simple test device comprising a cylinder with mirrors at each end, filled with a solution of recombinant GFP in water. This allowed them both to confirm that the GFP solution could amplify input energy into brief pulses of laser light and to estimate the concentration of GFP required to generate the laser effect.
The results provided the basis for development of a mammalian cell line that expressed GFP at the levels required for use in a biological laser.
Encouragingly, even at high pump energies, the resulting single-cell system was capable of emitting hundreds of laser pulses before bleaching with no indication that cell viability was compromised, Drs. Gather and Yun report. In fact, the spherical shape of the cell acted as a lens, refocusing the light and inducing emissions of laser light at lower energy levels than those required for the solution-based system. Killing the cells required a pump power that was orders of magnitude higher than the normal operating range, and at normal ranges cells were alive before and after laser operation. This means a biological laser should be able to self-heal, they suggest. “If we photobleach or damage some of the emitters, the cell can make new ones.”
A number of potential applications for the cellular laser technology immediately spring to mind in the field of biological imaging, the researchers note. Compared with regular fluorescence, the emission from a cellular laser is intense, directional, and narrowband and has characteristic temporal and spectral modes. These features could be harnessed for cellular sensing to detect intracellular processes with a new level of sensitivity. Properties of cell-based lasers may in addition lead to the development of in situ light amplification technologies for applications including photochemical therapeutics, disease diagnosis, and imaging.
Indeed, the scientists are already using their achievement as a springboard for further developments including building a prototype of the cellular laser in a microfluidic platform. One of their long-term goals will be finding ways to bring optical communications and computing, which are currently carried out using inanimate electronic devices, into the realm of biotechnology, Dr. Gather states. “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.”