Nanosensor Probes Single Living Cells

A nanosensor probe carrying a laser beam (blue) penetrates a living cell to detect the presence of a product indicating that the cell has been exposed to a cancer-causing substance.

A "nano-needle" with a tip about one-thousandth the size of a human hair pokes a living cell, causing it to quiver briefly. Once it is withdrawn from the cell, this ORNL nanosensor detects signs of early DNA damage that can lead to cancer.

To simulate exposure to a carcinogen, the cell has been incubated with a metabolite of a chemical called ben-zo[a]pyrene (BaP), a known cancer-causing environmental agent often found in polluted urban atmospheres. Under normal exposure conditions, the cell takes up BaP and metabolizes it. The BaP metabolite reacts with the cell's DNA, forming a DNA adduct, which can be hydrolyzed into a product called benzo(a)pyrene tetrol (BPT).

The nano-needle is really a 50-nm-diameter silver-coated optical fiber that carries a helium-cadmium laser beam. Attached to the optical fiber tip are monoclonal antibodies that recognize and bind to BPT. The laser light, which has a wavelength of 325 nm, excites the antibody-BPT complex at the fiber tip, causing the complex to fluoresce. The newly generated light travels up the fiber into an optical detector. The layer of silver is deposited on the fiber wall to prevent the laser excitation light and the fluorescence emitted by the antibody-BPT complex from escaping through the fiber.

This nanosensor of high selectivity and sensitivity was developed by a research group led by Tuan Vo-Dinh and his coworkers Guy Griffin and Brian Cullum. The group believes that, by using antibodies targeted to a wide variety of cell chemicals, the nanosensor can monitor in a living cell the presence of proteins and other species of biomedical interest.

"Parallel arrays of these nanosensors could be used to detect gene expression and protein production in target cells," Vo-Dinh says. "They also can be used to screen tiny amounts of drugs to determine which ones are most effective in blocking the action of disease-causing proteins in single cells. With advances in nanotechnology, we are now approaching the ultimate limit of assessing the health of individual human cells."