Probes Single Living Cells
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Once it is withdrawn from the cell, this ORNL nanosensor detects signs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
"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."