Catching Cancer with Carbon Nanotubes
A multidisciplinary team of investigators at Harvard and MIT have created a new device that can detect single cancer cells in a blood sample, potentially allowing doctors to quickly determine whether cancer has spread from its original site. The microfluidic device, described by a paper published in the journal Small, is about the size of a dime, and could also detect cancer-causing viruses such as hepatitis B and C and the human papilloma virus. It could eventually be developed into low-cost tests for doctors to use in developing countries where expensive diagnostic equipment is hard to come by, according to Harvard's Mehmet Toner, who led the team conducting this research.
Dr. Toner built an earlier version of the device four years ago. In that original version, blood taken from a patient flows past tens of thousands of tiny silicon posts coated with antibodies that stick to tumor cells. Any rare circulating cancer cells that touch the posts become trapped. However, some of these rare cells never encounter the posts at all, and given the scarcity of circulating tumor cells in the blood, missing any of them could confound the device's ability to detect cancer.
To solve that problem, Dr. Toner reasoned that if the posts were porous instead of solid, cells could flow right through them, making it more likely they would stick. To achieve that result, he enlisted the help of Brian Wardle from MIT, an expert in designing nano-engineered advanced composite materials to make stronger aircraft parts. Out of that collaboration came the new microfluidic device, studded with carbon nanotubes, that collects cancer cells eight times better than the original version.
Circulating tumor cells (cancer cells that have broken free from the original tumor) are normally very hard to detect, because there are so few of them — usually only several cells out of the millions of normal blood cells in a milliliter of blood. However, detecting these breakaway cells is an important way to determine whether a cancer has metastasized.
"Of all deaths from cancer, 90 percent are not the result of cancer at the primary site. They're from tumors that spread from the original site," said Dr. Wardle.
When designing advanced materials, Dr. Wardle often uses carbon nanotubes. Assemblies of the tubes are highly porous - a forest of carbon nanotubes, which contains 10 billion to 100 billion carbon nanotubes per square centimeter, is less than 1 percent carbon and 99 percent air. This leaves plenty of space for fluid to flow through. The MIT/Harvard team placed various geometries of carbon nanotube forest into the microfluidic device. As in the original device, the surface of each tube can be decorated with antibodies specific to cancer cells. However, because the fluid can go through the forest geometries as well as around them, there is much greater opportunity for the target cells or particles to get caught.
The researchers can customize the device by attaching different antibodies to the nanotubes' surfaces. Changing the spacing between the nanotube geometric features also allows them to capture different sized objects — from tumor cells, about a 1000 nanometers, or 1 micron, in diameter, down to viruses, which are only 40 nanometers in diameter. In fact, the researchers are now beginning to work on tailoring the device for HIV diagnosis. Toner's original cancer-cell-detecting device is now being tested in several hospitals and may be commercially available within the next few years.
This work is detailed in a paper titled, "Nanoporous Elements in Microfluidics for Multiscale Manipulation of Bioparticles." An abstract of this paper is available at the journal's website.