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Jefferson and Delaware researchers combine tiny nanotubes and antibodies to detect cancer
November 17, 2005By coating the surfaces of tiny carbon nanotubes with monoclonal antibodies, biochemists and engineers at Jefferson Medical College and the University of Delaware have teamed up to detect cancer cells in a tiny drop of water. The 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, Ph.D., professor of biochemistry and molecular biology at Jefferson Medical College of Thomas Jefferson University in Philadelphia and at the Kimmel Cancer Center at Jefferson, and Balaji Panchapakesan, Ph.D., assistant professor of electrical engineering at the University of Delaware in Newark, present their findings November 17, 2005 at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics 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 home 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. The MCF7 cells showed an eight-fold increase. "When cancer cell bind to antibodies, there is a rush of electrons from the nanotube device into the cell," Dr. Panchapakesan explains. "The semiconductor nanotubes become more conductive," says Dr. Wickstrom. "We saw a larger current increase for the MCF7 cells because it correlates with a greater expression of IGF1 receptors." 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 breast cancer cells don't give a spike if there is a non-specific antibody on the nanotube," he says, "and cells without that target don't cause a current jump whatever antibody is on the nanotubes.
"This method could be used for detection and it could be used for recurring circulating tumor cells or micrometastases remaining from the originally treated tumor," Dr. Wickstrom explains.
"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 Dr. 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."
Drs. Wickstrom and Panchapakesan 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.
The technique has limitations. "We don't know if we can detect more than one antigen at a time on a single cell,\\\
Thomas Jefferson University
The BT474 cancer cells, which had less IGF1R on their surfaces, caused a three-fold jump in current. The MCF7 cells showed an eight-fold increase. "When cancer cell bind to antibodies, there is a rush of electrons from the nanotube device into the cell," Dr. Panchapakesan explains. "The semiconductor nanotubes become more conductive," says Dr. Wickstrom. "We saw a larger current increase for the MCF7 cells because it correlates with a greater expression of IGF1 receptors." 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 breast cancer cells don't give a spike if there is a non-specific antibody on the nanotube," he says, "and cells without that target don't cause a current jump whatever antibody is on the nanotubes.
"This method could be used for detection and it could be used for recurring circulating tumor cells or micrometastases remaining from the originally treated tumor," Dr. Wickstrom explains.
"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 Dr. 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."
Drs. Wickstrom and Panchapakesan 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.
The technique has limitations. "We don't know if we can detect more than one antigen at a time on a single cell,\\\
Thomas Jefferson University
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Two-dimensional carbon layers, so-called graphenes, are regarded as a possible substitute for silicon in the semiconductor industry.
New study confirms exotic electric properties of graphene
First, it was the soccer-ball-shaped molecules dubbed buckyballs. Then it was the cylindrically shaped nanotubes. Now, the hottest new material in physics and nanotechnology is graphene: a remarkably flat molecule made of carbon atoms arranged in hexagonal rings much like molecular chicken wire.
Caltech scientists develop DNA origami nanoscale breadboards for carbon nanotube circuits
In work that someday may lead to the development of novel types of nanoscale electronic devices, an interdisciplinary team of researchers at the California Institute of Technology (Caltech) has combined DNA's talent for self-assembly with the remarkable electronic properties of carbon nanotubes, thereby suggesting a solution to the long-standing problem of organizing carbon nanotubes into nanoscale electronic circuits.
Breakthrough in industrial-scale nanotube processing
Rice University scientists today unveiled a method for the industrial-scale processing of pure carbon-nanotube fibers that could lead to revolutionary advances in materials science, power distribution and nanoelectronics.
Next-generation microcapsules deliver 'chemicals on demand'
Scientists in California are reporting development of a new generation of the microcapsules used in carbon-free copy paper, in which capsules burst and release ink with pressure from a pen.
Transforming Nanowires Into Nano-Tools Using Cation Exchange Reactions
A team of engineers from the University of Pennsylvania has transformed simple nanowires into reconfigurable materials and circuits, demonstrating a novel, self-assembling method for chemically creating nanoscale structures that are not possible to grow or obtain otherwise.
Study shows how carbon nanotubes can affect lining of the lungs
Carbon nanotubes are being considered for use in everything from sports equipment to medical applications, but a great deal remains unknown about whether these materials cause respiratory or other health problems.
Advance in 'nano-agriculture': Tiny stuff has huge effect on plant growth
With potential adverse health and environmental effects often in the news about nanotechnology, scientists in Arkansas are reporting that carbon nanotubes (CNTs) could have beneficial effects in agriculture.
A step toward better brain implants using conducting polymer nanotubes
Brain implants that can more clearly record signals from surrounding neurons in rats have been created at the University of Michigan. The findings could eventually lead to more effective treatment of neurological disorders such as Parkinson's disease and paralysis.
A recipe for controlling carbon nanotubes
Nanoscopic tubes made of a lattice of carbon just a single atom deep hold promise for delivering medicines directly to a tumor, sensors so keen they detect the arrival or departure of a single electron, a replacement for costly platinum in fuel cells or as energy‐saving transistors and wires.
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