Nano Laser Probes Cells

Researchers have developed a laser smaller than a red blood cell that can be tuned to emit different colors. They have incorporated the nanowire-based laser into a device that, by combining features from multiple microscopy techniques, could reveal new details about the structure and behavior of living cells.

The prototype nanowire microscope, developed by researchers at the University of California, Berkeley, and the Lawrence Berkeley National Laboratory, could eventually be used to probe cells with finely controlled amounts of force, while at the same time monitoring how these forces change the shape of cells and the locations of fluorescently tagged proteins. This could give researchers a better understanding of how cells work, which could offer clues about what happens when things go wrong, as occurs with cancer.

“This is truly beautiful work–a tour de force,” says Charles Lieber, a professor of chemistry at Harvard University. He says that the results are a “major advance” in the growing field of nanophotonics, adding that the nanowire laser “opens up many opportunities and will impact substantially imaging in chemistry and biology, as well as other fields.”

The new microscope consists of a nanowire laser that emits green light, held in place by an infrared laser. That’s done by exploiting the tiny forces generated by light that can draw very small objects to the focal point of a laser beam. The infrared laser also serves as an optical pump, providing a source of energy that drives the nanowire to emit green light. Images can be scanned by moving a sample back and forth in front of the laser and measuring the light transmitted through or reflected from the sample. What’s more, the nanowires can be used as mechanical probes for applying force and for tracing the shape of a cell membrane by monitoring the displacement of the nanowire as it moves across the membrane.

To make the device, the researchers began by chemically synthesizing nanowires made of potassium niobate, the same material used in green laser pointers. By varying the wavelength of the pumping laser, it’s possible to change the color the nanowire emits, which could be useful for illuminating different fluorescent protein markers.

To test the device, the researchers used the infrared laser to hold the nanowire in place while they moved a test pattern of nanoscopic gold ridges back and forth under it. By measuring the light transmitted through the sample, they were able to resolve the spacing of the lines to about 100 nanometers–about twice the resolution of an ordinary light microscope. This resolution is made possible by the narrowness of the nanowire, which is smaller than the wavelength of the light that the nanowire emits.

A similar approach to high resolution is used now in near-field microscopy, but it requires a more complex system, says Jan Liphardt, a professor of physics at the University of California, Berkeley, and one of the lead researchers on the project. “All of the complexity of generating visible light, getting it to the sample, getting it through the subwavelength aperture, and moving that with respect to the sample has been shrunk into one object, the single nanowire, which costs about one or two cents,” Liphardt says.

The researchers also demonstrated that they could cause an individual fluorescent microscopic bead to glow without exciting other beads mere micrometers away by placing the end of the nanowire against it. This tight focus could help improve the specificity of the measurements. Also, because the nanowire directs its beam away from the infrared laser, the device could ensure that the forces that hold the nanowire in place will not also disturb the location of organelles within the cell.

The researchers’ next steps include modifying the shape of the nanowire so that it can be better held in place–it tends to slide around in the optical trap. A cone or pear shape could give the device even better resolution and the researchers increased control over mechanical probing.