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Catching cancer with carbon nanotubes
By Dross at 2011-03-31 22:23
Catching cancer with carbon nanotubes

A Harvard bioengineer and an MIT aeronautical engineer 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 in the March 17 online edition of the journal Small, is about the size of a dime, and could also detect viruses such as HIV. 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, says Mehmet Toner, professor of biomedical engineering at Harvard Medical School and a member of the Harvard-MIT Division of Health Sciences and Technology. 

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 cancer cells that touch the posts become trapped. However, some cells might never encounter the posts at all. 

Toner thought if the posts were porous instead of solid, cells could flow right through them, making it more likely they would stick. To achieve that, he enlisted the help of Brian Wardle, an MIT associate professor of aeronautics and astronautics, and 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. 

Captured by nanotubes 

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 per 1-milliliter sample of blood, which can contain tens of billions of normal blood cells. 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,” Wardle says. 

When designing advanced materials, Wardle often uses carbon nanotubes — tiny, hollow cylinders whose walls are lattices of carbon atoms. 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 micron in diameter, down to viruses, which are only 40 nm. 

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. 

Rashid Bashir, director of the Micro and Nanotechnology Laboratory at the University of Illinois at Urbana-Champaign, says that the ability to filter specific particles, cells or viruses from a blood sample so they can be analyzed is a critical step towards creating handheld diagnostic devices. 

“Anything you can do to improve capture efficiency, or anything novel you can do to get the particles to interact with a surface more effectively, will help with sample preparation,” says Bashir, who was not part of the research team.

 



4 comments | 18789 reads

by gdpawel on Fri, 2011-04-01 21:35
Harvard and MIT scientists have developed a carbon nanotube device that could detect single cancer cells. Cancer cells that break free of a tumor are normally very hard to detect, because there are so few of them, usually only several cells per 1-milliliter sample of blood, which can contain tens of billions of normal blood cells. However, detecting these breakaway cells is an important way to determine whether a cancer has metastasized.

The original microfluidic device from four years ago featured tens of thousands of microscopic silicon posts coated with tumor-sticking antibodies: when cancer cells bumped into the posts, they’d stick. But if cancer cells didn’t bump into a silicon post, they’d go undetected. The group says their new version is eight times better.

When cancer cells migrate, there are usually only several cancer cells per 1-milliliter sample of blood containing billions of other cells, making cancer exceedingly difficult to detect. This new dime-sized microfluidic machine works in the same way, but the solid silicon tubes were switched out for highly porous carbon nanotubes. This allows the blood to actually flow through the tubes instead of just around them, increasing the likelihood of catching a cancer cell.

It is said that the experimental device may also be able to detect viruses such as HIV. Eventually, it could be turned into low-cost diagnostic kits, potentially allowing doctors to quickly determine whether cancer has spread from its original site.

Nanoporous Elements in Microfluidics for Multiscale Manipulation of Bioparticles

Grace D. Chen, Fabio Fachin, Marta Fernandez-Suarez, Brian L. Wardle, Mehmet Toner

Abstract

Solid materials, such as silicon, glass, and polymers, dominate as structural elements in microsystems including microfluidics. Porous elements have been limited to membranes sandwiched between microchannel layers or polymer monoliths. This paper reports the use of micropatterned carbon-nanotube forests confined inside microfluidic channels for mechanically and/or chemically capturing particles ranging over three orders of magnitude in size. Nanoparticles below the internanotube spacing (80 nm) of the forest can penetrate inside the forest and interact with the large surface area created by individual nanotubes. For larger particles (>80 nm), the ultrahigh porosity of the nanotube elements reduces the fluid boundary layer and enhances particle–structure interactions on the outer surface of the patterned nanoporous elements. Specific biomolecular recognition is demonstrated using cells (≈10 μm), bacteria (≈1 μm), and viral-sized particles (≈40 nm) using both effects. This technology can provide unprecedented control of bioseparation processes to access bioparticles of interest, opening new pathways for both research and point-of-care diagnostics.

While no cell can get through an individual nanotube, it is the blood plasma that flows through each tube, while the cells flow in the spaces between the tubes. When the liquid flows through each tube, it will tend to bring the tumor cells into contact with the tubes more than when the liquid flows between the posts, as in the older version. The nanotubes are in turn covered with antibodies that preferentially grab the tumor cells that are bumping into them.

