Harvard University engineers have built a laser that could allow researchers to peer into cells with ultrahigh resolution and watch cellular events as they happen. By adding nano antennae to infrared lasers, the researchers have made it possible to focus the light much more tightly. Indeed, the lasers could lead to imaging with at least 100 times greater resolution.
Until now, the resolution of the microscopes used for looking at the chemical composition of tissues has been constrained by a physical property of light called the diffraction limit. Using traditional lenses, light can only be focused into a beam as wide as half its wavelength; if a microscope uses mid-infrared light with a wavelength of 24 micrometers, it can only be focused onto a spot 12 micrometer wide. Considering the size of animal cells (10 micrometers), bacteria (1 micrometer), and viruses (tens of nanometers), this is far too large.
Last year, the Harvard researchers were the first to develop a practical system for overcoming the diffraction limit. Federico Capasso and Kenneth Crozier applied the technique to the lasers used to read and write discs in personal computers. This work may lead to highly dense DVD-like storage discs that hold hundreds of movies. (See “TR10: A New Focus for Light.”) Now the Harvard researchers have turned to a different kind of instrument, called a quantum-cascade laser, and a new field, biological imaging.
Quantum-cascade lasers were developed by Capasso and others at Bell Labs in 1994. These lasers are compact and sturdy and can be built to emit light at any wavelength throughout the range of the spectrum called the mid-infrared. Ranging from 3 to 24 micrometers, this light is useful for identifying different chemicals because mid-infrared light causes molecules to resonate at identifiable frequencies. Quantum-cascade lasers are used for sensing small amounts of gases, particularly pollutants, at levels as low as one part per billion.
Crozier and Capasso created a sharper focus for preexisting quantum-cascade lasers by carving two tiny gold bars where the light is emitted. They lay down a thin layer of gold, then carve it away to leave two rectangular antennae, each about one micrometer across. When the laser emits light, an intense electric field forms in the gap between the gold antennae, concentrating the light into a beam the same width as the gap, about 100 nanometers. A microscope using such a laser would also have a resolution of about 100 nanometers.
“An application where quantum-cascade lasers are currently not yet used is high-resolution imaging,” says Claire Gmachl, an electrical engineer at Princeton University who was involved in the development of quantum-cascade lasers at Bell Labs. Gmachl says that the technique shows the most promise for biological imaging at the cellular level. Microscopes using the new lasers should be able to detect, for example, changes in individual proteins on the surfaces of cells.
Using the optical antennae, says Crozier, the spot size of laser light is limited only by the gap between the gold bars. As nanofabrication techniques improve, it should be possible to make even higher-resolution optical microscopes.