PHILADELPHIA and NEWARK, Del., Dec. 7 -- By coating the surfaces of tiny carbon nanotubes with monoclonal antibodies, biochemists and engineers at Jefferson Medical College and the University of Delaware can detect cancer cells in a tiny drop of water. Their work is aimed at developing nanotube-based biosensors that can spot cancer cells circulating in the blood from a treated tumor that has returned or from a new cancer. The researchers, led by Eric Wickstrom, professor of biochemistry and molecular biology at Jefferson Medical College and Kimmel Cancer Center at Thomas Jefferson University, and Balaji Panchapakesan, assistant professor of electrical engineering at the University of Delaware in Newark, presented their findings Nov. 17 at a recent molecular targets and cancer therapeutics conference in Philadelphia.
The group took advantage of a surge in electrical current in nanotube-antibody networks when cancer cells bind to the antibodies. They placed microscopic carbon nanotubes between electrodes and then covered them with monoclonal antibodies –- so-called guided protein "missiles" that hone in on target protein antigens on the surface of cancer cells. The antibodies were specific for insulin-like growth factor 1 receptor (IGF1R), which is commonly found at high levels on cancer cells. They then measured the changes in electrical current through the antibody-nanotube combinations when two different types of breast cancer cells were applied to the devices. The researchers found that the increase in current through the antibody-nanotube devices was proportional to the number of receptors on the cancer cell surfaces. One type, human BT474 breast cancer cells, which do not respond to estrogen, had moderate IGF1R levels, while the other type, MCF7, which needs estrogen to grow, had high IGF1R levels. The BT474 cancer cells, which had less IGF1R on their surfaces, caused a three-fold jump in current, while the MCF7 cells showed an eight-fold increase.
The reseachers say that, when cancer cells bind to the antibodies, there is a rush of electrons from the nanotube device into the cell, and the semiconductor nanotubes become more conductive. Because the cells have a surface protein that is recognized by the antibody on the nanotubes, the current spike occurs only if a target cancer cell with the right antibody target binds to the nanotube array.
“The technique could be cost-effective and could diagnose whether cells are cancerous or not in seconds versus hours or days with histology sectioning,” says Panchapakesan. “It will allow for large-scale production methods to make thousands of sensors and have microarrays of these to detect the fingerprints of specific kinds of cancer cells.”
Wickstrom and Panchapakesan say they would like to test the technique on additional breast cancer markers and markers for other kinds of cancers to determine its utility and breadth. In future studies, researchers will add cancer cells to a drop of blood and apply the mixture to the nanotube detector to see how sensitive it is in detecting the cancer cells mixed in with real blood cells and proteins. Another test might involve using the device to try to detect specific types of cancer cells shed in the blood from tumors in animals.
At this point the researchers don't know if they can detect more than one antigen at a time on a single cell, and more study is needed. Ultimately, they say they would like to design an assay that can detect cancer cells circulating in the human bloodstream on a hand-held device no bigger than a cell phone.
For more information, visit: www.jefferson.edu