Reference: Grace D. Chen et al. “Nanoporous Elements in Microfluidics for Multiscale Manipulation of Bioparticles.” Small. DOI: 10.1002/smll.201002076

[url]http://onlinelibrary.wiley.com/doi/10.1002/smll.201002076/abstract

by gdpawel on Fri, 2011-04-01 21:36
A glass plate with a nanoscale roughness could be a simple way for scientists to capture and study the circulating tumor cells that carry cancer around the body through the bloodstream.

Engineering and medical researchers at the University of Michigan have devised such a set-up, which they say takes advantage of cancer cells' stronger drive to settle and bind compared with normal blood cells.

Circulating tumor cells are believed to contribute to cancer metastasis, the grim process of the disease spreading from its original site to distant tissues. Blood tests that count these cells can help doctors predict how long a patient with widespread cancer will live.

As important as the castaway cells are, scientists don't know a lot about them. They're rare, at about one per billion blood cells. And they are not all identical, even if they come from the same tumor. Existing tools for isolating them only catch certain types of cells - those that express specific surface proteins or are larger than normal blood cells.

For example, the commonly used, FDA-approved CellSearch system uses antibody-coated magnetic beads to seek out tumor cells and bind to them. But not all circulating tumor cells express the proteins these antibodies recognize. It is possible that the most dangerous ones, known as cancer stem or progenitor cells, may have shed that tell-tale coat, thereby evading approaches that rely on antibodies.

The researchers say their system could likely trap these stealth cancer stem cells - a feat no research team has accomplished yet.

"Our system can capture the majority of circulating tumor cells regardless of their surface proteins or their physical sizes, and this could include cancer progenitor or initiating cells," said Jianping Fu, assistant professor of mechanical engineering and biomedical engineering and a senior author of a paper on the technique published online in ACS Nano.

Fu and his engineering colleagues teamed up with U-M senior cancer researcher and breast cancer clinician Dr. Sofia Merajver and her team. This multidisciplinary group believes that while the device could one day improve cancer diagnosis and prognosis, its first uses would be for researchers to isolate live circulating tumor cells from blood specimens and study their biological and physical properties.

"Understanding the physical behavior and nature of these circulating tumor cells will certainly help us understand better one of the most difficult questions in cancer biology - the metastatic cascade, that is, how the disease spreads," Fu said. "Our system could provide an efficient and powerful way to capture the live circulating tumor cells and use them as a surrogate to study the metastatic process."

But capturing them, as challenging as it has proven to be, is only the beginning, said Merajver, who has spent the last 18 years studying cell signaling and the physical properties of highly aggressive cancer cells.

"The application of integrative biology is necessary to put together the story of how these cells behave in time to achieve successful metastases and thereby discover the routes to suppressing this deadly development," Merajver said. "Our collaboration with the Fu lab exemplifies the innovation needed for the war against cancer - team science from the lab all the way to the clinic."

In their experiments, the researchers used a standard and inexpensive microfabrication technique called "reactive ion etching" to roughen glass slides with a nanoscale resolution. Then, they spiked different blood samples with cancer cells derived from human breast, cervical and prostate tissues. When they poured the samples over the glass plates, the nanorough glass surfaces captured an average of 88 percent to 95 percent of the cancer cells.

Fu suggests why.

"Blood cells are intrinsically floating," Fu said. "Cancer cells including circulating tumor cells derived from solid tumors are presumably adherent cells. They can escape from the primary tumor while maintaining certain adhesion properties that allow them to attach and establish another tumor."

In other studies, researchers have noticed that circulating tumor cells tend to stick to rough surfaces. But the rough surfaces in those studies were coated with capture antibodies. These new nanorough surfaces do not require capture antibodies.

"Our method presents a significant improvement as it can be applied in principle to any cancer cell that comes from solid tumors," Fu said.
References:

The paper is titled "Nanoroughened Surfaces for Efficient Capture of Circulating Tumor Cells without Using Capture Antibodies." The university is pursuing patent protection for the intellectual property and is seeking commercialization partners to help bring the technology to market.

The first author is Weiqiang Chen, a doctoral student in the U-M Department of Mechanical Engineering. Researchers from the Chinese Academy of Sciences in Shanghai and the City University of Hong Kong also contributed, along with others in the U-M College of Engineering and the U-M Medical School. The research was supported by the National Science Foundation, the UM-SJTU Collaboration on Biomedical Technologies, the U-M Comprehensive Cancer Center, the Michigan Institute for Clinical & Health Research and the U-M Department of Mechanical Engineering.

University of Michigan

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