To date, lasers have been built from inanimate materials, such as purified gases, synthetic dyes or semiconductors. But now physicists in the US have shown how to induce lasing in a single living biological cell. By shining intense blue light onto fluorescent protein molecules in a cell, the team made the molecules generate intense, monochromatic, directional green light. This phenomenon could potentially be used to distinguish cancerous cells from healthy cells, claim the researchers.
The material used in the latest work is the green fluorescent protein (GFP), which is found in the jellyfish Aequorea victoria and has been used to image live cells since the 1960s. By combining the gene that encodes GFP with the DNA of any other protein, the GFP can be attached to that protein. The light it gives off can then be used to track the protein in living cells.
The natural fluorescence of GFP is incoherent, just like the light emitted by a normal light bulb. But physicists Malte Gather and Seok Hyun Yun, at the Massachusetts General Hospital and Harvard Medical School in Boston, thought it might be possible to amplify the protein’s light and so build a biological laser. A tantalizing prospect because almost any organism, from a bacterium to a cow, can be programmed to synthesize GFP.
Gather and Yun put human embryonic kidney cells into a Petri dish and then added the DNA that encodes for GFP to the cells. They then attached a drop of solution containing these re-programmed cells onto a mirror with a diameter of about 3 cm. They placed another, equal-sized, mirror above the solution, leaving a gap of about 200 μm between the mirrors. They then focused nanosecond-long blue laser pulses onto the space between the mirrors and moved the mirrors around, with the aid of a microscope, until they were able to shift a single cell into the beam's focus.
With the cell in place, the researchers gradually increased the power of the blue laser and watched how the green fluorescence changed as a result. Above a certain threshold – when the blue pulses had an energy of about 1 nJ – the energy of the emitted green light increased sharply and its spectrum narrowed to just a few well-defined peaks. This, the researchers say, is a clear signature of lasing because above this threshold there are enough protein molecules in an excited state to generate stimulated rather than spontaneous emission. The emitted green light is amplified as it bounces back and forth between the mirrors, as occurs in a conventional laser cavity.
Gather says that, to the best of his knowledge, this is the first time that a laser has been made from a living material. He mentions that scientists have previously mixed dead tissue with inorganic laser materials and seen coherent emission from the composite. But this latest material is made entirely from living tissue, and this remains alive even after emitting hundreds of laser pulses.
Gather believes that the latest work could eventually have important practical applications. Conventional machines, called cytometers, that analyse large numbers of cells usually provide just one parameter for each cell – brightness. More can be learned by studying cells under a microscope, but the long exposures required mean that this is a time-consuming process. In the GFP cell-laser, variations in intercellular structure, which introduce slight changes to the refractive index of the cell, alter both the spatial output of the laser light and its spectrum. Gather says that this additional information "might make it easier to distinguish between a cancerous cell and a benign cell, or a cell that has become infected with a virus".
The next step, says Gather, is to shrink the mirror cavity so that it is small enough to fit inside a cell, the typical diameter of which is between 10 and 20 μm. This may then allow imaging of cell-lasers inside a living animal, rather than having to extract cells for investigation in the lab. In this case the pumping laser could be supplied either from the outside by shining it through the body or by injecting light through optical fibres inserted into the body.
However, Gather emphasizes that it is difficult to predict precisely what applications could follow and adds that the motivation for the experiment was "largely basic scientific curiosity". The researchers were trying to answer the basic question, why do lasers not exist in nature? "Some astronomers claim there are star clusters that produce coherent light," Gather says, "but as far as I know, there is nothing on Earth that does so."
Writing in a "News and Views" commentary piece to accompany the paper, Steve Meech, a chemist at the University of East Anglia in the UK, says that "it is currently unclear what applications lie in store for cellular lasers". But he adds that "whatever the eventual applications, the advent of GFP in photonics certainly marks an exciting new avenue of research for this extraordinarily versatile protein".
The research appears on the website of Nature Photonics.