Researchers at MIT have found that carbon nanotubes can serve as highly sensitive biological sensors for detecting single molecules in living cells in real time. The study, published online in Nature Nanotechnology, is the first demonstration that nanoscale sensors can be used to detect and image multiple types of molecules in cells at the same time, at a sensitivity that far exceeds that of fluorescent dyes, the standard tool for molecular imaging. The researchers used the sensors to detect substances that damage DNA, including certain cancer drugs and toxins. The sensors could eventually be used to monitor the effectiveness of chemotherapy drugs, track molecular interactions in cells, and test for low levels of toxins in the environment.
Tiny detectors: A microscope image of carbon-nanotube sensors (green) emitting near-infrared fluorescence from inside live mouse fibroblast cells (red).
Michael Strano, an author of the paper and associate professor of chemical engineering at MIT, says that the work represents a leap forward in his goal to develop a nanoscale sensor for detecting molecules inside living cells. The tiny structures have recently shown promise for optical detection and imaging because they fluoresce when exposed to near-infrared light. This property is useful for biological imaging because near-infrared light can penetrate tissues more deeply than visible light can. And because cells do not fluoresce when exposed to near-infrared light, an near-infrared light-emitting sensor is easier to spot.
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The sensors developed in Strano’s lab are single-wall carbon nanotubes wrapped with a small piece of DNA. When a target molecule binds to the DNA, it causes a change in the light emitted by the nanotube; the change in the light signal can be detected by a microscope. The researchers used the sensors to detect molecules that damage DNA, including chemotherapy drugs, free radicals, and hydrogen peroxide.
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Strano says that the sensors offer several important advantages over fluorescent dyes. Not only can they detect and locate molecules, but different types of molecules will affect the properties of the emitted light differently. “When a molecule binds to it, it can change the wavelength or intensity of light that comes out,” Strano says. “Every toxin has a unique signature. So you’re not just detecting it; you can say something about what kind of toxin it is or what kind of drug it is.” In this study, the researchers used two different types of carbon nanotubes to distinguish between four different classes of toxins in living cells, but Strano believes that the sensors could be configured to detect many molecules within a sample or cell at once.
Green light: Single-walled carbon-nanotube sensors (green) clearly show up from inside . mouse cells.
Furthermore, the nanotube sensors can detect very small molecules that would be difficult to identify with other technologies, and at very low concentrations. In this study, the researchers could identify a single molecule of hydrogen peroxide, a small and volatile molecule. “In terms of sensitivity, we’ve reached the limit,” Strano says. And the optical signal of the nanotubes does not fade over time, a property called photobleaching that limits the effectiveness of fluorescent dyes.
James Heath, a chemist at Caltech who was not involved in the study, says that while questions remain about how these sensors compare with other approaches, they represent an impressive achievement. “A single platform that can be delivered into cells and then optically report on chemical events within the cell is very original, and it is amazing that this system works as well as it does,” he says.
The most immediate application of the technology is as a research tool, allowing scientists to find and study the behavior of chemical signals that were difficult to study before, because of size or low concentration. The sensors can be used to study the effects of antioxidants in cells, or could also be extended to tissues–for example, to study chemical reactions in cancer cells within a tumor.
However, Ravi Kane, a chemical and biological engineer at Rensselaer Polytechnic Institute, says that this class of sensors “could have numerous diagnostic applications.” Strano says that the technology could eventually be used in humans to give doctors a way to track the effectiveness of chemotherapy regimens and tailor dosages for individual patients. Although this study focuses on chemicals that interact with DNA, the sensors can be adapted for other purposes, depending on what is wrapped around the carbon nanotube. Strano’s lab has been using similar sensors to study glucose and brain neurotransmitters in cells and tissues.
